BEACHY et al.v.Beachy et al. V. Tas et al.

Patent Trials and Appeals BoardApr 28, 2014

13363934 - (J) (P.T.A.B. Apr. 28, 2014)

BoxInterferences@uspto.gov Paper No. 607 Telephone: 571-272-4683 Filed: 28April 2014 UNITED STATES PATENT AND TRADEMARK OFFICE PATENT TRIAL AND APPEAL BOARD ____________________ Interference 105,926 McK Interference 105,949 McK Technology Center 1600 ____________________ SINAN TAS and OKTAY AVCI, Patent 7,893,078 B2, Junior Party, v. PHILIP A. BEACHY, MICHAEL K. COOPER and JEFFREY A. PORTER, Application 13/364,121, and PHILIP A. BEACHY, JAMES K. CHEN and ANSSI JUSSI NIKOLAI TAIPALE, Application 13/363,934 Senior Party. ____________________ Before: FRED E. McKELVEY, DEBORAH KATZ, and JOHN G. NEW, Administrative Patent Judges. McKELVEY, Administrative Patent Judge. JUDGMENT In view of the Decision on Motions (Paper 605) and the Third Redeclaration 1 (Paper 606), it isâ€” 2 ORDERED that judgment be entered against junior party Sinan Tas and 3 Oktay Avci (Sinan Tas being the real party in interest) as to 4 2 (1) Count 3 of Interference 105,926 (Interference 105,926, 1 Paper 97.001, page 2) and 2 (2) Count 2 of Interference 105,949 (Interference 105,949, Paper 1, 3 page 8). 4 FURTHER ORDERED that Claims 1 of 1-23 of involved US Patent 5 7,893,078 B2 are CANCELED, 35 U.S.C. 135(a); and 6 FURTHER ORDERED that a copy of this judgment be entered in the 7 administrative records of 8 (1) Tas U.S. Patent 7,893,078 B2, 9 (2) Beachy application 13/364,121, and 10 (3) Beachy application13/363,934. 11 FURTHER ORDERED that a party seeking judicial review timely serve 12 notice on the Director of the United States Patent and Trademark Office. 13 37 C.F.R. Â§Â§ 90.1 and 104.2. 14 NOTICE: "Any agreement or understanding between parties to an interference, 15 including any collateral agreements referred to therein, made in connection with or 16 in contemplation of the termination of the interference, shall be in writing and a 17 true copy thereof filed in the Patent and Trademark Office before the termination 18 of the interference as between the said parties to the agreement or understanding." 19 35 U.S.C. 135(c); see also Bd.R. 205 (settlement agreements). 20 21 3 cc (via electronic mail): 1 2 Attorney for Tas: 3 4 Walter J. Steinkraus 5 Email: wsteinkraus@live.com 6 7 Dr. Sinan Tas, pro se 8 Email: sinan.tas1@gmail.com 9 10 Attorney for Beachy: 11 12 Anthony J. Zelano 13 Brion P. Heaney 14 John A. Sopp 15 Millen, White, Zelano & Branigan, PC 16 Email: Heaney@mwzb.com 17 Emai: zelano@mwzb.com 18 Email: sopp@mwzb.com 19 20 Oliver R. Ashe, Jr. 21 Ashe, PC 22 Email: oashe@ashepc.com 23 24 BoxInterferences@uspto.gov Paper 606 Telephone: 571-272-4683 Filed: 28 April 2014 UNITED STATES PATENT AND TRADEMARK OFFICE PATENT TRIAL AND APPEAL BOARD ____________________ Interference 105,926 McK Interference 105,949 McK Technology Center 1600 ____________________ SINAN TAS and OKTAY AVCI, Patent 7,893,078 B2, Junior Party, v. PHILIP A. BEACHY, MICHAEL K. COOPER and JEFFREY A. PORTER, Application 13/364,121, and PHILIP A. BEACHY, JAMES K. CHEN and ANSSI JUSSI NIKOLAI TAIPALE, Application 13/363,934 Senior Party. ____________________ Before: FRED E. McKELVEY, Administrative Patent Judge. THIRD REDECLARATION Consistent with the Decision on Motions (Paper 605) and other action taken 1 during the course of the interferences, the interferences are redeclared (37 C.F.R. 2 Â§ 41.203(c) (2013)) as follows: 3 2 Identification of the partes 1 Junior Party 2 Inventors: Sinan Tas (Turkey) 3 Oktay Avci (Turkey) 4 Patent: U.S. Patent 7,893,978 B2, issued 22 February 2011 5 based on application 10/682,584 6 filed 09 October 2003 7 Pat. Publication: 2010/0048725 A2 (25 February 2010) 8 Title: Use of cyclopamine in the treatment of basal 9 cell carcinoma and other tumors 10 Real party in interest: Sinan Tas 11 Senior Partyâ€”105,926 12 Inventors: Philip A. Beachy (Maryland) 13 James K. Chen (California) 14 Anssi Jussi Nikolai Taipale (Finland) 15 Application: 13/363,934, filed 01 February 2012 16 Title: Regulators of the hedgehog pathway, 17 compositions and uses related thereto 18 Real party in interest: Johns Hopkins University School of Medicine of 19 Baltimore, Maryland 20 Senior Partyâ€”105,949 21 Inventors: Philip A. Beachy (Maryland) 22 James K. Chen (California) 23 Jeffrey A. Porter (Massachusetts) 24 Application: 13/364,121, filed 01 February 2012 25 Title: Inhibitors of hedgehog signaling pathways, 26 compositions and uses related thereto 27 Real party in interest: Johns Hopkins University School of Medicine of 28 Baltimore, Maryland 29 3 Counts and claims of the parties 1 The counts are Count 2 and Count 3. There is no Count 1. Count 2 is the 2 sole count in Interference 105,949. Count 3 is the sole count in Interference 3 105,926. 4 Interference 105,926 5 Count 3 6 A method for treatment of a human subject having a basal cell 7 carcinoma tumor wherein Hedgehog/Smoothened signaling is utilized 8 for inhibition of apoptosis of the tumor cells, comprising 9 administering to the human subject a medicament comprising 10 cyclopamine or a pharmaceutically acceptable salt thereof, 11 wherein said medicament is administered in a dose that is 12 sufficient to induce apoptosis of said tumor cells and causes decrease 13 of size or disappearance of the tumor, 14 or 15 a method for treatment of a human subject having a basal cell 16 carcinoma tumor wherein Hedgehog/Smoothened signaling is utilized 17 for inhibition of apoptosis, comprising 18 administering to the human subject a medicament comprising 19 cyclopamine or a pharmaceutically acceptable salt thereof, 20 wherein said medicament is administered in a dose that is 21 sufficient to induce apoptosis of tumor cells and 22 causes decrease of size of the tumor. 23 The claims of the parties are: 24 Tas: 1-23â€”all designated as corresponding to Count 3 25 4 Beachy: 101-112 and 114-127â€”all designated as corresponding 1 to Count 3 2 With respect to Count 3, the parties have been accorded an earlier 3 constructive reduction to practice (i.e., benefit for the purpose of priority) of the 4 following applications: 5 Tas: PCT/TR01/00027 6 filed 02 July 2001 7 Beachy: Application 13/176,297 8 filed 05 July 2011 (Ex 1003) 9 Application 12/079,776 10 filed 28 March 2008 11 now US Patent 7,998,946 (Ex 1004) 12 Application 11/338,503 13 filed 23 January 2006 14 now US. Patent 7,7476,661 (Ex 1005) 15 Application 09/668,076 16 filed 13 October 2000 17 now U.S. Patent, 7,098,196 (Ex 1018) 18 Interference 105,949 19 Count 2 20 A method for treatment of a human subject having a basal 21 carcinoma tumor cell wherein Hedgehog/Smoothened signaling is 22 utilized for inhibition of apoptosis of the tumor cell, comprising 23 administering to the human subject a medicament comprising 24 cyclopamine, 25 wherein said medicament is administered in a dose that is 26 sufficient to induce apoptosis of said tumor cell and causes decrease 27 of size or disappearance of the tumor, 28 5 or 1 a method of therapy for a human subject having a basal cell 2 carcinoma tumor, comprising 3 administering to the human subject a therapeutically effective 4 amount of a medicament comprising cyclopamine and a 5 pharmaceutically acceptable carrier, 6 wherein in said tumor smoothened-dependent hedgehog 7 signaling is utilized for inhibition of apoptosis, and 8 said amount of cyclopamine selectively inhibits smoothened-9 dependent hedgehog signaling in said tumor and is sufficient to induce 10 apoptosis in said tumor and inhibits tumor cell proliferation. 11 The claims of the parties are: 12 Tas: 1-23â€”all designated as corresponding to Count 2 13 Beachy: 201-213â€”all designated as corresponding to Count 2. 14 With respect to Count 2, the parties have been accorded an earlier 15 constructive reduction to practice (i.e., benefit for the purpose of priority) of the 16 following applications: 17 Tas: PCT/TR01/00027 18 filed 02 July 2001 19 Beachy: Application 12/652,134 20 filed 05 January 2010 21 Application 11/270,984 22 filed 11 November 2005 23 Application 09/708,964 24 filed 08 November 2000 25 now US Patent 7,291,626 (Ex 1009) 26 6 Application 09/685,244 1 filed 10 October 2000 (Ex 2013)2 7 cc (via electronic mail): 1 2 Attorney for Tas: 3 4 Walter J. Steinkraus 5 Email: wsteinkraus@live.com 6 7 Dr. Sinan Tas, pro se 8 Email: sinan.tas1@gmail.com 9 10 Attorney for Beachy: 11 12 Anthony J. Zelano 13 Brion P. Heaney 14 John A. Sopp 15 Millen, White, Zelano & Branigan, PC 16 Email: Heaney@mwzb.com 17 Emai: zelano@mwzb.com 18 Email: sopp@mwzb.com 19 20 Oliver R. Ashe, Jr. 21 Ashe, PC 22 Email: oashe@ashepc.com 23 BoxInterferences@uspto.gov Paper 605 Telephone: 571-272-4683 Entered: 28 April 2014 UNITED STATES PATENT AND TRADEMARK OFFICE PATENT TRIAL AND APPEAL BOARD ____________________ Interference 105,926 McK Interference 105,949 McK Technology Center 1600 ____________________ SINAN TAS and OKTAY AVCI, Patent 7,893,078 B2, Junior Party, v. PHILIP A. BEACHY, MICHAEL K. COOPER and JEFFREY A. PORTER, Application 13/364,121, and PHILIP A. BEACHY, JAMES K. CHEN and ANSSI JUSSI NIKOLAI TAIPALE, Application 13/363,934, Senior Party. ____________________ Before: FRED E. McKELVEY, DEBORAH KATZ, and JOHN G. NEW, Administrative Patent Judges. NEW, Administrative Patent Judge. DECISION ON MOTIONS 37 C.F.R. Â§ 41.125 Interferences 105,926 & 105,949 2 I. INTRODUCTION 1 A. Background 2 Interferences 105,926 and 105,949 are before a panel of the Board for a decision 3 on motions. 4 The interferences have been consolidated. Paper 5. 5 Except for initial declaration papers, all papers related to Interference 105,949 6 appear in the file of Interference 105,926. 7 References to papers are to papers in Interference 105,926 unless otherwise noted. 8 Oral argument was requested. Paper 338; Paper 340 (corrected copy). 9 We have determined that oral argument is not needed in this case. 10 Tas submissions often failed to comply with our rules and established practice as 11 set out in our Standing Order (Paper 2). 12 We have considered the record submitted by Tas, as well as the more traditional 13 record submitted by Beachy, with the view of reaching the merits to the extent possible. 14 B. Abbreviations 15 The following appreciations are used in the record and this opinion. 16 BCC Basal cell carcinoma 17 Bcl-2 A protein that affects programmed cell death or â€œapoptosisâ€ 18 BCNS Basal cell nevus syndrome 19 Hh Hedgehog protein 20 Smo Smoothened protein 21 Interferences 105,926 & 105,949 3 C. Parties 1 1. Junior Party 2 The Junior Party is Sinan Tas and Oktay Avci (â€œTasâ€ 1 ). 3 The real party-in-interest is Dr. Sinan Tas. Paper 15. 4 2. Senior Party 5 The Senior Party is (1) Philip A. Beachy, Michael K. Cooper and Jeffrey A. Porter 6 (Application 13/364,121) and (2) Philip A. Beachy, James K. Chen and Anssi Jussi 7 Nikolai Taipale (Application 13/363,934) (â€œBeachyâ€). 8 The real party-in-interest is Johns Hopkins University School of Medicine of 9 Baltimore, Maryland. Curis, Inc., is identified as a licensee. Genentech is identified as a 10 sub-licensee. Paper 10. 11 D. Subject matter involved in interferences 12 1. The counts 13 Counts 2 and 3 are involved in these consolidated interferences. 14 2. Count 2 15 Count 2 is involved in Interference 105,949. 16 Count 2 reads (Interference 105,949, Paper 1, page 8): 17 Count 2 18 A method for treatment of a human subject having a basal 19 carcinoma tumor cell wherein Hedgehog/Smoothened signaling is 20 utilized for inhibition of apoptosis of the tumor cell, comprising 21 1 â€œTasâ€ refers to the party Tas and Oktay. We will refer to inventor Tas as â€œDr. Tasâ€ to distinguish between the party Tas and inventor Tas. Interferences 105,926 & 105,949 4 administering to the human subject a medicament comprising 1 cyclopamine, 2 wherein said medicament is administered in a dose that is 3 sufficient to induce apoptosis of said tumor cell and causes decrease 4 of size or disappearance of the tumor, 2 5 or 6 a method of therapy for a human subject having a basal cell 7 carcinoma tumor, comprising 8 administering to the human subject a therapeutically effective 9 amount of a medicament comprising cyclopamine and a 10 pharmaceutically acceptable carrier, 11 wherein in said tumor smoothened-dependent hedgehog 12 signaling is utilized for inhibition of apoptosis, and 13 said amount of cyclopamine selectively inhibits smoothened-14 dependent hedgehog signaling in said tumor and is sufficient to induce 15 apoptosis in said tumor and inhibits tumor cell proliferation. 3 16 17 The claims of the parties are: 18 Tas: 1-23â€”all designated as corresponding to Count 2 19 Beachy: 201-213â€”all designated as corresponding to Count 2. 20 2 This alternative of the count is based in large measure on Claims 15 and 20 of Tas Patent 7,893,078 B2 (Ex. 2001, cols. 13 and 14). 3 This alternative of the count is based in large measure on former Beachy Claim 27 (now Claim 201) (Ex. 1008, page 1) of Beachy application 13/364,121 (Ex.1003). Interferences 105,926 & 105,949 5 With respect to Count 2, the parties have been accorded an earlier constructive 1 reduction to practice (i.e., benefit for the purpose of priority) of the following 2 applications: 3 Tas: None 4 Beachy: Application 12/652,134 5 filed 05 January 2010 6 Application 11/270,984 7 filed 11 November 2005 8 Application 09/708,964 9 filed 08 November 2000 10 now US Patent 7,291,626 (Ex 1009) 11 Application 09/685,244 12 filed 10 October 2000 (Ex 2013) 13 3. Count 3 14 Count 3 is involved in Interference 105,926. 15 Count 3 reads (Paper 97.001, page 2): 16 Count 3 17 A method for treatment of a human subject having a basal cell 18 carcinoma tumor wherein Hedgehog/Smoothened signaling is utilized 19 for inhibition of apoptosis of the tumor cells, comprising 20 administering to the human subject a medicament comprising 21 cyclopamine or a pharmaceutically acceptable salt thereof, 22 Interferences 105,926 & 105,949 6 wherein said medicament is administered in a dose that is 1 sufficient to induce apoptosis of said tumor cells and causes decrease 2 of size or disappearance of the tumor, 4 3 or 4 a method for treatment of a human subject having a basal cell 5 carcinoma tumor wherein Hedgehog/Smoothened signaling is utilized 6 for inhibition of apoptosis, comprising 7 administering to the human subject a medicament comprising 8 cyclopamine or a pharmaceutically acceptable salt thereof, 9 wherein said medicament is administered in a dose that is 10 sufficient to induce apoptosis of tumor cells and causes decrease of 11 size of the tumor. 5 12 The claims of the parties are (Paper 1, pages 9-10): 13 Tas: 1-23â€”all designated as corresponding to Count 3 14 Beachy: 101-112 and 114-127â€”all designated as corresponding to 15 Count 3 16 With respect to Count 3, the parties have been accorded an earlier constructive 17 reduction to practice (i.e., benefit for the purpose of priority) of the following 18 applications: 19 Tas: None 20 4 This alternative of the count is based in large measure on Claims 15 and 20 of Tas Patent 7,893,078 B2 (Ex. 2011, cols. 13 and 14). 5 This alternative of the count is based in large measure on former Beachy Claims 62-63 (now Claims115-116) (Ex. 1002, page 1) of Beachy application 13/363,934 (Ex. 1001). Interferences 105,926 & 105,949 7 Beachy: Application 13/176,297 1 filed 05 July 2011 (Ex. 1003) 2 3 Application 12/079,776 4 filed 28 March 2008 5 now US Patent 7,998,946 (Ex. 1004) 6 7 Application 11/338,503 8 filed 23 January 2006 9 now US. Patent 7,7476,661 (Ex. 1005) 10 11 Application 09/668,076 12 filed 13 October 2002 13 now U.S. Patent, 7,098,196 (Ex. 1018) 14 15 E. Subject matter involved 16 To perform their normal functions, cells must transmit signals within their own 17 internal environment as well as transmit to and receive signals from other cells. 18 One such â€œsignaling pathwayâ€ is called the â€œHedgehog/Smoothenedâ€ cell signaling 19 pathway because it involves two proteins: â€œHedgehogâ€ and â€œSmoothened.â€ 20 The Hedgehog/Smoothened pathway relays information from the environment 21 outside of the cell to the interior of the cell where the information can cause a specific 22 effect. 23 The parties agree that it was known that tumor cell growth could be an effect of 24 signaling along the Hedgehog/Smoothened pathway. Paper 179, at 1; Ex. 2098, Â¶ 12. 25 Tumors occur when cells grow or â€œproliferateâ€ uncontrollably. Paper 96, at 1; 26 Ex. 2098, Â¶ 48. 27 Often, cells in the body go through a process called â€œapoptosis,â€ wherein a cell 28 receives regular signals that trigger it to undergo programmed cell death. Id. 29 Interferences 105,926 & 105,949 8 A mutation in the signaling pathway for initiating apoptosis may prevent this 1 normally-programmed cell death and can lead to the formation of tumors resulting from 2 the cells proliferating in an uncontrolled manner. (Paper 96, at 1; Ex. 2098, Â¶ 49.) 3 The Counts recite the administration of a drug called cyclopamine to a specific 4 type of tumor cell, a basal carcinoma cell (â€œBCCâ€). 5 Cyclopamine takes advantage of the Hedgehog/Smoothened apoptosis signaling 6 pathway to initiate apoptosis, which inhibits the BCCs from proliferating. 7 Cyclopamine is a steroid alkaloid having the chemical formula shown below: 8 9 Ex. 2001, col.2, ll. 5-15. 10 A dispute in this case involves the relationship of the effects of cyclopamine on 11 apoptosis, tumor cell proliferation, and the size and appearance of the tumor. 12 13 II. Tas Motion 2 14 A. Tas motionâ€”no interference-in-fact 15 Tas moves for entry of judgment based on no interference-in-fact. Paper 196. 16 The motion is limited to Count 2 (Interference 105,949). 17 Interferences 105,926 & 105,949 9 Contingent on Tas Motion 2 being granted, Tas further moves for entry of orders 1 related to â€œcase managementâ€ of Interference 105,949. 2 According to Tas, to succeed on the motion â€œTas must show that the alternatives of 3 the count [Count 2] define patentably distinct inventions such that the subject matter of 4 one [alternative of Count 2 assumed to be prior art and] taken with the prior art does not 5 render the other [alternative of Count 2] obvious. Paper 196, page 1:23-25. 6 B.. Beachy opposition 7 Beachy opposed. Paper 320. 8 According to Beachy, for Tas â€œ[t]o succeed on its motion, Tas was required to 9 prove that [the subject matter of]. . . Tasâ€™ involved claims 1-23, . . . treated as prior art, 10 would [not] have anticipated or rendered obvious any one of Beachyâ€™s involved claims 11 201-213 and [sicâ€”â€œorâ€] vice versa.â€ Paper 320, page 5:14-17. 12 Further according to Beachy, Tas did not conduct a proper â€œanalysis and, therefore, 13 did not satisfy its burden for the requested relief.â€ Paper 320, page 5:23-24. 14 C. Applicable principles 15 An interference exists only if there is an interference-in-fact. â€œAn interference 16 exists if the subject matter of a claim of one party [Tas in this case] would, if prior art, 17 have anticipated or rendered obvious the subject matter of a claim of the opposing party 18 [Beachy in this case] and vice versa.â€ 37 C.F.R. Â§ 41.203(a). 19 Section 41.203(a) codifies 6 in more explicit language a Board interpretation of 20 former Rule 1.601(j), 7 an interpretation found to be lawful by the Federal Circuit. 8 21 6 See (1) Notice of Proposed Rulemaking, 68 Fed. Reg. 66648, 66664 (col. 3 to 66665 (col. 1) (Nov. 26, 2003) and (4) Notice of Final Rule, 69 Fed. Reg. 49960, 49969 (col. 1) (Aug. 12, 2004). Interferences 105,926 & 105,949 10 When an interference is declared, an interference-in-fact is presumed to exist. 1 Case v. CPC International, Inc., 730 F.2d 745, 750 (Fed. Cir. 1984) (there is a 2 presumption that an interference-in-fact exits and a party contending otherwise has the 3 burden of proof); Bronshtein v. Roser, 61 USPQ2d 1745, 1753 (BPAI 2001) (when an 4 interference is declared, there is a presumption that there is an interference-in-fact). 5 D. Analysis 6 1. 7 Tas and Beachy appear to have a disagreement over whether Tas has made a 8 proper comparison of claimed subject matter, i.e., whether Tas compared the subject 9 matter of Tas claims vis-Ã -vis Beachy claims. 10 Beachy maintains that comparison of alternatives of Count 2 does not constitute a 11 comparison of Tas claims vis-Ã -vis Beachy claims. 12 7 Rule 1.601(j) (37 C.F.R. Â§ 1.601(j) (2004)): â€œAn interference-in-fact exists when at least one claim of a party that it designated to correspond to a count and at least one claim of an opponent that is designated to correspond to the count define the same patentable invention.â€ The Board interpreted the rule to require a â€œtwo-wayâ€ test, i.e., the claim of the party had to anticipate or render obvious the subject matter of a claim of the opponent as vice versa. See, e.g., Winter v. Fujita, 53 USPQ2d 1234, 1243 (BPAI 1999), reconsideration denied, 53 USPQ2d 1478 (BPAI 2000) (resolution of interference-in-fact issue involves two-way analysis) Pechiney v. Cryovac, Inc., Interference 105,092, Paper 67, pages 3-4 (BPAI June 30, 2004) (cited by Beachy at Paper 320, pages 3-4).. 8 Eli Lilly and Co. v. Board of Regents of the University of Washington, 334 F.3d 1264 (Fed. Cir. 2003) (Board interpretation of its rule to require a two-way test for interference-in-fact held to be lawful). Interferences 105,926 & 105,949 11 Our review of the motion reveals that Tas essentially has compared some Tas 1 claims with some Beachy claims. Tas claims 15 and 20 (one alternative of the count) 2 were analyzed by Tas vis-Ã -vis Beachy claim 27 (now Beachy Claim 201) (another 3 alternative of the count). 4 Therefore we will decide the motion on the basis of a comparison of Tas Claim 20 5 vis-Ã -vis Beachy Claim 201. 6 As will become apparent, the significant limitation of Tas Claim 20 (which appears 7 in independent Tas Claims 15) is â€œcauses decrease of size or disappearance of the tumorâ€ 8 and the significant limitation of Beachy Claims 201 is â€œinhibits basal tumor cell 9 proliferationâ€. 10 2. 11 Tas Claim 15 reads (italics added): 12 A method for treatment of a human subject having a tumor 13 wherein Hedgehog/Smoothened signaling is utilized for inhibition of 14 apoptosis of the tumor cells, comprising 15 16 administering to the subject a medicament comprising 17 cyclopamine or another compound that selectively inhibits 18 Hedgehog/Smoothened signaling, 19 wherein said medicament is administered in a dose that is 20 sufficient to induce apoptosis of said tumor cells and causes decrease 21 of size or disappearance of the tumor. 22 Tas Claim 20 reads (italics added): 23 A method according to claim 15, wherein said tumor is basal 24 cell carcinoma or trichoepithelioma or a melanocytic tumor. 25 26 Paper 16. 27 Interferences 105,926 & 105,949 12 The Tas alternative of Count 3 reads: 1 A method for treatment of a human subject having a basal 9 2 carcinoma tumor cell wherein Hedgehog/Smoothened signaling is 3 utilized for inhibition of apoptosis of the tumor cell, comprising 4 5 administering to the human subject a medicament comprising 6 cyclopamine, 7 8 wherein said medicament is administered in a dose that is 9 sufficient to induce apoptosis of said tumor cell and causes decrease 10 of size or disappearance of the tumor. 11 12 Paper No. 196, page 1. 13 14 Beachy Claim 201 reads (italics added): 15 A method of therapy for a human subject having a basal cell 16 carcinoma tumor, 17 18 comprising administering to the subject a therapeutically 19 effective amount of a medicament comprising cyclopamine and a 20 pharmaceutically acceptable carrier, 21 wherein in said tumor smoothened-dependent hedgehog 22 signaling is utilized for inhibition of apoptosis, and 23 24 said amount of cyclopamine selectively inhibits smoothened-25 dependent hedgehog signaling in said tumor and is sufficient to induce 26 apoptosis in said tumor and inhibits tumor cell proliferation. 27 28 Paper 11. 29 30 9 The reference to â€œbasalâ€ cell comes from Claim 20 and narrows â€œtumorâ€ as it appears in Claim 15 to â€œbasalâ€ cell tumors. Interferences 105,926 & 105,949 13 The Beachy alternative of Count 2 reads (italics added): 1 a method of therapy for a human subject having a basal cell 2 carcinoma tumor, comprising 3 4 administering to the human subject a therapeutically effective 5 amount of a medicament comprising cyclopamine and a 6 pharmaceutically acceptable carrier, 7 8 wherein in said tumor smoothened-dependent hedgehog 9 signaling is utilized for inhibition of apoptosis, and 10 11 said amount of cyclopamine selectively inhibits smoothened-12 dependent hedgehog signaling in said tumor and is sufficient to induce 13 apoptosis in said tumor and inhibits tumor cell proliferation. 14 15 Paper 196, page 1. 16 17 3. 18 The claim chart in Table 1 set out below compares the limitations of Tas 19 Claim 20 and Beachy Claim 201 (italics added). 20 Table 1 Tas Claim 20 Beachy Claim 201 A method for treatment of a human subject having a basal cell carcinoma tumor A method of therapy for a human subject having a basal cell carcinoma tumor comprising comprising administering to the subject a medicament comprising [a dose of] cyclopamine . . . administering to the subject a therapeutically effective amount of a medicament comprising Interferences 105,926 & 105,949 14 cyclopamine . . . that selectively inhibits Hedgehog/Smoothened signaling wherein said medicament is administered in a dose that said amount of cyclopamine selectively inhibits smoothened-dependent hedgehog signaling in said tumor and is sufficient to induce apoptosis of said basal tumor cells and causes decrease of size or disappearance of the tumor. is sufficient to induce apoptosis in said basal tumor and inhibits basal tumor cell proliferation. According to Tas, â€œcauses decrease of size or disappearance of the tumorâ€ is not 1 the same as â€œinhibits basal tumor cell proliferation. Paper 196, page 6:1-12. 2 Further according to Tas, â€œ[t]he Beachy . . . [Count 2] alternative does not require 3 tumor shrinkage or disappearance.â€ Paper 196, page 7:6-7. 4 Beachy states that â€œ[as] used . . . [in its application], â€˜proliferatingâ€™ and 5 â€˜proliferationâ€™ refer to cells undergoing mitosis [i.e., cell division].â€ Ex. 1010, Â¶ 0078. 6 If proliferation is inhibited, then the tumor does not grow. 7 Overlooked by Tas is the limitation â€œsufficient to induce apoptosis,â€ which appears 8 in both Tas Claim 20 and Beachy Claim 201. 9 According to Tas, â€œapoptosis is a regulated active cell deathâ€, in this case death 10 of a BCC tumor cell. Paper 92, page 1:13. See also involved Tas Patent, Ex. 2001, 11 col. 2:42 describing â€œapoptotic death and removal of these tumor cellsâ€¦.â€ 10 12 10 We have found the word â€œapoptosisâ€ only in the claims of involved Beachy application 13/364,121 (Ex. 1008) (published as US Patent Application Publication 2012/0183603 A1) (Ex. 2010). In connection with a discussion of the central nervous system, the word â€œapoptoticâ€ appears in Â¶ 0190 of the published application. . Interferences 105,926 & 105,949 15 When the BCC tumor cells die, (1) the tumor decreases in size and possibly 1 disappears as recited by Tas and (2) the tumor cells stop proliferating as recited by 2 Beachy. 3 In effect, both Tas and Beachy recite â€œresultâ€ limitations in their respective claims 4 that are a consequence of apoptosis having taken place, that in turn is a consequence of 5 treating a human subject having a basal cell carcinoma tumor with cyclopamine. 6 The results recited in both sets of claims are not inconsistent because when a tumor 7 decreases in size or disappears, its cells have stopped proliferating. 8 We have not overlooked the fact that Tas states the following in its patent 9 (Ex. 2001, col. 11:47-53) (italics added): 10 It is also clear that the therapeutic effectiveness described herein and 11 the rapid disappearance of treated tumors could not be possible 12 without the causation of tumor cell apoptosis since merely inhibiting 13 or slowing the tumor cell proliferation by cyclopamine would, at best, 14 help one only to keep the tumor at its pre-treatment size. 15 Beachy Claim 201 is not limited to â€œmerely inhibiting . . . tumor cell proliferation 16 by cyclopamineâ€; it also requires apoptosis. 17 Interferences 105,926 & 105,949 16 4. 1 (a) 2 Tas argues that the second alternative of Count 2 (Beachy Claim 201) should be 3 construed to be directed to a treatment wherein any cyclopamine dose producing 4 inhibition of proliferation of tumor cells would also produce their apoptosis. Paper 196, 5 page 4:7-9. 6 Tas continues to say that its â€œpatent and priority application PCT/TR01/00027 have 7 shown[ 11 ] that this is not the case with administration [of] cyclopamine to BCC tumors.â€ 8 Paper 196, page 4:10-11. 9 We fail to see the relevance of the argument. 10 Beachy Claim 201 calls for the dose to â€œbe sufficient to induce apoptosisâ€. 11 Accordingly, if some dose does not induce apoptosis, then the dose would not fall 12 within the scope of Beachy claim 201. 13 (b) 14 Tas argues that the subject matter of Beachy Claim 201 is not enabled by the 15 Beachy specification. Paper 196, page 6:5-6. 16 The argument is irrelevant. 17 In the context of a motion based on no interference-in-fact, the specifications of 18 both parties are presumed to be enabling and patentable over the prior art. 19 The premise of a no interference-in-fact motion is that while an opponent is 20 assumed to have prevailed on priority (and therefore is prior art), the party is nevertheless 21 11 A specification is not admissible to prove the truth of statements contained therein. Standing Order, Â¶ 152.2.1 (Paper 2, page 42). Nevertheless, we have considered the specifications for what is described therein. Interferences 105,926 & 105,949 17 entitled to its claims because the subject matter claimed by the opponent does not 1 anticipate or render obvious the subject claimed by the party. 2 Proof of an embodiment to establish priority necessarily involves proof that the 3 embodiment is enabling. 4 If a party believes that an opponentâ€™s specification is not enabling, then the proper 5 procedure is to list a motion for judgment based on lack of enablement in addition to a 6 motion based on no interference-in-fact. 7 Moreover, a motion based on no interference-in-fact is a threshold motion which 8 can terminate an interference. 9 In terminating the interference on the threshold issue of no interference-in-fact a 10 party does not get a pre-grant chance to attack an opponentâ€™s application or a post-grant 11 chance to attack an opponentâ€™s patent. 12 (c) 13 We have considered all other arguments made by Tas and find them unconvincing. 14 E. Decision 15 Tas Motion 2 will be denied. 16 17 F. Contingent request 18 Continent on Tas Motion 2 being granted, Tas requests that the interference not be 19 terminated to permit certain â€œcase management.â€ Paper 196, page 1:1-3. 20 The request was not authorized as part Tas Motion 2 or otherwise authorized as a 21 motion. 22 In any event, because Tas Motion 2 has been denied, there is no occasion to 23 consider or decide the contingent request by Tas that the interference not be terminated. 24 Interferences 105,926 & 105,949 18 The contingent request made by Tas will be dismissed. 1 2 III. Tas Motion 3 3 A. Background and discussion 4 Tas Motion 3 seeks entry of an order according Tas an earlier constructive 5 reduction to practice (i.e., benefit for the purpose of priority) of PCT/TR01/000027, filed 6 on 2 July 2001 (published as WO 02/078703 (the â€œâ€™703 applicationâ€)). Paper 195, 7 page 1. 8 Beachy Opposition 3 (Paper 321) states in relevant part (italics added): 9 Beachy does not consider . . . [Tas Motion 3] to be necessary/relevant 10 to the ultimate determination of priority for either Count 2 of Count 3. 11 Nevertheless, Beachy does not oppose the Board considering and 12 rendering a substantive decision . . . [Tas Motion 3]. For clarity of the 13 record and to avoid any inference that Beachy admits any factual 14 assertion in . . . [Tas Motion 3], Beachy hereby denies all factual 15 assertions in . . . [Tas Motion 3] . . . .â€ 16 The relevance of Tas Motion 3 is that if (1) Tas Motion 3 is granted and (2) Tas 17 Motions 4 and 17 seeking to deny Beachy benefit are also granted, Tas becomes senior 18 party. 19 Tas argues that the â€™703 application describes enabled embodiments within the 20 scope of Counts 2 and 3. Paper 195, page 16. 21 On the merits, Beachy does not oppose because a mere denial of all facts asserted 22 by Tas is not a response on the merits. 23 We agree with Tas that the â€™703 application describes enabled embodiments 24 within, and constitutes a constructive reduction to practice of, an invention within the 25 scope of Counts 2 and 3. Hunt v. Treppschuh, 523 F.2d 1386, 1389 (CCPA 1975) (an 26 Interferences 105,926 & 105,949 19 application need only disclose a single enabled embodiment within the scope of the count 1 to constitute a constructive reduction to practice of the invention of the count); see also 2 Weil v. Fritz, 572 F.2d 856, 865 n.16 (CCPA 1978) (â€œas Hunt v. Treppschuh *** 3 explains, â€˜the Â§ 112 paragraph, requirements need only be met for an embodiment within 4 the countâ€™ â€¦ where the count is drawn to a genus and the previously-filed application 5 discloses only a species thereofâ€); Falkner v. Inglis, 448 F.3d 1357, 1362 (Fed. Cir. 2006) 6 (same). 7 Claim charts appearing on pages 3-15 of the motion adequately set out how an 8 enabled embodiment of the subject matter of Counts 2 and 3 is described in the 9 Ê¼703 application. 10 Beachy does not explain why the claim charts are not adequate for the purpose on 11 which they are relied. 12 13 B. Decision 14 Tas Motion 3 will be granted. 15 As to Counts 2 and 3 Tas is accorded an earlier constructive reduction to practice 16 as of 2 July 2001 based on the Ê¼703 application. 17 18 IV. Tas Motion 4 19 Tas Motion 4 seeks entry of an order denying Beachy earlier constructive 20 reductions to practice as to Count 3. Paper 197. 21 Earlier constructive reductions to practice based on (1) Beachy application 22 13/363,934 (the â€œâ€™934 applicationâ€) (Ex. 2147) and Beachy application 09/688,076 (the 23 Interferences 105,926 & 105,949 20 â€œâ€™076 applicationâ€) (Ex. 1018) 12 (filed October 13, 2000) were accorded to Beachy when 1 Interference 105,926 was declared. Paper 1, pages 9-10. 2 According to Tas, the â€™076 application does not describe an enabling embodiment 3 within the scope of either alternative of Count 3. Paper 197, pages 1 and 18. 4 Count 3 is reproduced earlier in this opinion. 5 Tas presents several arguments in support of its motion. 6 7 Motion 4 Limitation (1) 8 A method for treatment of a human subject having 9 a basal cell carcinoma tumor 10 Tas maintains that the Beachy Ê¼076 application has no support for Limitation (1). Paper 197, page 21:13-14. Tas argues that the Beachyâ€™076 application does not have a working example of a method for treatment of a human subject having a basal cell carcinoma (BCC) tumor as recited in Count 3. Paper 197, page 21. According to Tas, the â€™076 application has no example of a treatment of a human 11 having BCC or any other tumor, nor does it describe a treatment of another animal, e.g., a 12 mouse, having a naturally occurring tumor. Id. 13 Tas argues that there is nothing in the â€™076 application from which a skilled person 14 could reasonably expect that a treatment of a tumor bearing human characteristics will 15 likely be applicable, let alone effective. Id. 16 Further according to Tas, nothing in the â€™076 application made the treatment for 17 tumor-bearing humans as shown in Ex. 2004 (Tas International Application 18 12 The â€™076 application issued as US Patent 7,098,196 B1 on 29 August 2006. Interferences 105,926 & 105,949 21 WO 02/078703) expected or anticipated. By â€œexpected or anticipatedâ€ we think Tas 1 argues that one skilled in the art would not have a reasonable expectation of success 2 based on the Ê¼076 application. 3 Rather, Tas seems to contend that the actual experimental results reported by 4 Beachy and the prior art teach against it. Paper 197, page 22 (citing Tas testimony set 5 out in Ex. 2098 at Â¶Â¶ 12, 13, 20-24, 27, 36, 40 and references therein). 6 Tas argues further that a statement of an ability of subject compounds (those 7 described as useful by Beachy) to block pathway activity in cells suggests that they may 8 be broadly useful in the treatment of certain sporadic tumors, and that mentioning BCC 9 as being one of the â€œcertain sporadic tumors,â€ does not show possession of a treatment of 10 a human having BCC. Paper 197, page 22 (citing Beach US Patent 7,098,196 B1, 11 Ex.1018, col. 67, ll.27-40â€”the patent is based on the Beachy Ê¼076 application). 12 Tas argues that statements made in the â€™076 application that the disclosed tumor 13 treatment will be effective in a human patient would not lead a person of ordinary skill to 14 conclude that it would likely be applicable, let alone effective. Paper 197, page 23. 15 Tas contends that, at the time the â€™076 patent was constructively reduced to 16 practice (i.e., â€œfiledâ€), the art had not shown a treatment of either a human or an animal 17 using cyclopamine or another selective inhibitor of Hh signaling sufficient to satisfy a 18 skilled person that the treatment would be applicable or effective in humans (i.e., that a 19 likelihood of success would have been expected). Id. 20 Beachy responds that the â€™076 application describes the treatment of BCC tumors 21 in humans. Paper 322, page 7. 22 Beachy quotes the following portions of the â€™076 application to support its 23 contention (Paper 322, page 8 (bold in original), citing Ex. 1018, col. 48:16-22): 24 Interferences 105,926 & 105,949 22 In still another embodiment, the subject method can be used in 1 the treatment of human cancers, particularly basal cell 2 carcinomas and other tumors of epithelial tissues such as the skin. 3 For example, subject compounds can be employed, in the subject 4 method, as part of a treatment for basal cell nevus syndrome (BCNS), 5 and other . . . human carcinomas, adenocarcinomas, sarcomas and the 6 like. 7 The â€™076 application also states (Paper 322, page 8 (bold in original), citing 8 Ex. 1018, col. 50:13-18): 9 These compounds may be administered to humans and other 10 animals for therapy by any suitable route of administration, including 11 orally, nasally, as by, for example, a spray, rectally, intravaginally, 12 parenterally, intracisternally and topically, as by powders, ointments 13 or drops, including buccally and sublingually. 14 The â€˜076 application goes on to further state (Paper 322, page 8 (bold in 15 original), citing Ex. 1018, col. 66:3-19):, 16 Whatever the mechanism, such inhibitors may have utility in 17 trea[t]ment of disorders caused by inappropriate Shh pathway 18 activation. Patients with Basal Cell Nevus Syndrome (also termed 19 Gorlin's syndrome), an autosomal dominant disorder associated with 20 heterozygous loss-of function mutations in the human Ptc1 gene, 21 display increased incidence of numerous tumors, most notably 22 basal cell carcinoma (BCC), medulloblastoma, rhabdomyosarcoma 23 and fibrosarcoma. Loss-of-function mutations in Ptc1 or activating 24 mutations in Smo in addition are found in ~40% of sporadic BCC and 25 ~25% of primitive neuroectodermal tumors. The ability of 26 cyclopamine and its derivatives to block pathway activation by both 27 of these types of mutations suggests that these plant-derived 28 compounds or others that influence the activity of Smo may be 29 valuable as therapeutic agents. 30 Interferences 105,926 & 105,949 23 The Ê¼076 defines effective amount as follows (Paper 322, pages 8-9, citing 1 Ex. 1018, col. 10:8-15): 2 An â€œeffective amountâ€ of a subject compound, with respect to 3 the subject method of treatment, refers to an amount of the antagonist 4 in a preparation which, when applied as part of a desired dosage 5 regimen brings about, e.g., a change in the rate of cell proliferation 6 and/or the state of differentiation of a cell and/or rate of survival of a 7 cell according to clinically acceptable standards for the disorder to be 8 treated or the cosmetic purpose. 9 10 The Ê¼076 application also states (Paper 322, page 9, citing Ex. 1018, col. 38:9-12 11 and col. 34:27-33) (emphasis added): 12 For instance, the subject compounds can be utilized to cause such 13 transformed cells to become either post-mitotic or apoptotic. 14 15 and 16 17 One aspect of the present invention relates to a method of 18 modulating a differentiated state, survival, and/or proliferation of a 19 cell, such as a normal cell or a cell having a â€¦ hedgehog gain-of-20 function, or smoothened gain-of-function, by contacting the cells with 21 a compound as set forth above according to the subject method and as 22 the circumstances may warrant. 23 According to Beachy, Tasâ€™ real argument is that the Ê¼076 application does not have 24 a sufficient number of â€œworking examplesâ€ such that one skilled in the art would have 25 considered Beachy to be in possession of the subject matter of Count 3. Paper 322, 26 page 9:14-18. 27 Interferences 105,926 & 105,949 24 We find that Tas has not established that a working example is necessary to 1 adequately describe and enable an embodiment within the scope of Count 3. Ariad 2 Pharmaceuticals, Inc. v. Eli Lilly and Co., 598 F.3d 1336, 1352 (Fed. Cir. 2010): 3 There are, however, a few broad principles that hold true across 4 all cases. We have made clear that the written description 5 requirement does not demand either examples or an actual reduction 6 to practice; a constructive reduction to practice that in a definite way 7 identifies the claimed invention can satisfy the written description 8 requirement. 9 See also Falkner v. Inglis, 448 F.3d 1357, 1366 (Fed. Cir. 2006) (â€œthe absence of 10 examples involving poxviruses in the Inglis applications does not render the written 11 description inadequateâ€). 12 Beachy understands Tas to assert that the contemporaneous art â€œtaught awayâ€ from 13 the use of cyclopamine in humans. Paper 322, page 10. 14 Dr. Tas is said to have written Dr. William Gaffield in 2000 to obtain cyclopamine 15 for the experiments described in the Tas involved patent. Ex. 2098, Â¶ 5:18 et seq.; 16 Ex. 1114, Â¶ 57:22-23. 17 Dr. Gaffield is listed as a co-author of a 1999 paper entitled A Looking Glass 18 Perspective: Thalidomide and Cyclopamine, in CELL AND MOLECULAR BIOLOGY, 19 discussing the use of cyclopamine as a potential â€œlead compound in drug developmentâ€ 20 for human therapeutics. Ex. 1112, pages 581-586 and in particular Abstract (page 579) 21 and Table 1 (page 584). See also Ex. 1114, Â¶Â¶ 55-56 (Second Declaration of Thomas 22 Curranâ€”a witness for Beachy). 23 Dr. Tas also testified that he was familiar with an article published in NATURE 24 entitled Effects of oncogenic mutations in Smoothened and Patched can be reversed by 25 Interferences 105,926 & 105,949 25 cyclopamine (listing Dr. Jussi Taipale as co-author) and which describes the use 1 of cyclopamine as a potential therapeutic agent for the treatment of basal cell 2 carcinoma tumors. Ex. 2098, page 8, ll. 8-9 and page 18, ll. 3-10; Ex. 2035, Abstract and 3 page 1007, Figs. 3c and 3d). 4 The Taipale et al. article describes the desirability of using therapeutic agents that 5 primarily affect pathways active during embryonic development, but not required for 6 survival in adults. Ex. 2035, page 1005, col. 1). 7 Beachy argues that, contrary to Tasâ€™ argument, Taipale et al. did not teach that the 8 administration of cyclopamine to humans for the treatment of BCC would jeopardize 9 â€œvital functionsâ€ that were â€œcritical to the survivalâ€ of the adult. Paper 322, page 15:2-5. 10 Beachy points to a brief review by Dr. Carol Wicking et al. entitled The role of 11 Hedgehog signaling in tumorigenesis, accepted for publication on 5 July 2001 in CANCER 12 LETTERS (Ex. 1041) just days after Tas filed his application on 2 July 2001 (Ex. 2004). 13 Paper 322, page 15. 14 CANCER LETTERS notes that â€œ[o]ne agent which has arisen as a possible treatment 15 for BCCs is . . . cyclopamine.â€ Ex. 1041, page 4, col. 2 (Â¶ identified as â€œ4. Possible 16 therapies for hedgehog-related BCCsâ€). 17 Beachy argues that the teachings of these prior and contemporary art references 18 reflect the beliefs of those skilled in the art that cyclopamine could be considered as a 19 viable therapeutic agent for treating BCC tumors in humans. Paper 322, page 15. 20 Beachy further argues that portions of Tas Motion 4 are not consistent with a 21 position taken by Tas in an amendment seeking to overcome the prior art. Paper 322, 22 pages 16-17. 23 Interferences 105,926 & 105,949 26 According to counsel for Tas (lead counsel in these interferences), â€œa 1 skilled artisan would have been motivated to administer a Hedgehog antagonist to a 2 patient having such a tumor with expectation of achieving inhibition of tumor 3 cell proliferation and inhibition of tumor growth.â€ Amendment; Ex. 2071, page 8:9-11. 4 Whether an application contains an adequate written description is an issue of fact. 5 In re Alton, 76 F.3d 1168, 1171 (Fed. Cir. 1996). To satisfy the written description 6 requirement of Â§ 112, the disclosure of an application must reasonably convey to a skilled 7 artisan that the inventor had possession of the claimed subject matter as of the filing date. 8 Ariad, 598 F.3d at 1351 (citing Vasâ€“Cath Inc. v. Mahurkar, 935 F.2d 1555, 1562â€“63 9 (Fed.Cir.1991)). 10 â€œ[T]he specification [also] must [1] describe an invention understandable to that 11 skilled artisan and [2] show that the inventor actually invented the invention claimed.â€ 12 Ariad, 598 F.3d at 1351. 13 Whether an application contains an enabling disclosure is a question of law. In re 14 Wands, 858 F.2d 731, 735 (Fed. Cir. 1988). To satisfy the enablement requirement of 15 Â§ 112, the specification must enable one of ordinary skill in the art to practice the claimed 16 invention. Id. 17 Enablement is not precluded by the necessity for some experimentation. Id. 18 However, experimentation needed to practice an invention must not be undue 19 experimentation. Id. at 737. 20 Whether undue experimentation would have been required to make and use an 21 invention is a question of law to be resolved on the basis of the underlying facts. Enzo 22 Biochem, Inc. v. Calgene, Inc., 188 F.3d 1362, 1369 (Fed. Cir. 1999); Warnerâ€“Lambert 23 Co. v. Teva Pharm. USA, Inc., 418 F.3d 1326, 1337 (Fed. Cir. 2005). 24 Interferences 105,926 & 105,949 27 On the record before us, we agree with Beachy that furnishing an â€œexampleâ€ is not 1 necessary. See Ariad, 598 F.3d at 1352. 2 We find that the â€œtaught awayâ€ argument made by Tas is not convincing. 3 We further find that the quotations of â€˜076 application set out above would 4 reasonably convey to one skilled in the art that the Beachy inventors had possession of 5 the subject matter of Count 3 as of the relevant filing date. 6 Beachy explicitly teaches: â€œthe subject method can be used in the treatment of 7 human cancers, particularly basal cell carcinomas and other tumors of epithelial tissues 8 such as the skinâ€ Ex. 1018, col. 48:16-22. 9 The â€™076 application also describes (1) methods by which cyclopamine may be 10 administered, (2) appropriate dosages, and (3) how the subject medicament works within 11 the cancerous cell. 12 We find that Tas has not established that the â€™076 application fails to satisfy the 13 written description requirement of Â§ 112 with respect to disputed Limitation (1). 14 We conclude, in view of the portions of the Ê¼076 application set out above, that Tas 15 has failed to establish that the â€™076 application is not enabling as to the subject matter of 16 Count 3. 17 Nor has Tas sustained its burden of showing that undue experimentation would 18 have been needed to practice the invention defined by Count 3. 19 The â€™076 application describes (1) effective dosages, (2) methods of 20 administration, and (3) a spectrum of conditions against which administration of the 21 cyclopamine may be effective as BCC cells. 22 23 24 Interferences 105,926 & 105,949 28 Motion 4, Limitation (2) 1 Wherein Hedgehog/Smoothened signaling is 2 utilized for inhibition of apoptosis 3 Tas maintains that Beachy has no support for disputed Limitation (2). Paper 197, 4 page 23:17-19 and page 24:1. 5 Tas argues that Beachy offers mostly vague statements as written description 6 support of the limitation â€œHedgehog/Smoothed signaling is utilized for inhibition of 7 apoptosisâ€ in a tumor cell. Id. at page 25:9-10 (relying on (1) Ex. 2030â€”a preliminary 8 amendmentâ€”and (2) Ex. 2098, Â¶Â¶ 56-67â€”testimony of Dr. Tas). 9 Tas argues that Beachyâ€™s proofs have no relevance to a tumor class in which Hh 10 signaling is used for inhibition of apoptosis. Id. at page 25:12-13. 11 According to Tas, the phrases inhibiting â€œ[S]moothened-dependent pathway 12 activationâ€ and â€œcounteract the phenotypic effects of unwanted activation of a hedgehog 13 pathwayâ€ say nothing about a pathway that inhibits apoptosis of tumor cells. Id. 14 at 25:13-15. 15 Tas further argues that Beachy provides no basis for its contention that induction of 16 apoptosis would not also induce apoptosis in normal cells. Id. at page 26:2-3. 17 Tas contends that this lack of support becomes relevant when considering that the 18 only tumors to which Beachy administered cyclopamine have normal cells making up to 19 more than half of all of the cells. Id. at 26:3-6. 20 Beachy responds that BCC tumor cells are tumor cells in which smoothened-21 dependent hedgehog signaling is utilized for inhibition of apoptosis, i.e., that this is an 22 inherent property of BCC tumor cells regardless of whether an Hh inhibitor is 23 administered to the BCC tumor. Paper 322, page 20:13-14. 24 Interferences 105,926 & 105,949 29 Otherwise, the administration of a hedgehog inhibitor, such as cyclopamine, to a 1 BCC tumor would not result in inhibiting Smoothened-dependent Hh signaling to induce 2 apoptosis of BCC tumor cells. Id. at page 20:16-19 (citing Ex. 1088, Â¶Â¶ 23-28 and 3 51-59â€”First Declaration of Dr. Thomas Curran). 4 Dr. Curran testified that as of 2000-2001, a person having ordinary skill in the art 5 would have expected â€œthat inactivation of the Hh pathway in BCCs would result in 6 increased levels of apoptosis.â€ Ex. 1088, Â¶ 25:5-7. 7 Dr. Curran further testified that â€œit is now well-established that the administration 8 of cyclopamine in amounts sufficient to inhibit the Hh pathway â€¦ results in an increase 9 in apoptosis.â€ Ex. 1088, Â¶ 26:11-13 (emphasis in original). 10 Dr. Curranâ€™s testimony is supported by contemporary scientific literature discussed 11 in paragraphs 27-32 of his testimony. 12 We find Dr. Curranâ€™s testimony credible. 13 On the other hand, Tas does not point to any credible evidence to contradict 14 Dr. Curranâ€™s testimony. 15 We decline to give much weight to Tasâ€™ arguments with respect to its own 16 invention, or whether induction of apoptosis in BCC tumor cells would also involve 17 normal cells, with respect to the issue of whether the Ê¼076 application fails to meet the 18 written description or enablement requirements of Â§ 112. 19 To the extent that there is a conflict between the testimony given by disinterested 20 witness Dr. Curran (Ex. 1088) and that given by interested witness Dr. Tas (Ex. 2098), 21 we credit Dr. Curranâ€™s testimony over Dr. Tasâ€™ testimony. 22 Dr. Curranâ€™s testimony is consistent with disclosure in the â€™076 application. 23 Interferences 105,926 & 105,949 30 The Ê¼076 application discloses that â€œthe subject method can be used in treating or 1 preventing basal cell carcinoma or other hedgehog pathway-related disorders.â€ Ex. 1018, 2 col. 8:31-33. 3 Consequently, we find that Tas has not met is burden of demonstrating that the 4 Ê¼076 fails to meet the written description and conclude that Tas has not met its burden of 5 establishing non-enablement of disputed Limitation (2). 6 7 Motion 4 Limitation (3) 8 Comprising administering to the human subject 9 a medicament comprising cyclopamine or 10 a pharmaceutically acceptable salt thereof 11 Tas argues that, when viewed in light of the prior art, a skilled person would have 12 had strong reasons to believe that it would not be feasible to administer cyclopamine or 13 another selective inhibitor of Hh/Smo signaling to a human with BCC for therapeutic 14 benefit. Paper 197, page 26. 15 According to Tas, neither the Ê¼076 application nor any another Beachy publication 16 published prior to 2 July 2001 provides any reason for a person of ordinary skill to 17 believe that cyclopamine would feasibly be applicable to a tumor patient, let alone be 18 therapeutically successful. Id. 19 Therefore, Beachy is said to fail to satisfy the written description and enablement 20 of this limitation. 21 We have related supra our reasoning as to why the evidence adduced by Beachy 22 convincingly contradicts Tasâ€™ â€œteaching awayâ€ argument, and we repeat that reasoning 23 here. 24 Interferences 105,926 & 105,949 31 Moreover, we have also related supra that we find that Beachy explicitly teaches 1 the administration of cyclopamine or a pharmaceutically acceptable salt thereof to a 2 human subject. 3 Consequently we find that Tas has not met is burden of demonstrating that the 4 Beachy application does not meet the written description and enablement requirements of 5 Â§ 112 as to disputed Limitation (3). 6 7 Motion 4, Limitation (4) 8 Wherein said medicament is administered in a dose 9 that is sufficient to induce apoptosis of said tumor cells 10 Tas argues that neither the Beachy Specification, nor any other Beachy publication 11 prior to Tasâ€™ application, describes administration of cyclopamine, or other selective 12 inhibitor of Hh/Smo signaling, that successfully induced apoptosis of tumor cells. 13 Paper 197, page 27:1-4. 14 According to Tas, a skilled person reading the Beachy Specification, as well as the 15 prior art at the time of invention, would believe that the prior art taught against such a 16 dose. Id. at page 27:5. 17 Tas contends that such a skilled person would not learn from the disclosures of the 18 Ê¼076 application that a dose of cyclopamine could cause a decrease of survival of cells. 19 Id. at page 27:9-10. 20 Tas further contends that the Ê¼076 application does not disclose that apoptosis of 21 tumor cells will be induced by the administration of cyclopamine. Id. at page 27:11-12. 22 Tas still further contends that the Ê¼076 application does not specify a dose that will 23 induce apoptosis in BCC tumor cells. Id. at page 27:12. 24 Interferences 105,926 & 105,949 32 For these reasons, Tas argues that the Ê¼076 application fails to provide adequate 1 written description support and enablement to Count 3. 2 With respect to â€œeffective doseâ€, the Ê¼076 application states: 3 An â€œeffective amountâ€ of a subject compound, with respect to the 4 subject method of treatment, refers to an amount of the antagonist in a 5 preparation which, when applied as part of a desired dosage regimen 6 brings about, e.g., a change in the rate of cell proliferation and/or the 7 state of differentiation of a cell and/or rate of survival of a cell 8 according to clinically acceptable standards for the disorder to be 9 treated or the cosmetic purpose. 10 11 and 12 For instance, the subject compounds can be utilized to cause such 13 transformed cells to become either post-mitotic or apoptotic. 14 Ex. 1018, col. 10:8-15 and col. 38: 9-12. 15 Based on the dose disclosure of the Ê¼076 application, we hold that Tas has not met 16 its burden of demonstrating that the Ê¼076 application fails to meet the written description 17 and enablement requirements of Â§ 112 as to disputed Limitation (4). 18 Interferences 105,926 & 105,949 33 Motion 4, Limitation (5) 1 And causes decrease of size or disappearance of the tumor 2 Tas argues that a skilled person reading Example 3 of the Ê¼076 application 3 describing experiments with nude mice would not see evidence of the causation of the 4 decrease in size of even a tumor graft. Paper 197, Motion 4, page 28 (citing Ex. 1018, 5 col. 133:55 to col. 135:3). 6 According to Tas, the nude mice employed in the study have large proportions of 7 normal host cells reacting to the foreign transformed cells, and that it was well known in 8 the prior art that an observed change of size of a graft of foreign cells following an 9 administration could be due to an effect on the normal host cells and would not occur 10 even in a mouse having a naturally occurring tumor. Tas Motion 4, Paper 197, page 29 11 (citing, but not explaining the significance of, Exs. 2019, 2020, 2045, 2069). 12 Further according to Tas, the Ê¼076 application nude mice descriptions do not 13 amount to causation of a decrease in size of a tumor in a human. Id. 14 Beachy relies on the testimony of Dr. Curran: 15 If one of ordinary skill in the art were in possession of a method of 16 treating BBC tumors in humans that involved the administration of 17 sufficient amounts of cyclopamine to inhibit Hh signaling in the tumor 18 cells, to reduce proliferation of tumor cells, to induce apoptosis in 19 tumor cells â€¦ and to achieve inhibition of tumor growth, then one of 20 ordinary skill would have reasonably expected that the same method 21 would also result in a decrease in tumor size, especially taking into 22 account additional factors such as naturally occurring apoptosis in the 23 BCC tumor and sloughing of skin cells. To make an analogy: 24 imagine that the tumor is a water-filled container with a hole in it. 25 Water must continuously run to keep the container filled with water 26 since water will continuously drip out through the hole. If you turned 27 off the water, the water level in the container starts to drop due to the 28 Interferences 105,926 & 105,949 34 leak and eventually all of the water runs out. In this analogy, the 1 running water is cellular proliferation within the tumor, and the hole 2 in the container (allowing water to drop out) is, for example, apoptosis 3 that occurs naturally in the BCC tumor â€¦. If the cellular proliferation 4 (running water) is shut off, e.g., through Hh signaling pathway 5 inhibition, the naturally occurring apoptosis in the BCC tumor will 6 continue (the water will continue to drip out of the container), and the 7 tumor size will shrink (the water will run out of the container, and 8 eventually the container will run dry). 9 10 Ex. 1114, Â¶ 96). 11 We find Dr. Curranâ€™s explanation credible and we accord it considerable weight. 12 Based on Dr. Curranâ€™s testimony we conclude that Tas has not met its burden of 13 showing that the â€™076 application fails to satisfy the requirements of Â§ 112 with respect to 14 disputed Limitation (5). 15 16 â€œCarnival barking,â€ â€œGambling on both sides,â€ and â€œplagiarismâ€ 17 Tas argues that the Beachy Specification engages in â€œcarnival barkingâ€ (i.e., 18 claiming that its invention can perform an impossibly wide spectrum of effects), 19 â€œgambling on both sidesâ€ (i.e., the treatments are so varied and expansive the inventors 20 cannot actually have conceived what the compounds will do beyond those limited 21 experiments reported in their examplesâ€). Paper197, pages 18-21. 22 We have related supra our reasoning with respect to how the Beachy Specification 23 satisfies the written description requirement with respect to each of the disputed 24 limitations of Count 3. 25 Moreover, Tas cites no legal authority to suggest that any of these arguments are at 26 all relevant to a Â§ 112 analysis, nor can we find any such authority. 27 Interferences 105,926 & 105,949 35 Because none of these arguments are actually relevant to the analysis of whether 1 the Specification meets the written description or enablement requirements of Â§ 112, we 2 find them to be without merit. 3 Because Tas has failed to meet its burden of demonstrating that the 4 â€™076 application is unpatentable under 35 U.S.C. Â§ 112, Tasâ€™ Motion 4 will be denied. 5 6 V. Tas Motion 6â€”lack of written description and indefiniteness 13 7 A. Tas motion 8 Tas moves for entry of judgment as to Beachy Claims 101-112 and 114-127 of 9 involved Beachy application 13/364,934 (Interference 105,926) and Beachy Claims 10 201-213 of involved Beachy application 13/364,121 (Interference 105,949) based on 11 (1) lack of a written description and (2) indefiniteness. Paper 198, page 1. 12 Beachy has opposed. Paper 323. 14 13 Tas has replied. Paper 331. 14 15 13 Tas Motion 6 is a combination of authorized Tas Motions 6, 13, 15 and 16. 14 Beachy characterizes its opposition as one â€œRegarding Beachy Written Description and Enablement.â€ Paper 323, page 1. We believe Beachy intended to refer to â€œIndefinitenessâ€ rather than â€œEnablement.â€ Tas was not authorized to file a motion for judgment based on an alleged lack of enablement. Interferences 105,926 & 105,949 36 B. Lack of Written Description 1 Motion 6, Limitation (1) 2 â€œTreatment of a human having a tumorâ€ 3 Beachy Claims 101-112, 114-127, and 201-213 4 Many of the arguments presented on behalf of Tas in connection with 5 Tas Motion 6 are the same as those advanced in connection with Tas Motion 4. 6 Tas argues that the Beachy applications fail to describe the treatment of a human 7 having any tumor or an animal having a naturally-occurring tumor, as a means of 8 disclosing to a person of ordinary skill that the treatment will be therapeutically effective 9 in a human. Paper 198, Motion 6, page 23:15-17. 10 Tas argues that the Beachy applicationsâ€™ descriptions that tumor treatment will be 11 effective in tumor-bearing human would not lead a skilled person, familiar with the prior 12 art, to conclude that such treatment would likely be applicable, let alone effective. Id. at 13 page 23:17-20. 14 Tas further argues that when the Beachy applications were filed, the contemporary 15 art did not teach treatment of a human using cyclopamine sufficiently to satisfy a skilled 16 person that their treatment will be applicable or effective in human. Id. at page 23:20 to 17 page 24:3. 18 Tas still further argues that, as of the filing dates, the only treatments that had been 19 done were performed on tumor cells in culture and in nude mice having foreign tumor 20 cell grafts. Id. at page 24:3-6. 21 According to Tas, the results of these treatments taught away from a use inducing 22 apoptosis of tumor cells in a human. Id. at page 24:6. 23 Interferences 105,926 & 105,949 37 Tas contends that prior to its own filing there were substantial reasons to believe 1 that a human could not be effectively treated with cyclopamine to achieve any therapeutic 2 benefit. Id. at page 24:9-11. 3 Beachy argues that the involved Beachy applications describe the treatment of 4 tumors in humans. Paper 323, page 13:3-5. 5 For example, in support of its argument Beachy relies on the following. 6 In still another embodiment, the subject method can be used in the 7 treatment of human cancers, particularly basal cell carcinomas and other 8 tumors of epithelial tissues such as the skin. For example, subject 9 compounds can be employed, in the subject method, as part of a treatment 10 for basal cell nevus syndrome (BCNS), and other . . . human carcinomas, 11 adenocarcinomas, sarcomas and the like. 12 13 Ex. 1018, col. 48:16-22 (Beachy application 09/688,076 now US Patent 7,098,196 B1); 14 Ex. 1013, p. 63, ll. 24-28 (Beachy application 09/685,244) (italics added). 15 These compounds may be administered to humans and other 16 animals for therapy by any suitable route of administration, including 17 orally, nasally, as by, for example, a spray, rectally, intravaginally, 18 parenterally, intracisternally and topically, as by powders, ointments 19 or drops, including buccally and sublingually. 20 21 Ex. 1018, col. 50:13-18; Ex. 1013, p. 66:18-21 (italics added). 22 Whatever the mechanism, such inhibitors may have utility in 23 treament [sic] of disorders caused by inappropriate [Hh] pathway 24 activation. Patients with Basal Cell Nevus Syndrome (also termed 25 Gorlin's syndrome), an autosomal dominant disorder associated with 26 heterozygous loss-of function mutations in the human Ptc1 gene, 27 display increased incidence of numerous tumors, most notably basal 28 cell carcinoma (BCC), medulloblastoma, rhabdomyosarcoma and 29 fibrosarcoma. Loss-of-function mutations in Ptc1 or activating 30 mutations in Smo in addition are found in ~40% of sporadic BCC and 31 Interferences 105,926 & 105,949 38 ~25% of primitive neuroectodermal tumors. The ability of 1 cyclopamine and its derivatives to block pathway activation by both 2 of these types of mutations suggests that these plant-derived 3 compounds or others that influence the activity of Smo may be 4 valuable as therapeutic agents. 5 6 Ex. 1018, col. 66:3-19 (italics added). 7 An â€œeffective amountâ€ of a subject compound, with respect to the 8 subject method of treatment, refers to an amount of the antagonist in a 9 preparation which, when applied as part of a desired dosage regimen 10 brings about, e.g., a change in the rate of cell proliferation and/or the 11 state of differentiation of a cell and/or rate of survival of a cell 12 according to clinically acceptable standards for the disorder to be 13 treated or the cosmetic purpose. 14 15 Ex. 1018, col. 10:8-15; Ex. 1013, page 17:16-21. 16 17 For instance, the subject compounds can be utilized to cause such 18 transformed cells to become either post-mitotic or apoptotic. 19 20 Ex. 1018, col. 38:9-12; Ex. 1013, page 49:7-8. 21 The subject smoothened antagonists may also be used to inhibit 22 proliferation (or other biological consequences) in cells or tissues 23 characterized as having a patched loss-of-function phenotype, a 24 smoothened gain-of-function phenotype or a hedgehog gain-of- 25 function phenotype. 26 27 Ex. 1018, col. 7:55-60; Ex. 1013, page 14:18-22. 28 Beachy repeats its argument (made in Beachy Opposition 4) that its applications 29 need not provide working examples of human experiments to satisfy the written 30 description requirements of 35 U.S.C. Â§ 112. Paper 323, page 14:31 to page 15. 31 Interferences 105,926 & 105,949 39 Beachy also repeats its arguments (made in Beachy Opposition 4) with respect to 1 Tasâ€™ â€œteaching awayâ€ arguments; viz., that the teachings of the contemporary art would 2 not have caused a person of ordinary skill in the art to expect that a human could not be 3 effectively treated with cyclopamine to achieve any therapeutic benefit. Id. at page 15:16 4 to page 17:14. 5 In our decision with respect to Motion 4, we state why we agree with Beachyâ€™s 6 arguments. 7 For the same reasons we are not persuaded with respect to these same arguments in 8 connection with Tas Motion 6. 9 Tas has not met its burden of showing that the Beachy Specifications fail to satisfy 10 the requirements of Â§ 112 with respect to disputed Limitation (1). 11 12 Motion 6, Limitation (2) 13 Smoothened-dependent hedgehog signaling 14 is utilized for inhibition of apoptosis 15 (Claims 101-112, 114, 117-127, 201-213) 16 Tas repeats its argument made with respect to the corresponding limitation of 17 Count 3 in Tas Motion 4. Paper 198, page 24:12 to 26:8. 18 We have discussed why we are not convinced by these same arguments with 19 respect to Tas Motion 4. 20 For the same reasons, we are similarly not convinced with respect to the same 21 arguments with respect to Tas Motion 6. 22 Tas has not met its burden of showing that the Beachy Specifications fail to satisfy 23 the requirements of Â§ 112 with respect to disputed Limitation (2). 24 25 Interferences 105,926 & 105,949 40 Motion 6, Limitation (3) 1 Determining that smoothened-dependent hedgehog signaling 2 is utilized for inhibition of apoptosis in said tumor 3 (Claims 115-116) 4 Tas essentially repeats the arguments that it employed with respect to Motion 4, 5 Limitation (2). Paper 198, page 24:12 to page 26:8. 6 We have discussed why we are not persuaded by those arguments in connection 7 with our decision on Tas Motion 4. 8 For the same reasons, we are not convinced with respect to the same arguments 9 made in connection with Tas Motion 6. 10 Tas has not met its burden of showing that the Beachy Specifications fail to satisfy 11 the requirements of Â§ 112 with respect to disputed Limitation (3). 12 Motion 6, Limitation (4) 13 Wherein said medicament is administered in a dose 14 that induces apoptosis in said tumor 15 (Claims 101-114, 126, 127, 201-213) 16 Tas relies upon essentially the same arguments that it made with respect to the 17 corresponding limitation of Count 3 in its Motion 4. Paper 198, Motion 6, page 26:14 to 18 page 28:16. 19 We have discussed why we are not persuaded by those arguments with respect to 20 Motion 4. 21 For the same reasons, we are not convinced with respect to the same arguments in 22 connection with Tas Motion 6. 23 Tas has not met its burden of showing that the Beachy Specifications fail to satisfy 24 the requirements of Â§ 112 with respect to disputed Limitation (4). 25 Interferences 105,926 & 105,949 41 1 Motion 6, Limitation (5) 2 Said medicament is administered in a dose that is sufficient 3 to induce apoptosis of said tumor cells 4 (Claims 115-116) 5 Tas essentially repeats the arguments that it employed in connection with 6 Motion 4. Paper 198, page 28:6-16. 7 We have discussed why we are not persuaded by those arguments in connection 8 with Motion 4. 9 For the same reasons, we are not persuaded with respect to the same arguments in 10 connection with Tas Motion 6. 11 Tas has not met its burden of showing that the Beachy Specifications fail to satisfy 12 the requirements of Â§ 112 with respect to disputed Limitation (5). 13 14 Motion 6, Limitation (6) 15 A tumor in which smoothened-dependent hedgehog signaling 16 is used for inhibition of apoptosis and â€¦ administering 17 to the subject an effective amount of medicament 18 (Claims 117-125) 19 Tas essentially repeats the arguments that it made in connection with Motion 6, 20 Limitations (2) to (5). Paper 198, page 28:17-22. 21 Because we were not persuaded by Tasâ€™ arguments with respect to those 22 limitations, we are likewise not persuaded by Tasâ€™ arguments with respect to this 23 limitation. 24 Tas has not met its burden of showing that the Beachy Specifications fail to satisfy 25 the requirements of Â§ 112 with respect to disputed Limitation (6). 26 Interferences 105,926 & 105,949 42 Motion 6, Limitation (7) 1 Causes decrease of size of the tumor 2 (Claims 101-112, 114-127) 3 Tas essentially relies on the same arguments that it made with respect to the 4 corresponding limitation of Count 3. Paper 198, page 28:23 to page 29:9. 5 We have discussed why we are not persuaded by those arguments with respect to 6 Motion 4. 7 For the same reasons, we are not persuaded with respect to the same arguments in 8 connection with Tas Motion 6. 9 Tas has not met its burden of showing that the Beachy Specifications fail to satisfy 10 the requirements of Â§ 112 with respect to disputed Limitation (7). 11 12 Motion 6, Limitation (8) 13 Smoothened-dependent hedgehog signaling is used for inhibition 14 (or selective inhibition) of differentiation 15 (Claims 103, 105, 106-111, 117-125, 202-211) 16 and 17 said dose is sufficient to induce differentiation in said tumor 18 (Claims 103,105-111) 19 Tas argues that the Beachy Specifications do not disclose to a person of ordinary 20 skill that Smo-dependent Hh signaling is used for inhibition of differentiation. 21 Paper 198, page 29:14-15. 22 According to Tas, Ex. 1009 (Beachy US Patent 7,291,626 B1) discloses that Hh 23 signaling induces differentiation of cells. Id. (citing, e.g., Ex. 1009, col 7: 28-29 and 24 col. 8:31-34). 25 Interferences 105,926 & 105,949 43 By contrast, Tas argues that Ex. 1018 (Beachy US Patent 7,098,196 B1) discloses 1 a greater degree of differentiation in tumor grafts in cyclopamine- or KAAD-2 cyclopamine-injected nude mice, relative to the tomatidine-injected mice. Id. at 3 page 29:14-21. 4 However, Tas contends that a person of ordinary skill in the art would have known 5 that subcutaneous injection of foreign tumor cells into nude mice commonly induces 6 varying differentiation of tumor cells by itself, in the absence of administration of a drug. 7 Id. at page 29, l. 21 to page 30, l. 10; see also p. 11, ll. 1-5 (citing Ex. 2043 15 and 8 Ex. 2044 16 ). 9 Tas also argues that it was recognized in the contemporary art that, due to a 10 variableâ€”but significant residual immune response of nude mice against the 11 subcutaneously injected foreign tumor cellsâ€”a person of ordinary skill would have 12 known that it was necessary to determine that an observed treatment effect on 13 differentiation of the grafted tumor cells was not due to an effect on the normal host cells. 14 Paper 198, page 30:6-10 (citing, e.g., Ex. 2043â€”Boukamp, n.15). 15 Beachy argues that one of ordinary skill in the art would have understood that the 16 observed decrease in proliferation was attributable to cyclopamine inhibiting the Hh 17 pathway, which would also result in inducement of apoptosis (due to, for example, lower 18 levels of Bcl-2 protein) and increased differentiation of tumor cells. Paper 323, 19 15 Boukamp et al., Environmental Modulation of the Expression of Differentiation and Malignancy in Six Human Squamous Cell Carcinoma Cell Lines, 45 CANCER RESEARCH 5582 (1985). 16 Helson et al., Human Neuroblastoma in Nude Mice, 35 CANCER RESEARCH 2594 (1975). Interferences 105,926 & 105,949 44 page 5:18 to page 6:2 (citing Ex. 1025 17 ; Ex. 1027 18 ; Ex. 1088, Â¶Â¶ 24- 35 (First Curran 1 declaration); Ex. 1114, Â¶ 95 (Second Curran declaration). 2 We are persuaded by Beachyâ€™s arguments. 3 In his second declaration, Dr. Thomas Curran quotes from the â€™076 application: 4 An â€œeffective amountâ€ of a subject compound, with respect to the 5 subject method of treatment, refers to an amount of the antagonist in a 6 preparation which, when applied as part of a desired dosage regimen brings 7 about, e.g., a change in the rate of cell proliferation and/or the state of 8 differentiation of a cell and/or rate of survival of a cell according to 9 clinically acceptable standards for the disorder to be treated or the cosmetic 10 purpose. 11 12 Ex. 1114, Â¶ 94 (quoting Ex. 1018, col. 10:8-15) (italics added). 13 Dr. Curran further quotes from the disclosure of the â€™076 application: 14 One aspect of the present invention relates to a method of 15 modulating a differentiated state, survival, and/or proliferation of a 16 cell, such as a normal cell or a cell having a ptc loss-of-function, 17 hedgehog gain-of-function, or smoothened gain-of-function, by 18 contacting the cells with a compound as set forth above according to 19 the subject method and as the circumstances may warrant. 20 21 Ex. 1114, Â¶ 94 (quoting Ex. 1018, col. 34:27-33). 22 Dr. Curran was of the opinion that â€œBeachy also specifically teaches that the 23 subject compounds, such as cyclopamine, could be administered in doses sufficient to 24 17 Fan et al., Induction of basal cell carcinoma features in transgenic human skin expressing Sonic Hedgehog, 3 NATURAL MEDICINE 788 (1997). 18 Fan et al., Sonic Hedgehog Opposes Epithelial Cell Cycle Arrest, 147 J. OF CELL BIOLOGY 71 (1999) Interferences 105,926 & 105,949 45 induce various biological effects, including apoptosis [and differentiation].â€ Ex. 1114, 1 Â¶ 94. 2 Accordingly, Dr. Curran reasoned that one of ordinary skill in the art would have 3 recognized the above-identified statement as consistent with the fact that (1) aberrant 4 activation of the Hh pathway in BCC tumors results in increased levels of Bcl-2 and, 5 therefore (2) inhibition of the pathway would result in decreased levels of Bcl-2 protein 6 and, (3) hence, increased levels of apoptosis [and differentiation].â€ Ex. 1114, Â¶ 95. 7 We are persuaded by Beachyâ€™s arguments and proofs. The â€™076 application 8 discloses that: 9 The subject compounds may be formulated as a pharmaceutical 10 preparation comprising a pharmaceutically acceptable excipient. 11 Smoothened antagonists of the invention and/or preparations 12 comprising them may be administered to a patient to treat conditions 13 involving unwanted cell proliferation, e.g., cancer and/or tumors (such 14 as medulloblastoma, basal cell carcinoma, etc.), non-malignant 15 hyperproliferative disorders, etc. Smoothened agonists can also be 16 used to regulate the growth and differentiation of normal tissues. In 17 certain embodiments, such compounds or preparations are 18 administered systemically and/or locally, e.g., topically. 19 20 Ex. 1018, col. 7:1-12 (italics added). Furthermore, Ex. 1027 (Fan et al., supra n.18) 21 discloses that: â€œCell cycle exit before outward migration and terminal differentiation is a 22 cardinal feature of normal stratified epithelium. Here we report that [Hh] inhibits this 23 processâ€ and that â€œ[o]ur findings indicate that [Hh] action promotes cellular proliferation 24 by opposing cell cycle arrest [and the subsequent differentiation]. Ex. 1027, page 74, 25 col. 1 (under Discussion) and page 75, col. 2, last Â¶; see also Ex. 1088, Â¶ 28 (First Curran 26 declaration). 27 Interferences 105,926 & 105,949 46 The literature supports, and is consistent with, Dr. Curranâ€™s statement that one of 1 ordinary skill in the art would have appreciated that that aberrant activation of the Hh 2 pathway in BCC tumors resulted in increased levels of Bcl-2 and, therefore, inhibition of 3 the pathway would result in decreased levels of Bcl-2 and, hence, increased levels of 4 apoptosis and differentiation. Ex. 1114, Â¶ 95. 5 Based on Dr. Curranâ€™s testimony, we are not persuaded by Tasâ€™ conjecture that the 6 differentiation of injected tumor cells is merely a confounding experimental artifact. 7 Tas has not met its burden of showing that the Beachy Specifications fail to satisfy 8 the requirements of Â§ 112 with respect to disputed Limitation (8). 9 10 Motion 6, Limitation (9) 11 Wherein said amount of cyclopamine is not toxic to 12 the subject and causes reduced side effects 13 (Claims 104-105; 203) 14 Tas asserts that the Beachy applications lack any description of a human being 15 administered cyclopamine and also that it lacks any description of the induction of tumor 16 cell apoptosis in any species. Paper 198, Motion 6, page 30:11-17. 17 As a result, Tas maintains that the Beachy applications lack written description 18 demonstrating no toxicity or reduced side effects of cyclopamine in humans. Id. 19 Beachy responds by noting that the written description requirement of Â§ 112 does 20 not require actual examples of human administration of cyclopamine. Paper 323, 21 page 29:5-6. 22 Beachy further responds to Tasâ€™ argument that the Beachy Specifications â€œhave no 23 description of apoptosis and, therefore, no description of no toxicity or reduced side 24 Interferences 105,926 & 105,949 47 effectsâ€ with the argument that it made with respect to the corresponding limitations in 1 Motion 3. Id. at page 29. 2 Beachy still further responds by noting that in its earliest filings, Beachy described 3 hedgehog antagonists as often exerting cystostatic, rather than cytotoxic, effects on 4 epithelial cells, including hair follicle cells. Id. at page 29:11-14 (citing Ex. 1016, 5 page 43, second full Â¶ (Beach Provisional Application 60/081,263); see also Ex. 1114, 6 Â¶Â¶ 67-68 (Second Curran Declaration). 7 We agree with Beachy. 8 We have discussed our reasoning with respect to why Beachy need not provide 9 examples of human experimentation to satisfy the written description requirement of 10 Â§ 112. 11 Moreover, Beachyâ€™s 1998 Provisional Application recites: 12 Moreover, because a hedgehog antagonist will often be cytostatic to 13 epithelial cells, rather than cytotoxic, such agents can be used to protect hair 14 follicle cells from cytotoxic agents which require progression into S-phase 15 of the cell-cycle for efficacy, e.g. radiation-induced death. Treatment by the 16 subject method can provide protection by causing the hair follicle cells to 17 become quiescent, e.g., by inhibiting the cells from entering S phase, and 18 thereby preventing the follicle cells from undergoing mitotic catastrophe or 19 programmed cell death. 20 21 Ex. 1016, page 43, second full Â¶. 22 Furthermore, in his Second Declaration, Dr. Curran testifies that: 23 Prior to the Tas filing, evidence had been published showing that a 24 Hedgehog antagonist, while inducing the regression of BCC-like 25 structures in a skin punch assay from an embryonic mouse model, had 26 no cytotoxic effect on normal skin cells as shown by their normal 27 histology. (See Ex. 1065, Baxter et al. WO 2001/26644, page 126, 28 line 23 - page 127, line 17). This work was subsequently published in 29 Interferences 105,926 & 105,949 48 Williams et al., Identification of a small molecule inhibitor of the 1 Hedgehog signaling pathway: Effects on basal cell carcinoma-like 2 lesions, PROC NATL ACAD SCI USA 100(8): 4616-21 (April 2003; 3 Ex. 1034). Note that compound D of Baxter et al. WO 2001/26644 4 (Ex. 1065) is the same compound as CUR-61414 of the Williams et 5 al. publication (Ex. 1034). One of ordinary skill in the art also knows 6 that, in most adult tissues, Hh pathway activity is present in many 7 fewer cellular sites than in the developing embryo, primarily 8 functioning in tissue maintenance and repair. (Ex. 1021, Scales et al., 9 Abstract; Ex. 2063, Lipinski RJ et al., Abstract). Therefore, one of 10 ordinary skill in the art would not have expected the administration of 11 a Hedgehog inhibitor to adversely selectively cause normal cells to 12 â€œsuccumb.â€ The involved Beachy â€˜076 specification specifically 13 contemplates the effect (cytostatic rather than cytotoxic) of Hedgehog 14 inhibitors on hair follicle cells that have active Hedgehog signaling: 15 Moreover, because a subject compound will often be cytostatic 16 to epithelial cells, rather than cytotoxic, such agents can be used 17 to protect hair follicle cells from cytotoxic agents which require 18 progression into S-phase of the cell-cycle for efficacy, e.g. 19 radiation induced death. [Ex. 1018, Beachy â€˜076 application, 20 col. 46, ll. 30-34]. 21 22 Ex. 1114, Â¶ 67 (page 42:9 to page 43:13) (boldface added). 23 Based on Dr. Curranâ€™s testimony, we find that a person of ordinary skill in the art 24 would have known at the time of Beachyâ€™s filings, that Hh inhibitors are cytostatic rather 25 than cytotoxic, and consequently would have known that Beachy was in possession of 26 cyclopamine that was not toxic and reduced side effects. 27 Tas has not met its burden of demonstrating that disputed Limitation (9) fails the 28 written description requirement of Â§ 112. 29 30 Interferences 105,926 & 105,949 49 Motion 6, Limitation (10) 1 Administering to the subject an effective amount 2 (or a therapeutically effective amount) of a medicament 3 comprising cyclopamineâ€ 4 (Claims 117-125, 202-211) 5 and 6 inhibits tumor cell proliferation 7 (or inhibits proliferation of said tumor) 8 (Claims 201-205) 9 Tas argues that, prior to the Tas invention, a person of ordinary skill would believe 10 that the only expected benefit of administering a selective inhibitor of Hh/Smo signaling 11 to a human with a BCC tumor by administration would be reduced proliferation of tumor 12 cells resulting in reduced tumor growth. Paper 198, page 30:21-23. 13 According to Tas, a skilled artisan would have been warned against such an 14 administration for â€œmultiple reasons.â€ 15 Tas argues (1) that proliferation and apoptosis of cells are regulated by different 16 mechanisms, (2) that the inhibition of tumor cell proliferation does not necessarily induce 17 apoptosis and (3) can, in fact, cause inhibition of apoptosis, depending on the particular 18 signals. Id. at page 31:4-7 (citing Ex. 2009 19 and references therein 20 ). 19 19 Lipponen, Apoptosis in breast cancel: relationship with other pathological parameters, 6 ENDORINE-RELATED CANCER 13 (1999). 20 We have not considered the â€œreferences thereinâ€. See DeSilva v. DiLeonardi, 181 F.3d 865, 866-67 (7th Cir 1999) (a brief must make all arguments accessible to the judges, rather than ask them to play archaeologist with the record; Halliburton Energy Services, Inc. v. M-I LLC, 514 F.3d 1244, 1250 n.2 (Fed. Cir. 2008) (a skeletal argument, really nothing more than an assertion, does not preserve a claim; Judges are not like pigs, hunting for truffles buried in briefs, quoting United States v. Dunkel, 927 F.2d 955, 956 (7th Cir. 1991). Interferences 105,926 & 105,949 50 Based on the foregoing, Tas argues that a reduced proliferation of tumor cells does 1 not provide written description of induction of apoptosis. Id. at page 31:9-11. 2 Beachy points out that none of Tasâ€™ arguments presented with respect to this 3 limitation dispute that Beachy provides an adequate description of inhibiting proliferation 4 of tumor cells and inhibiting tumor growth. Paper 323, page 30:3-5. 5 This is significant, argues Beachy, because one of ordinary skill in the art would 6 have known that inhibition of the Hh pathway in a BCC tumor cell resulting in inhibition 7 of tumor growth would also induce apoptosis (through decreased levels of the Bcl-2 8 protein) and therefore cause a decrease in tumor size. Id. at page 30:6-10 (citing 9 Ex. 1088, Â¶ 55; Ex. 1114, Â¶ 95 (testimony of Dr. Curran)). 10 With respect to Tasâ€™ contention that the background frequency of apoptosis in the 11 absence of treatment does not provide for their decrease of size and that proliferation and 12 apoptosis of cells are â€œregulated differently,â€ Beachy disagrees. 13 Beachy argues that, as the level of proliferating tumor cells decreases and the 14 apoptotic index increases (due to both induced and naturally-occurring apoptosis), one of 15 ordinary skill in the art would reasonably expect the tumor to decrease in size and/or 16 disappear because the cell loss caused by apoptosis would not be compensated by the 17 generation of new tumor cells by proliferation. Id. at page 30 (again citing Dr. Curranâ€™s 18 testimony at Ex. 1088, Â¶Â¶ 55; Ex. 1114, Â¶ 95). 19 Furthermore, Beachy argues that one of ordinary skill in the art would have 20 understood that the observed decrease in proliferation was attributable to cyclopamine 21 inhibiting the Hh pathway, which would also result in inducement of apoptosis (due to 22 Interferences 105,926 & 105,949 51 lower levels of Bcl-2 protein) and increased differentiation of tumor cells. Id. at 1 page 30:20 to page 4 (citing Dr. Curranâ€™s testimony at Ex. 1114, Â¶ 95). 2 Beachy also disputes Tasâ€™ statement that: â€œâ€¦and would not obtain an induction of 3 apoptosis of tumor cells that would cause decrease of size or disappearance of a tumor 4 (Â¶[Â¶] 14, 15, 18, 48-51).â€ Paper 323, page 31:11-13 (quoting Paper 198, page 31:3-4) 5 (emphasis by Beachy). 6 Beachy asserts that no such limitation appears in any Beachy claim, any Tas claim, 7 or either Count 2 or Count 3. Id. at page 31:13-14. 8 Rather, Beachy argues that the relevant Beachy claims recite administering a 9 sufficient dose of cyclopamine to (1) induce apoptosis and (2) cause a decrease of size or 10 disappearance of a tumor. Id. at page 31:14-16. 11 Beachy contends that one of ordinary skill in the art would understand that a tumor 12 can decrease in size after administration of cyclopamine for reasons other than apoptosis 13 of tumor cells, or for reasons in conjunction with apoptosis, e.g., reduction of tumor cell 14 proliferation, naturally-occurring apoptosis and sloughing off of epithelial cells. 15 Paper 323, page 31: 16-19 (citing Dr. Curranâ€™s testimony at Ex. 1088, Â¶Â¶ 51-57). 16 Tasâ€™ arguments are not persuasive. 17 We find no credible factual support for Tasâ€™ contention that: 18 [A] skilled person was however warned against such an 19 administration for multiple reasons and, if he or she had at al decided 20 to administer, would administer the lowest dose effective and would 21 not obtain an induction of apoptosis of tumor cells that would cause 22 decrease of size or disappearance of a tumor. 23 24 Paper 198, page 30:23 to page 31:4 25 Interferences 105,926 & 105,949 52 Moreover, Exhibit 2009, 21 Antti Sarastea and Kari Pulkkic, Morphologic and 1 biochemical hallmarks of apoptosis, 45 CARDIOVASCULAR RESEARCH 528â€“537 (2000), 2 provides a general review of â€œthe current knowledge on the molecular mechanisms of 3 apoptosis as they relate to the morphologic hallmarks and their implications for the 4 detection of apoptosis in cardiac tissueâ€. 5 But Tas points to nothing in the reference, or the references contained therein, that 6 credibly supports its contention that â€œinhibition of tumor cell proliferation does not 7 induce their apoptosis and can, in fact, cause inhibition of apoptosis depending on the 8 particular signals.â€ Ex. 2009, Abstract (emphasis added); Paper 198, page 31:4-7. 9 In his First Declaration, Dr. Curran opines that: 10 [a] method of treating BCC tumors in humans by the administration of 11 cyclopamine in amounts sufficient to result in a decrease of proliferation of 12 BCC tumor cells would have taught or suggested a method to achieve 13 apoptosis and a decrease of size or disappearance of the BCC tumor. One of 14 ordinary skill in the art would have understood that the observed decrease in 15 proliferation was attributable to cyclopamine inhibiting the Hh pathway, 16 which would also result in inducement of apoptosis (due to lower levels of 17 Bcl-2 protein) and increased differentiation of tumor cells. As the level of 18 proliferating tumor cells decreases and the apoptotic index increases (due to 19 both induced and naturally-occurring apoptosis), one of ordinary skill in the 20 art would reasonably expect the tumor to decrease in size and/or disappear 21 because the cell loss caused by apoptosis would not be compensated by the 22 generation of new tumor cells by proliferation. 23 24 Ex. 1088, Â¶ 55. 25 Dr. Curran further opined, in his Second Declaration, that: 26 21 Antti Sarastea et al., Morphologic and biochemical hallmarks of apoptosis, 45 CARDIOVASCULAR RESEARCH 528â€“537 (2000). Interferences 105,926 & 105,949 53 one of ordinary skill in the art would have known that [Hh] induced 1 bcl-2 and thus potentially resists apoptosis (Ex. 1027, Fan et al. 1999) and 2 that bcl-2 is expressed in BCCs (Ex. 1025, Fan et al. 1997). Accordingly, 3 one of ordinary skill in the art would have recognized the above-identified 4 statement as consistent with the fact that aberrant activation of the Hh 5 pathway in BCC tumors resulted in increased levels of Bcl-2 and, therefore, 6 inhibition of the pathway would result in decreased levels of Bcl-2 and, 7 hence, increased levels of apoptosis. 8 9 Ex. 1114, Â¶ 95 (see also Ex. 1088, Â¶Â¶ 24-35). 10 We find that Dr. Curranâ€™s characterization of the contemporary art at the time of 11 filing to be credible. 12 Dr. Curran testifies that it was known in the art (see, e.g., Exs. 1025, 1027) that 13 increased expression of Hh-induced Bcl-2 protein in BCC cells rendered those cells 14 resistant to apoptosis and that inhibition of Bcl-2 expression consequently decreased the 15 cellsâ€™ resistance to apoptosis. Ex. 1114, Â¶ 95; Ex. 1088, Â¶Â¶ 24-35. 16 Furthermore, we reject Tasâ€™ argument that the language of the Beachy claims 17 requires that the induction of apoptosis directly causes the decrease in size or 18 disappearance of a tumor. 19 None of the language of the Beachy claims requires that causal link, as Beachy 20 successfully argues. 21 Rather, as Dr. Curran states: 22 One of ordinary skill in the art would have understood that the 23 observed decrease in proliferation was attributable to cyclopamine 24 inhibiting the Hh pathway, which would also result in inducement of 25 apoptosis (due to lower levels of Bcl-2 protein) and increased 26 differentiation of tumor cells. As the level of proliferating tumor cells 27 decreases and the apoptotic index increases (due to both induced and 28 naturally-occurring apoptosis), one of ordinary skill in the art would 29 Interferences 105,926 & 105,949 54 reasonably expect the tumor to decrease in size and/or disappear 1 because the cell loss caused by apoptosis would not be compensated 2 by the generation of new tumor cells by proliferation. 3 4 Ex. 1088, Â¶ 55. 5 Tasâ€™ position is not consistent with Dr. Curranâ€™s credible testimony. 6 We accept Dr. Curranâ€™s testimony that suppression of the Hh pathway by 7 cyclopamine resulting in decreased tumor cell proliferation was known in the art at the 8 time of invention. 9 Tas has not met its burden of demonstrating that disputed Limitation (10) fails the 10 written description requirement of Â§ 112. 11 â€œCarnival barking,â€ â€œGambling on both sides,â€ and â€œplagiarismâ€ 12 We have discussed our reasoning with respect to these allegations in addressing 13 similar arguments made in connection with Tas Motion 4. 14 Tas cites no legal authority to suggest that any of these arguments are relevant to a 15 Section 112 analysis, nor are we aware of any such authority. 16 Because none of these arguments are related to an analysis of whether the 17 Specification meets the written description or enablement requirements of Â§ 112, we find 18 them to be without merit. 19 20 C. Indefiniteness 21 Tas argues that the Beachy claims are unpatentable under 35 U.S.C. Â§ 112 as 22 indefinite when read in light of the prior art. Paper 198, page 31. 23 Interferences 105,926 & 105,949 55 According to Tas, it is unclear from the claims whether Smo-dependent Hh 1 signaling is utilized for inhibition of apoptosis of normal cell types or of transformed 2 cells in the tumor. Id. at page 31:14-15 3 Further according to Tas, the only actual administration to a tumor-bearing subject 4 described in the Beachy applications is to a nude mouse having a graft of foreign 5 transformed cells. Id. at page 31:17-18. 6 Tas argues that it is well-known that an observed effect in such grafts can be due to 7 a primary effect on the normal host cells rather than to the transformed cells and would 8 not occur even in a mouse having a naturally occurring tumor, let alone in humans. Id. at 9 page 31:18 to page 32:1. 10 Tas further argues that the Beachy applications contain no description that would 11 show to the person of ordinary skill that Hh/Smo signaling is utilized for inhibition of 12 apoptosis of a cell type in a tumor. Tas further argues that the Beachy applications do not 13 disclose any dosage of cyclopamine for the induction of apoptosis of any cell type in any 14 tumor. Tas reasons, therefore, that person of ordinary skill would not have a reference to 15 rely upon to decide what is meant by â€œsmoothened dependent Hedgehog signaling is 16 utilized for inhibition of apoptosis.â€ Id. at page 32:14-19. 17 Tas still further argues further that while Beachy claims 103, 105-11, 117-126, 18 202-211, and 213, Beachyâ€™s Example 3 purports to disclose the induction of 19 differentiation, nevertheless a skilled person would discern no evidence of such 20 differentiation and would be unable to determine that an induction of differentiation is 21 caused by administration of cyclopamine. 22 Interferences 105,926 & 105,949 56 Tas next argues that the claim term â€œeffective amountâ€ cannot be reasonably 1 construed because the Beachy Specifications disclose no basis for the claimed 2 classification of tumors. Id. at page 33:8-14. 3 Tas also argues that it cannot be determined from the Beachy applications the 4 amount or dose that would be effective in producing the multiple claimed effects. Id. 5 at page 33:13-14. 6 Tas claims that it was unknown in prior art that cyclopamine or other selective 7 inhibitors of Smo-dependent Hh signaling can induce apoptosis of tumor cells and, 8 further, that it was unknown that different amounts or doses are required to produce 9 apoptosis and other effects. Id. at page 33:14-18. 10 Furthermore, argues Tas, a skilled person reading the Example 3 of the Beachy 11 applications, which describes the use of nude mice, would not know what an effective 12 amount would be to produce a given effect on normal cells or on transformed cells in a 13 tumor. Id. at page 33:17-19. 14 Beachy argues that Tasâ€™ allegations regarding indefiniteness are irreparably 15 confused and entangled with its written description arguments (which, in turn, are 16 entangled with enablement arguments that are based on a misunderstanding of the 17 relevant prior art). Paper 323, page 35:8-11. 18 According to Beachy, Tas repeats arguments relating to the presence of working 19 examples in the Beachy Specificationsâ€™ disclosures, and concludes that one skilled in the 20 art would be unable to decide what is meant by the term â€œsmoothened-dependent 21 Hedgehog signaling is utilized for inhibition of apoptosis.â€ Id. at page 34:18 to 22 page 35:2. 23 Interferences 105,926 & 105,949 57 â€œWhether a claim is [unpatentable] for indefiniteness requires a determination 1 whether those skilled in the art would understand what is claimed when the claim is read 2 in light of the specification.â€ Morton Intâ€™l, Inc. v. Cardinal Chem. Co., 5 F.3d 1464, 3 1470 (Fed. Cir. 1993). 4 The party challenging indefiniteness in an interference bears the burden of proving 5 unpatentability by a preponderance of the evidence. Bruning v. Hirose, 161 F.3d 681, 6 685 (Fed. Cir. 1998) (the burden of proof on the issue of patentability of the claims of a 7 patent in an interference where applications are co-pending is by a preponderance of the 8 evidence); Bilstad v. Wakalopulos, 386 F.3d 1116, 1120 (Fed. Cir. 2004). 9 Tas Motion 6 does not articulate a coherent or convincing argument that a person 10 of ordinary skill would fail to understand what is claimed when the Beachy claims are 11 read in light of the specifications. 12 Tas relies on factually unsupported assertions as to what a skilled artisan might or 13 might not understand, in an attempt to poke holes in the experimental examples presented 14 in the Beachy applications, but adduces no direct credible evidence to indicate that the 15 claims, when viewed in light of the specifications, are indefinite. 16 Exhibits offered by Tas (e.g., Exs. 2019, 2020, 2045, 2072, 2073, 2098) are 17 generally directed to the properties of tumor cells in xenografts, but Tas adduces these 18 only to attack Example 3. 19 These arguments are irrelevant to an analysis of indefiniteness and Tas points to no 20 direct credible proof that a person of ordinary skill, having read the Specifications, would 21 fail to understand what is being claimed. 22 Tas thus fails to meet this burden, and we conclude that Tas has filed to establish 23 that the Beachy claims are unpatentable as indefinite under 35 U.S.C. Â§ 112. 24 Interferences 105,926 & 105,949 58 D. Conclusion 1 Because Tas has failed to meet its burden of demonstrating that claims of 2 the Beach â€™934 application and the Beach â€™121 application are unpatentable under 3 35 U.S.C. Â§ 112 for lack of written description or indefiniteness, Tasâ€™ Motion 6 will be 4 denied. 5 6 VI. Tas Motion 14 7 Tas moves to designate Tas claims 1, 3, 5 and 23 as not corresponding to Counts 2 8 and 3. Paper 199, page 1. 9 Tas independent claim 1 recites: 10 1. A method for inducing apoptosis of tumor cells in a tumor-bearing 11 patient, comprising 12 13 determining that Hedgehog/Smoothened signaling is utilized for 14 inhibition of apoptosis of tumor cells and 15 16 administering to the patient cyclopamine or a pharmaceutically 17 acceptable salt thereof in a dose that is sufficient to induce apoptosis of said 18 tumor cells and to cause decrease of size or disappearance of the tumor. 19 20 Tas claim 3 recites: 21 3. The method according to claim 2, characterized in that a dose 22 sufficing to induce apoptosis of the tumor cells causes a smaller proportion 23 of normal tissue cells or no normal tissue cells to undergo apoptosis. 24 25 Tas claim 5 recites: 26 5. The method according to claim 4, characterized in that a dose 27 sufficing to induce differentiation and apoptosis of the tumor cells causes a 28 Interferences 105,926 & 105,949 59 smaller proportion of normal tissue cells or no normal tissue cells to undergo 1 differentiation and apoptosis. 2 3 Tas claim 23 recites: 4 5 23. A method for causing decrease of size or disappearance of a tumor in 6 a human, comprising 7 8 determining that Hedgehog/Smoothened signaling is utilized for 114 9 inhibition of apoptosis of the tumor cells and 10 11 administering to him or to her a medicament comprising cyclopamine 12 or a pharmaceutically acceptable salt thereof or another selective inhibitor of 13 Hedgehog/Smoothened signaling to induce apoptosis of the tumor cells to 14 cause decrease of size or disappearance of the tumor. 15 16 Tas claims reproduced from a clean copy of claims submitted by Tas. Paper 16. 17 See also Ex. 2001. 18 We have considered Tas Motion 14 (Paper 199), Beachy Opposition 14 19 (Paper 324) and Tas Reply 14 (Paper 332). 20 For essentially the reasons articulated in Beachy Opposition 14, as herein 21 discussed, we agree with Beachy and disagree with Tas. 22 Accordingly, Tas Motion 14 will be denied. 23 As noted by Beachy (Paper 324, page 7), Bd.R. 207(b)(2) states: â€œA claim 24 corresponds to a count if the subject matter of the count, treated as prior art to the claim, 25 would have anticipated or rendered obvious the subject matter of the claim.â€ 26 27 Interferences 105,926 & 105,949 60 Therefore, to succeed Tas must demonstrate by a preponderance of the evidence, 1 that the subject matter of Counts 2 and 3, if treated as prior art, would not have 2 anticipated or rendered obvious the subject matter of claims 1, 3, 5, and 23. 3 The rationale in support of Bd.R. 207(b)(2) is explained in University of Southern 4 California v. Depuy Spine, Inc., Interference 105,653, Paper 133, pages 9-10 (BPAI 5 Nov. 23, 2010) (relevant material quoted on pages 7-8 of Beachy Opposition 14 6 (Paper 332)). 7 The basic failure of proof on the part of Tas is a failure to deal with the subject 8 matter of the counts. 9 Rather, except for a few unsupported and conclusory assertions that the claims do 10 not correspond to the count, Tas presents its interpretation of the Beachy application 11 disclosuresâ€”that in large measure are not relevant to a proper analysis. Paper 324, 12 page 8:21-22; page 9:17 to page 10:6; page 12:7-9. 13 We agree with Beachyâ€™s observations related to Tas Claims 3 and 5. Paper 323, 14 page 11:8-19. 15 We also agree with the remaining arguments presented in Beachy Opposition 14 16 (Paper 324) responding to arguments made in Tas Motion 14 (Paper 199). 17 For the reasons given, we hold that Tas has failed to meet the burden imposed by 18 Bd.R. 207(b)(2) and therefore Tas Motion 14 is denied. 19 20 VII. Tas Motion 17 21 Tas moves to deny Beachyâ€™s involved application 13/364,121 an earlier 22 constructive reduction to practice (i.e., benefit for the purpose of priority) of: 23 (1) Beachy application 09/685,244 (Ex. 1013) and 24 Interferences 105,926 & 105,949 61 (2) Beachy application 09/708,964 (now US Patent 7,291,626 B1) 1 (Ex. 1009) as to Count 2. 2 Paper 200, page 1:1-2. 3 The arguments presented and evidence relied upon by Tas in support of Tas 4 Motion 17 are essentially the same as those made in connection with Tas Motion 4 5 (seeking denial of benefit) and Tas Motion 6 (seeking judgment based on lack of written 6 description and indefiniteness). 7 With respect to Tas Motion 17, Tas seeks relief based on alleged lack of a written 8 description for the following limitations 22 : 9 10 Tas Motion 17, Limitation (1) 11 A method for treatment of a human subject having a basal cell carcinoma 12 tumor cell [sic. A basal cell carcinoma tumor]â€ (or) â€œA method of therapy 13 for a human subject having a basal cell carcinoma tumorâ€ 14 15 Tas Motion 17, Limitation (2) 16 17 â€œComprising administering to the human subject a medicament comprising 18 cyclopamineâ€ (or) â€œcomprising administering to the human subject a 19 therapeutically effective amount of a medicament comprising cyclopamine 20 or a pharmaceutically acceptable carrierâ€ 21 22 Tas Motion 17, Limitation (3) 23 â€œWherein Hedgehog/Smoothened signaling is utilized for inhibition of 24 apoptosis of the tumor cellâ€ (or) â€œwherein said tumor smoothened-dependent 25 hedgehog signaling is utilized for inhibition of apoptosisâ€ 26 27 22 See Paper No. 200 (page numbers not supplied in document) Interferences 105,926 & 105,949 62 Tas Motion 17, Limitation (4) 1 2 â€œAnd said amount of cyclopamine selectively inhibits smoothened-3 dependent hedgehog signaling in said tumor and is sufficient to induce 4 apoptosis in said tumor and inhibits tumor cell proliferationâ€ (and) â€œWherein 5 said medicament is administered in a dose that is sufficient to induce 6 apoptosis of said tumor cellâ€ 7 8 Tas Motion 17, Limitation (5) 9 10 â€œCauses decrease in size or disappearance of the tumorâ€ 11 12 â€œCarnival barking,â€ â€œGambling on both sides,â€ and â€œplagiarismâ€ See Paper 200, 13 pages 16-18. Our reasoning with respect to each of the limitations and the additional 14 arguments made by Tas is set out in our discussion concerning Tas Motion 4 and Tas 15 Motion 6 and need not be repeated here. 16 For the reasons given in connection with denial of Tas Motion 4 and Tas Motion, 17 we also deny Tas Motion 1. 18 Tas has failed to sustain its burden with respect to Tas Motion 17. 19 Tas Motion 17 will be denied. 20 21 VIII. Beachy Motion 1 22 A. Introduction 23 Beachy moves for judgment against all of Tasâ€™ involved claims 1-23 as lacking 24 written description and/or enablement and/or as being indefinite. Paper 181, page 1:3-5: 25 (1) Tas Claims 2-20 and 23: Beachy argues that there is a lack of a 26 written description and a lack of enablement as to â€œanother compoundâ€ or â€œanother 27 inhibitorâ€. Id. at page 1:6-7. 28 Interferences 105,926 & 105,949 63 (2) Tas Claim 7: Beachy argues that there is lack of a written description 1 and lack of enablement as to â€œderivative of cyclopamineâ€. Id. at, page 1:8. 2 (3) Tas claims 1-23: Beach argues that the term â€œapoptosisâ€ renders the 3 claims indefinite. Id. at page 1:9-10. 4 The following claims are believed to be representative of the Tas claims at issue 5 (italics added). 6 Independent Tas Claim 1 recites: 7 A method for inducing apoptosis of tumor cells in a tumor-8 bearing 1 patient, comprising 9 10 determining that Hedgehog/Smoothened signaling is utilized 11 for inhibition of apoptosis of tumor cells and 12 13 administering to the patient cyclopamine or a pharmaceutically 14 acceptable salt thereof in a dose that is sufficient to induce apoptosis 15 of said tumor cells and to cause decrease of size or disappearance of 16 the tumor. 17 18 Independent Tas Claim 2 recites: 19 A method for treatment of a patient having a tumor wherein 20 21 Hedgehog/Smoothened signaling is utilized for inhibition of 22 apoptosis of the tumor cells, comprising 23 24 administering to the patient a medicament comprising 25 cyclopamine or another compound that selectively inhibits 26 Hedgehog/Smoothened signaling, wherein said medicament is 27 administered in a dose that is sufficient to induce apoptosis of said 28 tumor cells and causes decrease of size or disappearance of the tumor. 29 30 Dependent Tas Claim 7 recites: 31 Interferences 105,926 & 105,949 64 The method according to any one of claims 2 to 5, wherein said 1 another compound that selectively inhibits Hedgehog/Smoothened 2 signaling is a derivative of cyclopamine. 3 4 Independent Tas Claim 23 recites: 5 A method for causing decrease of size of disappearance of a 6 tumor in a human, comprising 7 8 determining that Hedgehog/Smoothened signaling is utility for 9 inhibition of apoptosis of the tumor cells and 10 11 administering to . . . [the human] a medicament comprising 12 cyclopamine or a pharmaceutically acceptable salt thereof or another 13 selective inhibitor of Hedgehog/Smoothened signaling to induce 14 apoptosis of the tumor cells to cause decrease of size or disappearance 15 of the tumor. 16 17 Ex. 2001, col. 12:22-38 and 64-67 and col. 14:36-45 (italics added). 18 19 B. Written Description 20 1. â€œAnother Compoundâ€ 21 According to Beachy, Tas introduced the â€œanother compoundâ€ claims into the Tas 22 application by an amendment filed more than six years after the October 9, 2003 filing 23 date of Tas application 10/682,584 (now the involved Tas patent Ex. 2001) (the â€œâ€™584 24 applicationâ€). Paper 181, page 21:17-20 (citing Ex. 1071, page 21:17-20). 25 Beachy contends that the â€œanother compoundâ€ was not described, either expressly 26 or inherently, in either the application or the original claims of either the Tas US â€™584 or 27 the Tas PCT â€™027 (Ex. 2004) applications as originally filed. Id. at page 21:20-23 (citing 28 First Decl. of Lawrence I. Kruse (Ex. 1070), Â¶Â¶ 27, 29, 31-33). 29 Interferences 105,926 & 105,949 65 Beachy further contends that the Tas specification does not provide, as part of its 1 invention, any description by way of chemical name, structure, formula, etc., of an 2 inhibitor other than cyclopamine. Id. at page 21:24 to page 22:2 (citing Ex. 1070, 3 Â¶Â¶ 19-21 and Exs. 2001, 2002, 2004, 1064, 1067-1068). 4 Beachy still further contends that the Tas disclosure relating to a â€œderivative of 5 cyclopamineâ€ does not provide written support for the recitation of â€œanother compoundâ€ 6 in Tas claims 2-20 and 23. Paper 181, page 22:4-5. 7 Beachy witness Dr. Lawrence Kruse testified that one of ordinary skill in the art 8 would have understood â€œanother compoundâ€ to refer to something significantly, and 9 potentially infinitely, broader than the disclosed â€œderivative of cyclopamine.â€ Ex. 1070 10 Â¶ 27:2-4. 11 Beachy argues that, logically, an undefined genus of compounds (such as 12 â€œderivative of cyclopamineâ€) cannot provide a written description for an even broader 13 (and potentially infinite) genus of compounds (such as â€œanother compoundâ€). Paper 181, 14 page 22:14-17. 15 Beachy argues further that, even if a person skilled in the art could conclude that 16 the concept of using â€œanother compoundâ€ is disclosed in the original Tas disclosure, Tas 17 Claims 2-20 and 23 nonetheless fail to satisfy the written description requirement because 18 the Tas Specification does not disclose any species of â€œanother compound.â€ Id. at 19 page 23:2-3 and 10-11; Ex. 1070 Â¶ 28. 20 Beachy points to the Federal Circuitâ€™s holding in Ariad which states that â€œâ€¦ a 21 sufficient description of a genus requires the disclosure of either a representative number 22 of species falling within the scope of the genus or structural features common to the 23 Interferences 105,926 & 105,949 66 members of the genus so that one of skill in the art can â€˜visualize or recognizeâ€™ the 1 members of the genus.â€ Paper 181, page 24 (quoting Ariad, 598 F.3d at 1350). 2 Beachy contends that â€œzeroâ€ cannot constitute â€œa representative number of 3 speciesâ€ and, therefore, the Tas specification does not provide adequate written support 4 for the â€œanother compoundâ€ recitations in claims 2-20 and 23. Id. at page 23 (citing 5 Ex. 1070, Â¶Â¶ 19-21, 27; Ex. 2001; Ex. 2004; Ex. 1064; Ex. 1067-68). 6 Tas responds that Beachy is taking the claim term â€œanother compoundâ€ out of 7 context. Paper 317, page 12:10-11. 8 According to Tas, the claim term â€œcyclopamine or another compound that 9 selectively inhibits Hedgehog/Smoothened signalingâ€ defines exactly the same set of 10 compounds as the term â€œa selective inhibitor of Hedgehog/Smoothened signaling.â€ 11 Id. at page 12:11-14. 12 Tas argues that the Specification has written description and enablement of use of 13 a selective inhibitor of Hh/Smo signaling for treatment of a human having a tumor 14 wherein Hh/Smo signaling is utilized for inhibition of apoptosis of tumor cells. Id. at 15 page 12:14-16. 16 Tas argues further that the set of compounds recited in dependent claim 6 is 17 exactly the same as â€œa selective inhibitor of Hh/Smo signaling that binds to the biological 18 target of cyclopamine.â€ Id. at page 12:17 to page 13:1. 19 Dependent claim 6 recites: â€œ[t]he method according to any one of claims 2 to 5, 20 wherein said another compound that selectively inhibits Hedgehog/Smoothened signaling 21 is a compound that binds to the same biological target as cyclopamine to exert said 22 inhibition.â€ Ex. 2001, col. 12:59-63. 23 Interferences 105,926 & 105,949 67 Tas argues that the written description and enablement of the subject matter 1 claimed does not require any special description or showing of structure of â€œanotherâ€ 2 compound. Paper 317, page 13:5-6. 3 According to Tas, a broad genus of selective inhibitors of Hh/Smo signaling, 4 including those structurally totally unrelated to cyclopamine, were generally known in the 5 art. Id. at page 13:7-8. 6 Tas points to Johan Ericson et al., Two critical periods of Sonic Hedgehog 7 signaling required for the specification of motor neuron identity, 87 CELL, 661-673 8 (1996) (Ex. 2052), which is said to teach generation of â€œpolyclonal (H4) and monoclonal 9 (MAb 5E1) antibodies [directed] against the biologically active amino-terminal fragment 10 of SHH (SHH-N)â€ and that addition of â€œH4 IgG blocked the SHH-N-mediated induction 11 of floor plate cells and motor neurons.â€ Id. at page 3:11-13 (citing Ex. 2052 at page 662). 12 Tas also points to John P. Incardona et al., The teratogenic Veratrum alkaloid 13 cyclopamine inhibits Sonic hedgehog signal transduction, 125 DEVELOPMENT 3553-3562 14 (1998) (Ex. 2054) said to describe employment of anti-Shh polyclonal H4 antibodies to 15 selectively inhibit Hh activity, but which also states that veratramine, which is formed by 16 acid aromatization of cyclopamine, does not cause cyclopia in sheep (presumably by 17 failing to selectively inhibit Hh signaling). Ex. 2054 at page 3556). 18 Tas also offers Exhibits 2107, 2109-2111 and 2035 to demonstrate that other 19 inhibitors of Smo/Hh signaling were known in the art at the time of invention. Paper 317, 20 pages 3-4. 21 Tas further contends that Beachy misapplies the law, arguing that, in Ariad, there 22 was no compound that inhibited NF-KB activity at the time of the application and that 23 Interferences 105,926 & 105,949 68 there was no prior art describing a compound known to inhibit NF-KB activity. Id. at 1 page 18:5-13 2 In the present case, Tas argues that a genus of compounds having over a dozen 3 structurally diverse species that selectively inhibit Hh/Smo signaling was common 4 general knowledge besides the cyclopamine used for the exemplification of invention. 5 Id. at page 18:11-13. 6 Tas also argues that, contrary to Beachyâ€™s assertions, the limitation â€œanother 7 compound that selectively inhibits Hh/Smo signalingâ€ â€œis inherent and necessarily 8 implicit in the original application and description of the disclosed treatment of target 9 tumors.â€ Id. at page 18:14- 18 (citing Lockwood v. American Airlines, Inc., 107 F.3d 10 1565, 1572 (Fed. Cir. 1997). 11 According to Tas, the limitation is necessarily disclosed in the original application. 12 Id. at 18. 13 Beachy replies that Tasâ€™ argument is without merit and, factually, reveals Dr. Tasâ€™ 14 lack of understanding of the involved technology. Paper 334, page 2:3-4. 15 According to Beachy, the relevant legal analysis is not whether those skilled in the 16 art were aware of a genus of structurally diverse selective inhibitors of the Hh/Smo 17 pathway. Id. at page 2:5-7. 18 Rather, Beachy argues that the issue is whether the original Tas application would 19 have conveyed to one skilled in the art that Dr. Tas was aware of a broad genus of 20 selective inhibitors that Dr. Tas believed could be used in his claimed methods. Id. at 21 page 2:7-9. 22 Beachy asserts that there is no statement anywhere in the original Tas application 23 to suggest that Tas believed his claimed methods encompassed a broad genus of Hh 24 Interferences 105,926 & 105,949 69 pathway inhibitors having unlimited structural diversity and completely undefined modes 1 of achieving inhibition of the pathway. Id. at page 2:10-13. 2 Rather, according to Beachy, Tas described and exemplified a single compound: 3 cyclopamine. Id. at, page 2:13-14. 4 Beachy presents additional arguments in support of its response to Tas Opposition 5 1. Id. at page 2:3 to page 4:17. 6 We are persuaded by Beachyâ€™s arguments. 7 Section 112 requires that the description must â€œclearly allow persons of ordinary 8 skill in the art to recognize that [the inventor] invented what is claimed.â€ Vasâ€“Cath Inc. 9 v. Mahurkar, 935 F.2d 1555, 1563 (Fed. Cir. 1991) (citing In re Gosteli, 872 F.2d 1008, 10 1012 (Fed. Cir. 1989)). 11 The test for sufficiency is whether the disclosure of the application relied upon 12 reasonably conveys to those skilled in the art that the inventor had possession of the 13 claimed subject matter as of the filing date. Ariad, 598 F.3d at 1351. 14 Tas points to the contemporary scientific art in an attempt to demonstrate that 15 selective Hh pathway inhibitors were well-known in the art and, based on that art, 16 contends that a person of ordinary skill in the art would thus have known that Tas had 17 possession of the claim term â€œanother compoundâ€ as comprised by the selective Hh 18 inhibitors then described and used in the scientific literature. 19 However, the use of â€œanother compound that selectively inhibits 20 Hedgehog/Smoothened signalingâ€ does not define the entire scope of Tasâ€™ invention. 21 On the contrary, the remainder of the limitation of claim 2 recites: â€œwherein said 22 medicament is administered in a dose that is sufficient to induce apoptosis of said tumor 23 cells and causes decrease of size or disappearance of the tumor.â€ 24 Interferences 105,926 & 105,949 70 Tas points to no reference that indicates that any of the known selective Hh 1 signaling inhibitors at the time of invention were known to be at all effective in the 2 treatment of tumors so as to cause them to decrease in size or disappear. 3 For example, Exhibit 2107 describes the effect of Hh suppression on zebrafish 4 retinal differentiation. Exhibit 2108 demonstrates that Hh signaling suppression results 5 in partial cyclopia and other specific midline abnormalities in zebrafish, suggesting a 6 genetic model for human holoprosencephaly. 7 Exhibit 2109 and Exhibit 2110 suggest that the 20 kDa NH2-terminal fragment of 8 Hh plays an important role in ptc receptor activation in the hedgehog signaling 9 mechanism. 10 Exhibit 2011 explores the role of Hh on both proliferation and cell-type 11 determination in pituitary gland development. 12 Exhibit 2052 demonstrates the role played by Hh in regulating the generation of 13 floor plate cells and motor neurons. 14 None of these prior art references speak to the subject matter of the invention 15 recited in Tas Claim 2, viz., the treatment of tumors; indeed Beachy persuasively argues 16 that these effects are generally focused at Hh signaling activity at a level upstream of the 17 ptc mutation (which is commonly found in BCC tumor cells) and are therefore not 18 particularly relevant respect to treatment of tumors. See Paper 334, page 4. 19 Taken in toto, we can find little support based on the prior art called to our 20 attention by Tas to establish that a person of ordinary skill would have known that Tas 21 was in possession of (1) â€œanother compound that selectively inhibits 22 Hedgehog/Smoothened signalingâ€ that (2) would be effective in the reduction in size and 23 disappearance of tumors. 24 Interferences 105,926 & 105,949 71 Moreover, Tasâ€™ reliance on In re Smythe, 480 F.2d 1376, 1384 (CCPA 1973) is 1 misplaced. 2 Tas cites Smythe as holding that one need not â€œinclude descriptions of the very 3 many structural or functional equivalents of disclosed elements or steps which are already 4 stored in the minds of those skilled in the arts, ready for instant recall upon reading the 5 descriptions of specific elements or stepsâ€ as support for its argument that, because 6 selective Hh signaling inhibitors were known in the art, a person of ordinary skill would 7 have known that Tas had possession of â€œanother compound.â€ Paper 317, page 13:13-19 8 However, as Beachy correctly points out, the case in Smythe was not one in which 9 there was â€œany unpredictability such that appellantsâ€™ description of air or other inert gas 10 would not convey to one skilled in the art knowledge that appellants invented an analysis 11 system with a fluid segmentizing medium.â€ Smythe, 480 F.2d at 1383. 12 The Smythe court elaborated that: â€œ 13 [I]n other cases, particularly but not necessarily, chemical cases, 14 where there is unpredictability in performance of certain species or 15 subcombinations other than those specifically enumerated, one 16 skilled in the art may be found not to have been placed in possession 17 of a genus or combination claimed at a later date in the prosecution 18 of a patent application. 19 20 Id. (citing, e.g., In re DiLeone (DiLeone II), 436 F.2d 1033 (CCPA 1971), and In re 21 DiLeone (DiLeone I) 436 F.2d 1404 (CCPA 1971). 22 In the instant case, which deals with a method of using a chemical composition in 23 the treatment of tumors, we find that Tas has not established that there is sufficient 24 certainty that a person of ordinary skill in the art, and knowing the then current state of 25 the art, would have known that Tas had in its possession â€œanother compound that 26 Interferences 105,926 & 105,949 72 selectively inhibits Hedgehog/Smoothened signalingâ€ that would be effective in the 1 reduction in size and disappearance of tumors. 2 Given the uncertainty of the chemical arts, and the nature of the proofs adduced by 3 Tas, we conclude that Tas claims 2-6, 8-20 and 23 are unpatentable under 35 U.S.C. 4 Â§ 112 for lack of written description. 5 Because we find the claims unpatentable for lack of written description, we do not 6 reach Beachyâ€™s arguments that the claims are also unpatentable under 35 U.S.C. Â§ 112 for 7 lack of enablement with respect to this limitation. 8 9 2. â€œDerivative of cyclopamineâ€ 10 The Tas Specification explicitly provides the following definition of the claim term 11 â€œderivative of cyclopamineâ€: 12 It is specifically contemplated that molecules can be derived from 13 cyclopamine or synthesized in such a way that they possess structural 14 features to exert similar receptor binding properties and 15 biological/therapeutic effects as cyclopamine. Such a molecule is 16 called here a â€œderivative of cyclopamineâ€ and defined as follows: A 17 molecule that contains the group of atoms of the cyclopamine 18 molecule required for the binding of cyclopamine to its biological 19 target but contains also modifications of the parent cyclopamine 20 molecule in such ways that the newly derived molecule continues to 21 be able to bind specifically to the same biological target to exert the 22 biological effects of cyclopamine disclosed herein. Such 23 modifications of cyclopamine may include one or more permissible 24 replacement of or a deletion of a molecular group in the cyclopamine 25 molecule or addition of a molecular group (particularly a small 26 molecular group such as the methyl group) to the cyclopamine 27 molecule, provided that the resultant molecule is stable and possesses 28 the capability of specific binding to the same biological target as 29 cyclopamine to exert the biological effects described herein. 30 Interferences 105,926 & 105,949 73 Derivation of such new molecules from cyclopamine can be readily 1 achieved by those skilled in the art and the possession or lack of the 2 biological effects of cyclopamine in the newly derived molecule can 3 also be readily determined by those skilled in the art by testing for the 4 biological effects disclosed herein. 5 6 Ex. 2001, col. 6, ll. 1-26. 7 Beachy argues that Tas Claim 7 lacks adequate written description under 35 U.S.C. 8 Â§112, first paragraph with respect to the claim term â€œderivative of cyclopamineâ€. 9 Paper 181, page 23:15 to page 24:4. 10 According to Beachy, the Tas disclosure fails to provide â€œeither a representative 11 number of species falling within the scope of the genus or structural features common to 12 the members of the genus so that one of skill in the art can â€˜visualize or recognizeâ€™ the 13 members of the genus.â€ Id. (quoting Ariad, 598 F.3d at 1350). 14 Furthermore, argues Beachy, Tasâ€™ definition of a â€œderivative of cyclopamineâ€ fails 15 to identify a single representative species of a derivative of cyclopamine by name, 16 formula, or structure. Id. at page 24:8-9. 17 Beachy argues that one of ordinary skill in the art would have understood that, in 18 addition to not identifying any specific â€œderivative of cyclopamine,â€ the Tas application 19 does not identify which, if any, â€œpermissibleâ€ additions, deletions, or replacements of 20 molecular groups on the cyclopamine molecule would result in a derivative molecule 21 having the functional properties identified in the definition of â€œderivative of 22 cyclopamineâ€ (e.g., â€œstructural features to exert similar receptor binding properties and 23 biological/therapeutic effects as cyclopamineâ€; â€œcontaining the group of atoms of the 24 cyclopamine molecule required for the binding of cyclopamineâ€; or â€œcontinues to be able 25 Interferences 105,926 & 105,949 74 to bind specifically to the same biological target to exert the biological effects of 1 cyclopamine disclosed hereinâ€). Id. at page 13:19-14:11. 2 Tas responds by arguing that the prior art evidence taught that cyclopamine and a 3 single derivative species of cyclopamine inhibits Hh/Smo signaling at the level of Smo. 4 Paper 317, page 21:7-8 (citing Ex. 2035 23 ). 5 Tas also responds by arguing that Beachy does not explain why the Beachy 6 specification, if taken as prior art, discloses numerous derivatives of cyclopamine. Id. at 7 page 21:9-12(citing Ex. 1018 at cols. 19:41 to 32:16 and 69:25 to 133:54). 8 We are persuaded by Beachyâ€™s arguments. 9 The Tas Specification provides not a single example of a cyclopamine derivative. 10 The definition of cyclopamine derivatives that appears in the Tas Specification, 11 apart from single statement suggesting that small molecular groups, such as methyl might 12 be suitable, is indeterminate with respect to the nature of the substitutions or 13 rearrangements that might be made. 14 It is also indefinite as to specific substitutions or locations on the cyclopamine that 15 might be made â€œin such a way that they possess structural features to exert similar 16 receptor binding properties and biological/therapeutic effects as cyclopamine.â€ Ex. 2001, 17 col. 6:1-4. 18 The Tas Specification also fails to specify any of the structural features common to 19 the members of the genus. 20 23 Talpale et al., Effects of oncogenic mutations in Smoothened and Patched can be reversed by cyclopamine, 406 NATURE1005 (2000). Interferences 105,926 & 105,949 75 Rather, the Tas Specification provides only generalized descriptions of what might 1 possibly constitute a derivative of cyclopamine. 2 The level of detail required to satisfy the written description requirement of Â§ 112 3 varies depending on the nature and scope of the claims and on the complexity and 4 predictability of the relevant technology. Capon v. Eshhar, 418 F.3d 1349, 1357-58 5 (Fed. Cir. 2005). 6 With respect to generic claims in the chemical arts, the Federal Circuit has held 7 that a sufficient description of a genus generally requires the disclosure of either a 8 representative number of species falling within the scope of the genus or structural 9 features common to the members of the genus so that one of skill in the art can â€œvisualize 10 or recognizeâ€ the members of the genus. Ariad, 598 F.3d at 1350 (citing Eli Lilly, 119 11 F.3d at 1568-69). 12 The Tas Specification satisfies neither of these requirements; it provides no 13 disclosure of any species of cyclopamine derivative, nor does it identify with any 14 specificity any structural features common to the members of the genus. 15 Furthermore, Tasâ€™ argument that a person of ordinary skill would appreciate from 16 the prior art that Tas possessed cyclopamine derivatives is not persuasive. 17 Tas offers but a single example of a single derivative of cyclopamine in the prior 18 art that had an inhibitory effect on Hh/Smo signaling: 3-keto, N-aminoethyl 19 aminocaproyl dihydrocinnamoyl cyclopamine (KAAD-cyclopamine). Ex. 2035, 20 page 1007:1-2. 21 We find that a single disclosure of a single effective derivative is not sufficient in 22 this case to establish that a person of skill in the art would appreciate that Tas had 23 possession of the genus. 24 Interferences 105,926 & 105,949 76 Moreover, with respect to Tasâ€™ argument that Beachy fails to explain why the 1 Beachy [Specification], â€œtaken as prior artâ€ is not an admission that cyclopamine 2 derivatives were indeed well-known in the prior art, Tas adduces no proof that the 3 information in the Beachy Specification (Ex. 1018) was known to those skilled in the art 4 prior to the Tas filing date. 24 5 Section 112 requires that one of skill in the art can â€œvisualize or recognizeâ€ the 6 claimed genus based on the Specificationâ€™s disclosure, i.e., it must demonstrate 7 constructive possession. Eli Lilly, 119 F.3d at 1568; Ariad, 598 F.3d at 1352. 8 We find that the Tas Specification fails to do so because it fails to provide any 9 examples of species of cyclopamine derivatives and further fails to adequately describe 10 structural features common to the members of the genus. 11 Furthermore, the state of the prior art was not so developed that a person of skill in 12 the art would believe that Tas was in possession of the genus and species. 13 We therefore conclude that claim 7 is unpatentable under 35 U.S.C. Â§112 for lack 14 of written description. 15 We do not reach Beachyâ€™s argument with respect to lack of enablement of this 16 claim limitation. 17 18 C. Indefiniteness 19 Beachy argues that Tas claims 1-23 are indefinite under 35 U.S.C. Â§ 112, second 20 paragraph, with regards to the term â€œapoptosis.â€ Paper 181, page 30:7-8. 21 24 The Beachy â€™076 application was filed on October 13, 2000, but was not published, and issued as US Patent 7,098,196 B1 on August 29, 2006. The Tas â€™584 application was filed on October 9, 2003 and issued as US 7,893,078 B2 on Feb. 22, 2011. Interferences 105,926 & 105,949 77 According to Beachy, each of the Tas claims require the induction of â€œapoptosisâ€ 1 in tumor cells, among other biological effects, following the administration of a 2 medicament. Id. at page 31:4-5. 3 Beachy contends that there is no dispute that one of ordinary skill in the art in the 4 years 2001-2003 would have understood the term â€œapoptosisâ€ to refer to a particular type 5 of cell death that is characterized by particular morphological and biochemical hallmarks. 6 Id. at page 31:11-14 (citing Ex. 2006, Abstract, pp. 244-251, Fig. 5; Ex. 1043, p. 55; 7 Ex. 2008, pp. 528-30; Ex. 1048, p. S99; Ex. 1046, p. 218; Ex. 1045, Â¶15). 8 Beachy argues that, in the 2001-2003 timeframe, one of ordinary skill in the art 9 would have known that specific techniques and assays were used to evaluate whether 10 cells have undergone apoptosis. Id. at page 31:16-18. 11 Specifically, Beachy argues that during 2001-2003, those of ordinary skill 12 in the art relied upon highly precise and highly quantitative morphological techniques 13 evaluate several specific morphological characteristics of an apoptotic cell. Id. at page 14 31:19 to page 32:1 (citing Ex. 2006, pages 244-251, Fig. 5; Ex. 1043, page 55; Ex. 2008, 15 pages 528-30; Ex. 1048, page S99; Ex. 1046, page 218; Ex. 1045, Â¶15-16). 16 Beachy points out that those of ordinary skill in the art employed particular 17 biochemical assays such as DNA-laddering and TUNEL assays. Id. at page 32:3-5 18 (citing Ex. 2008, Abstract; Ex. 1045, Â¶Â¶ 22-25). 19 According to Beachy witness Dr. Andreas Strasser, one of ordinary skill in the art 20 understood that it was necessary to employ these techniques to evaluate the unique 21 morphological and biochemical hallmarks of an apoptotic cell. Id. at page 32:5-8 (citing 22 Ex. 2008, Abstract; Ex. 1045, Â¶Â¶19, 20, 22-25). 23 Interferences 105,926 & 105,949 78 Dr. Strasser testified that one skilled in the art would have understood that the use 1 of these techniques was important in assuring that the term â€œapoptosisâ€ was properly 2 being used to describe a particular type of programmed cell death. Id. at page 32:8-12 3 (citing Ex. 1045, Â¶Â¶ 19, 22-25). 4 Beachy argues that the experiments disclosed in the Tas Specification did not 5 describe art-recognized techniques in stating a conclusion that the topical administration 6 of cyclopamine induced â€œapoptosisâ€ of tumor cells. Id. at page 32:13-15 (citing 7 Ex. 2001; Ex. 2002; Ex. 2004; Ex. 1045, Â¶Â¶ 26, 28, 29, 30, 31, 32). 8 According to Beachy, one of ordinary skill in the art would have considered the 9 morphological images to be of poor quality and insufficient to identify apoptotic cells. 10 Id. at page 32:16-18(citing Ex. 1045, Â¶ 31). 11 Beachy further contends that one of ordinary skill in the art would have recognized 12 that Tas did not employ any biochemical techniques to assess apoptotic activity. Id. at 13 page 32:18-20 (citing Ex. 2001; Ex. 1045, Â¶Â¶26, 30). 14 Therefore, Beachy argues that one of ordinary skill in the art would have 15 recognized that Tas did not employ the art-recognized techniques for characterizing 16 apoptotic activity and, consequently, that Tasâ€™ use of the term â€œapoptosisâ€ was not 17 substantiated. Id. at page 33:1-3 (citing Ex. 2001; Ex. 2002; Ex. 2004; Ex. 1045, Â¶Â¶ 26, 18 28, 29, 30, 31, 32). 19 Beachy contends that one of ordinary skill in the art would have considered Tasâ€™ 20 use of the term â€œapoptosisâ€ as diverging from the ordinary or common meaning of the 21 term, and that Tas did so without reasonable clarity, deliberateness, or precision. Id. at 22 page 33:4-8 (citing Ex. 1045, Â¶Â¶53-54). 23 Interferences 105,926 & 105,949 79 Beachy argues further that one of ordinary skill in the art would have further 1 questioned Tasâ€™ use of the term â€œapoptosisâ€ because Tas relies upon the observation of 2 â€œcystic spacesâ€ within the treated tumors. Id. at page 33:9-12. 3 One of ordinary skill in the art is said to have not recognized â€œcystic spaces,â€ 4 which Beachy contends may occur for reasons wholly unrelated to apoptosis. Id. at 5 page 33:11-12 6 Therefore, Beachy argues that one of ordinary skill in the art would have 7 considered the reference to cystic spaces as evidence of apoptotic activity to further 8 suggest that Tas was using the term â€œapoptosisâ€ in an unconventional manner. Id.at 9 page 33:16-19 (citing Ex. 1060, pages 262, 264, 265, Figs. 3-4; Ex. 1061, page 826; 10 Ex. 1062, page 3; Ex. 1045, Â¶Â¶33-34). 11 According to Beachy, one of ordinary skill in the art, knowing that there can be 12 significant levels of apoptotic activity in BCC tumors prior to any treatment, would have 13 recognized that Tasâ€™ experiments described in the Specification did not have proper 14 controls to exclude the possibility that any observed apoptosis was not induced by the 15 administration of cyclopamine. Id. at page 34:3-5 (citing Ex. 2006, page 253; Ex. 1045, 16 Â¶ 50). 17 Therefore, Beachy argues, one of ordinary skill in the art would not have known 18 how Tas could have distinguished naturally occurring apoptosis from induced apoptosis, 19 thereby making it impossible to discern the metes and bounds of Tasâ€™s claims. Id. at page 20 34:6-8 (citing Ex. 2006, page 253; Ex. 1045, Â¶ 50). 21 Beachy summarizes by arguing that, by applying the ordinary meaning of the term 22 â€œapoptosisâ€ and the art-accepted criteria for assessing apoptosis, one skilled in the art 23 Interferences 105,926 & 105,949 80 would not consider the data presented in the Tas Specification as satisfying the Tas 1 claims. Id. at page 34:10-14 (citing Ex. 1045, Â¶Â¶ 53-54). 2 On the other hand, argues Beachy, applying a non-conventional interpretation of 3 the term â€œapoptosisâ€ to refer to undefined and imprecise morphological characteristics, 4 no biochemical hallmarks, and the presence of â€œcystic spaces,â€ one skilled in the art 5 would very likely reach an opposite conclusion. Id. at page 34:15-18 (citing Ex. 1045, 6 Â¶Â¶ 53-54). 7 Beachy argues that this ambiguity presents an insoluble dilemma for one of 8 ordinary skill in the art attempting to interpret the scope of Tas claims 1-23, thereby 9 rendering the claims indefinite under Â§ 112. Id. at page 34:19 to page 35:1. 10 In response, Tas argues that apoptosis was a term widely used and well 11 understood in prior art and its morphological features were common knowledge. 12 Paper 317, page 22:2-3. 13 According to Tas, identification of cells undergoing apoptosis on the basis of 14 morphological criteria was routinely practiced in the art. Id. at page 22:3-4 (citing 15 Ex. 2098, Â¶ 47-49; Exs. 2008, 2019, Ex. 2047, Exs. 2123-2128). 16 Tas argues that examination of hematoxylin- and eosin- stained tissue sections 17 under high magnification (x1000) was particularly recognized to provide a reproducible, 18 quantitative means to identify cells undergoing apoptosis. Id. at page 22:5-7 (citing 19 Ex. 2127; Ex. 2001; Ex. 2004). 20 Tas argues Dr. Strasser admits that the use of morphological criteria for 21 identification of the cells undergoing apoptosis was well known in prior art. Id. at 22 page 22:10-12 (citing Ex. 1045, Â¶ 16-19). 23 Interferences 105,926 & 105,949 81 Tas argues that the use of morphological criteria for identification and counting of 1 apoptotic cells in stained tissue sections was a preferred and widely-practiced method in 2 the art at the time of invention, due to its reproducibility, practicality, suitability to 3 clinical practice. Id. at page 23:8-12 (citing Ex. 2047, Exs. 2123-2125, Ex. 2127). 4 Tas argues further that Beachy provides no evidence that the examples presented in 5 the Tas Specification cannot be replicated or that use of â€œstate of the artâ€ biochemical 6 markers suggested by Beachy would lead to a different conclusion. Id. at page 22:13-15. 7 According to Tas, Beachyâ€™s contention that a skilled person would not recognize 8 what was meant by the claim term â€œapoptosisâ€ unless it was determined by an alleged 9 â€œstate of the artâ€ method is baseless. Id. at page 22:15-17. 10 Tas also disputes Beachyâ€™s argument that that â€œTas did not use art-recognized 11 techniquesâ€ for detection of apoptotic cells, lacked controls to determine the frequency of 12 naturally-occurring apoptosis in tumor cells, and that â€œTasâ€™ reference to cystic spaces as 13 evidence of apoptotic activityâ€ further suggests a divergent use of the apoptosis term, are 14 misrepresentations. Id. at page 24:8-12 15 Tas cites prior Exhibits 2008, 2009, 2123-2125, 2127, 2128 as indicative of what 16 constituted â€œart-recognizedâ€ techniques. Id. at page 24:12-13. 17 Tas also points to its Specification as disclosing both controls and that the 18 appearance of cystic spaces are a consequence of massively and rapidly induced 19 apoptotic elimination of tumor cells (and not as evidence of apoptotic activity). Id. at 20 page 24:12-13 (citing Ex. 2004, page 4:13-15). 21 Beachy replies that neither the words nor the photographs contained in the Tas 22 disclosure discuss or reflect any art-recognized morphological features that are unique to 23 Interferences 105,926 & 105,949 82 apoptotic cells (which Tas exhibits describe as blebs, spikes and blisters. Paper 334, 1 page 12:7-10 (citing, e.g., Ex. 2047, page 1102)). 2 Importantly, argues Beachy, several Tas exhibits emphasize the technical 3 difficulties associated with assessing apoptotic activity in tissue sections, the 4 considerable variation of apoptosis within untreated tumors, and the potential bias 5 and lack of reproducibility in experiments using a small number of samples, such as 6 those in the Tas specification. Id. at page 12:10-14 (citing Ex. 1114, Â¶Â¶ 37-45; Ex. 2009, 7 page 14; 1st col). 8 â€œWhether a claim is invalid for indefiniteness requires a determination whether 9 those skilled in the art would understand what is claimed when the claim is read in light 10 of the specification.â€ Morton Intâ€™l, Inc. v. Cardinal Chem. Co., 5 F.3d 1464, 1470 (Fed. 11 Cir. 1993). 12 Claims can be indefinite when: (1) a claim recites means-plus-function elements 13 without disclosing corresponding structure in the specification; includes a numeric 14 limitation; (2) the claims fail to disclose which of multiple methods of measuring that 15 number should be used; (3) a claim term is â€œcompletely dependent on a person's 16 subjective opinionâ€; and (4) a claim term does not have proper antecedent basis where 17 such basis is not otherwise present by implication or the meaning is not reasonably 18 ascertainable. Halliburton Energy Services, Inc. v. M-I LLC, 514 F.3d 1244, 1249 (Fed. 19 Cir. 2008). 20 The common thread in indefiniteness cases is that claims were held indefinite only 21 where a person of ordinary skill in the art could not determine the bounds of the claims, 22 i.e., the claims are insolubly ambiguous. Id. 23 We are not persuaded by Beachyâ€™s arguments. 24 Interferences 105,926 & 105,949 83 It is true that the Tas Specification does not provide an explicit definition of 1 â€œapoptosisâ€. 2 But there is no dispute that the term had a well-defined meaning in the art at the 3 time of Tasâ€™ invention. 4 Beachy witness Dr. Strasser testified that, in 2001, the terms â€œapoptosisâ€ and 5 â€œprogrammed cell deathâ€ were largely considered synonymous and were defined as a 6 form of cell death in which the cell receives physiological (e.g., growth factor 7 withdrawal) or pathological (e.g., treatment with DNA damage inducing 8 chemotherapeutic drugs) signals that trigger a programmed sequence of events leading to 9 the ultimate elimination of the cell. (Ex. 1045, Â¶ 15). 10 Dr. Strasser further testified that: 11 Apoptosis can be characterized by a series of morphological changes 12 in cells. These changes include: (a) shrinkage of the cell and nucleus, 13 (b) condensation of chromatin (pyknosis), (c) nuclear fragmentation 14 (karyorrhexis) [nucleus breaks into discrete chromatin bodies or 15 nucleosomal fragments due to DNA degradation], (d) membrane 16 budding ultimately leading to formation of membrane-bound vesicles, 17 i.e., so-called apoptotic bodies, and (e) elimination of apoptotic cells 18 and bodies by phagocytosis. 19 20 Ex. 1045, Â¶ 16 (citing Ex. 2006, pages 244-251, Fig. 5; Ex. 1043, page 55; Ex. 2008, 21 pages 528-30; Ex. 1048, page S99; Ex. 1046, page 218). 22 Dr. Strasser still further testified that: 23 The Tas Paper on Apoptosis (Paper No. 92) refers to morphological 24 features and criteria associated with apoptosis, but this paper does not 25 state what morphological features/criteria are used to identify 26 apoptosis in Tasâ€™ PCT â€™027 (Ex. 2002), US â€™584 (Ex. 2004), and USP 27 â€™078 (Ex. 2001). Similarly, Tasâ€™ PCT â€™027, US â€™584, and USP â€™078 28 also refer to morphological features and criteria associated with 29 Interferences 105,926 & 105,949 84 apoptosis, but do not state what morphological features/criteria are 1 used to identify apoptosis in those documents. 2 3 Ex. 1045, Â¶ 28. 4 Dr. Strasser, after giving examples, concluded that the illustrations in the Tas 5 Specifications â€œfail to meet the art-recognized minimum requirements for determining 6 that apoptosis is present or is evident, especially with regards to determining a 7 quantitative amount of apoptosisâ€ and that â€œTas does not present the results from any 8 assay techniques based on biochemical markers, such as employing the TUNEL assay, 9 which was conventionally used in apoptosis studies, including throughout 2001-2004.â€ 10 Ex. 1045, Â¶ 30. 11 However, the indefiniteness analysis under 35 U.S.C. Â§ 112 does not address 12 whether the quality of the analysis produced in the examples of the Specification meets 13 â€œart-recognized standards,â€ but rather whether the claim term â€œapoptosis,â€ when viewed 14 in light of the Tas Specification, would be insolubly ambiguous to a person of ordinary 15 skill in the contemporary art. Halliburton, 514 F.3d at 1249. 16 We find that Beachy has not met its burden in this respect. 17 Beachy admits that the term apoptosis was well-known at the time of invention, 18 but adduces insufficient evidence to demonstrate that a person of ordinary skill in the art 19 at the time of Tasâ€™ invention would have found Tasâ€™ employment of the term â€œapoptosisâ€ 20 in the claims to have been insolubly ambiguous. 21 Furthermore, Dr. Strasser seems to admit that the Tas Paper refers to 22 morphological features and criteria associated with apoptosis, but does not state that the 23 criteria discussed in the Tas Paper are ambiguous or confusing when compared with the 24 prior art. 25 Interferences 105,926 & 105,949 85 Beachy voices a number of criticisms of the experimental methodology and the 1 quality of the figures disclosed in the Tas Specification, but these concerns do not amount 2 to a showing of indefiniteness. 3 More to the point, Beachy does not convincingly demonstrate that the disclosures 4 of the Tas Specification contradict or differ from the teachings of the prior art in such a 5 way that would present an insoluble ambiguity to the artisan of ordinary skill. 6 Consequently, Beachy has not met its burden of showing that a person of ordinary 7 skill in the art would have been irretrievably confused by what Tas meant when using the 8 term â€œapoptosis.â€ 9 Beachyâ€™s Motion 1 seeking judgment against Tas Caims 1-23 on the ground of 10 indefiniteness will be denied. 11 12 D. Decision on Beachy Motion 1 13 Beachy Motion 1 for judgment against claims 2-20 and 23 as being unpatentable 14 under 35 U.S.C. Â§ 112 for lack of written description will be granted. 15 Beachy Motion 1 for against claims 1-23 as being unpatentable under 35 U.S.C. 16 Â§ 112 as indefinite will be denied. 17 18 IX. Beachyâ€™s Contingent Motions and Responsive Motion 3 19 A. Beachy Motion 2 20 Beachy Motion 2 is contingent on the Board granting Tas Motions 4 and/or 17 (to 21 deny Beachy priority benefit). Paper 311, page 1 at 1. 22 Because we have denied Tas Motions 4 and 17, we need not reach Beachy 23 Contingent Motion 2. 24 Interferences 105,926 & 105,949 86 Beachy Motion 2 will be dismissed as moot. 1 2 B. Beachy Motion 3 3 Beachy Responsive Motion 3 is contingent upon the Board granting Tas Motion 6 4 and entering judgment against all of Beachyâ€™s claims involved in the interference. 5 Paper 312, page 1. 6 Because we have denied Tas Motion 6, we need not reach Beachy Responsive 7 Motion 3. 8 Beachyâ€™s Motion 3 will be dismissed as moot. 9 10 X. Motions to strike 11 Both parties have filed motions to strike. Paper 345 (Tas Motion 18) and 12 Paper 342 (Beachy Motion 4). 13 We have elected to consider all arguments on the merits and therefore deny both 14 motions to strike. 15 Both motions will be denied. 16 17 XI. Order 18 Upon consideration of the motions filed, and for the reasons given, it is 19 ORDERED that Tas Motion 2 is denied. 20 FURTHER ORDERED that Tas Motion 3 is granted. 21 FURTHER ORDERED that Tas Motion 4 is denied. 22 FURTHER ORDERED that Tas Motion 6 is denied. 23 FURTHER ORDERED that Tas Motion 14 is denied. 24 Interferences 105,926 & 105,949 87 FURTHER ORDERED that Tas Motion 17 is denied. 1 FURTHER ORDERED that Tas Motion 18 is denied. 2 FURTHER ORDERED that Beachy Motion 1 is granted as to lack of written 3 description and denied as to indefiniteness. 4 FURTHER ORDERED that Beachy Motion 2 is dismissed. 5 FURTHER ORDERED that Beachy Motion 3 is dismissed. 6 FURTHER ORDERED that Beach Motion 4 is denied. 7 8 XII. Disposition of interferences 9 The earliest date accorded to Tas is subsequent to the earliest date accorded to 10 Beachy. 11 In its priority statement, Tas does not allege a date of invention prior to the date 12 accorded to Beachy. 13 Accordingly, on the issue of priority, junior party Tas has not established that it 14 can prevail on priority. 15 A judgment against Tas on the issue of priority is entered in a separate paper. 16 17 Interferences 105,926 & 105,949 88 cc (via email): 1 2 Attorney for Tas: 3 4 Walter J. Steinkraus 5 Email: wsteinkraus.@live.com 6 7 Dr. Sinan Tas, pro se 8 Email: sinan.tas1@gmail.com 9 10 Attorney for Beachy: 11 12 Anthony J. Zelano 13 Brion P. Heaney 14 John A. Sopp 15 Millen, White, Zelano & Branigan, PC 16 Email: zelano@mwzb.com 17 Email: Heaney@mwzb.com 18 Email: sopp@mwzb.com 19 20 Oliver R. Ashe, Jr. 21 Ashe, PC 22 Email: oashe@ashepc.com 23 24

BEACHY et al. V. Beachy et al. V. Tas et al.