Ex Parte Carmeliet et alDownload PDFPatent Trial and Appeal BoardMar 24, 201713785253 (P.T.A.B. Mar. 24, 2017) Copy Citation United States Patent and Trademark Office UNITED STATES DEPARTMENT OF COMMERCE United States Patent and Trademark Office Address: COMMISSIONER FOR PATENTS P.O.Box 1450 Alexandria, Virginia 22313-1450 www.uspto.gov APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO. 13/785,253 03/05/2013 Peter CARMELIET BJS-5117-34 2450 23117 7590 03/28/2017 NIXON & VANDERHYE, PC 901 NORTH GLEBE ROAD, 11TH FLOOR ARLINGTON, VA 22203 EXAMINER GAMBEL, PHILLIP ART UNIT PAPER NUMBER 1644 NOTIFICATION DATE DELIVERY MODE 03/28/2017 ELECTRONIC Please find below and/or attached an Office communication concerning this application or proceeding. The time period for reply, if any, is set in the attached communication. Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the following e-mail address(es): PTOMAIL@nixonvan.com pair_nixon @ firsttofile. com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte PETER CARMELIET, DESIRE COLLEN, SANDRO De FALCO, and RUVO MENOTTI1 Appeal 2016-000702 Application 13/785,253 Technology Center 1600 Before JEFFREY N. FREDMAN, JOHN G. NEW, and RYAN H. FLAX, Administrative Patent Judges. NEW, Administrative Patent Judge. 1 Appellants state the real parties-in-interest are Life Sciences Research Partners VZW and Vlaams Interuniversitair Instituut Voor Biotechnologie Vzw. App. Br. 3. Appeal 2016-000702 Application 13/785,253 DECISION ON APPEAL Appellants file this appeal under 35 U.S.C. § 134(a) from the Examiner’s Final Rejection of claims 1, 2, 4, 5, 7, and 9. Specifically, claims 1, 2, 4, and 5 stand rejected as unpatentable under 35 U.S.C. § 102(b) as being anticipated by M.J. Bottomley et al., Placenta growth factor (PIGF) induces vascular endothelial growth factor (VEGF) secretion from mononuclear cells and is co-expressed with VEGF in synovial fluid, 119 Clin. Exp. Immunol. 182-88 (2000) (“Bottomley”). Claims 1, 2, 4, 5, 7, and 9 stand rejected as unpatentable under 35 U.S.C. § 103(a) as being obvious over the combination of Bottomley, Shitara et al. (US 6,986,890 Bl, January 17, 2006) (“Shitara”), Boulton et al. (WO 99/24056, May 20, 1999) (“Boulton”), and Ferrara et al. (US 6,455,283 Bl, September 24, 2002) (“Ferrara”).2,3 2 The Examiner also made the following rejections under the doctrine of nonstatutory obviousness-type double patenting: (1) claims 1, 2, 4, 5, 7, and 9 over claim 1 of U.S. Patent No. 7,357,929; (2) claims 1, 2, 4, 5, 7, and 9 over claims 1—9 of U.S. Patent No. 7,482,004; (3) claims 1, 2, 4, 5, 7, and 9 over claims 1—7 of U.S. Patent No. 7,867,490; and (4) claims 1, 2, 4, 5, 7, and 9 over claims 1—6 of U.S. Patent No. 8,758,748. App. Br. 8. These rejections have been withdrawn by the Examiner. Ans. 3. 3 Appellants assert: The following statements, objection and provisional rejections of the Office Action dated October 29, 2014, are not presented for review as not being appealable: • The objection to claim 7 and withdrawn claims 8 and 10 stated on page 3 of the Office Action dated October 29, 2014; 2 Appeal 2016-000702 Application 13/785,253 We have jurisdiction under 35 U.S.C. § 6(b). We AFFIRM. • The provisional obviousness-type double patenting rejection of claims 1, 2, 5, 7 and 9 over claims 1—17 of copending U.S. Application No. 13/785,559 stated on page 9 of the Office Action dated October 29, 2014; • The provisional obviousness-type double patenting rejection of claims 1, 2, 5, 7 and 9 over claims 10-10 of copending U.S. Application No. 13/785,643 stated on page 9 of the Office Action dated October 29, 2014; • The provisional obviousness-type double patenting rejection of claims 1, 2, 5, 7 and 9 over claims 8—16 of copending U.S. Application No. 14/170,997 stated on page 9 of the Office Action dated October 29, 2014; • The statement - without a statutory basis for a rejection - on page 9 of the Office Action dated October 29, 2014 that “Claims 1, 2, 4, 5, 7 and 9 are directed to an invention not patentable distinct from claim 1 of commonly assigned U.S. Patent No. 7,357,929 (1449)... for the reasons above”; • The statement - without a statutory basis for a rejection - on page 9 of the Office Action dated October 29, 2014 that “Claims 1, 2, 4, 5, 7 and 9 are directed to an invention not patentable distinct from ... claims 1—7 of commonly assigned U.S. Patent No. 7,867,490 (1449)... for the reasons above”; and • The statement - without a statutory basis for a rejection - on page 9 of the Office Action dated October 29, 2014 that “Claims 1, 2, 4, 5, 7 and 9 are directed to an invention not patentable distinct from ... claims 1—6 of commonly assigned U.S. Patent No. 8,758,748 (1449)... for the reasons above.” App. Br. 7 n.6. Because Appellants explicitly do not contest the above- noted rejections on appeal, we summarily affirm the rejections. 3 Appeal 2016-000702 Application 13/785,253 NATURE OF THE CLAIMED INVENTION Appellants’ invention is directed to molecules that can inhibit the binding of placental growth factor (“P1GF”) to its receptor (“VEGFR-1”), such as monoclonal antibodies and tetrameric peptides, and to the use of these molecules to treat pathological processes. Abstract. REPRESENTATIVE CLAIM Claim 1 is representative of the claims on appeal and recites: 1. A method of suppressing inflammation in a mammal by administering to a mammal in need of suppressing inflammation an antibody or a fragment thereof that specifically binds to placental growth factor and that neutralizes the activity of placental growth factor, such that said inflammation is suppressed. App. Br. 24. ISSUES AND ANALYSES We agree with, and adopt, the Examiner’s findings and conclusion that the appealed claims are anticipated by, and obvious over, the combined cited prior art under 35 U.S.C. §§ 102(b) and 103(a). We address the arguments raised by Appellants below. A. Rejection of claims E 2, 4, and 5 under 35 U.S.C. $ 102(b) Issue Appellants argue the Examiner erred in finding Bottomley discloses a method of suppressing inflammation by administering to a mammal in need an antibody or a fragment thereof that specifically binds to placental growth factor. App. Br. 8. 4 Appeal 2016-000702 Application 13/785,253 Analysis Appellants argue the Examiner incorrectly relies upon the teachings of Bottomley as disclosing the disputed limitation. App. Br. 9. Appellants assert Bottomley discloses: “Placental growth factor (P1GF) induces vascular endothelial growth factor (VEGF) secretion from mononuclear cells and is co-expressed with VEGF synovial fluid,” and that a “combination of a monoclonal and a biotinylated polyclonal antibody specific for P1GF” were used to measure “SF [synovial fluid] and plasma P1GF levels ... by an in- house EFISA.” Id. (quoting Bottomley 183). However, Appellants argue, Bottomley does not disclose administering to a mammal in need of suppressing inflammation an antibody or a fragment thereof that specifically binds to placental growth factor and that neutralizes the activity of placental growth factor. Id. at 10. Appellants point to page 187 of Bottomley, upon which the Examiner relies, and which discloses: We suggest that specific modulation of VEGF and P1GF is a rational therapeutic target for inhibition of angiogenesis in the joint. In the immediate future, this could be achieved by direct injection into the joint of neutralizing humanized anti-VEGF and anti-PIGF antibodies, or better still, injection of recombinant soluble flt-1 receptor which would potentially neutralize both factors. In the long term, orally active signal transduction inhibitors that block the down-stream consequences of VEGF and P1GF receptor triggering may prove to be the effective angiogeneisis suppressive agents in clinical practice. App. Br. 10-11 (emphasis added, internal reference omitted). Appellants argue Bottomley does not place the presently claimed methods in the hands 5 Appeal 2016-000702 Application 13/785,253 of the public, as they contend would be required to anticipate the claimed invention. Id. at 11. We agree with the Examiner. “[Invalidity based on anticipation requires that the assertedly anticipating disclosure enabled the subject matter of the reference and thus of the patented invention without undue experimentation.” Elan Pharms., Inc. v. Mayo Foundation for Med. Educ. and Research, 346 F.3d 1051, 1052 (Fed. Cir. 2003). Furthermore: “A claimed invention cannot be anticipated by a prior art reference if the allegedly anticipatory disclosures cited as prior art are not enabled.” Amgen, Inc. v. Hoechst Marion Roussel, Inc., 314 F.3d 1313, 1354 (Fed. Cir. 2003); see also Bristol-Myers Squibb v. Ben Venue Labs., Inc., 246 F.3d 1368, 1374 (Fed. Cir. 2001) (“To anticipate, the reference must also enable one of skill in the art to make and use the claimed invention”). Section 112 requires that the patent specification enable “those skilled in the art to make and use the full scope of the claimed invention without ‘undue experimentation’” in order to extract meaningful disclosure of the invention and, by this disclosure, advance the technical arts. Invitrogen Corp. v. Clontech Labs. Inc., 429 F.3d 1052, 1070—71 (Fed. Cir. 2005). We are not persuaded by Appellants’ arguments that the disclosures of Bottomley at page 187 fail to anticipate the claims on appeal because we find the recited passage enables the claimed invention. The cited disclosure of Bottomley provides sufficient disclosure to allow a person skilled in the art to make and use the full scope of the claimed invention, i.e., “administer[ ] to a mammal ... an antibody or a fragment thereof that specifically binds to placental growth factor and that neutralizes the activity of placental growth factor,” without undue experimentation. 6 Appeal 2016-000702 Application 13/785,253 In particular, Bottomley teaches the target population, “a mammal in need of suppressing inflammation,” by specifically recognizing “P1GF may therefore play a key role in the production of VEGF in the inflammatory joint” of rheumatoid arthritis patients. See Bottomley, abstract. Bottomley also teaches “pharmacological inhibition of angiogenesis resulting in suppression of arthritis has been reported in experimental models” and “this could be achieved by direct injection into the joint of neutralizing humanized anti-VEGF and anti-PIGF antibodies.” Bottomley 187, col. 1. Thus, Bottomley suggests suppressing rheumatoid arthritis, an inflammatory condition in a mammal, by treatment of specific anti-PLGF antibodies that neutralize placental growth factor, satisfying the elements of claim 1. We therefore agree with the Examiner that the cited disclosure of Bottomley is sufficiently enabled because it would tell a person of ordinary skill in the art how to practice Appellants’ claims without undue experimentation. Because we find Bottomley discloses an enabled disclosure we affirm the Examiner’s rejection of the claims. B. Rejection of claims E 2, 4, 5, 7, and 9 under 35 U.S.C. $ 103(a) Issue Appellants argue the Examiner erred because the alleged deficiencies of Bottomley, related by Appellants supra, are not cured by the teachings or suggestions of Shitara, Boulton, and Ferrara. App. Br. 13. Analysis Appellants argue that, as acknowledged by the Examiner, “Shitara et al. differs from the claimed methods by not teaching employing anti- 7 Appeal 2016-000702 Application 13/785,253 placental growth factor antibodies (P1GF) as a means of treating pathological conditions involving VEGF.” App. Br. 13 (quoting Final Act. 7). Further, argue Appellants, the Examiner acknowledges that Shitara does “not teach employing anti-placental growth factor antibodies (P1GF) as a means of treating pathological conditions involving” transforming growth factor-beta (TGF-P) or tumor necrosis factor-alpha (TNF-a).” Id. (citing Bottomley 187). Appellants dispute the Examiner’s finding that an “antibody or a fragment thereof that specifically binds to placental growth factor and that neutralizes the activity of placental growth factor,” as required by the Appellants’ invention, is “equivalent” to an antibody that might specifically bind VEGF, as taught by Shitara. App. Br. 13 (citing Final Act. 7). Appellants contend that Boulton fails to teach or suggest that P1GF is a consequence of proliferative diabetic retinopathy (“PDR”) or one of many possible causes of PDR. App. Br. 14. According to Appellants, in the absence of demonstration of such a causative relationship in the prior art, a person of ordinary skill would not have expected the removal of P1GF to effectively treat PDR. Id. Furthermore, Appellants argue, Boulton’s teachings that: “inhibitors of P1GF ... are able to reduce, prevent or regress ocular angiogenesis” and that “P1GF and functional derivatives or fragment thereof may also be used to prevent ocular revascularization in conditions such as the PDRs, ...” are contradictory with respect to whether P1GF activity should be decreased or increased in order to prevent ocular angiogenesis. Id. at 14—15 (citing Boulton 3, 4). Appellants, therefore, argue that a person of ordinary skill would not, having understood the combined cited prior art, including Boulton, have a reasonable expectation 8 Appeal 2016-000702 Application 13/785,253 of therapeutic success in any modulating P1GF in an eye disorder such as PDR. Id. at 15. Appellants argue further that Ferrara teaches: “a thorough knowledge of the signal transduction pathways of VEGFs and angiopoietins is essential for their use in therapeutic settings.” App. Br. 15 (quoting Ferrara 1359). Appellants contend Boulton neither teaches nor suggests these basic criteria described by Ferrara, rather, Appellants argue the disclosures of Appellants’ Specification is based on thorough analysis of P1GF-/- knockout mice challenged with multiple pathologies and reproduction of the knockout phenotypes with an antibody neutralizing P1GF activity. Id. Appellants argue further that Ferrara teaches a further alleged isoform of VEGF, VEGF-E, which is known to bind PDGF receptors. App. Br. 16 (citing D.G. Gilbertson et al., Platelet-derived Growth Factor C (PDGF-C), a Novel Growth Factor That Binds to PDGF a andReceptor, 276 (29) J. Biol. Chem. 27406—14 (2001) (“Gilbertson”)). Appellants therefore contend Ferrara relates to a signaling pathway that is unrelated to P1GF and is therefore irrelevant to Appellants’ claimed invention. Id. The Examiner responds that Shitara teaches methods of treating diseases associated with VEGF, which can form P1GF-VEGF dimers (see Bottomley Abstr.), including rheumatoid arthritis with antagonistic antibodies, including monoclonal and humanized antibodies as well as the claimed antigen-binding fragments. Ans. 8—9 (citing Shitara generally and specifically cols. 8—28). The Examiner acknowledges Shitara does not teach employing anti-PIGF antibodies as the means of treating pathological conditions involving VEGF. Id. at 9. However, the Examiner finds Bottomley teaches targeting P1GF for inhibition of pathological angiogenesis 9 Appeal 2016-000702 Application 13/785,253 that fuels inflamed joints in patients with rheumatoid arthritis by neutralizing humanized anti-PIGF antibodies. Id. (citing Bottomley 187). The Examiner finds Boulton teaches inhibitors of P1GF in treating pathological conditions encompassed by the claimed methods and described in Appellants’ Specification, as well as teaching that neutralizing antibodies against P1GF as inhibitors of P1GF. Ans. 9 (citing, e.g., Boulton 3—7; Examples 1,2; Claims). With respect to Appellants’ argument that the teachings of Boulton are contradictory, the Examiner finds Boulton teaches that P1GF or functional derivatives/fragments may be used to stimulate or inhibit angiogenesis depending upon the specific condition to be treated and that there is no ambiguity about neutralizing antibodies against P1GF as inhibitors of various pathological conditions. Ans. 9—10. The Examiner also finds Ferrara teaches the use of antagonistic antibodies to treat various diseases and conditions associated with VEGF, including the use of polyclonal, monoclonal, humanized and human antibodies as well as other modifications. Ans. 10 (citing, e.g., Ferrara cols. 54—59; 59-63). The Examiner finds, with respect to Appellants’ argument that the teachings of Ferrara are not relevant because, in view of Gilbertson, the Examiner relies on Ferrara as teaching generally the use of antagonistic antibodies to treat various diseases and conditions associated with VEGF. Id. We are not persuaded by Appellants’ arguments. As we observed supra, Bottomley explicitly teaches: “In the immediate future, this [inhibition of P1GF- and VEGF-modulated angiogenesis] could be achieved by direct injection into the joint of neutralizing humanized anti-VEGF and anti-PIGF antibodies, or better still, injection of recombinant soluble flt-1 10 Appeal 2016-000702 Application 13/785,253 receptor which would potentially neutralize both growth factors.” Bottomley 187. We agree with the Examiner that Bottomley sets forth a teaching or suggestion sufficient to establish obviousness to a person of ordinary skill in the art. Furthermore, Boulton explicitly teaches the use of anti-PIGF antibodies as a means of treating “conditions at least partially characterised by abnormal ocular angiogenesis such as retinal neovascularisation, subretinal neovascularisation, glaucomatous neovascularisation, rubeosis or corneal neovascularization” by blocking antibody binding activity. See Boulton, Abstr., 4—7, 12). We agree with the Examiner that a person of ordinary skill, comprehending the teachings of the combined cited prior art, would find it obvious to combine the references and arrive at Appellants’ claimed invention. With respect to Appellants’ argument that the disclosures of Boulton are contradictory, we disagree. Boulton teaches: The inventors[ ] have found that inhibitors of P1GF, which are preferred modulators of P1GF activity, are able to reduce, prevent or regress ocular angiogenesis. The term “inhibitor” is used herein to mean a compound which will reduce or limit the physiological effect of P1GF at its receptor by decreasing the amount of P1GF that is available for combination with its receptor. For example, this may be achieved by preventing the production or secretion of P1GF, degrading P1GF or sequestering P1GF. These inhibitors of P1GF are useful for treating conditions such as the VPRs (particularly the Proliferative Diabetic Retinopathies (PDRs)) and for the reduction, prevention or regression of subretinal neovascularisation, iris neovascularisation resulting in glaucoma, rubeosis, cornea neovascularisation and particularly retinal neovascularisation and for modulating the rapid progression of diabetic retinopathy that occurs in pregnant females with diabetes. . . . 11 Appeal 2016-000702 Application 13/785,253 [T]he inhibitor may be an agent which prevents P1GF combining with its receptor such as a neutrali[z]ing antibody against P1GF (PLGF 1 or 2) or a soluble receptor for P1GF.... P1GF and functional derivatives or fragments thereof may also be used for treating conditions at least partially characterised by abnormal ocular angiogenesis. P1GF and functional derivatives or fragments thereof may be used to stimulate or inhibit angiogenesis depending upon the specific condition to be treated. For instance, P1GF and functional derivatives or fragments thereof may be used to promote revascularisation of ischaemic retina (e.g. following venous occlusion and diabetes). P1GF and functional derivatives or fragment thereof may also be used to prevent ocular revascularisation in conditions such as the PDRs, corneal neovascularisation, rubeosis, iris neovascularisation resulting in glaucoma, preretinal neovascularisation, choroidal (subretinal) neovascularisation as well as in such conditions as retrolental neovascularisation which occurs in retinopathy of prematurity or following vitrectomy for PDR. Boulton 3^4. We agree with the Examiner that reading this passage as a whole, Boulton discloses that, in different circumstances, up or down regulation of P1GF may be desirable and possible. In conditions such as ischemic retina, angiogenesis is a desirable outcome that can be promoted by using P1GF. However, it is also evident that, in cases where angiogenesis is undesirable, inhibition of P1GF by inhibitory factors, including anti-PIGF antibodies, can inhibit angiogenesis. See Medichem, S.A. v. Rolabo, S.L., 437 F.3d 1157, 1165 (Fed. Cir. 2006) (A “given course of action often has simultaneous advantages and disadvantages, and this does not necessarily obviate motivation to combine.”). We are not persuaded, therefore, that the disclosures of Boulton and the other prior art references cited by the Examiner would not lead a person of ordinary skill in the art to Appellants’ 12 Appeal 2016-000702 Application 13/785,253 claimed invention. We therefore affirm the Examiner’s rejection of the claims on this ground. DECISION The Examiner’s rejection of claims 1, 2, 4, and 5 as unpatentable under 35 U.S.C. § 102(b) is affirmed. The Examiner’s rejection of claims 1, 2, 4, 5, 7, and 9 as unpatentable under 35 U.S.C. §103(a) is affirmed. No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. § 1.136(a)(1). See 37 C.F.R. § 1.136(a)(l)(iv). AFFIRMED 13 Copy with citationCopy as parenthetical citation