Ex Parte Maione

Patent Trial and Appeal BoardFeb 14, 2019

12559994 (P.T.A.B. Feb. 14, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE 12/559,994 09/15/2009 23557 7590 02/19/2019 SALIW ANCHIK, LLOYD & EISENSCHENK A PROFESSIONAL ASSOCIATION PO Box 142950 GAINESVILLE, FL 32614 UNITED ST A TES OF AMERICA FIRST NAMED INVENTOR Theodore E. Maione 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 ATTORNEY DOCKET NO. CONFIRMATION NO. CYT.103 9449 EXAMINER MIKNIS, ZACHARY J ART UNIT PAPER NUMBER 1654 NOTIFICATION DATE DELIVERY MODE 02/19/2019 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): euspto@slepatents.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte THEODORE MAIONE 1 Appeal2018-000902 Application 12/559,994 Technology Center 1600 Before JEFFREY N. FREDMAN, DEBORAH KATZ, and JOHN G. NEW, Administrative Patent Judges. NEW, Administrative Patent Judge. DECISION ON APPEAL 1 According to Appellant, the real party in interest is Cytogel Pharma, LLC. Appeal Br. 1. Appeal2018-000902 Application 12/559,994 SUMMARY Appellant files this appeal under 35 U.S.C. Â§ 134(a) from the Examiner's Final Rejection of claims 4, 11, 12, and 14--17. Specifically, claims 4, 11, 12, and 14--17 stand rejected as unpatentable under 35 U.S.C. Â§ 103(a) as obvious over Zadina et al. (US 5,885,958, March 23, 1999) ("Zadina"), Pepta Nova, Endomorphin-1, Pepta Nova GmbH (2008) available at: https ://www.peptanova.de/product/ endomorphin-1 / (last visited February 4, 2019) ("Pepta Nova"), and Chemical Book, Endomorphin-1 (Human, Bovine) ACOH H20 (2008), available at: https ://www.chemicalbook.com/ProductList_En. aspx? kwd=Endomorphin-1 %20(Human,%20Bovine )%20ACOH (last visited February 8, 2019) ("Chemical Book"). Claims 15 and 17 stand rejected as unpatentable under 35 U.S.C. Â§ 112, second paragraph as being indefinite. Claims 4 and 11 also stand provisionally rejected as unpatentable under the non-statutory doctrine of obviousness-type double patenting over claims 1 and 4--7 of US Ser. No. 14/401,731. We have jurisdiction under 35 U.S.C. Â§ 6(b). We AFFIRM. NATURE OF THE CLAIMED INVENTION Appellant's invention is directed to a pharmaceutical composition including salts of mu (morphine) opiate receptor peptides. See Spec. 1. REPRESENTATIVE CLAIM Claim 4 is representative of the claims on appeal and recites: 4. A pharmaceutical composition comprising the acetate salt of a peptide having the amino acid sequence of SEQ ID NO: 13, and a pharmaceutically-acceptable carrier. 2 Appeal2018-000902 Application 12/559,994 App. Br. 9. ISSUES AND ANALYSIS We agree with, and adopt, the Examiner's findings and conclusion that the appealed claims would have been obvious over the cited prior art references. We address the arguments raised by Appellant below. A. Claims 4, 11, 12, and 14--17 as unpatentable under 35 U.S.C. Â§ 103(a) Issue 1 Appellant argues that the Examiner erred by finding that Zadina provides a reasonable expectation that the acetate salt of SEQ ID NO: 13 ( cyclic endomorphin-1) would be useful as a pharmaceutical composition. App. Br. 3. Analysis The Examiner finds that Zadina teaches mu-opiate receptor peptides including H-Tyr-c-[D-Lys-Trp-Phe ], which "corresponds to the claimed peptide of SEQ ID NO 13." Final Act. 4 (citing Zadina, col. 2, 1. 30; claim 2). Appellant refers to this peptide as "cyclic endomorphin-1," which we use in our discussion below. Spec. 5. The Examiner finds that Zadina also teaches linear endomorphin-1, H-Tyr-Pro-Trp-Phe-NH2 (SEQ ID NO: 1 ), as an alternative mu-opiate receptor peptide. See Final Act. 6 (see Zadina, col. 2, 1. 18). We find Zadina teaches that cyclic endomorphin-1 is an analog of linear endomorphin-1. See Zadina, col. 4, 11. 4--16. The Examiner finds that Zadina teaches pharmaceutical preparations containing the mu-opiate receptor peptides as a free base or salt. Final Act. 5 (citing Zadina col. 5, 11. 32-35; claim 16). The Examiner finds that the pharmaceutical preparations 3 Appeal2018-000902 Application 12/559,994 may include solutions. Id. The Examiner acknowledges that Zadina does not teach the acetate salt of cyclic endomorphin-1. Id. The Examiner finds that it was conventionally known in the art that native non-cyclic endomorphin-1 (having a related sequence of Tyr-Pro-Trp- Phe, but being linear rather than cyclic) was sold commercially as an acetate salt. Final Act. 5. To support this finding, the Examiner cites Pepta Nova and Chemical Book for evidence that linear endomorphin-1 acetate was commercially available prior to the filing of the subject claims. Id. The Examiner concludes that: "[i]t would have been obvious to one of ordinary skill in the art to make the peptide taught in Zadina in an acetate salt form because this salt form is a commercially viable product." Final Act. 6. The Examiner finds that there would have been a reasonable expectation of success because the acetate salt of linear endomorphin-1 was on sale, and preparing salt forms of a specific peptide was routine. Id. Appellant argues that Zadina "does not provide a reasonable expectation that the acetate salt of SEQ ID NO: 13 would be useful as a pharmaceutical composition." App. Br. 3. Appellant argues, "the Examiner is stating that every salt of every Zadina peptide could be used as a pharmaceutical composition to provide analgesic relief to a patient." Id. Appellant argues, in contrast, that Bansal et al., Salt Selection in Drug Development, 32 PHARMA. TECH. 4, (2008)2 ("Bansal"): "establishes that not all salts are useful pharmaceutically," and "Appellants' specification, at page 7, provides data showing that certain salts of SEQ ID NO: 13 do not exhibit useful pharmaceutical activity." Id. (underlining in original) 2 Available at: http://www.pharmtech.com/salt-selection-drug-development (last visited February 5, 2019). 4 Appeal2018-000902 Application 12/559,994 We are not persuaded by Appellant's argument. Appellant focuses on the lack of a specific salt in Zadina's pharmaceutical preparations. However, "[ n ]on-obviousness cannot be established by attacking references individually where the rejection is based upon the teachings of a combination of references .... [The reference] must be read, not in isolation, but for what it fairly teaches in combination with the prior art as a whole." In re Merck & Co., 800 F.2d 1091, 1097 (Fed. Cir. 1986). As cited by the Examiner, Zadina teaches pharmaceutical preparations containing pharmaceutically effective amounts of cyclic endomorphin-1, or salts thereof, and a pharmaceutically acceptable carrier. Zadina col. 2, 11. 18, 30; col. 5, 11. 32-35; col. 27, 11. 4---6. We do not agree that this teaching indicates all salts would be useful in pharmaceutical preparations, rather that Zadina teaches there was a need in the art for pharmaceutically effective salts of the disclosed peptides, including cyclic endomorphin-1 and linear endomorphin-1. The combination with Pepta Nova and Chemical Book provides a finite number of known solutions, i.e., one, to the need for pharmaceutically effective salts established by Zadina. See KSR Int 'l Co. v. Teleflex Inc., 550 U.S. 398,421 (2007) ("When there is a design need or market pressure to solve a problem and there are a finite number of identified, predictable solutions, a person of ordinary skill has good reason to pursue the known options within his or her technical grasp.") The resulting combination of the prior art is a pharmaceutical composition comprising the acetate salt of cyclic endomorphin-1 and a pharmaceutically-acceptable carrier. "In determining whether the subject matter of a patent claim is obvious, neither the particular motivation nor the avowed purpose of the patentee controls. What matters is the objective reach of the claim. If the claim extends to what is obvious, it is invalid 5 Appeal2018-000902 Application 12/559,994 underÂ§ 103." KSR Int 'l Co. v. Teleflex Inc., 550 U.S. 398, 419 (2007). Because the objective reach of the claims is taught by the prior art, we are not persuaded that the Examiner has erred. Issue 2 Appellant argues that the Examiner erred in finding that selecting the acetate salt was predictable. App. Br. 4. Analysis Appellant argues that "the discovery of a pharmaceutical salt is unpredictable," citing several technical references for support. See App. Br. 5. Appellant argues that Bansal teaches: "[i]n spite of the numerous advantages associated with salt forms, developing them is not always feasible." App. Br. 4. Appellant argues that Bansal teaches: "the acetate salt was chosen less than 3% of the time and the free base or acid was selected over 40% of the time." Id. Appellant further points to Berge et al. (Pharmaceutical Salts, 66 J. PHARMA. SCI. 1-19 (1977) ("Berge") and Gould (Salt Selection/or basic drugs, 33 INTL. J. PHARMACEUTICS 201-217 (1986)) ("Gould") as establishing that selecting pharmaceutical salts is unpredictable. See App. Br. 5. The Examiner finds that Bansal teaches "the availability of high- throughput screening and prevalence of acetate salts suggest the formation of such is not an unpredictable process, but merely one that requires routine experimentation." Final Act. 12. We are not persuaded that the Examiner has erred in determining the predictability of the art because the "case law is clear that obviousness cannot be avoided simply by a showing of some degree of unpredictability in the art so long as there was a reasonable probability of success." Pfizer, 6 Appeal2018-000902 Application 12/559,994 Inc. v. Apotex, Inc., 480 F.3d 1348, 1364 (Fed. Cir. 2007). In Pfizer, our reviewing court found "irrefutable evidence shows that a skilled chemist at the time would simply make known pharmaceutically-acceptable salts of whatever active ingredient with which he or she was working at the time." Id. at 1362. As applied to the Examiner's rejection, the acetate salt was a known pharmaceutically-acceptable salt, specifically used for linear endomorphin-1, which Zadina lists as an alternative peptide to cyclic endomorphin-1. As for Bansal' s teaching that the acetate salt was chosen less than 3 % of the time, we do not find this dispositive, particularly given the teachings of Pepta Nova and Chemical Book specifically identifying the acetate salt. See also Pfizer, 480 F.3d at 1363. ("[t]hat benzene sulphone was only used in creating 0.25% of FDA-approved drugs is not highly probative, much less dispositive.") Issue 3 Appellant argues that the Examiner misapplies Pfizer in finding a rationale to combine Zadina with Pepta Nova and Chemical Book. App. Br. 5---6. Analysis Appellant argues that The Pfizer case involved optimization of physical properties, rather than discovery of useful biological activity and, unlike the present case, the prior art specifically pointed to the salt that was claimed. In the current case no such motivation existed in the prior art to make a pharmaceutical formulation using the acetate salt of SEQ ID NO: 13, nor would there have been any expectation that the acetate salt would have excellent biological activity. App. Br. 6. 7 Appeal2018-000902 Application 12/559,994 We are not persuaded by Appellant's argument that Pfizer requires a "specific motivation" to arrive at the acetate salt of cyclic endomorphin-1. Rather, a reason to combine the relevant prior art teachings to achieve the claimed invention does not have to be found explicitly in the prior art references sought to be combined, but ... "may be found in any number of sources, including common knowledge, the prior art as a whole, or the nature of the problem itself." Pfizer, 480 F.3d at 1362. As discussed above, Zadina teaches pharmaceutical preparations that may include salts of linear endomorphin-1 and its analog, cyclic endomorphin-1. Pepta Nova and Chemical Book teach the acetate salt of endomorphin-1. Because cyclic endomorphin-1 is an analog of linear endomorphin-1, the compounds "possess a 'sufficiently close relationship ... to create an expectation,' in light of the totality of the prior art, that the new compound will have 'similar properties' to the old." Aventis Pharma Deutsch/and GmbH v. Lupin, Ltd., 499 F.3d 1293, 1301 (Fed. Cir. 2007). Therefore, we are not persuaded that the Examiner erred in determining the claims prima facie obvious over the prior art. Issue 4 Appellant argues that the Examiner erred for failing to consider evidence ofnonobviousness. App. Br. 6-7. Analysis Appellant argues that "the claimed acetate salt of SEQ IN NO: 13 exhibits unexpected advantages in comparison to other salts of SEQ ID NO: 13 as well as in comparison to the acetate salt of the [ endomorphin-1] peptide." App. Br. 6-7. As evidence, Appellant submits "the experimental results report at page 7 of the Appellant's specification show the excellent 8 Appeal2018-000902 Application 12/559,994 activity of the acetate salt, even compared to, for example the hydrochloride salt." App. Br. 7. Appellant also submits the Declaration of Dr. Maione where "[ r ]epresentative of results that have been obtained when testing [ cyclic endomorphin-1 acetate] ... shows the profound superiority of [ cyclic endomorphin-1 acetate] to the acetate salt of endomorphin-1 (EM-I) (and, for that matter to morphine) in the standard rat tail flick assay." Id. We are not persuaded by Appellant's evidence of unexpected results because the evidence does not establish "that there is a difference between the results obtained and those of the closest prior art, and that the difference would not have been expected by one of ordinary skill in the art at the time of the invention." Bristol-Myers Squibb Co. v. Teva Pharms. USA, Inc., 752 F.3d 967, 977 (Fed. Cir. 2014). We first examine the test results of the Specification. As argued by Appellant, Example 1 indicates that cyclic endomorphin-1 HCl salt shows no activity as compared to cyclic endomorphin-1 acetate. See Spec. 7. However, cyclic endomorphin-1 HCl is not the closest prior art and was not cited by the Examiner to reject the claims. Moreover, Example 1 appears to indicate that cyclic endomorphin-1 acetate retains the activity of cyclic endomorphin-1 free base, rather than provide any unexpected properties. See id. We also examine the Declaration of Dr. Maione. Even if we accept that the evidence establishes the superiority of cyclic endomorphin-1 acetate over linear endomorphin-1 acetate and morphine, we find that results were not unexpected. We find that Zadina teaches cyclic endomorphin-1 "was found to bind to theÂµ receptor with about 15-fold higher affinity than [linear endomorphin-1], [and] to have ... about IO-fold greater analgesic potency." Zadina col. 9, 11. 23-29. We find that Zadina further teaches "[t]his cyclic 9 Appeal2018-000902 Application 12/559,994 peptide also proved more potent than morphine in producing analgesia in mice after IV injection." Zadina col. 9, 11. 29-32. The teachings of Zadina establish it would have been expected that cyclic endomorphin-1, including salts thereof, would have superior properties to both linear endomorphin-1 and morphine. Therefore, we do not find Appellant's evidence persuasive of nonobviousness. Appellant does not argue the dependent claims separately, relying on their arguments for claim 4. We consequently affirm the Examiner's rejection of claims 4, 11, 12, and 14--17. B. Claims 15 and 17 are unpatentable under 35 U.S.C. Â§ 112, second paragraph The Examiner rejected claims 15 and 17 under 35 U.S.C. Â§ 112, second paragraph, as being indefinite. Final Act. 15. Claims 15 and 17, which recite a suspension, depend from claim 14, which recites a solution. Appellant does not argue or otherwise mention the indefiniteness rejection in their Appeal Brief. See Ans. 6. We consequently summarily affirm the Examiner's rejections on this ground. See 37 C.F.R. Â§ 4I.37(c)(iv) ("[A]ny arguments or authorities not included in the appeal brief will be refused consideration by the Board for purposes of the present appeal"). C. Claims 4 and 11 are unpatentable under the non-statutory doctrine of obviousness-type double patenting The Examiner provisionally rejected claims 4 and 11 over claims 1 and 4--7 of Application No. 14/401,731. Final Act. 18. Appellant does not argue or otherwise mention the obviousness-type double patenting rejection in their Appeal Brief. See Ans. 6. We consequently summarily affirm the Examiner's rejections on this ground. See 37 C.F.R. Â§ 4I.37(c)(iv) 10 Appeal2018-000902 Application 12/559,994 DECISION The Examiner's rejection of claims 4, 11, 12, and 14--17 as obvious under 35 U.S.C. Â§ 103(a) is affirmed. The Examiner's rejection of claims 15 and 17 as indefinite under 35 U.S.C. Â§ 112, second paragraph is affirmed. The Examiner's rejection of claims 4 and 11 under the non-statutory doctrine of obviousness-type double patenting is affirmed. AFFIRMED 11