Gruenenthal GmbH

Patent Trials and Appeals Board

Mar 31, 2022

2021005256 (P.T.A.B. Mar. 31, 2022)

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. 15/245,855 08/24/2016 Klaus SCHIENE 107101-240 KGB 9804 27384 7590 03/31/2022 Briscoe, Kurt G. Norris McLaughlin, PA 7 Times Square, 21st Floor New York, NY 10036-6524 EXAMINER CRUZ, KATHRIEN ANN ART UNIT PAPER NUMBER 1627 NOTIFICATION DATE DELIVERY MODE 03/31/2022 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): mgonzalez@norris-law.com nmanfredi@norris-law.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE ____________ BEFORE THE PATENT TRIAL AND APPEAL BOARD ____________ Ex parte KLAUS SCHIENE and PETRA BLOMS-FUNKE Appeal 2021-005256 Application 15/245,855 Technology Center 1600 ____________ Before RICHARD M. LEBOVITZ, JEFFREY N. FREDMAN, and ULRIKE W. JENKS, Administrative Patent Judges. LEBOVITZ, Administrative Patent Judge. DECISION ON REQUEST FOR REHEARING Appellant1 requests a rehearing under 37 C.F.R. § 41.79 (“Req. Reh’g”) of the Decision on Appeal entered January 12, 2022 (“Dec.”). The request is granted, but we are not persuaded to change the outcome of the Decision. A new ground of rejection, pursuant to 35 U.S.C. § 41.50(b) is also entered under 35 U.S.C. § 112, first paragraph, for lack of enablement. 1 We use the word “Appellant” to refer to “applicant” as defined in 37 C.F.R. § 1.42. Appellant identifies the real party in interest as Grünenthal GmbH. Appeal Br. 1. Appeal 2021-005256 Application 15/245,855 2 STATEMENT OF THE CASE In the Final Office Action, the Examiner rejected claims 1, 2, 5-10, 22-26, 30, 33-37, 40-43, 52, and 53 under 35 U.S.C. § 103(a) as obvious in view of Buschmann, Wilder-Smith, and Garcia-Alonso and claim 44 as obvious in view of Buschmann, Wilder-Smith, Garcia-Alonso, and Ward. Dec. 2. Both rejections under § 103 were affirmed in the Decision, but because we expanded on the evidence and reasoning of the Examiner, the obviousness rejection of claim 53 was designated as a new ground of rejection. Dec. 15-16. Appellant requests reconsideration of the decision to affirm the rejections. We grant this request to the extent that one of Appellant’s arguments is persuasive. But this argument does not change the outcome of the Decision. In reviewing Appellant’s Request for Reconsideration, we have reached the conclusion that the Examiner overlooked a deficiency in the enablement of claim 53. Consequently, we make a new ground of rejection of claim 53 under 35 U.S.C. § 112, first paragraph, as lacking enablement for its full scope. This is a new ground of rejection pursuant to 35 U.S.C. § 41.50(b). OBVIOUSNESS REJECTIONS Claim 53 is the only claim addressed in the Request for Rehearing. Claim 53 is directed to “composition comprising synergistic combination” of (a) at least one 3-(3-Dimethylamino-l-ethyl-2-methyl-propyl)-phenol compound and (b) one or more non-steroidal anti-inflammatory drugs (NSAIDs) selected from the group consisting of Diclofenac, Diclofenac- Sodium, Ibuprofen, Metamizol, Metamizol-Sodium, and Ketoprofen. (3-(3- Appeal 2021-005256 Application 15/245,855 3 Dimethylamino-l-ethyl-2-methyl-propyl)-phenol is also known as “tapentadol.” Appellant’s principal argument throughout the Reply Brief is that there was no motivation to make the claimed composition comprising a “synergistic combination” of components (a) and (b) because synergy is unexpected and would not have been predictable. We have considered this argument, but do not find it persuasively demonstrates an error in the Decision. Initially, we acknowledge Appellant’s argument about the adequacy of the guidance in the Specification for making a composition that could achieve the same blood levels for compounds (a) and (b) that were achieved when (a) and (b) were separately administered intravenously and intraperitoneally as disclosed in the working examples in the Specification. Req. Reh’g 17-21. Appellant’s arguments and evidence are persuasive. This specific objection to the unexpected results is therefore withdrawn. We do not renew this objection to the claims under the § 112, first paragraph, enablement rejection. As explained in the Decision, there was adequate reason to have combined (a) tapentadol with (b) an NSAID selected from the group consisting of Diclofenac, Diclofenac-Sodium, Ibuprofen, Metamizol, Metamizol-Sodium, and Ketoprofen as recited in claim 53. Dec. 7. Appellant attempts to rebut this determination by limiting the claim to “synergistic” combinations of (a) and (b). While it is true that we stated in the Decision that synergy between the compounds “would not have been predictable” (Dec. 7), we did not conclude that all combinations of (a) and (b) possess synergy. Rather, the Decision explained the evidence for synergy Appeal 2021-005256 Application 15/245,855 4 provided by Appellant was only for a certain ratio between the compounds and only for one stereoisomer of tapentadol. Dec. 9. Appellant’s Specification does not show that every combination of (a) and (b) encompassed by claim 53 produces synergy. Appellant argued this is irrelevant because the claim is limited to only “synergistic” combinations of (a) and (b). Req. Reh’g 4. The Decision addressed this issue by citing Application of Kollman, 595 F.2d 48 (CCPA 1979) in which claims to a “synergistic herbicidal composition” were found deficient because synergy had not been shown for the full scope of the claim, despite the term “synergistic” excluding any non-synergistic compositions. Dec. 11-12. Appellant argues Kollman is distinguishable because the primary reference (“Bayer”) in the rejection disclosed both components and the only difference was the weight ratio: Appellant therein did not allege that the “synergistic” limitation of claim 1 was itself distinguishing over Bayer nor could he because synergism might have been inherent in the Bayer compositions. Thus, appellant therein was rightly forced to base patentability on the criticality of the claimed weight ratio and this, in turn, required that he show that the unexpected synergy was observed over the entirety of the weight range claimed and over the genus of components (B) claimed. Req. Reh’g 13. Appellant states that the “present situation” is “altogether different” because “there is no single prior art reference already combining instant components (a) and (b) in a single composition.” Id. This argument is not persuasive. The claim in Kollman was directed to a “synergistic herbicidal composition” comprising compounds (A) and (B) in ratio of about “about 1:10 to about 20:1.” Kollman, 595 F.2d at 49. The Appeal 2021-005256 Application 15/245,855 5 court held that the claim was not anticipated by the Bayer reference (“it is apparent there is no suggestion of the required FENAC/diphenyl ether ratio. Accordingly, we reverse the [§] 102 rejection.”). Id. at 55. But the claims were also rejected as obvious under § 103 in view of Bayer. For the obviousness rejection, Kollman had the burden to show that the claimed ratio was not obvious based on the Bayer reference. Kollman sought to meet this burden by establishing unexpected results, namely synergy between (A) and (B), the same strategy employed by Appellant in this appeal. Appellant does not identify a persuasive difference between obviousness based on a single reference as in Kollman and obviousness based on two or more references as in the instant rejection. The burden is still the same: to provide rebuttal arguments or evidence, such as evidence of “unexpected results.” And just like the claims in Kollman, the claimed “synergistic combination” is not limited to the specific conditions that provide the synergistic results. Consequently, we are not persuaded that Kollman is inapplicable to Appellant’s claims. We emphasize that there is a reason to put tapentadol and an NSAID “selected from the group consisting of Diclofenac, Diclofenac-Sodium, Ibuprofen, Metamizol, Metamizol-Sodium, and Ketoprofen” together in one composition, making the composition prima facie obviousness. Dec. 7. One of the rationales as to why the claim is obvious is based on the Kerkhoven case which held that it is obvious to combine two compositions when each is described as useful for the same purpose. Id. Appellant argues that the reason to combine (a) and (b) based on Kerkhoven is defective because there was no reasonable expectation of success that a synergistic composition could be made. Req. Reh’g 7. Appeal 2021-005256 Application 15/245,855 6 Appellant asserts the obviousness rejection ignored the term “synergistic” in the claim. This argument does not persuade us that the Decision erred in affirming the rejection. “[O]n examination the PTO bears the initial burden of presenting a prima facie case of unpatentability. If that burden . . . is met, the burden shifts to the applicant, to come forward with evidence and argument to rebut the prima facie case. In re Piasecki, 745 F.2d 1468, 1472 (Fed. Cir. 1984).” In re Huping Hu, 848 F.App’x. 416 (Fed. Cir. 2021). Here, the Examiner established that a combination of analgesics had been used in the prior art to treat pain. Dec. 4 (citing Final Act. 11-13).2 Based on this teaching and the Kerkhoven rationale, we agreed with the Examiner that it was prima facie obvious to put the (a) and (b) together, both of which are analgesic compounds. The resulting “synergy” of the composition is at least preliminarily an inherent property of combining the two. As explained in Honeywell International Inc. v. Mexichem Amanco Holding, 865 F.3d 1348, 1355 (Fed. Cir. 2017): What is important regarding properties that may be inherent, but unknown, is whether they are unexpected. All properties of a composition are inherent in that composition, but unexpected properties may cause what may appear to be an obvious composition to be nonobvious. See, e.g., In re Papesch, 315 F.2d 381, 391 (C.C.P.A. 1963) (emphasizing that “[f]rom the standpoint of patent law, a compound and all of its properties are inseparable; they are one and the same thing,” and yet in comparing the similarity of the one compound to another, 2 Final Act. 12 (“Wilder-Smith (herein after Smith) teaches the combination of tramadol and diclofenac resulted in improved analgesia compared with monotherapy (See abstract). Wilder-Smith discloses tramadol, 100 mg and diclofenac 75 mg (abstract).”). Appeal 2021-005256 Application 15/245,855 7 “[t]here is no basis in law for ignoring any property in making such a comparison”). Appellant has had the opportunity to rebut the preliminary obviousness determination, which Appellant did by providing evidence that the synergy is unexpected. We agreed with Appellant that the synergy was demonstrated unexpectedly for the specific ratios and tapentadol enantiomer employed in the examples described in the Specification. Spec. ¶¶ 85-94. Our objection is that the unexpected results are not commensurate with the scope of the claim. That is, the results do not show that the whole scope of claim 53 is nonobvious because not all combinations within the scope of the claim were shown to be unexpected. Appellant characterizes this requirement as “a ‘feel good’ requirement” and inapplicable to the current claims because they are directed to synergistic combinations. Req. Reh’g 14-15. We decline to adopt this position. It is axiomatic that, “for objective evidence to be accorded substantial weight, its proponent must establish a nexus between the evidence and the merits of the claimed invention.” In re GPAC Inc., 57 F.3d 1573, 1580 (Fed. Cir. 1995). In particular, the objective indicia “must be tied to the novel elements of the claim at issue” and “be reasonably commensurate with the scope of the claims.” Institut Pasteur & Universite Pierre Et Marie Curie v. Focarino, 738 F.3d 1337, 1347 (Fed. Cir. 2013). A nexus is missing between the full scope of claim 53 and the examples in the Specification using specific ratios between (a) and (b) and a specific tapentadol enantiomer. Specifically, Appellant does not establish that every combination of (a) and (b) is synergistic, but rather only shows it for one specific ratio and one tapentadol stereoisomer for each combination. The claim, however, while limited to only “synergistic” combinations, does not recite the features Appeal 2021-005256 Application 15/245,855 8 in the claim responsible for the synergistic effect. Limiting the claim to only “synergistic” combinations does not eliminate Appellant’s burden “of showing that a nexus exists between the claimed features of the invention and the objective evidence offered to show non-obviousness.” WMS Gaming, Inc. v. International Game Technology, 184 F.3d 1339, 1359 (Fed. Cir. 1999); GPAC, 57 F.3d at 1580. The features which provide the nexus between the invention and the evidence of non-obviousness - namely the synergistic ratio between (a) and (b) and the single tapentadol stereoisomer - are not recited in the claim. Accordingly, we decline to modify the outcome of the Decision afforming the rejection of claim 53 as obvious in view of Buschmann, Wilder-Smith, and Garcia-Alonso. NEW GROUND OF REJECTION Pursuant to 35 U.S.C. § 41.50(b), we set forth the following new ground of rejection: Claim 53 is rejected under 35 U.S.C. § 112, first paragraph, as lacking enablement for the full scope of the claim. Analysis “[T]o be enabling, the specification of a patent must teach those skilled in the art how to make and use the full scope of the claimed invention without ‘undue experimentation.’” In re Wright, 999 F.2d 1557, 1561 (Fed. Cir. 1993) (citing In re Vaeck, 947 F.2d 488, 495 (Fed. Cir. 1991)). [The] scope of the claims must bear a reasonable correlation to the scope of enablement provided by the specification to persons of ordinary skill in the art. . . . In cases involving Appeal 2021-005256 Application 15/245,855 9 unpredictable factors, such as most chemical reactions and physiological activity, the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved. In re Fisher, 427 F.2d 833, 839 (CCPA 1970). Claim 53 is directed to a “composition comprising a synergistic combination” of (a) at least one tapentadol compound and (b) one or more non-steroidal anti-inflammatory drugs (NSAIDs) selected from the group consisting of Diclofenac, Diclofenac-Sodium, Ibuprofen, Metamizol, Metamizol-Sodium, and Ketoprofen. There is no restriction in claim 53 on the amounts of, and ratio between, tapentadol and the NSAID in the “synergistic combination.” The Specification, however, refers to a weight ratio as being responsible for the synergy: If these components are present in the composition in such a weight ratio that a synergistic effect is observed after administration to the patients, the overall administered dose may be lowered, so that fewer undesired side-effects will occur. Spec. ¶ 6. In yet a further embodiment of the inventive combination components (a) and (b) are present in such a weight ratio that the resulting composition will exert a synergistic effect upon administration to a patient. Suitable weight ratios can be determined by methods well known to those skilled in the art, e.g. via the Randall-Selitto test described below. Spec. ¶ 40. Consistently, the Specification describes experiments that establish synergy for limited combinations of (a) and (b) at specific weight ratio. Spec. ¶¶ 85-94. In a rat model, tapentadol was administered intravenously and the NSAID intraperitoneally. Spec. ¶¶ 89, 92. The Specification discloses using the Randall-Selitto test to determine a synergistic effect Appeal 2021-005256 Application 15/245,855 10 between the tapentadol and NSAID. Spec. ¶ 85. The results are analyzed in accordance with Tallarida et al. Spec. ¶ 87. The Specification discloses that the synergy between the two compounds (“supraadditive”) (Spec. ¶¶ 89, 92) occurs at a specific weight ratio: From the table 1 given above, the ratio of A and Diclofenac- Sodium can be calculated to be 1:77.5, the ratio of A to Ibuprofen to be 1:73.8. Spec. ¶ 91. The ratio of A and (+)-Naproxen used in the experiments [shown in Table 2] was 1:87.3, the ratio of A and Ketoprofen 1:119 and the ratio of A and Metamizol-Sodium was 1:46.9. Spec. ¶ 94. “A” is the 1R, 2R enantiomer of tapentadol. Spec. ¶ 89. The Specification does not disclose any other ratio that produced the supraadditive and synergistic results in the rat model. The Specification also discloses: “Suitable weight ratios can be determined by methods well known to those skilled in the art, e.g. via the Randall-Selitto test described below. Spec. ¶ 40. However, Appellant’s position based on the prior art is that synergy between the two claimed compounds is unpredictable: “Overall, the picture is one of complete unpredictability.” Appeal Br. 19. Appellant explains: “Synergy, as is well known to persons skilled in the art, is something that must be determined empirically, as has once again been proven on the totality of this record.” Id. If synergy is unpredictable and must be determined empirically, then the Specification must establish empirically that ratios other than those shown in the Specification to be actually synergistic, are also synergistic. Appeal 2021-005256 Application 15/245,855 11 Predictability is one of the “Wands factors” that must be considered when making an enablement rejection. In re Wands, 858 F.2d 731 (Fed. Cir. 1988). The factors are as follows: (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims. Wands, 858 F.2d at 737. The lack of predictability, as admitted by Appellant, weighs against a finding that the full scope of claim 53 is enabled by the limited disclosure in the Specification. The claim breadth, another of the Wands factors, is not restricted to specific amounts of (a) and (b) or a weight ratio between them, yet only one example for each of the claimed NSAIDs is shown empirically in the Specification. There is no guidance in the Specification on how to select other amounts and other weight ratios of (a) and (b) - the latter which the Specification expressly states is necessary to achieve synergy. Spec. ¶¶ 6, 40. This was explained in the Decision. Dec. 13 (“Appellant has not provided an adequate explanation, supported by objective evidence, that the one data point for each of the synergistic combinations in Table 1 and 2 of the Specification shows a trend in the data that all ratios outside these values would also provide synergy. See Kollman; Kao, 639 F.3d at 1068.”) The claim covers all four of different enantiomers of tapentadol achieve synergy, but synergy is shown with only one. The Decision explained: The examples in the Specification only uses the IR, 2R enantiomer, but the claim is not restricted to this compound. Appellant argues that “the tested members are structurally close Appeal 2021-005256 Application 15/245,855 12 to and, therefore, representative of the non-tested members.” Reply Br. 11. We take notice of the fact that enantiomers contain the same type and number of atoms, but differ in their three-dimensional structure. Appellant has not provided objective evidence that each of the four different enantiomeric configurations would provide the same type of synergy shown by the one enantiomer tested. Dec. 12. Although the Decision raised both these latter objections to the scope of claim 53, Appellant did not provide an adequate response to it. Indeed, Appellant did not believe it necessary to respond because of its faulty contention that prima facie obviousness had not been established.3 Weighing the state of the prior art, the unpredictability of the art, the breadth of the claims (not restricted to specific ratio or enantiomer), and the lack of guidance on how to select other amounts and ratios, we find that claim 53 is not enabled for its full scope. There is no reasonable correlation between the scope of the claim and the empirical evidence disclosed in the Specification. Fisher, 427 at 839. 3 Req. Reh’g 9 (“The Board’s criticisms of Appellant’s specification data, assuming for the sake of argument they were valid, do not stand in the way of the allowance of claim 53 since the Board has not, for the reasons given above, made out a prima facie case of the obviousness of claim 53.). Appeal 2021-005256 Application 15/245,855 13 Outcome of Decision on Rehearing: Claims Rejected 35 U.S.C. § Reference(s)/Basis Denied Granted New Ground 1, 2, 5- 10, 22- 26, 30, 33-37, 40-43, 52, 53 103 Buschmann, Wilder-Smith, Garcia-Alonso 1, 2, 5- 10, 22- 26, 30, 33-37, 40-43, 52 53 44 103 Buschmann, Wilder-Smith, Garcia-Alonso, Ward 44 53 112 Enablement 53 Overall Outcome 1, 2, 5- 10, 22- 26, 30, 33-37, 40-44, 52 53 53 Appeal 2021-005256 Application 15/245,855 14 Final Outcome of Appeal after Rehearing: Claims Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed New Ground 1, 2, 5- 10, 22- 26, 30, 33-37, 40-43, 52, 53 103 Buschmann, Wilder-Smith, Garcia-Alonso 1, 2, 5- 10, 22- 26, 30, 33-37, 40-43, 52 53 44 103 Buschmann, Wilder-Smith, Garcia-Alonso, Ward 44 53 112 Enablement 53 Overall Outcome 1, 2, 5- 10, 22- 26, 30, 33-37, 40-43, 52 53 TIME PERIOD FOR RESPONSE This Decision contains a new ground of rejection pursuant to 37 C.F.R. § 41.50(b). 37 C.F.R. § 41.50(b) provides “[a] new ground of rejection pursuant to this paragraph shall not be considered final for judicial review.” 37 C.F.R. § 41.50(b) also provides that the Appellant, WITHIN TWO MONTHS FROM THE DATE OF THE DECISION, must exercise one of the following two options with respect to the new ground of rejection to avoid termination of the appeal as to the rejected claims: (1) Reopen prosecution. Submit an appropriate amendment of the claims so rejected or new Evidence relating to the claims so rejected, or both, and have the matter reconsidered by the Appeal 2021-005256 Application 15/245,855 15 examiner, in which event the proceeding will be remanded to the examiner. . . . (2) Request rehearing. Request that the proceeding be reheard under § 41.52 by the Board upon the same Record. . . . Further guidance on responding to a new ground of rejection can be found in the Manual of Patent Examining Procedure § 1214.01. GRANTED 37 C.F.R. 41.50(b)