Case Western Reserve UniversityDownload PDFPatent Trials and Appeals BoardNov 10, 20202019006093 (P.T.A.B. Nov. 10, 2020) 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. 14/605,729 01/26/2015 M. Edward Medof CWR-018221US CON-1 7013 68705 7590 11/10/2020 TAROLLI, SUNDHEIM, COVELL & TUMMINO, LLP 1300 EAST NINTH STREET SUITE 1700 CLEVELAND, OH 44114 EXAMINER GAMBEL, PHILLIP ART UNIT PAPER NUMBER 1644 NOTIFICATION DATE DELIVERY MODE 11/10/2020 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): docketing@tarolli.com rkline@tarolli.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE _________________ BEFORE THE PATENT TRIAL AND APPEAL BOARD _________________ Ex parte M. EDWARD MEDOF, MICHAEL G. STRAINIC, and YOUNG A. CHOI _________________ Appeal 2019-006093 Application 14/605,729 Technology Center 1600 _________________ Before FRANCISCO C. PRATS, JEFFREY N. FREDMAN, and DEBORAH KATZ, Administrative Patent Judges. KATZ, Administrative Patent Judge. DECISION ON APPEAL Appellant1 seeks our review,2 under 35 U.S.C. § 134(a), of the Examiner’s decision to reject claims 44–51, 53–55, 57, and 58.3 We have jurisdiction under 35 U.S.C. § 6(b). We AFFIRM. 1 We use the word “Appellant” as defined in 37 C.F.R. § 1.42. Appellant identifies the real party-in-interest as Case Western Reserve University. (Appeal Br. 2.) 2 We consider the Final Office Action issued June 6, 2018 (“Final Act.”), the Appeal Brief filed February 28, 2019 (“Appeal Br.”), the Examiner’s Answer issued on June 12, 2019 (“Ans.”), the Reply Brief filed August 12, 2019 (“Reply Br.”). 3 Claims 1–43 have been canceled and claims 52 and 56 withdrawn. (See Ans. 3.) Appeal 2019-006093 Application 14/605,729 2 The Examiner rejected claims 44–51, 53–55, 57, and 58 under 35 U.S.C. § 112, first paragraph, for lack of both a sufficient written and a enabling description. (See Final Act. 2–14.) The Examiner also rejected claims 44–51, 53–56, 57, and 58 under 35 U.S.C. § 101, as claiming the same invention as claims 1–3, 5–8, 10, 11, and 13–18 of prior U.S. Patent 8,940,299. (See Final Act. 14–15.) Appellant’s Specification explains that receptors for components of the complement cascade, called “C5aR” and “C3aR,” can play a role in attracting phagocytic cells to tumor beds and allowing these cells to ingest complement opsonized tumor cells. (See Spec. ¶ 3.) Appellant’s claims recite methods based on the discovery that blocking the complement- receptor (“C5a/C3a-C5aR/C3aR”) interactions with antagonists can decrease cancer cell proliferation and induce cancer cell death in a process called apoptosis. (See id. at ¶ 36.) Appellant’s independent claim 44 recites:4 A method of inducing apoptosis in a cancer cell expressing a C3a receptor (C3aR) and a C5a receptor (C5aR), the method comprising: administering amounts of a C3a antagonist and a C5a antagonist directly or locally to the cancer cell; wherein the amounts of the C3a antagonist and the C5a antagonist administered to the cancer are effective to induce apoptosis in the cancer cell, and wherein the C3a antagonist inhibits C3a mediated C3aR signaling of the cancer cell and the C5a antagonist inhibits C5a mediated C5aR signaling of the cancer cell. 4 Claim 44 has been modified by adding indentations to separate elements of the recited method. Appeal 2019-006093 Application 14/605,729 3 (Appeal Br. 23.) Independent claim 48 is similar to claim 44. (See Appeal Br. 24.) Independent claim 55 is also similar, but is limited to antibodies against C3a and C5a as the antagonists to induce apoptosis. (See id. at 25.) Appellant elected antibodies against C3a and C5a as the species of C3a antagonist and C5a antagonist and melanoma as the species of cancer to be reviewed for prosecution. (See Ans. 3; see Response to Election Requirement filed June 29, 2017.) Written Description The written description requirement of 35 U.S.C. § 112, first paragraph, requires us to determine “whether the disclosure of the application relied upon reasonably conveys to those skilled in the art that the inventor had possession of the claimed subject matter as of the filing date.” Ariad Pharm., Inc., v. Eli Lilly & Co., 598 F3d 1336, 1351 (Fed. Cir. 2010). “The purpose of [the written description] provision is to ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent specification.” Reiffin v. Microsoft Corp., 214 F.3d 1342, 1345 (Fed. Cir. 2000). In regard to the unpredictable biotechnology arts, disclosure of one or only a few species may be insufficient to support a claim to a genus that encompasses them because “there may be unpredictability in the results obtained from species other than those specifically enumerated.” Noelle v. Lederman, 355 F.3d 1343, 1350 (Fed.Cir.2004). When claims recite a functionally-defined genus, the specification must show sufficient species with the function to show that the genus was actually invented. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, Appeal 2019-006093 Application 14/605,729 4 1299 (Fed. Cir. 2014) (holding claims limited to the functional element “koff rate constant of 1x10-2s-1 or less” lacked written description support because the specification described only one type of antibody). The Federal Circuit has held that “a sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus. Id. (quoting Regents of the University of California v. Eli Lilly & Co., 119 F.3d 1559, 1568–69 (Fed. Cir. 1997)). Appellant’s Specification presents the results of experiments showing abrogation of C5a/C3a-C5aR/C3aR signaling in tumor cells to induce apoptosis. (See Spec. ¶¶ 104–105.) First, in Example 3, murine tumors were cultured in vitro with a mixture of one particular anti-C5a monoclonal antibody and one particular anti-C3a monoclonal antibody, both commercially available, and assayed for levels of the indicators of cell death Fas and FasL, as well as Bcl-2/Bcl-xl and Bax/Bim. (See Id. at ¶¶ 87, 104.) The experiment also included in vitro treatment with C5aR and C3aR antagonists. (See id. at ¶ 104.) The Specification states that by 24 hours the mixture of antibodies resulted in increased expression of Fas and FasL, down regulation of Bcl-2/Bcl-xl transcripts, and up-regulation of Bax/Bim transcripts, consistent with increased apoptosis. (See Spec. ¶¶ 36, 104–105, Figs. 9–12.) Appellant characterizes these results as showing that blocking the C3a and C5a interactions with their receptors by both C3a antagonists and C5a antagonists induces apoptosis in cancer cells expressing C3aR and C5aR. (See Appeal Br. 11.) Appeal 2019-006093 Application 14/605,729 5 Example 3 also includes the results of experiments in which melanoma cells were assessed for tumor growth in vivo using SCID and wild type mice inoculated with tumor cells and administered a mixture of C5aR/C3aR antagonist or the monoclonal antibodies against C5a and C3a or both antagonists and antibodies. (See Spec. ¶¶ 106, 107.) The Specification reports that each treatment protocol prolonged survival of the SCID mice. (See Spec. ¶ 106.) A combination therapy of antagonist and antibodies prolonged the survival of inoculated wild type mice. (See Spec. ¶ 107.) The Examiner finds that the disclosure in Example 3 of one anti-C3a antibody and one anti-C5a antibody is insufficient to describe the genus of antibodies recited in the method of claim 44 because the Specification does not identify information about other antibodies that can inhibit C3a/C5a mediated signaling and induce apoptosis in cancer cells. (See Final Act. 4; see Ans. 5–6.) The Examiner finds that because antibodies were known to have a high level of polymorphism, one of ordinary skill would conclude that the inventors were not in possession of structural attributes to induce apoptosis as required in claim 44. (See Final Act. 6.) To support these findings, the Examiner cites Rudikoff,5 Colman,6 Kussie,7 and Chen,8 which 5 Rudikoff et al., “Single amino acid substitution altering antigen-binding specificity,” PNAS 79:1979–83 (1982). 6 Colman, “Effects of amino acid sequence changes on antibody-antigen interaction,” Research in Immunology 145:33–36 (1994). 7 Kussie et al., “A Single Engineered Amino Acid Substitution Changes Antibody Fine Specificity,” J. Immunol. 152:146–52 (1994). 8 Chen et al., “Enhancement and destruction of antibody function by somatic mutation: unequal occurrence is controlled by V gene combinatorial associations,” EMBO J. 14:2784–94 (1995). Appeal 2019-006093 Application 14/605,729 6 teach that even minor amino acid changes can affect the antigen-binding characteristics of an antibody. (See Final Act. 6.) The Examiner also finds that the disclosure of a single anti-C3a antibody/anti-C5a antibody pair in Appellant’s Specification fails to sufficiently describe the full scope of claim 44 because inducing apoptosis in cancer cells through complement is complex, involving many different pathways with potentially disparate effects. (See id. at 7.) In support, the Examiner cites to two post-filing date publications: Rutkowski9 and Darling.10 (See id. at 7.) Rutkowski teaches that complement components can play complicated roles in the tumor microenvironment, including direct and antibody-dependent cell mediated cytotoxic defenses against tumors. (See Rutkowski at 1460.) Darling teaches that C5a agonists can be useful in the effectiveness of tumor vaccines and that, in general, the full roll of C5a in tumorigenesis is unknown, possibly being concentration dependent at the tumor site. (See Darling 7–9.) Darling indicates that even in 2015, well after Appellant’s earliest filing date in 2008, “additional studies [were] warranted to confirm and compare the effects of C5a at various concentrations, and perhaps in diverse microenvironment, in regard to its pro- and antitumor activity.” (Darling 9.) Given the unpredictable effects of anti-C3a and anti-C5a antibodies and the complexity of the complement pathways targeted, the Examiner concludes that a single experiment with one set of antibodies does not provide sufficient written description support 9 Rutkowski et al., “Cancer and the Complement Cascade,” Mol. Cancer Res. 8:1453–65 (2010). 10 Darling et al., “Immunological Effects and Therapeutic Role of C5a in Cancer,” Expert Rev. Clin. Immunol. 11:255–63 (2015). Appeal 2019-006093 Application 14/605,729 7 for the full scope of claim 44, encompassing any antibody against C3a and against C5a. (See Final Act. 8.) Appellant argues that the Examiner errs because the Specification allows persons of ordinary skill in the art to recognize that Appellant was in possession of C3a antagonists and C5a antagonists and because the Specification shows that administration of a C3a antagonist and a C5a antagonist would induce apoptosis in cancer cells expressing C3aR and C5aR. (See Appeal Br. 7.) Appellant argues that the disclosure of representative compositions or of distinguishing structural features common to members of the claimed genus can be sufficient written description support. (See id., citing Lilly, 119 F.3d at 1568.) According to Appellant, C3a antagonists and C5a antagonists were well known to skilled artisans at the time of filing and were commercially available. (See Appeal Br. 8–11, citing Spec. ¶ 87.) Appellant argues further that Example 3 demonstrates that the combination of anti-C3a antibody and anti-C3b antibody disabled C5a-receptor and C3a-receptor signal transduction and induced apoptosis and, thus, those in the art would have recognized that the inventors were in possession of the claimed method. (See Appeal Br. 11, citing Spec. ¶¶ 101– 108.) Appellant’s arguments are unpersuasive because they do not sufficiently address the Examiner’s findings, based on Rudikoff, Colman, Kussie, and Chen, that not all anti-C3a or anti-C5a antibodies will necessarily have the same effects given that even small differences in antibodies can cause disparate actions. Appellant also fails to sufficiently address the Examiner’s findings, based on Rutkowski and Darling, that Appeal 2019-006093 Application 14/605,729 8 interactions with the complement pathway are not always predictable and can be affected by variables such as the concentration of components. Appellant argues that although claim 44 encompasses antibodies, Appellant is not claiming antibodies to a newly characterized antigen and, therefore, Amgen Inc. v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017), cited by the Examiner, is not controlling. (See Appeal Br. 11; see Reply Br. 3.) We disagree because the holding of Amgen is not based merely on the newness of the antigen, but also on the functional language recited in the claim at issue. See Amgen, 872 F.3d at 1378 (“We cannot say that this particular context, involving a ‘newly characterized antigen’ and a functional genus claim to corresponding antibodies, is one in which the underlying science establishes that a finding of ‘make and use’ (routine or conventional production) actually does equate to the required description of the claimed products.” (emphasis added)). The claim at issue in Amgen recites not just an antibody, but one that binds to certain residues of a biological protein and “blocks binding” of that protein to another. Id. at 1372. Thus, like Appellant’s current claims, the claims at issue in Amgen are characterized by their function. Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341 (Fed. Cir. 2011), is similarly informative for the written description issues of Appellant’s claims. In that case, the court explained: Claiming antibodies with specific properties, e.g., an antibody that binds to human TNF-α with A2 specificity [indicating the ability to bind TNF-α in a specific location], can result in a claim that does not meet written description even if the human TNF-α protein is disclosed because antibodies with those properties have not been adequately described. Appeal 2019-006093 Application 14/605,729 9 Id. at 1352. Even though claim 44 encompasses antibodies to known antigens, it requires certain functions of these antibodies. Under Amgen, Centocor, and similar cases,11 Appellant must present sufficient evidence that one of ordinary skill would have understood the inventors were in possession of not just one antibody that binds C3a and one antibody that binds C5a, but a representative number of antibodies demonstrating possession of the full scope of antibodies with the functional characteristic of being “effective to induce apoptosis in the cancer cell” and of inhibiting C3a mediated C3aR and C5a mediated C5aR signaling in the cancer cell. We are not persuaded that the disclosure of one antibody pair meeting the claimed functional limitations in Example 3 of the Specification is sufficient. Even if other antibodies were known, Appellant does not direct us to evidence that all other anti-C3a and anti-C5a antibodies, or indeed any other antibodies, would result in an induction of apoptosis in cancer cells. (Contra Reply Br. 5, citing Spec. ¶ 41.) Given the variability of different 11 See AbbVie, 759 F3d at 1299; see also Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1350 (Fed. Cir. 2010) (“We have also held that functional claim language can meet the written description requirement when the art has established a correlation between structure and function. But merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing that one has invented a genus and not just a species. . . . In fact, this case similarly illustrates the problem of generic claims. The claims here recite methods encompassing a genus of materials achieving a stated useful result, i.e., reducing NF-κB binding to NF-κB recognition sites in response to external influences. But the specification does not disclose a variety of species that accomplish the result.”) (citations omitted). Appeal 2019-006093 Application 14/605,729 10 antibodies, the complexity of the complement pathway, and the general unpredictability of the art the Examiner demonstrates by citing research, we are not persuaded that one of ordinary skill would understand the inventors were in possession of the full scope of claim 44 without some definition of structure-function relationship between anti-C3a and anti-C5a antibodies and induction of apoptosis or inhibition of C3a and C5a signaling. We are not persuaded that those of ordinary skill would know which other anti-C3a and anti-C5a antibodies would meet these functional requirements because Appellant’s Specification does not provide evidence that any other antibodies would do so. Because Appellant fails to persuade us that claim 44, limited to the elected species of an antibody as the C3a antagonist and an antibody as the C5a antagonist, is supported by a sufficient written description, we would not be persuaded that the full scope of claim 44, encompassing any C3a and C5a antagonist, is supported by a sufficient written description. In addition, because Appellant does not argue for the separate patentability of any of the claims rejected for a lack of sufficient written description, we are not persuaded that any other claims are sufficiently supported. Accordingly, the Examiner did not err in rejecting Appellant’s currently pending claims under 35 U.S.C. § 112, first paragraph. Enablement The Examiner rejects all of Appellant’s claims as lacking an enabling disclosure under 35 U.S.C. § 1112, first paragraph. (See Final Act. 8–14.) A patent specification must enable one of ordinary skill in the art “to practice the claimed invention without undue experimentation.” Nat’l Recovery Techs., Inc. v. Magnetic Separation Sys., Inc., 166 F.3d 1190, 1196 Appeal 2019-006093 Application 14/605,729 11 (Fed. Cir. 1999) (emphasis omitted). Whether undue experimentation would be required is determined by analyzing a number of factors, including (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. In re Wands, 858 F.2d 731, 737 (Fed. Cir. 1988). Appellant does not argue for the separate patentability of any of the rejected claims. We focus on claim 48, which recites: A method of treating cancer in a subject in need thereof, the method comprising: administering directly or locally to cancer cells expressing C3aR and C5aR of the subject therapeutically effective amounts of a C3a antagonist and a C5a antagonist, wherein the amounts of C3a antagonist and C5a antagonist administered to the cancer cells induce apoptosis in the cancer cells, and the C3a antagonist inhibits C3a mediated C3aR signaling of the cancer cell and the C5a antagonist inhibits C5a mediated C5aR signaling of the cancer cell. (Appeal Br. 24.) Claim 55 similarly recites a method of treating cancer in a subject by administering C3a and C5a antibodies to induce apoptosis. (See Appeal Br. 25.) We note at the outset that although Appellant elected melanoma as the species of cancer for the Examiner’s search, we review the rejection as if the requirement for an election was withdrawn. (See Ans. 3 (acknowledging the election of species, but stating that “[u]pon search and in the interest of compact prosecution, the election of species has been extended to all species of cancer (e.g., see claims 54, 58).”) Appeal 2019-006093 Application 14/605,729 12 The Examiner finds that Appellant’s claims are broad, being unlimited as to antibody or the environment of the cancer cells targeted, as well as encompassing treatment of cancer in human patients. (See Final Act. 12.) The Examiner finds further that in vitro studies, like the study presented in Example 3, would not necessarily reflect the relative efficacy of the claimed therapeutic strategy to induce apoptosis in cancer with the claimed antibodies. (See id.) For example, the Examiner notes that treatment of cancer in human patients may start only after cancer has been established for some time, a condition not reflected in in vitro experiments. (See id.; see Ans. 16.) Furthermore, as discussed above, the Examiner cites to Rutkowski for its teaching of the complicated roles complement plays in the tumor microenvironment, including as direct and antibody-dependent cell mediated cytotoxic defenses against tumors, and to Darling for its teachings that the full roll of C5a in tumorigenesis was unknown at the time of filing and that additional studies were warranted even years after filing to understand its pro- and antitumor activity. (See Final Act. 13; see Ans. 16–18, see Rutkowski 1460; see Darling 9.) The Examiner concludes: The specification describes experimental models that do not provide sufficient predictability of treating cancer as well as inhibiting C3a/C5a mediated signaling and inducing apoptosis in cancer cells that reflect the complexity and unpredictability of achieving such results in tumor microenvironment by a broad range of cancer cells encompassed by the scope of the claimed methods. This description of experimental models without more is a starting point, a direction for further research. (Ans. 19.) Appeal 2019-006093 Application 14/605,729 13 Appellant argues that the amount of direction or guidance disclosed in the Specification is sufficient to enable a skilled artisan to make and use the method of claim 48 using only routine experimentation. (See Appeal Br. 13.) Appellant argues that the Specification shows that in certain cancer cells expressing C3aR and C5aR, that C3aR and C5aR signaling promotes cancer cell survival and that inhibition of this signaling can induce apoptosis. (See id. at 14, citing Spec. ¶¶ 35–37, 101; see Reply Br. 7.) Appellant argues further that Example 3 is a working example of blocking C3a and C5a interactions with their receptors by administering antagonists against the receptors. (See Appeal Br. 15.) Appellant concludes: Thus, the specification of the present application clearly allows one skilled in the art to recognize what is claimed based on the disclosure of the . . . specific C3a antagonists and C5a antagonists, the fact that C3a antagonists and C5a antagonists were well known at the time of filing the application, the described mechanism of action the C3a antagonists and C5a antagonists, and the fact that the specification and claims are limited to specific cancer cell types, i.e., cancer cells expressing C3aR and C5aR. (Appeal Br. 16.) We are not persuaded by this argument because Appellant does not address the knowledge in the art of the complex role of complement in tumorigenesis and thus in treating cancer in patients through complement. Appellant does not address the Examiner’s finding that [i]n contrast to appellant’s arguments, including reliance . . . upon mechanisms of action, it is maintained that applicant relies upon experimental murine tumor models based upon defined conditions (e.g., administering [antagonist] of at the same time of administering cancer cell lines), implantation of tumor cell lines and not testing tumor cells implanted into the organ of origin in models or spontaneous/ chemically induce tumors that allow for a more suitable Appeal 2019-006093 Application 14/605,729 14 interaction between tumor cells and the surrounding stroma and provide more relevant information about the role for complement in the modulation of the tumor microenvironment, where the complexity and unpredictability in the context of treating cancer via C3a/C5a complement inhibitors are addressed by [Rutkowski] et al. and Darling et al. (See Ans. 18–19.) In light of the post-filing date teachings of Rutkowski and Darling, we are not persuaded by Appellant’s argument that Example 3 alone would provide enough information for one of ordinary skill in the art to make a use a method of treating cancer in a subject, as recited in claim 48. We note further that the results provided in the figures cited in Example 3 are ambiguous about the effects of anti-C3a and anti-C5a antibodies on survival of mice injected with tumor cells. Specifically, Example 3 refers to experiments using different treatments on melanoma cells in SCID12 mice. (See Spec. ¶ 106.) The Specification reports that Figure 13A shows the results of administering C3aR-antagonist along with C5aR-antagonist, which “prolonged survival.” (Id.) Figure 13A depicts two survival curves, one showing longer survival times than the other. Although the two curves use different symbols, there is no legend to indicate which treatment these symbols represent. The Specification reports, further, that Figure 13B shows the results of administering anti-C3a antibody along with anti-C5a antibody, which “prolonged survival even longer.” (Spec. ¶ 106.) Figure 13B is reproduced below. 12 SCID refers to severe combined immunodeficient mice, which lack a potential adaptive immune effects against inoculated tumor cells. (See Spec. ¶ 106.) Appeal 2019-006093 Application 14/605,729 15 Figure 13B depicts one survival curve and a legend with “PBS cont” and “RA” indicating the same symbol. The control and “RA” treatments are both depicted as the same symbol in the legend provided. Appellant fails to direct us to an explanation, either in the Specification or by one who can testify to the understanding of an ordinarily skilled artisan, how Figure 13B demonstrates that the combination of anti-C3a and anti-C5a antibodies increased survival over control. It is not clear how the treatment survival curve differs from the control curve or even if both curves are present. We note further that Figure 13C is reported to depict survival of tumor-injected SCID mice with a combination of C5aR antagonist/C3a antagonist and anti-C5a/anti-C3a antibody, which “showed that the combination prolonged survival markedly most efficiently.” (Spec. ¶ 106.) The curve indicated to be “RA” in the legend of Figure 13C, though, appears to be the same as the single curve depicted in Figure 13B. Without further explanation as to how one of ordinary skill in the art would understand these Appeal 2019-006093 Application 14/605,729 16 figures, we are not persuaded that the results discussed in Example 3 are strong enough to present an enabling description of the claimed methods. Finally, we note that although the Specification reports experiments with C5aR/C3aR antagonists and anti-C3a/anti-C5a antibodies in wild-type mice, the results obtained with anti-C3a/anti-C5a antibodies alone are not discussed. (See Spec. ¶ 107.) Again, we are not persuaded that the Example 3 alone provides an enabling description of the claimed methods because it is not clear that the results in even two different types of mice are consistent. In general, we are not persuaded that Appellant’s Specification would indicate to one of ordinary skill in the art how to make or use a method of treating cancer in a subject in need thereof by administering amounts of anti- C3a and anti-C5a antibodies, as required in claim 48. Despite Appellant’s arguments that the teachings of Rutkowski and Darling are only “generalized concerns,” (Appeal Br. 17), the lack of clarity in the results of Appellant’s own studies tends to reinforce rather than refute the complexity and unknown role of complement in tumorigenesis. Accordingly, Appellant fails to persuade us that the Examiner erred in rejecting claim 48 or any other claim as lacking an enabling description under 35 U.S.C. § 112, first paragraph. Statutory Double-Patenting The Examiner rejects claims 41–51, 53–55, and 57–58 under 35 U.S.C. § 101 as claiming the same invention as claims 44–51, 53–55, 57, and 58of commonly assigned U.S. Patent 8,940,299 (the ’299 patent”). (See Appeal 2019-006093 Application 14/605,729 17 Final Act. 14.) The Examiner explains that this is a statutory double- patenting rejection. (See Final Act. 14.) Claim 1 of the ’299 patent recites: A method of inducing apoptosis in a cancer cell expressing a C3a receptor (C3aR) and a C5a receptor (C5aR), the method comprising: administering amounts of a C3aR antagonist and a C5aR antagonist directly or locally to the cancer cell; wherein the amounts of the C3aR antagonist and the C5aR antagonist administered to the cancer cell are effective to substantially reduce or substantially inhibit the activity of protein kinase B (PKB) in the cancer cell and induce apoptosis in the cancer cell, and wherein the C3aR antagonist inhibits C3a mediated C3aR signaling of the cancer cell and the C5aR antagonist inhibits C5a mediated C5aR signaling of 60 the cancer cell. (’299 Patent 23:59–24:3.) The Examiner finds that the only difference between claim 1 of the ’299 patent and Appellant’s currently pending claims, for example claim 44, is that claim 1 recites “wherein the amounts of the C3aR antagonist and the C5aR antagonist administered to the cancer cell are effective to substantially reduce or substantially inhibit the activity of protein kinase B (PKB) in the cancer cell” as well as being effective to induce apoptosis. (See Final Act. 14.) The Examiner finds that the limitation of claim 1 is inherent to the method of claim 44, pointing to Appellant’s currently pending claim 57. (See Final Act. 14.) We disagree that the claims of the ’299 patent and Appellant’s currently pending claims differ only in the limitation regarding protein kinase B. Instead, as Appellant argues, claim 1 of the ’299 patent recites administering a C3aR antagonist and a C5aR antagonist, whereas the currently pending claims recite administering a C3a antagonist and a C5a antagonist. (See Appeal Br. 20.) Thus, even if reducing or substantially Appeal 2019-006093 Application 14/605,729 18 inhibiting the activity of protein kinase B is inherent administering C3aR and C5aR antagonists, administering antagonists to these receptors is not the same as administering antagonists to C3a and C5a. Because the claims of the ’299 patent are not directed to the same invention as Appellant’s currently pending claims, we do not sustain the Examiner’s rejection under 35 U.S.C. § 101 for double-patenting. Conclusion Upon consideration of the record and for the reasons given, we affirm the Examiner’s rejection. In summary: Claims Rejected 35 U.S.C. § Basis Affirmed Reversed 44–51, 53–55, 57, 58 112, first paragraph Written description 44–51, 53–55, 57, 58 44–51, 53–55, 57, 58 112, first paragraph Enablement 44–51, 53–55, 57, 58 44–51, 53–55, 57, 58 101 Statutory Double Patenting 44–51, 53–55, 57, 58 Overall Outcome 44–51, 53–55, 57, 58 No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. § 1.136. AFFIRMED Copy with citationCopy as parenthetical citation