DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Applicant's preliminary amendment filed on 02/09/2024 is acknowledged.
Claim 1 is pending.
3. The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION. —The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
4. Claim 1 is rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
(i) Claim 1 is indefinite in the recitation of a “PD-1 axis binding antagonist,” because the term “binding” implies a physical interaction, while the term “axis” denotes a concept, therefore, it is unknown what interacts with what and to what effect.
(ii) Claim 1 is further indefinite in the recitation of a “PD-1 axis binding antagonist,” because it is unknown which components of PD-1-mediated signaling pathways are encompassed by “PD-1 axis.” A skilled artisan would be aware that PD-1 interacts with PD-L1, PD-L2, SHP-1 and SHP-2, among others, PD-L1 interacts with CD80, etc., and it is unclear which of these and/or other molecules are encompassed by the “axis.”
(iii) Claim 1 is further indefinite in the recitation of a “PD-1 axis binding antagonist,” because it is unknown which function(s) of the respective component(s) are antagonized.
(iv) Claim 1 is further indefinite in the recitation of TIGIT “activity,” because it is unknown which activities are encompassed by the claim.
In view of the above, a person of ordinary skill in the art cannot unequivocally interpret the metes and bounds of the claims so as to understand how to avoid infringement. Applicant is reminded that any amendment must point to a basis in the specification so as not to add New Matter. See MPEP 714.02 and 2163.06.
5. The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102 of this title, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
6. Claim 1 is rejected under 35 U.S.C. 103 as being unpatentable over the combined teachings of Maecker et al. (US 20140341902) and Clark et al. (US 20090258013), optionally further in view of Goding et al. (2013), and/or Gao et al. (US 20100316646) (all cited on IDS; see each document in its entirety).
Maecker teaches that an optimal cancer treatment would combine inhibition of PD-1 receptor/ligand interaction with an agent that contributes additional immune enhancing properties not provided by PD-1 axis blockade alone (e.g. [0005]).
Clark reviews the mechanisms of immune regulation in normal and pathological conditions, in particular the roles of regulatory molecule TIGIT (e.g. [0003]-[0008]).
Clark further teaches a working example of antagonistic anti-TIGIT antibody 10A7 (e.g. [0032], [0042], [0044], [0145], [0146], [0373], [0388]-[0393], and Figs 9, 19, 21)which blocks TIGIT-induced inhibition of T cell proliferation, increase in IL-10 secretion by T cells, and suppression of cytokine production by monocyte-derived dendritic cells (e.g. [0371], [0389], [0406], and Figs. 7 and 24). TIGIT-positive T cells suppress proliferation of not only of TIGIT-negative T cells, but also of antigen presenting cells when present in a mixed population of immune cells, and inclusion of an anti-TIGIT antibody greatly reduces this effect (e.g. [0147]). TIGIT expression is increased in breast cancer tissues relative to normal tissues, where TIGIT expression correlates with CD4+ immune cell infiltrates in tumors (e.g. [0150]).
Clark further teaches that TIGIT antagonists such as antibodies are useful for treating cancer (e.g. [0023], [0150], [0218], [0241], [0279], [0349], [0352], [0353]), in particular in combination with tumor growth inhibitors and anti-tumor antibodies (e.g. [0352], [0353]). The dosages for the growth inhibitory agent may be lowered due to the combined action (synergy) of the growth inhibitory agent and a TIGIT antagonist [0353]. In treating cancer, TIGIT antagonists are administered, alone or in combination with other agents, to stimulate T cell activation and response to tumor antigens (e.g. [0241], [0352]). Clark teaches that enhancement of the immune response can result in rejection or regression of the neoplasm, and so molecules that enhance the T lymphocyte response can be used therapeutically to treat cancer (e.g. [0349]). Molecules that suppress immune response to a neoplasm can be expressed by the neoplastic cells themselves or their expression can be induced by the neoplasm in other cells, and antagonism of such inhibitory molecules (e.g. with an antibody) enhances immune-mediated tumor rejection (e.g. [0349]).
Thus, Maecker teaches that an optimal cancer treatment would combine PD-1/PD-L1 axis blockade with an agent that contributes additional immune enhancing properties not provided by PD-1 blockade alone, and according to Clark, antagonistic anti-TIGIT antibodies possess such properties. Clark teaches that treatment of cancer by blocking TIGIT can be combined with other agents that stimulate anti-tumor immune response, or antagonists of molecules that suppress anti-tumor immune response. According to Maecker, PD-1 receptor/ligand interactions suppress anti-tumor immune response, and antibodies that block this interaction stimulate anti-tumor immune response. Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the blockade of PD-1 receptor/ligand interaction with the blockade of TIGIT, since both Maecker and Clark provide motivation to do so. One of ordinary skill in the art would have a reasonable expectation of success, because both PD-1 signaling blockade and TIGIT signaling blockade are taught to be useful in cancer treatment. Furthermore, “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose…. [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). See MPEP 2144.06.
Further motivation to combine antagonistic anti-PD-1 and anti-TIGIT antibodies would have been provided by Goding, who reviews that in the setting of tumor recurrence, coexpression of PD-1, TIGIT, LAG-3, and TIM-3 on effector T cells inhibits their anti-tumor activity (p. 4899). Indeed, Goding found that during tumor recurrence in a melanoma model, chronically exhausted tumor-infiltrating T cells express high levels of these four inhibitory receptors (p. 9401). Under these conditions, PD-1 blockade alone was ineffective to restore anti-tumor immune response, whereas simultaneous blockade of PD-1 and LAG-3 mediated disease regression (p. 4905). Since the relative contribution of the four inhibitory receptors to immune evasion may vary between tumor types and/or individual tumors, a skilled artisan would have been motivated to utilize the other five pairwise combinations (PD1/TIGIT, PD1/TIM3, TIGIT/LAG3, TIGIT/TIM3, and LAG3/TIM3) of inhibitory receptor antagonists, in order to maximize the chances of positive clinical outcomes in a heterogeneous population of cancer patients.
Additional motivation to combine antagonistic anti-PD-1 and anti-TIGIT antibodies would have been provided by Gao, who teaches lymphocyte inhibitory receptor zB7R1. A person of ordinary skill in the art would have been aware that zB7R1 is an at-recognized synonym of TIGIT. Gao teaches that zB7R1 antagonists, such as antibodies, can be used to enhance anti-tumor T cell responses, thereby treating cancer (e.g. [0012]-[0015], [0044], [0045]). Gao contemplates that in treating cancer, zB7R1 antagonists “may be synergistically combined with immunotherapies based on modulation of other T cell costimulatory pathways, and with ICOS, PD-1, CTLA-4 and/or BTLA modulation in particular” [0068].
Accordingly, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
7. The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP §§ 706.02(l)(1) - 706.02(l)(3) for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
8. Claim 1 is rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of U.S. Patents No. 9873740, 10611836 and 10626174 (all cited on IDS).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are anticipated by the claims of each of the above-listed patents, which recite methods for treating cancer comprising administering a PD-L1 binding antagonist and an agent that decreases or inhibits TIGIT signaling, expression and/or activity (see claim 1 of each patent).
9. Claim 1 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of the following copending applications (“*” denotes those cited on IDS):
USSN PG Pub. No. Exemplary claims
18/968331 20250295766 4
18/754676 20240424092 504
18/749129 20240408009 1 and 73
18/402031 20240287182 1
18/423520 20240207398 21
18/552383 20240173391 1 and 9
17/159063 20210395366* 284
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are anticipated by the claims each of the copending applications which, at least in the exemplary claims specified above, recite methods of treating cancer comprising administering a PD1/PD-L1 signaling inhibitor and a TIGIT inhibitor.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
10. Conclusion: no claim is allowed.
11. Any inquiry concerning this communication or earlier communications from the examiner should be directed to ILIA I OUSPENSKI whose telephone number is (571)272-2920. The examiner can normally be reached 9 AM - 5:30 PM.
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/ILIA I OUSPENSKI/ Primary Examiner, Art Unit 1644
/JULIE WU/ Supervisory Patent Examiner, Art Unit 1643