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 amendment, filed on 04/14/2026, is acknowledged.
3. Claims 76-95 are pending.
4. Applicant’s election without traverse of Group I, claims 76-94 directed to methods of treating cancer with anti-TIGIT antibody and the species of lung cancer, and antibody against PD-1 or PD-L1 as the second agent, filed on 04/14/2026, is acknowledged.
5. Claims 80-81 and 95 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions.
6. Claims 76-79 and 82-94 are under examination as they read on methods of treating cancer with anti-TIGIT antibody and the species of lung cancer, and antibody against PD-1 or PD-L1 as the second agent.
7. Applicant’s IDS, filed 12/26/2023, is acknowledged.
8. The following is a quotation of 35 U.S.C. 112(a) (Pre-AIA 35 U.S.C. 112, first paragraph):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
9. Claims 76 and 84-94 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 84 encompasses a broad genus of tumor infiltrating T-cells which are activated by the antibody (the anti-TIGIT antibody recited in claim 76).
Claim 85 encompasses a broad genus of vaccines inducing an immune response against the cancer.
Claim 86 encompasses a broad genus of natural killer cells whose cytotoxicity against the cancer is enhanced by the antibody.
Claim 87 encompasses a broad genus of second antibody against tan antigen expressed on the surface of cells of cancer.
Claim 88 encompasses a broad genus of second antibody against an antigen expressed on the surface of an immune cell.
Claim 89 encompasses a broad genus of second antibody against an antigen express on the surface of a T-cell or a natural killer cell.
Claim 91 encompasses a broad genus of cell-based therapies.
Claim 92 encompasses a broad genus of inhibitor of one or more immune-checkpoint receptors or ligands.
Claim 93 encompasses a broad genus of inhibitors of CTLA-4, PD-1, PD-L1, TIM-3, LAG-3, BTLA, VIST, CD96, A2aR, A2bR, Arginase, CD39, CD73, IDO or TDO.
However, there does not appear to be an adequate written description in the specification as-filed of the essential structural feature that provides the recited function of treating or effecting prophylaxis of a cancer, activated by the antibody, inducing an immune response against the cancer, which is enhanced by the antibody, natural killer cells whose cytotoxicity against the cancer is enhanced by the antibody, an effector mediated cytotoxicity of the second antibody against the cancer is enhanced by the antibody.. The Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, ¶ 1 "Written Description" Requirement make clear that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the genus.
Possession is not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features. See University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895. Sufficient description to show possession of such a genus may be achieved by means of a recitation of a representative number of tumor infiltrating T-cells which are activated by the antibody; vaccines inducing an immune response against the cancer, which is enhanced by the antibody; natural killer cells whose cytotoxicity against the cancer is enhanced by the antibody; a second antibody against an antigen expressed on the surface of cells of cancer, whereby an effector mediated cytotoxicity of the second antibody against the cancer is enhanced by the antibody; a second antibody against an antigen expressed on the surface of an immune cell, cell-based therapy; an inhibitor of one or more immune-checkpoint receptors or ligands including CTLA-4, PD-1, PD-L1, TIM-3, LAG-3, BTLA, VISTA, CD96, A2aR, A2bR, Arginase, CD39, CD73, IDO and TDO, falling within the scope of the genus or of a recitation of structural features common to members of the genus, which features constitute a substantial portion of the genus. See Eli Lilly, 119F.3d at 1568, 43 USPQ2d at 1406. Applicant fails to provide representative species of the claimed genus.
Without a correlation between structure and function, the claim does little more than define the claimed invention by function. That is not sufficient to satisfy the written description requirement. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406 (“definition by function … does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is”).
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the written description inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116.). Consequently, Applicant was not in possession of the instant claimed invention. See University of California v. Eli Lilly and Co. 43 USPQ2d 1398.
Applicant is invited to point to clear support or specific examples of the claimed invention in the specification as-filed.
10. Claims 76-79 and 82-94 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as containing subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The instant claims are drawn to a large genus of methods which have not been developed yet to the point where a specific benefit exists in currently available form.
The claims are directed to the method of treating or effecting prophylaxis of a cancer including lung cancer comprising administering to a subject having or at risk of having the cancer anti-TIGIT antibody HuTIG1 comprising the CDRs of SEQ ID NOs: 11-16.
Factors to be considered in determining whether undue experimentation is required to practice the claimed invention are summarized In re Wands (858 F2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)). The factors most relevant to this rejection are the scope of the claim, the amount of direction or guidance provided, the lack of sufficient working examples, the unpredictability in the art and the amount of experimentation required to enable one of skill in the art to practice the claimed invention.
The specification discloses the expression of TIGIT was determined using HuTIG1-IgG1.AA antibody conjugated to Alexa647 dye. In all instances, background was determined using a modified Fluorescence Minus One (FMO) method in which all the fluorochromes used in the staining panel were added with the exception of the target antibody (i.e. HuTIG1-IgG1.AA). Rather, the target antibody was replaced with an IgG specific isotype control antibody of the same conjugation. FIG. 32B shows representative histograms of anti-TIGIT staining on tumor infiltrating lymphocytes (TILs) at various expression levels, shown in FIG. 32A. Light histograms represent modified FMO. Dark histograms represent HuTIG1-IgG1.AA staining [0238].
The specification fails to treat or prevent any cancer with the claimed anti-TIGIT antibody. Sundstrom et al (Cancer Immunology, Immunotherapy (2025) 74:272) teach that TIGIT has garnered interest as a next-generation anti-cancer immunotherapy target, yet its development has been marred by recent clinical failures. Sundstrom et al teach that human monotherapy trials with IgG1 anti-TIGIT have disappointed (see abstract). Sundstrom et al teach that while TIGIT is an appealing target, clinical trials have been mixed. Several companies have recently discontinued their anti-TIGIT projects. As of early 2025, Merck, Roche, BMS, and Novartis have either halted trials or terminated their agreements on IgG1 anti-TIGIT development. The primary reason for these terminations does not appear related to safety, but rather it is attributed to a disappointing lack of monotherapy effect on overall patient survival. There is a perception that anti-TIGIT is not likely to achieve the block buster monotherapy response of anti-PD-1 (page 1, right col, 2nd ¶).
Sundstrom et al that the choice of an IgG1 scaffold likely contributed to the lack of efficacy of early anti-TIGIT antibodies (page 2, left col., 1st ¶).
Sundstrom et al teach that in the CT26 colon cancer model mIgG2a anti-TIGIT monotherapy was ineffective [9] (Table 1). This implied that neither TIGIT blockade nor Fc-mediated effector functions have a strong anti-tumor effect in this model (page 3, 2nd ¶). Blockade of TIGIT was not a primary reason for the antitumor efficacy, as these tumors grew well in TIGIT-deficient mice. Rather, the effects were Fc mediated. The MC38 model was also evaluated by Dixon [10], where the authors did not observe a monotherapy effect of mIgG1 (see Table 1 and page 3, left col., 2nd ¶).
Sundstrom teaches that tiragolumab and vibostolimab were discontinued in late 2024 and belrestotug in early 2025. There are still ongoing phase 2/3 trials with domvanalimab that have shown promising results in lung, ovarian, and gastric cancers.
Sundstrom et al teach that the dual blockade of TIGIT and PD-1 did not significantly impact tumor growth, unless combined with the neoantigen vaccine.
In view of the lack of predictability of the art to which the invention pertains the lack of established clinical protocols for effective cancer therapies with anti-TIGIT antibodies, undue experimentation would be required to practice the claimed methods with a reasonable expectation of success, absent a specific and detailed description in applicant's specification of how to effectively practice the claimed methods and absent working examples providing evidence which is reasonably predictive that the claimed methods to treat cancer, commensurate in scope with the claimed invention.
Regarding in vivo methods which rely on generally unpredictable mechanisms, ''The amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art.'' In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). The “amount of guidance or direction'' refers to that information in the application, as originally filed, that teaches exactly how to make or use the invention. The more that is known in the prior art about the nature of the invention, how to make, and how to use the invention, and the more predictable the art is, the less information needs to be explicitly stated in the specification. In contrast, if little is known in the prior art about the nature of the invention and the art is unpredictable, the specification would need more detail as to how to make and use the invention in order to be enabling (MPEP 2164.03).'' The MPEP also states that physiological activity can be considered inherently unpredictable.
Further, in Rasmusson v. SmithKline Beecham Corp., 75 USPQ2d 1297-1303 (CAFC 2005), the court states “If mere plausibility were the test for enablement under section 112, applicants could obtain patent rights to “inventions” consisting of little more than respectable guesses as to the likelihood of their success. When one of the guesses later proved true, the 'inventor' would be rewarded the spoils instead of the party who demonstrated that the method actually worked. That scenario is not consistent with the statutory requirement that the inventor enable an invention rather than merely proposing an unproved hypothesis.”
The MPEP states that the issue of "correlation" is also dependent on the state of the prior art. In other words, if the art is such that a particular model is recognized as correlating to a specific condition, then it should be accepted as correlating unless the examiner has evidence that the model does not correlate. Even with such evidence, the examiner must weigh the evidence for and against correlation and decide whether one skilled in the art would accept the model as reasonably correlating to the condition. See MPEP 2164.02.
The burden of enabling the prevention of a disease (i.e. the need for additional testing) would be greater than that of enabling a treatment due to the need to screen those mammals susceptible to such diseases and the difficulty of proof that the administration of the drug was the agent that acted to prevent the condition. Further, the specification does not provide guidance as to how one skilled in the art would go about screening those patients susceptible to cancer within the scope of the presently claimed invention. Nor is sufficient guidance provided as to a specific protocol to be utilized in order to prove the efficacy of the presently claimed anti-TIGIT antibody in preventing cancer state.
Reasonable correlation must exist between the scope of the claims and scope of the enablement set forth. In view on the quantity of experimentation necessary the limited working examples, the nature of the invention, the state of the prior art, the unpredictability of the art and the breadth of the claims, it would take undue trials and errors to practice the claimed invention.
11. No claim is allowed.
12. The art made of record and not relied upon is considered pertinent to applicant's disclosure:
(i) Anderson et al., Preclinical characterization of AB154, a fully humanized anti-TIGIT antibody, for use in combination therapies. Cancer Immunology Research. Cancer Immunol Res (2019) 7 (2_Supplement): A124.
(ii) Anderson et al. Characterization of AB154, a Humanized, Non-Depleting α-TIGIT Antibody Undergoing Clinical Evaluation in Subjects with Advanced Solid Tumors. Poster P260, SITC 2019. November 7-10, 2019. National Harbor, Maryland .
(iii) Anderson et al. Characterization of AB154, a humanized anti-TIGIT antibody, for use in combination studies. AACR Cancer progress report, 79(13) suppl 1,| July 01 2019. Abstract 1557.
(iv) US 11820824 B2
The `824 patent claims methods of inhibiting binding of TIGIT to CD155 comprising contacting TIGIT with the anti-TIGIT antibody or antigen-binding fragment thereof.
(v) US 12415854 B2
The ``854 patent claims methods of treating cancer comprising administering to a subject having cancer an effective regime or a therapeutically effective amount of an anti-TIGIT antibody or antigen-binding fragment thereof that specifically binds to human TIGIT.
13. Any inquiry concerning this communication or earlier communications from the examiner should be directed to MAHER M HADDAD whose telephone number is (571)272-0845. The examiner can normally be reached on Monday-Friday from7:00AM to 4:30PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu, can be reached at telephone number 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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June 3, 2026
/MAHER M HADDAD/ Primary Examiner, Art Unit 1644
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