Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
The Amendment filed 2/26/2026 in response to Office Action of 1128/2025, is acknowledged and has been entered. Claims 1-11, 16-18, 20, 22, and 24-25 are now pending. Claims 1, 6, 16, 18, 24, and 25 are amended.
The 35 U.S.C. 112(a) written description rejection is withdrawn in view of amendments.
Claims 1-11, 16-18, 20, 22, and 24-25 are currently being examined.
Priority
Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e).
Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
Maintained Rejection
(Amendments addressed)
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(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.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
Claims 1-11, 16-18, 20, 22, and 24-25 remain rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating tumor or cancer comprising administering an anti-PD-1 antibody and an anti-HER2 antibody-drug conjugate or an anti-CTLA-4 antibody, does not reasonably provide enablement for treating tumor or cancers comprising administering an anti-PD-1 antibody and any therapeutic agent. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
Breadth of the claims: The claims are drawn to a method for treating a tumor or cancer, comprising administering to a patient in need an effective amount of an anti-PD-1 antibody and a therapeutic agent, wherein the therapeutic agent is an anti-VEGF antibody, an anti-CTLA-4 antibody, an anti-HER2 antibody, an anti-CD20 antibody, an anti-Trop2 antibody, an anti-HER2 antibody-drug conjugate, and an anti-Trop2 antibody-drug conjugate. Claim 24 is drawn to the pharmaceutical composition comprising an anti-PD-1 antibody and a therapeutic agent, wherein the anti-VEGF antibody, an anti-CTLA-4 antibody, an anti-HER2 antibody, an anti-CD20 antibody, an anti-Trop2 antibody, an anti-HER2 antibody-drug conjugate, and an anti-Trop2 antibody-drug conjugate. Thus, the claims are drawn to the combination of an anti-PD-1 antibody and any of the agents listed above.
State of the Art: It is well known that the art of anti-cancer therapy is highly unpredictable. Lopez et al (Combine and conquer: challenges for targeted therapy combinations in early phase trials. Nat Rev Clin Oncol. 2017;14(1):57-66) teaches that the challenges include finding the best combination to explore and that the scale of biological complexity of the mechanisms of resistance to targeted treatment is large and requires several novel approaches. Lopez also teaches that there are hundreds of targeted treatments and the number of combinations trials outweigh the number of patients who can be entered into trials to evaluate them. Lopez also teaches that combination therapy in clinic results into issues including toxicity, pharmacokinetic interactions and finding the correct timing and context of using these combinations [pg 3, 2nd paragraph] Furthermore, Gura (Science, 1997, 278:1041-1042) teaches that researchers face the problem of sifting through potential anticancer agents to find ones promising enough to make human clinical trials worthwhile and teach that since formal screening began in 1955, many thousands of drugs have shown activity in either cell or animal models that only 29 have actually been shown to be useful for chemotherapy See p. 1041, see 1st and 2nd para. Furthermore, Kaiser (Science, 2006, 313: 1370) teaches that 90% of tumor drugs fail in patients. See 3rd col., 2nd to last para. Chames et al (British J. of Pharmacology, 2009, 157, 220-233) teach that there are several challenges to development therapeutic antibodies. These challenges include functional limitations such as inadequate pharmacokinetics, tissue accessibility and impaired interactions with the immune system (Abstract). Additionally, Chames teaches several limitations of therapeutic antibodies such as affinity between the antibody and its antigen, competition with patient’s IgG, and efficiency issues in triggering the immune response (pages 224-225). More specifically, de Miguel M et al (Clinical Challenges of Immune checkpoint inhibitors. Cancer Cell. 2020 Sep 14;38(3):326-333) teaches the complication and challenges surrounding immune checkpoint inhibitors, including toxicity and efficacy. [whole document] Thus, it is unpredictable to claim that an anti-PD-1 antibody can be combined with any therapeutic agent, including other therapeutic antibodies.
Presence or Absence of Examples: The specification discloses in Example 1: method for preparing antibodies, these antibodies include, antibody A (anti-PD-1 antibody, see paragraph 0049 of published specification], antibody B (anti HER2 antibody, see paragraph 0045 of published specification), and antibody C (anti-CTLA-4 antibody). Example 3 discloses the combination of an anti-PD-1 antibody with HER-2 Antibody drug conjugate for the treatment of human gastric cancer cells. Example 4 discloses the combination of anti-PD-1 antibody and anti-CTLA-4 antibody for the treatment of cancer cells. The instant specification does not disclose any other examples of any other therapeutic agent, or any other target antibody, other than an anti-HER2 antibody or anti-CTLA-4, in combination with instantly claimed anti-PD-1 antibody.
Predictability: Reasonable correlation must exist between the scope of the claims and scope of enablement set forth, and it cannot be reasonably predicted that administration of an anti-PD-1 antibody can be combined with any other therapeutic agent and treat cancer or tumors.
Quantity of Experimentation: Undue experimentation would be required to determine which therapeutic agent is administered with the claimed anti-PD-1 antibody to treat tumor and, as claimed. MPEP 2164.01 recites that “The test of enablement is not whether any experimentation is necessary, but whether, if experimentation is necessary, it is undue. In re Angstadt, 537 F.2d 498, 504, 190 USPQ 214, 219 (CCPA 1976)”. The experimentation needed to practice this method is undue and unreasonable as it requires determining exactly which agent can be combined with the claimed anti-PD-1 antibody, and is not routine in the art as these diseases are unrelated and comprise various subgroups within each disease state. A person skilled in the art will not be able to use the invention without undue experimentation. (In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988))
Accordingly, the instant claims do not comply with the enablement requirement of §112, since to practice the invention claimed in the patent a person of ordinary skill in the art would have to engage in undue experimentation, with no assurance of success.
Response to Arguments
Applicants amended the claim to specify the therapeutic agent but did not provide any argument that the one of skilled in the art would have been enabled to combine an anti-PD-1 antibody with any anti-VEGF antibody, any anti-CD20 antibody, any anti-Trop2 antibody, or any anti-Trop2 antibody-drug conjugate. As noted above, anti-cancer therapy is highly unpredictable. The prior art demonstrates the complications and challenges to find combinations, including antibody combinations. These challenges include: toxicity, interactions and appropriate dosing regimens. Furthermore, Kaiser (Science, 2006, 313: 1370) teaches that 90% of tumor drugs fail in patients. See 3rd col., 2nd to last para. Chames et al (British J. of Pharmacology, 2009, 157, 220-233) teach that there are several challenges to development therapeutic antibodies. Chames also teaches several limitations of therapeutic antibodies such as affinity between the antibody and its antigen, competition with patient’s IgG, and efficiency issues in triggering the immune response (pages 224-225). More specifically, de Miguel M et al (Clinical Challenges of Immune checkpoint inhibitors. Cancer Cell. 2020 Sep 14;38(3):326-333) teaches the complication and challenges surrounding immune checkpoint inhibitors, including toxicity and efficacy.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/SARAH A ALSOMAIRY/Examiner, Art Unit 1646
/Zachariah Lucas/Supervisory Patent Examiner, Art Unit 1600
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