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
Response to Amendment
The amendment filed 7/15/2026 has been entered. Newly amended Claims 1-9 and 11-18 are pending in the application.
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied and constitute the complete set presently being applied to the instant application.
Claims 7 and 11-12 remain withdrawn. New Claims 13-18 are examined with Claims 1-6 and 8-9 as being directed to the same Group I.
Response to Applicant’s Arguments
Applicant argues the amendments to Claim 9 limit the scope of diseases to particular embodiments and no longer embrace prevention. The argument is fully considered but not persuasive. First, several broad genera are recited in Claim 9 in addition to the specific cancers, including autoimmune disorders and infectious disease. Second, the extant term “treating” includes curing as taught by applicant on Page 18, Line 21 of the specification. The particular capability of the compounds to cure the broad genera of complicated diseases is not enabled or addressed by amendment. The rejection is reissued as amended below.
Claim Objections
Claim 9 is objected to because “to the a subject” should read “to a subject”.
Claim Rejections - 35 USC § 112(b)
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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 18 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, 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.
First, Claim 18 recites “the pharmaceutical composition”. No pharmaceutical composition is recited in Claim 9. There is no clear antecedent basis. Second, “is used to” is not a clear limiting method step. Methods are required to recite positive method steps. See MPEP 2173.05(q) teaching it “is appropriate to reject a claim that recites a use but fails to recite steps”. Again, no steps are recited in Claim 18. Third, “a patient” is recited. It is unclear if this is a different patient from the subject of Claim 9 or some different individual. The following amendment is suggested to resolve the above issues: “wherein the subject has chronic hepatitis B (CHB), and wherein the administration improves T cell function in the subject.” Or applicant may amend the claim to recite specifically treating CHB if that is the intended meaning of the claim.
Claim Rejections - 35 USC § 112(a)
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 9, 13, 15-18 are 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 stabilizing or alleviating disease related to the activity or expression of PD-1/PD-L1 as well as the curing of infectious disease, does not reasonably provide enablement for the treatment (including curing) of autoimmune diseases and cancers. 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.
In In re Wands, 8 USPQ2d 1400 (1988), factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have need described. They are:
1. the nature of the invention,
2. the state of the prior art,
3. the predictability or lack thereof in the art,
4. the amount of direction or guidance present,
5. the presence or absence of working examples,
6. the breadth of the claims,
7. the quantity of experimentation needed, and
8. the level of the skill in the art.
The nature of the invention (1) and breadth of the claims (6)
The nature of the invention and breadth of Claims 9, 13, and 15-18 is the treatment of PD-1/PD-L1 associated cancers, infectious diseases, and autoimmune disorders and species thereof. Page 18, Line 21 of the specification provides that the term “treat” includes stabilize, alleviate, and cure.
The state of the prior art (2) and the predictability or lack thereof in the art (3)
Regarding treatment which includes curing, known methods of administering PD-1 and PD-L1 inhibitors often do not result in complete remission let alone a “cure” to cancer. Arakawa (Journal of Thoracic Oncology Vol. 15 No. 8. 1-2) reports on cases of NSCLC which recur as SCLC after treatment with the aforementioned therapeutic genus to which the claimed compounds of Formula I belong (Page 1, Para 1). It is therefore unclear how one of skill in the art would reasonably predict that administration of the compounds of Formula I would “cure” diseases known for recurring and developing resistance to the particular class of therapeutics.
Chronic lymphocytic leukemia (CLL) as recited in Claim 13 is not known to be curable with the agents claimed. Shadman (JAMA.2023;329(11):918-932) teaches “The only potential cure for CLL is allogeneic hematopoietic cell transplant, which remains an option after use of targeted agents” (Abstract). Shadman clearly precludes therapeutic agents from curative therapy of CLL.
With respect to autoimmune diseases, ulcerative colitis is recited in Claim 16 and has no known cure. Pravda (World J Gastroenterol 2025 July 14; 31(26): 108375. 1-13) highlights “the critical need for innovative research directions and methodologies to uncover the cause and develop a cure for this disease” (Abstract). Further, regarding rheumatoid arthritis (RA) of Claim 17, Yin (Current Opinion in Immunology 2025, 94:102561. 1-10) teaches several barriers to “curing” RA; “While treat-to-target paradigms and disease- modifying antirheumatic drugs ameliorate clinical outcomes, sustained drug-free remission (SDFR) or even cure remains elusive, underscoring the need for innovative strategies addressing underlying immunopathogenic mechanisms. Prolonged SDFR implies cure or eradication of disease, but there is no consensus definition of cure because it has rarely been contemplated in RA. Pathogenic immune circuit resilience, stromal hyperactivation, persistent structural abnormalities, and genetic susceptibilities constitute multifactorial barriers to a cure” (Abstract). Not only is a cure difficult to evaluate, but several pathological factors not addressed by applicant play a role in the ability of any therapy or agent to actually cure RA.
Several disease classes and specific embodiments are uncurable at the time of, or several years following, the effective filing date of the claims.
The amount of direction or guidance present (4) and the presence or absence of working examples (5)
Regarding curing, applicant offers an assay in Example A on Pages 39-40 demonstrating binding capacity of the compounds. However, applicant fails to explicate how this binding activity would serve to cure cancers or diseases which are known to be difficult to treat with multifactorial pathologies. Applicant fails to demonstrate through experiments or a mechanistic explanation how the compounds of Formula I could cure diseases associated with PD-1/PD-L1 activity—even those particular embodiments listed throughout Claims 9, 13, and 15-18.
The quantity of experimentation needed (7)
The quantity of experimentation needed is extremely difficult, novel, and undue experimentation; the ability of the claimed method to cure the listed cancers, among other complex autoimmune diseases, is nearly impossible to determine and not at all enabled by the experiments disclosed in the specifications of the application. It is further noted that the scope of compounds of Claim 1 is extremely broad, encompassing different tricycles bonded to other bi/monocycles which are structurally diverse and disparately substituted. The scope of diseases and compounds used in the methods are so broad that undue experimentation is required to practice the current scope of the claims to determine stabilizing, alleviating, or—if possible—curing capabilities of the methods.
The level of the skill in the art (8)
The level of skill in the art is high. However, treatment of cancers alone with PD-(L)1 inhibitors is extremely difficult and notably unpredictable. Curing autoimmune diseases is even more difficult. Even someone of the highest skill in the pharmaceutical arts could not predict which diseases might be cured or alleviated by the vast array of compounds as claimed.
Thus, the specification fails to provide sufficient support of the broad use of the Formula I compounds of the instant claims for the treatment of the claimed diseases.
Conclusion
Claims 9, 13, and 15-18 are rejected. Claim 9 is objected to. Claims 1-6 and 8 are allowable.
Claim 14 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Applicant’s amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 extension fee 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.
Inquiries
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Richard G. Peckham whose telephone number is (703)756-4621. The examiner can normally be reached 7:30am - 4:30pm.
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/RICHARD GRANT PECKHAM/Examiner, Art Unit 1627
/Kortney L. Klinkel/Supervisory Patent Examiner, Art Unit 1627
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