DETAILED ACTION
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 .
Status of the Application
Claims 15, 16, 20, 21, 23, 25, 27, 36, 38, 43, 47, 110-120 are pending. Based on election of species combination venetoclax (BH3 protein mimetic), MYLS22 (OPA1 inhibitor) and azacitidine (hypomethylating agent), claims 25, 119 and 120 are withdrawn.
Claims 15, 16, 20, 21, 23, 27, 36, 38, 43, 47, 110-118 are under current examination.
Amendment necessitated new claim rejection as set forth below.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 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 15, 16, 20, 21, 23, 27, 36, 38, 43, 47, 110-118 are rejected under 35 U.S.C. 112(a), as failing to comply with the written description requirement (NEW MATTER). 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. The subject matter of instant claims 15, 16, 20, 21, 23, 27, 36, 38, 43, 47, 110-118, filed on 05/01/2019 is not properly described in the application as filed. In particular, there was no indication in original specification as filed for (a) for a combination of a BH3 protein mimetic and an agent that inhibits expression and/or activity of OPA1 and HAX1;
b) none of the compounds of claims 20, 114 except venetoclax; claim 38, 118 except azacitidine
C) MYLS22, which was in fact discovered in 2020, i.e., after filing of the application;
and therefore, raise doubt as to possession of the claimed invention at the time of filing. Applicant is required to cancel the new matter in the reply to this Office Action.
Claims 15, 16, 20, 21, 23, 27, 36, 38, 43, 47, 110-118 are rejected under 35 U.S.C. 112(a), 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.
The instant claims are directed to a method of treating leukemia or MDS comprising administering “BH3 protein mimetic”, “agent that inhibits---CLPB, OPA1, HAX1 or combination thereof”, “hypomethylating agent”, “CDK9 inhibitor”. Said genus of compounds is not adequately defined in the instant specification other than:
“agent that inhibits---CLPB”= Formula I, Formula II, guanidinium hydrochloride;
“agent that inhibits--- OPA1”= MYLS22
“BH3 protein mimetic”=as in the instant claims 20 and 114,
“hypomethylating agent”, “CDK9 inhibitor” = as in claim 38 and 118
“agent that inhibits---HAX1”= No Example
The MPEP states that for a generic claim, the genus can be adequately described if the disclosure presents a sufficient number of representative species in examples that encompass the genus. (MPEP § 2163). A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that "only describe[d] one type of structurally similar antibodies" that "are not representative of the full variety or scope of the genus."). An adequate written description of a chemical invention also requires a precise definition, such as by structure, formula, chemical name, or physical properties, and not merely a wish or plan for obtaining the chemical invention claimed. See, e.g., Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 927, 69 USPQ2d 1886, 1894-95 (Fed. Cir. 2004) (The patent at issue claimed a method of selectively inhibiting PGHS-2 activity by administering a non-steroidal compound that selectively inhibits activity of the PGHS-2 gene product, however the patent did not disclose any compounds that can be used in the claimed methods. While there was a description of assays for screening compounds to identify those that inhibit the expression or activity of the PGHS-2 gene product, there was no disclosure of which peptides, polynucleotides, and small organic molecules selectively inhibit PGHS-2. The court held that "[w]ithout such disclosure, the claimed methods cannot be said to have been described."). If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. Furthermore, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co. the court stated:
"A written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as by structure, formula, [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials." Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) ("In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus ...") Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
Additionally, in Carnegie Mellon University v. Hoffman-La Roche Inc., Nos. 07-1266, -1267 (Fed. Cir. Sept. 8, 2008), the Federal Circuit affirmed that a claim to a genus described in functional terms was not supported by the specification’s disclosure of species that were not representative of the entire genus. The Guidelines for Examination of Patent Applications under the 35 USC § 112, first paragraph, “Written Description” Requirement”, published at Federal Register, Vol. 66, No. 4, pp. 1099-1111 outline the method of analysis of claims to determine whether adequate written description is present. The first step is to determine what the claim as a whole cover, i.e., discussion of the full scope of the claim. Second, the application should be fully reviewed to understand how applicant provides support for the claimed invention including each element and/or step, i.e., compare the scope of the claim with the scope of the description. Third, determine whether the applicant was in possession of the claimed invention as a whole at the time of filing. Each of these factors has been considered, with the most relevant factors discussed below. For each claim drawn to a genus, each of these factors is to be considered to determine whether there is disclosure of a representative number of species that would lead one skilled in the art to conclude that applicant was in possession of the claimed invention. Where skill and knowledge in the art is high, adequate written description would require fewer species to be disclosed than in an art where little is known; further, more species would need to be disclosed to provide adequate written description for a highly variable genus.
With respect to the scope of the claims, the full scope includes a method of treating leukemia or MDS comprising administering “BH3 protein mimetic”, “agent that inhibits---CLPB, OPA1, HAX1 or combination thereof”, “hypomethylating agent”, “CDK9 inhibitor”. For example, the instant claims do not include a structure of genus that “BH3 protein mimetic”, “agent that inhibits---CLPB, OPA1, HAX1 or combination thereof”, “hypomethylating agent”, “CDK9 inhibitor”. For instance, one compound OPA1 inhibitor, 3 compounds for CLPB, no example for HAX1 vs. millions of compounds and combinations thereof as claimed. Thus, the specification or instant claims fails to satisfy the functional definition of the genus of compounds. Further, the specification or instant claims do not include derivatives of any of agents or inhibitor that satisfies the functional definition of the genus. "The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention."). Problems satisfying the written description requirement for original claims often occur when claim language is generic or functional, or both. Ariad, 593 F.3d at 1349, 94 USPQ2d at 1171 ("The problem is especially acute with genus claims that use functional language to define the boundaries of a claimed genus. In such a case, the functional claim may simply claim a desired result, and may do so without describing species that achieve that result. But the specification must demonstrate that the applicant has made a generic invention that achieves the claimed result and do so by showing that the applicant has invented species sufficient to support a claim to the functionally-defined genus."
Comparison of the scope of the claims and the scope of the specification reveals that the scope of the claims is broader than that supported by the specification. There is guidance in the specification regarding:
“agent that inhibits---CLPB”= Formula I, Formula II, guanidinium hydrochloride;
“agent that inhibits--- OPA1”= MYLS22
“BH3 protein mimetic”=as in the instant claims 20 and 114,
“hypomethylating agent”, “CDK9 inhibitor” = as in claim 38 and 118
“agent that inhibits---HAX1”= No Example
However, the instant claims encompass millions of compounds and combinations thereof. There are no drawings, structural or empirical formulas that sufficiently define the genus of compounds that fulfill the instant function, to allow one to determine the scope of possible compounds.
Functional language at the point of novelty, as herein employed by applicants, is admonished in University of California v. Eli Lilly and Co. 43 USPQ2d 1398 (CAFC, 1997) at 1406: stating this usage does “little more than outline goal appellants hope the recited invention achieves and the problems the invention will hopefully ameliorate”. The CAFC further clearly states that “[A] written description of an invention involving a chemical genus, like a description of a chemical species, requires a precise definition, such as by structure, formula, [or] chemical name, of the claimed subject matter sufficient to distinguish it from other materials” at 1405 (emphasis added), and that “It does not define any structural features commonly possessed by members of the genus that distinguish from others. One skilled in the art therefore cannot, as one can do with a fully described genus, visualize or recognize the identity of the members of the genus. A definition by function, as we have previously indicated, does not suffice to define the genus…” at 1406 (emphases added).
Having analyzed the claims with regard to the written description guidelines, the specification does not disclose a representative number of compounds or relate the functional language of “BH3 protein mimetic”, “agent that inhibits---CLPB, OPA1, HAX1 or combination thereof”, “hypomethylating agent”, “CDK9 inhibitor” to a structure sufficient to describe said compounds. Thus, one of ordinary skill in the art would be led to conclude that applicants were not in possession of the invention commensurate with the scope of the claims, at the time the application was filed.
Claim Rejections - 35 USC § 112
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.
Claims 15, 16, 20, 21, 23, 27, 36, 38, 43, 47, 110-118 are 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, or for pre-AIA the applicant regards as the invention.
Claims 15, 16, 20, 21, 23, 27, 36, 38, 43, 47, 110-118 are indefinite as these claims recite compounds in terms of functional definition “BH3 protein mimetic”, “agent that inhibits---CLPB, OPA1, HAX1 or combination thereof”, “hypomethylating agent”, “CDK9 inhibitor”. The structure of such compounds is unclear from their functional definitions.
However, for compact prosecution these definitions are interpreted as
“agent that inhibits---CLPB”= Formula I, Formula II, guanidinium hydrochloride;
“agent that inhibits--- OPA1”= MYLS22
“BH3 protein mimetic”=as in the instant claims 20 and 114,
“hypomethylating agent”, “CDK9 inhibitor” = as in claim 38 and 118.
Dependent claims do not cure above deficiencies and are also indefinite.
Appropriate correction required.
Response to Arguments
Applicant’s remarks and amendment, filed on 10/15/2025, have been fully considered but not found persuasive.
Applicant argued over written description that BH3 protein mimetics are art recognized class of molecules and specification provides examples with veneotoclax and AMG-176. Applicant argued that specification specifies CLPB inhibitors including anti-CLPB antibodies, CLPB antisense, small molecule inhibitors, e.g., formula I and II and guanidinium hydrochloride with example 4 showing CLPB function depletion at molecular level and experiments showing CLPB inhibition can enhance the efficacy of venetoclax and azacytidine combined treatment. Applicant argued that specification provides OPA1 inhibitors including antiOPA1 antibodies, OPA antisense and small molecule inhibitors, e.g., MYLS22 and examples how loss of OPA1 function leads to sensitizing AML cells to apoptosis. Applicant argued that although no HAX1 are known at the time of the present application applicant provided HAX1 inhibitors including antiHAX1 antibodies, HAX1 antisense molecules and how HAX1 inhibition may lead to sensitizing AML cells to apoptosis. Applicant argued that hypomethylating agents, CDK9 are art recognized. Applicant argued on 112b rejection similar to 112a that structure is apparent from functional definition.
This is not found persuasive and the instant claims stand rejected. This is because (1) the instant claims are not just drawn to compounds but a combination and effect of such combination on leukemia and MDS; (2) Just providing two examples of BH3 protein mimetic, veneotoclax and AMG-176 vs. claiming every BH3 protein mimetic (in thousands), known or yet to be discovered and their combinations, on effects such as patients resistant to BH3 protein mimetic and treating leukemia and MDS does not fulfill the requirement of representative species and their effect on treatment as claimed; (3) Further, the instant application fails to provide common structural feature connecting BH3 protein mimetic of varied structure and/or representative species examples from each class and function in the combination, such as patients developing resistance etc.; (4) Similarly by just providing three examples of CLPB inhibitors, formula I and II and guanidinium hydrochloride vs. claiming every CLPB inhibitor, known or yet to be discovered and their combinations, does not fulfill the requirement of representative species and their effect on treatment as claimed; (5) specifying anti-CLPB antibodies, CLPB antisense, small molecule inhibitors without actually providing sequences or structure of such small molecule inhibitors, is just a functional definition or statement that does not satisfy representative species and written description requirement; (6) providing experiments at molecular level how CLPB function depletion at molecular level can enhance the efficacy of venetoclax and azacytidine combined treatment, does not support that every CLPB inhibitor, structurally different will function with venetoclax and azacytidine; (7) Importantly, the instant claims are not drawn to simply a combination of CLPB, azacitidine and ventoclax but to any combination with BH3 protein mimetic etc.; (8) The Examiner did not raise the question of enablement that whether CLPB function depletion at molecular level can enhance the efficacy of venetoclax and azacytidine combined treatment but to written description that the instant application does not provide representative examples of species of CLPB inhibitors and millions of combinations as claimed; (9) Similarly by just providing one examples of OPA1 inhibitor, MYLS22 vs. claiming OPA1 inhibitor, yet to be discovered and their combinations, does not comply with the requirement of representative species and their effect on treatment as claimed; (10) the Examiner also notes that MYLS22 was actually the first OPA1 inhibitor and was discovered after the filing of the instant application. Additionally, applicant provided no generic structure or any other inhibitor of OPA1, supporting that the instant application fails to comply with the written description requirement; (11) applicant agreed that no HAX1 are known at the time of the present application and at the same time argued that somehow providing functional definition and how HAX1 inhibition may lead to sensitizing AML cells to apoptosis supports written description requirement. Contrary to applicant’s, this in fact shows that application does not comply with written description requirement. By just providing how silencing a gene may lead to sensitizing AML cells to apoptosis does not provide any support that instant application complies with written description with respect to representative number of species of HAX1 inhibitors, especially, in light of the fact that no inhibitor of HAX1 was known at the time of filing of the instant application; 12) With regards to applicant’s argument that hypomethylating agents, CDK9 are art recognized is not found persuasive. This is because even if there are some compounds are known under categories of hypomethylating agents, CDK9 does not mean that these compounds will function similarly with BH3 protein mimetic and combination with CLPB1 or OPA1 or HAX1; 13) With regards to applicant’s same argument over functional definition and unclear structure is also not found persuasive. This is because applicant has not provided any genus of structure that matches such functional definition.
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 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.
Conclusion
No Claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PANCHAM BAKSHI whose telephone number is (571)270-3463. The examiner can normally be reached M-Thu 7-4.30 EST.
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/PANCHAM BAKSHI/Primary Examiner, Art Unit 1623