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 .
Priority
The instant application claims priority to US 63/085,612, filed September 30, 2020. A method of combining the anti-A2AR antibody with an agonist to a stimulatory receptor on an immune cell or cell therapy, as recited in claims 28 and 33, are not described in US 63/085,612. Thus, claims 28-33 are examined with the filing date of September 30, 2021.
Should Applicant disagree with the above analysis, they may point to the paragraphs in US 63/085,612 where an agonist to a stimulatory receptor on an immune cell or cell therapy, as recited in claims 28 and 33, are described.
Claim Objections
Claims 1-6, 9, 10, 14, 17, 26, and 40 are objected to because of the following informalities:
In claims 1-6, 9, 10, 14, 17, 26, and 40, the commas following “antibody” and “thereof” are unnecessary. The claims would read more smoothly if those commas were removed.
Appropriate correction is required.
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 26, 28-33 and 40 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 enablement requirement. The claim(s) contains 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.
Claim 26 recites a method of treating a cancer in a subject. Note that claim 26 is indefinite and being interpreted for the purpose of compact prosecution as requiring the administration of the antibody of claim 1. The instant Specification defines treatment on page 24 to include prophylaxis or prevented administration of the antibody. Thus, claim 26 is broad and encompasses administering the anti-A2AR antibody to any subject, regardless of whether or not the subject presently has cancer, for the treatment, encompassing prevention, of any cancer.
While the level of ordinary skill in the art is high, the level of unpredictability in the art is also high. Cancer development is understood to begin with genetic alteration and the resulting promotion and progression resulting in karyotypic instability and malignant growth; see Pitot et al. (Cancer. 73(3): 962-970; Published: August 1, 1993). The initiation, promotion, and progression of this genetic instability is multifactorial and can be brought about by a plethora of chemical, physical, or biologic carcinogens; see Pitot et al. Following the development of a single malignant cell, several enabling characteristics or hallmarks, including sustained proliferative signaling, avoidance of apoptosis, and immune evasion, further the progression of cancer; see Hanahan et al. (Cell. 144(5): 646-674; Published: March 4, 2011). While there exist several models for introducing genetic instability, there is currently no animal model to recapitulate the transition from immune surveillance to immune evasion and escape.
The nature of carcinogenesis clearly lies in genetic instability and, thus, a mode of cancer prevention should aim to reverse genetic instability. Yet, the nature of this invention aims to limit tumor progression while simultaneously addressing immune evasion through co-administration of an immune-oncology agent – thereby addressing enabling characteristics or hallmarks of cancer, but not the initiation itself.
Applicant has demonstrated the efficacy of the anti-A2AR antibody to block the action of adenosine, present in excess in the tumor microenvironment, in tumor cells (HEK293T or Expi293) and human and non-human primate T cells, in vitro; see Examples 5, 6, and 7. It is noted that anti-A2AR antibodies for the treating – not prevention or prophylaxis – of cancer is art enabled; see Leone et al. (Computational and Structural Biotechnology Journal. 13: 265-272; Published: April 8, 2015). However, Applicant has not demonstrated the claimed combination or compositions efficacy in preventing cancer. Nor has Applicant provided any guidance regarding preventative treatment, including preventative dosing regimens, how to identify a subject how would benefit from preventative treatment, or when to initiate preventative treatment.
The amount of experimentation to required to formulate such guidance would be enormous. One would have to demonstrate the efficacy of the combination or composition in several models inducing genetic instability across several different types of cancers and determine the appropriate regimen (doses and frequency) for use of the combination or composition in a preventative setting. Further, one would have to conduct population analysis to identify definitive characteristics which indicate that a subject is at risk of developing any cancer to a degree that would outweigh potential adverse effects of treatment with the claimed combination or composition.
Thus, considering the high level of skill in the art, the state of the art, the level of predictability, and the guidance and examples provided, the experimentation required to enable the full scope of the claimed invention would not be reasonable.
The claimed invention would be reasonably enabled for a method of treating cancer in a subject having cancer. Such language would exclude treatment as a preventative or prophylaxis for which the invention is not enabled.
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.
Claims 31 and 32 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 31 recites “sulfamonomethoxine 1” and “sulfamethizole 2”. It is unclear what the “1” and “2” indicate. Specifically, it is unclear how “sulfamonomethoxine 1” and “sulfamethizole 2” differs from sulfamonomethoxine and sulfamethizole. For the purpose of compact prosecution, “sulfamonomethoxine 1” and “sulfamethizole 2” are interpreted as sulfamonomethoxine and sulfamethizole.
In claim 32, the word “and” or “or” before “YH001” is missing. It is unclear whether all three agents are needed to meet claim 32 or simply one agent. For the purpose of compact prosecution, claim 32 is interpreted as requiring only one CTLA4 inhibitor.
Additionally, claim 32 contains the trademark/trade name “YH001”. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe a CTLA4 inhibitor and, accordingly, the identification/description is indefinite. At the time of filing the structure associated with the identifier YH001 was unknown to one of ordinary skill in the art and the instant Specification does not provide the structure of YH001. Thus, the name “YH001” is indefinite. Further, the parenthetical in “YH001 (Encure Biopharma)” makes unclear whether Encure Biopharma is required and exemplary. Note that while BMS-936559 in claim 31 is also a trade name, the identifier is not indefinite because Cogswell et al. (US 9,212,224 B2; Published: December 15, 2015) and Korman et al. (US 7,943,743 B2; Published: May 17, 2011) describe the structure associated with the identifier BMS-936559.
Double Patenting
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 § 2146 et seq. 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 filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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/apply/applying-online/eterminal-disclaimer.
Claims 1-4, 9, 14, 17-19, 26, 28, and 40 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 8-14, 27-29, 36, and 38 of copending Application No. 18/851,748 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding instant claim 1, copending claim 1 recites an anti-A2AR antibody comprising CDRs which comprise SEQ ID NOs: 90, 91, 10, 11, 92, 14, and 15 or 16. Instant SEQ ID NO: 8 is identical to residues 6-10 of copending SEQ ID NO: 90. Instant SEQ ID NO: 9 is identical to copending SEQ ID NO: 91 when copending X7 is H or N and X8 is H. Instant SEQ ID NO: 3 is identical to residues 3-10 of copending SEQ ID NO: 10. Instant SEQ ID NO: 30 is identical to copending SEQ ID NO: 92. Instant SEQ ID NO: 26 is identical to copending SEQ ID NO: 14. Instant SEQ ID NO: 31 is identical to both copending SEQ ID NOs: 15 and 16.
Regarding instant claims 2, 3, 9, and 40, copending claims 2 and 3 recites the sequences of the six CDRs with variable residues. Instant SEQ ID NOs: 1, 4, and 6 are identical to residues 6-10 of copending SEQ ID NOs: 1, 2, and 3, respectively. Instant SEQ ID NOs: 2, 5, and 7 are identical to copending SEQ ID NOs: 4, 6, and 8, respectively. Instant SEQ ID NO: 3 is identical to residues 3-10 of copending SEQ ID NOs: 10 and 11. Instant SEQ ID NOs: 25 and 28 are identical to copending SEQ ID NOs: 12 and 13, respectively. Instant SEQ ID NO: 26 is identical to copending SEQ ID NO: 14. Instant SEQ ID NOs: 27 and 29 are identical to copending SEQ ID NOs: 15 and 16, respectively.
Regarding instant claim 4, instant SEQ ID NO: 21, 22, and 23 are 100% identical to copending SEQ ID NO: 1, 2, and 3, respectively, and instant SEQ ID NOs: 12 and 15 are 100% identical to copending SEQ ID NOs: 10 and 11, respectively.
Regarding instant claim 14, copending claims 8-14 teach anti-A2AR antibodies comprising humanized framework regions as evidenced by copending Tables 3 and 4.
Regarding instant claims 17-19, copending claims 27-29 teach a polynucleotide encoding the antibody, an expression vector comprising the polynucleotide, and a recombinant cell comprising the polynucleotide.
Regarding instant claims 26 and 28, copending claims 36 and 38 teach method of treating cancer comprising administering the anti-A2AR antibody and an additional therapeutic agent.
Thus, copending claims 1-3, 8-14, 27-29, 36, and 38 read on instant claims 1-4, 9, 14, 17-19, 26, 28, and 40 in an anticipatory manner.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 29-32 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 8-14, 27-29, 36, and 38 of copending Application No. 18/851,748 in view of Mittal et al. ( Cancer Research. 74(14): 3652-3658; Published: July 15, 2014).
The teachings of Application No. 18/851,748 as related to claim(s) 1-4, 9, 14, 17-19, 26, 28, and 40, from which these claims depend are given previously in this Office action and are fully incorporated here.
While the copending claims teach a method of treating cancer comprising administering the anti-A2AR antibody in combination with an additional therapeutic agent, the copending claims do not exemplify the additional therapeutic agent. The copending claims do not teach administering the anti-A2AR antibody with an anti-PD-1 or anti-CTLA4 immunotherapy.
Regarding instant claims 29-32, Mittal et al. teaches that combination therapy of an A2AR inhibitor with an immune checkpoint inhibitor (anti-PD-1, anti-CTLA4, or anti-TIM3 antibody) in a C57BL/6 mice model reduced lung metastases; see Figure 1. Mittal et al. teaches that immunotherapies, including nivolumab and ipilumumab, have demonstrated remarkable clinical efficacy; see Introduction.
It would have been obvious to one of ordinary skill in the art to combined the A2AR inhibitor of the copending claims with immunotherapy, including nivolumab and ipilumumab, for the treatment of cancer. Because Mittal et al. demonstrates that the combinations were successful at reducing lung metastases and that nivolumab and ipilumumab are efficacious immunotherapies, one would have had a reasonable expectation of success treating cancer with a combination comprising the anti-A2AR antibody of the copending claims with nivolumab or ipilumumab.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art
before the effective filing date of the application, as evidenced by the references.
This is a provisional nonstatutory double patenting rejection.
Claim 33 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 8-14, 27-29, 36, and 38 of copending Application No. 18/851,748 in view of Harvey et al. (WO 2020/185739 A1; Published: September 17, 2020).
The teachings of Application No. 18/851,748 as related to claim(s) 1-4, 9, 14, 17-19, 26, 28, and 40, from which these claims depend are given previously in this Office action and are fully incorporated here.
While the copending claims teach a method of treating cancer comprising administering the anti-A2AR antibody in combination with an additional therapeutic agent, the copending claims do not exemplify the additional therapeutic agent. The copending claims do not teach administering the anti-A2AR antibody with an agonist to a stimulatory receptor.
Regarding instant claim 33, Harvey et al. teaches teaches a method of treating cancer comrpsing administering an agonist anti-ICOS antibody; see claim 1. Harvey et al. teaches that the agonist anti-ICOS antibody may be administered in combination with an anti-A2AR antagonist; see paragraph 00220.
It would have been obvious to one of ordinary skill in the art and one would have had a reasonable expectation of success administering the anti-A2AR antagonist of the copending claims with the anti-ICOS agonist antibody taught by Harvey et al. for the treatment of because Harvey et al. teaches that such a combination would inhibit tumor growth and the anti-A2AR antagonist and anti-ICOS agonist are each used for the treatment of cancer.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art
before the effective filing date of the application, as evidenced by the references.
This is a provisional nonstatutory double patenting rejection.
Subject Matter Free of the Art
Claims 5, 6, and 10 are 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.
Claims 5, 6, and 10 recite heavy and light chain variable regions comprising SEQ ID NOs: 35-40 and 41-43. SEQ ID NOs: 35-40 are not taught by the prior art nor claimed in copending Application No. 18/851,748. Additionally, the combination of framework regions in SEQ ID NOs: 35-40 are not taught in the prior art nor in copending Application No. 18/851,748.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KATHERINE ANN HOLTZMAN whose telephone number is (571)270-0252. The examiner can normally be reached Monday - Friday 7:30am - 5:00pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Janet Epps-Smith can be reached at (571)272-0757. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/KATHERINE ANN HOLTZMAN/Examiner, Art Unit 1646
/JULIET C SWITZER/Primary Examiner, Art Unit 1682