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 Claims
Applicant’s election for continued examination without traverse of the species of antibody 6G11, SEQ ID NOs: 171-176, 23, and 27, filed in the reply on 06/02/2025 is acknowledged.
Currently claims 3, 5-16, 18-20, 22, and 27-28 are currently pending and under examination.
Priority
Acknowledgment is made of applicant's claim for foreign priority based on an application filed in Europe on 07/17/2019. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Therefore, the effective filing date for the purpose of examination is 07/17/2019.
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 5, 7-10, 13-20, 22, and 28, 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 5 recites a patient having tumor infiltrating lymphocytes “with medium or high PD-1 expression.” These are relative terms as it is unclear what constitutes “medium” or “high” expression of PD-1. The metes and bounds of the claim are unclear rendering the scope of the claim unascertainable. Claims 7-10, 13-20, 22, and 28 depend from claim 5 but do not remedy the deficiencies introduced by claim 5 and are also therefore rejected under 35 U.S.C. 112(b) 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.
Regarding claims 16, and 18-20, the phrase “and/or” renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). Furthermore, the phrase “full-size antibody, a chimeric antibody, a single chain antibody, and an antigen-binding fragment thereof retaining the ability to bind an Fc receptor via its Fc region” in claim 18 renders the claim indefinite because standard antigen binding fragments (Fab) and single chain antibody fragments (scFv) lack an Fc region and are thereby unable to bind an Fc receptor via its Fc region. This wording renders the scope of the claim unascertainable and the metes and bounds of the claim unclear. See MPEP § 2173.05(d).
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 14 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 13 limits to solid cancer, but claim 14 which depends from claim 13 has a list that includes Hodgkin lymphoma and PMBCL which are hematologic malignancies. Therefore, dependent claim 14 expands rather than limiting the scope of claim 13. Applicant may cancel the claim, amend the claim to place the claim in proper dependent form, rewrite the claim in independent form, or present a sufficient showing that the dependent claim complies with the statutory requirements.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 6 is rejected under 35 U.S.C. 101 because the claimed invention is directed to a law of nature without significantly more. The claim recites “wherein medium or high PD-1 expression indicates that the patient will benefit from combined treatment”. This judicial exception is not integrated into a practical application because the claim does not rely on or use this law of nature in any further steps. The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception because it recites measuring PD-1 at a high level of generality, and includes any and all methods of doing so. However, this does not add significantly more to the exception, as measuring PD-1 was standard in the field at the time the application was filed (see Chen et al., Morris et al., and Yanaba et al).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
1. Claims 3, 5, 13-20, 22, and 27-28 are rejected under 35 U.S.C. 103 as being unpatentable over Dahan et al. (Cancer Cell, 28(3):285-295, 2015, cited on pg. 1 of IDS filed on 09/30/2022) in view of Arlauckas et al. (Sci Transl Med, 9(389):1-20, 2017, cited on pg. 1 of IDS filed on 09/30/2022), and Roghanian et al. (Cancer Cell, 27(4):273-488, 2015, cited on pg. 3 of IDS filed on 09/30/2022).
Regarding claims 3 and 5, Dahan teaches that antitumor activity of antibodies to PD-1/PD-L1 is modulated by Fc gamma receptor (FcγR) engagement (Summary). Specifically, they report that anti-PD-1 antibody tumor activity in vivo is compromised by FcγR binding while anti-PD-L1 antibodies showed augmented anti-tumor activity upon FcγR binding to its Fc regions (Summary). Therefore, Dahan identifies the problem that FcγR interactions diminish anti-PD-1 efficacy in vivo and motivates skilled artisans to address FcγR-mediated interference when using anti-PD-1 therapy.
Furthermore, Arlauckas provides mechanistic confirmation using in vivo imaging which showed that tumor-associated macrophages capture anti-PD-1 antibodies from PD-1 expressing CD8 T cells via Fcγ receptors thereby reducing drug on target and overall efficacy (Summary). Arlauckas thus reinforces the concept that macrophage FcγR dependent processes underlie resistance to anti-PD-1 therapy and that blocking FcγR-mediated effects would preserve PD-1 high T cells during treatment.
In addition, Roghanian teaches FcγRIIb (CD23B) antibodies as a therapeutic class that overcomes resistance to cancer therapy treatment with rituximab and enhances antitumor responses (Summary). Roghanian specifically provides human IgG1 Fc-competent antibodies that bind FcγRIIb (Results) and thus supplies a known, clinically relevant antibody tool against FcγRIIb to pair with other antibodies to improve antitumor efficacy (Significance).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used the findings of Dahan and Arlauckas which teach FcγR engagement as detrimental for anti-PD-1 antibody activity against tumors and combine it with the anti-FcγRIIb antibodies taught by Roghanian which showed the antitumor efficacy of blocking FcγR-mediated processes with anti- FcγRIIb antibodies. One of ordinary skill in the art would have been motivated to combine anti-PD-1 antibody tumor therapy as taught by Dahan and Arlauckas with anti-FcγRIIb antibodies taught by Roghanian with a reasonable expectation of success as the teachings discussed above show that blocking FcγR mediated processes improve and enhance long term anti-PD-1 cancer therapeutic efficacy. Thus, the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art at the time the invention was made.
Regarding claims 13-15, the cited references address solid tumors (Dahan, Arlauckas), lymphomas (Roghanian), and general oncologic use of anti-PD-1 and anti-FcγRIIb antibodies. Selecting particular tumor types as recited in claims 13-15 reflects obvious application of anti-PD-1 and anti-FcγRIIb antibody combination therapy to known PD-1 responsive tumors identified in Dahan/Arlauckas and the broader PD-1 literature.
Regarding claims 16, and 18-20, and 22 the use of human/humanized IgG (i.e. IgG1, IgG4) and Fc-competent antibodies that bind activating FcγRs are routine and well-known formats as taught in the art cited above. Dahan and Arlauckas teach the use of clinically relevant anti-PD-1 (IgG4) antibodies and discuss Fc engagement (Results) and Roghanian teaches human IgG1 Fc-binding anti-FcγRIIb antibodies (Results).
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Regarding claims 27-28, Roghanian teaches human anti- FcγRIIb antibodies with defined CDRs/variable regions and experimental disclosure sufficient to render variants and antibody clones to FcγRIIb as recited in instant claims 27-28 as routine. Furthermore, the elected variable region and CDRs of species 6G11 is disclosed in the prior art (see below) with 100% sequence identity. Heavy chain variable region SEQ ID NO: 23 encompassing CDRs 171-173 is disclosed by SEQ ID NO: 12 in Cragg et al. (WO2012022985, cited on pg.2 of IDS filed on 11/16/2022).
Light chain variable region SEQ ID NO: 27 encompassing CDRs 174-176 is disclosed by SEQ ID NO: 27 in Frendeus et al. (GB2526139, cited on pg. 2 of IDS filed on 11/16/2022).
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2. Claims 6-12 are rejected under 35 U.S.C. 103 as being unpatentable over Dahan, Arlauckas, and Roghanian as applied to claims 3, 5, 13-20, 22, and 27-28 above, and further in view of Zelba et al. (Cancer Immunol Immunother., 67(12):1845-1851, 2018).
Zelba teaches quantifying PD-1 molecules per cell by flow cytometry using the anti-PD1 antibody EH12.2H7 (Materials and Methods) thereby enabling better stratification of patients by PD-1 level (Abstract, Results). Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used the findings of Dahan and Arlauckas which teach FcγR engagement as detrimental for anti-PD-1 antibody activity against tumors, combine it with the anti-FcγRIIb antibodies taught by Roghanian which showed the antitumor efficacy of blocking FcγR-mediated processes with anti- FcγRIIb antibodies and implement this with the teachings of Zelba’s quantification method to measure PD-1 expression with a known anti-PD-1 antibody flow cytometry method. One of ordinary skill in the art would have been motivated to do so as selection of a percentage of tumor infiltrating T lymphocytes (TILs) and molecule per cell threshold as recited in instant application claim 11 constitutes routine optimization of a known analytic method to enhance selection of patients most affected by the FcγR-mediated problem identified by Dahan and Arlauckas. Thus, the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art at the time the invention was made.
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.
1. Claims 3, 5-16, 18-20, 22, and 27-28 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, and 3-14 of U.S. Patent No. 12371498 (‘198) in view of view of Dahan et al., and Arlauckas et al., and further in view of Zelba et al. (cited above).
Patent ‘198 teaches the combined use of 1) an antibody molecule that specifically binds FcγRIIb via its Fab region, and 2) an immune cell depleting or deactivating antibody molecule that specifically binds to a receptor present on an immune cell that suppresses anti-cancer immunity and which immune cell depleting or deactivating antibody molecule has an Fc region that binds to at least one activating Fcγ receptor, in treatment of FcγRIIb-negative cancers. However, Patent ‘198 does not teach the combination of this anti FcγRIIb antibody with an anti-PD-1 antibody nor measure the PD-1 expression as recited in instant application claims. The teachings of Dahan, Arlauckas and Zelba as discussed previously, address these deficiencies.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used the findings of Dahan and Arlauckas which teach FcγR engagement as detrimental for anti-PD-1 antibody activity against tumors and combine it with the anti-FcγRIIb antibodies taught by Patent ‘198. One of ordinary skill in the art would have been motivated to combine anti-PD-1 antibody tumor therapy as taught by Dahan and Arlauckas with the anti-FcγRIIb antibody as taught by Patent ‘198 with a reasonable expectation of success as the teachings discussed above show that blocking FcγR mediated processes improve and enhance long term anti-PD-1 cancer therapeutic efficacy. It would also have been obvious to take this combination anti-PD-1/ anti-FcγRIIb antibody and combine it with the teachings of Zelba’s quantification method to measure PD-1 expression with a known anti-PD-1 antibody flow cytometry method. One of ordinary skill in the art would have been motivated to do so as selection of a percentage of tumor infiltrating T lymphocytes (TILs) and molecule per cell threshold as recited in instant application claim 11 constitutes routine optimization of a known analytic method to enhance selection of patients most affected by the FcγR-mediated problem identified by Dahan and Arlauckas.
Thus, the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art at the time the invention was made.
2. Claims 3, 5-16, 18-20, 22, and 27-28 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. 11623005 (‘005) in view of Dahan et al., and Arlauckas et al., and further in view of Zelba et al. (cited above) for the same reasons discussed above.
3. Claims 3, 5-16, 18-20, 22, and 27-28 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 12344673 (‘673) in view of Dahan et al., and Arlauckas et al., and further in view of Zelba et al. (cited above) for the same reasons discussed above.
4. Claims 3, 5-16, 18-20, 22, and 27-28 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-32 of U.S. Patent No. 10525129 (‘129) in view of Dahan et al., and Arlauckas et al., and further in view of Zelba et al. (cited above) for the same reasons discussed above.
5. Claims 3, 5-16, 18-20, 22, and 27-28 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 21-25 of copending Application No. 18/177,050 (‘050) in view of Dahan et al., and Arlauckas et al., and further in view of Zelba et al. (cited above) for the same reasons discussed above. This is a provisional nonstatutory double patenting rejection.
6. Claims 3, 5-16, 18-20, 22, and 27-28 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 3-7, 11-18 of copending Application No. 18/008,141 (‘141) in view of Dahan et al., and Arlauckas et al., and further in view of Zelba et al. (cited above) for the same reasons discussed above. This is a provisional nonstatutory double patenting rejection.
7. Claims 3, 5-16, 18-20, 22, and 27-28 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-5, 10, 19, 21, 27, 37, and 51 of copending Application No. 19/031,514 (‘514) in view of Dahan et al., and Arlauckas et al., and further in view of Zelba et al. (cited above) for the same reasons discussed above. This is a provisional nonstatutory double patenting rejection.
8. Claims 3, 5-16, 18-20, 22, and 27-28 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2-3, 5-7, 10, 15, 17, 21, 25-28 of copending Application No. 18/844,583 (‘583) in view of Dahan et al., and Arlauckas et al., and further in view of Zelba et al. (cited above) for the same reasons discussed above. This is a provisional nonstatutory double patenting rejection.
9. Claims 3, 5-16, 18-20, 22, and 27-28 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 6-19, 40-44 of copending Application No. 18/281,530 (‘530) in view of Dahan et al., and Arlauckas et al., and further in view of Zelba et al. (cited above) for the same reasons discussed above. This is a provisional nonstatutory double patenting rejection.
Conclusion
No claim is allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DENNIS GEORGE whose telephone number is (571)270-0340. The examiner can normally be reached M-F 8:30am - 5pm EST.
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/DENNIS GEORGE/Examiner, Art Unit 1644
/DANIEL E KOLKER/Supervisory Patent Examiner, Art Unit 1644
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