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 amendment filed on 03/06/2026 is acknowledged. Following the amendment, claims
6, 16, 18-20, and 22 are currently amended. Claims 30-34 are added. Claims 3, 5-16, 18-20, 22, 27-28, and 30-34 are currently pending and under examination.
Election/Restrictions
In Applicant’s response (Remarks dated 06/02/2025) to the election of species requirement, Applicant identified the elected 6G11 species as comprising CDR SEQ ID NOs: 171-176 and SEQ ID NOs: 23 and 27. The Examiner relied on that express identification and searched SEQ ID NO: 27 in preparing the prior Office Action dated 10/09/2025. However, upon further review, the Specification and claim 28 identify the variable region sequences corresponding to 6G11 as SEQ ID NOs: 23 and 47. To clarify the record and ensure examination of the disclosed elected species, the Examiner additionally searched SEQ ID NO: 47. Both SEQ ID NO: 27 and SEQ ID NO: 47 produced 100% sequence matches to prior art predating the effective filing date. Accordingly, Applicant’s erroneous identification of SEQ ID NO: 27 does not alter the patentability determination or the prior 35 U.S.C. 103 rejection.
Claim Rejections - 35 USC § 112
112(a) Rejection
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 6 and 34 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 written description requirement. The claims contain 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 applications subject to pre-AIA 35 U.S.C. 112, the inventors, at the time the application was filed, had possession of the claimed invention.
Regarding claim 6, the newly added limitation requires a diagnostic test comprising contacting a patient with both the anti FcγRIIb antibody, the anti PD-1 antibody and determining PD-1 expression on the patient’s tumor infiltrating T lymphocytes (TILs). The Specification describes the diagnostic test as determining PD-1 expression, such as by flow cytometry or immunohistochemistry using an anti PD-1 detection antibody (paragraph 0059, pg. 5). It does not describe contacting a patient sample with both claimed therapeutic antibodies as part of that diagnostic test. The experiments employing both antibodies instead concern phagocytosis or therapeutic efficacy. Accordingly, the original disclosure does not reasonably convey possession of the newly claimed diagnostic method. The originally filed claim likewise recited only determining PD-1 expression, not contacting the sample with both antibodies.
Regarding claim 34, the Specification discloses 32,951 PD-1 molecules per cell as the average expression of an experimentally generated medium PD-1 Jurkat cell population (Example 1, pg. 20). The Specification expressly uses approximately 15,500 molecules per cell – the bottom 5% cutoff of that population – as the lower limit defining medium or high expression (paragraph 0161, pg. 20). The Specification therefore does not reasonably convey possession of 32,951 molecules per cell as the newly claimed open ended patient selection threshold.
112(b) Rejection
Applicant’s arguments, see pg. 9, filed 03/06/2026, with respect to rejection of claims 5, 7-10, 13-20, 22, and 28 under 35 U.S.C. 112(b) have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground of rejection is made in view of Applicant’s amendment filed 03/06/2026.
Claims 6, 30-31, and 34 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.
Regarding amended claim 6, the claim is directed to determining whether a patient will benefit from combined treatment but merely requires determining PD-1 expression. The claim does not identify what expression level, percentage of cells, or other result indicates that the patient will benefit. It is also unclear how contacting the sample with the first anti FcγRIIb antibody contributes to determining PD-1 expression and whether the second anti PD-1 antibody serves as a therapeutic antibody, a detection reagent, or both. The relationship between the contacting step, the expression determination, and the determination of treatment benefit is therefore unclear.
Regarding claims 30-31, the language stating that “the first antibody molecule and the second antibody molecule is selected” does not clearly establish whether each antibody is independently selected from the listed alternatives or whether both antibodies must possess the same listed format or antibody type.
Regarding claim 34, “at least 32,951 molecules/cell” does not specify whether the value must be present on every tumor-infiltrating T lymphocyte, on a particular percentage of such cells, or as an average or median of the tested population. Thus, the claim does not clearly define when the patient satisfies the recited medium or high PD-1 expression level.
112(d) RejectionApplicant’s arguments, see pg. 10, filed 03/06/2026, with respect to the rejection of claim 14 under 35 U.S.C. 112(d) have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground of rejection is made in view of further review of claim 7.
Claim 7 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 claim 5 upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 5 already requires tumor infiltrating T lymphocytes having medium or high PD-1 expression. The Specification identifies tumor infiltrating T lymphocytes as tumor infiltrating CD3 positive lymphocytes. Therefore, claim 7’s additional recitation that the T lymphocytes are CD3 positive merely restates a characteristic already required by claim 5 and does not impose a further limitation. 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
Applicant’s arguments, see pg. 10, filed 03/06/226, with respect to rejection of claim 6 under 35 U.S.C. 101 have been fully considered and are persuasive. The rejection of 10/09/2025 has been withdrawn.
Claim Rejections - 35 USC § 103
Applicant's arguments filed 03/06/2026 have been fully considered but they are not persuasive.
Claims 3, 5, 13-20, 22, 27-28, and 30-33 are rejected under 35 U.S.C. 103 as being unpatentable over Dahan et al. in view of Arlauckas et al. and Roghanian et al. (cited in Office Action dated 10/09/2025). Claims 6-12, and 34 are further rejected in view of Zelba et al. (cited in Office Action dated 10/09/2025).
Dahan teaches that Fcγ receptor engagement compromises the antitumor activity of Fc competent anti PD-1 antibodies and that anti PD-1 activity is improved in the absence of FcγRIIb. Arlauckas further demonstrates that tumor associated macrophages remove Fc competent anti PD-1 antibodies from PD-1 positive CD8 positive TILs through Fcγ receptor interactions and expressly indicates that anti PD-1 therapy may be improved by blocking those interactions. Roghanian teaches known antagonistic, Fc competent human IgG1 antibodies that specifically bind FcγRIIb through their Fab regions and retain Fcγ receptor binding through their Fc regions.
Accordingly, one of ordinary skill would have been motivated to administer or provide an Fc competent anti FcγRIIb antibody with an Fc competent anti PD-1 antibody to block the FcγRIIb mediated macrophage processes identified by Dahan and Arlauckas. This would preserve anti PD-1 antibody on PD-1 positive antitumor T cells and improve anti PD-1 activity. Roghanian is relied upon for a known antibody tool capable of implementing the FcγRIIb blockade, not for an identical tumor cell mechanism.
A person of ordinary skill in the art would also have had reason to apply the combination to patients having elevated PD-1 expression of TILs because greater PD-1 target expression permits greater anti PD-1 antibody binding and therefore greater opportunity for the FcγR mediated removal identified by Arlauckas. Zelba teaches quantifying PD-1 molecules per cell using flow cytometry and the EH12.2H7 antibody. Once PD-1 expression recognized as relevant to FcγR mediated anti PD-1 removal, selection of particular cell percentages and expression cutoffs would have constituted routine optimization of a known measurable variable.
The antibody formats recited in claims 16, 18-20, 22, and 30-33 are likewise taught or suggested by the references, including Fc competent human IgG1 anti FcγRIIb antibodies and clinically relevant anti PD-1 antibodies. Regarding claims 27-28, the elected 6G11 CDR and variable region sequences are disclosed with 100% sequence identity in the cited prior art and therefore do not patentably distinguish the claimed method.
Applicant’s teaching away argument (pgs. 11-12 of Remarks dated 03/06/2026) is not persuasive. Although Dahan and Arlauckas discuss reducing FcγR binding of the anti PD-1 antibody, neither reference criticizes or discourages receptor blockade. Arlauckas expressly identifies blocking FcγR interactions as a means of improving anti PD-1 therapy, and Dahan specifically implicates FcγRIIb. Disclosure of an alternative solution does not constitute teaching away from the claimed solution. The present application characterizes Dahan Arlauckas as identifying FcγR mediated impairment of anti PD-1 activity, while asserting the claimed distinction in the particular Fc competent anti FcγRIIb combination and PD-1 expression selection. The PCT “A” citation classification is not controlling in examination under U.S. law.
Furthermore, Applicant’s distinction of Roghanian as involving rituximab internalization (pgs. 12-13 of Remarks dated 03/06/2026) is also unpersuasive because the references need not employ identical biological mechanisms. Roghanian supplies a known antagonistic Fc competent anti FcγRIIb antibody, while Dahan and Arlauckas provide the reason to employ that antibody in anti PD-1 therapy.
Finally, the asserted results have been considered but are not commensurate with the breadth of the claims, which encompass broad genera of antibodies, cancers, patients, and treatment conditions. Claim 3 does not require enhanced efficacy, and the remaining claims do not require the particular magnitude of improvement demonstrated with the specific antibodies and experimental models relied upon by Applicant. The rejection is therefore maintained.
Double Patenting
Applicant's arguments filed 03/06/2026 have been fully considered but they are not persuasive.
1. Claims 3, 5, 7-16, 18-20, 22, and 27-28, and 30-34 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, and 3-14 of U.S. Patent No. 12371498 (‘498) in view of view of Dahan et al., and Arlauckas et al., and further in view of Zelba et al. (cited in previous Office Action dated 10/09/2025).
2. Claims 3, 5, 7-16, 18-20, 22, and 27-28, and 30-34 remain 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.
3. Claims 3, 5, 7-16, 18-20, 22, and 27-28, and 30-34 remain 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.
4. Claims 3, 5, 7-16, 18-20, 22, and 27-28, and 30-34 remain 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.
5. Claims 3, 5, 7-16, 18-20, 22, and 27-28, and 30-34 remain 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.
6. Claims 3, 5, 7-16, 18-20, 22, and 27-28, and 30-34 remain 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.
7. Claims 3, 5, 7-16, 18-20, 22, and 27-28, and 30-34 remain 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.
8. Claims 3, 5, 7-16, 18-20, 22, and 27-28, and 30-34 remain 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.
9. Claims 3, 5, 7-16, 18-20, 22, and 27-28, and 30-34 remain 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.
Regarding the provisional nonstatutory double patenting rejections based on the copending applications, the request to hold the rejections in abeyance is noted. The claims of the involved applications presently remain pending and patentably indistinct, and other substantive rejections remain outstanding. Accordingly, the provisional rejections are maintained subject to reconsideration should the claims or status of the involved applications change.
Regarding the issued patents, Applicant’s reliance on differences in the disclosed mechanisms does not establish patentable distinctness. The double patenting determination is based on the scope of the patented claims, considered with the cited references, rather than whether the Specifications describe identical therapeutic mechanisms. The reference patents claim anti FcγRIIb antibodies and their use with Fc bearing antibodies. Dahan and Arlauckas provide reason to employ such antibodies with an Fc competent anti PD-1 antibody to reduce FcγR mediated interference, and Zelba teaches PD-1 expression quantification.
Applicant’s argument concerning U.S. Patent No. 12371498 (‘498) is likewise unpersuasive. Although the patented claims encompass anti FcγRIIb antibodies lacking and Fc region, they also encompass antibodies having reduced FcγR binding. The instant claims require only that the antibody bind an Fcγ receptor through its Fc region and do not require normal or unimpaired FcγR binding. Thus, the reduced binding embodiment is not excluded by the instant claim language.
Accordingly, the nonstatutory and provisional nonstatutory double patenting rejections are maintained.
Conclusion
No claim is allowable.
Applicant's amendment necessitated the new grounds 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.
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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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu can be reached at (571) 272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/DENNIS GEORGE/Examiner, Art Unit 1644
/MISOOK YU/ Supervisory Patent Examiner, Art Unit 1641
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