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 .
Claim Status
Applicant’s reply filed on 03/05/2026 is acknowledged. Claims 17, 27 and 33 are amended. Claims 1, 10, 12-16, 19-22, 25-26, 39 are cancelled. Claims 69-71 are newly added.
Claims 17-18, 27-29, 33, and 69-71 are pending and under examination.
Objections/Rejections Withdrawn
The following objections and rejections are withdrawn in view of the amendments filed 03/05/2026:
The objection to the Nucleotide and/or Amino Acid Sequence Disclosures pertaining to sequence identifiers missing in the Brief Description of the Drawings.
The objection to the Specification for a minor informality.
The objection to claims 1, 26, and 39 for a minor informality.
The rejection of claim 14 under 35 U.S.C. 112(d).
The rejection of claims 10, 16, 17, 18, 27-29 and 33 under 35 U.S.C. 112(a), written description.
The rejection of claim 16 under 35 U.S.C. 112(a), scope of enablement.
Rejections Maintained
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 17 and newly added 69-71 remain/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Alt (WO2018/204303A1, published 11/08/2018, IDS filed 10/28/2024).
The disclosure of Alt is directed to novel anti-PD1 antibody reagents and discloses the generation of the antibodies of the instant invention from the same parent antibody 17D8 (see Abstract, and Alt Table 1).
Regarding claim 17, pertaining to a composition, kit or combination comprising the antibody, antibody reagent, antigen-binding portion thereof, or CAR of claim 1 and (ii) an immunosuppressive agent, Alt discloses the antibody of claim 1 and co-administration with interferon alpha ([00142], Line 7). Alt discloses the following antibodies of instant claim 17 with corresponding sequences shown below:
Clone Name
Instant
Alt
397-27-25
CDRs SEQ ID NO: 3-8
Heavy chain SEQ ID NO: 1
Light chain SEQ ID NO: 2
Heavy chain SEQ ID NO: 168
Light chain SEQ ID NO: 223
319-9-15
CDRs SEQ ID NO: 19-24
Heavy chain SEQ ID NO: 17
Light chain SEQ ID NO: 18
Heavy chain SEQ ID NO: 95
Light chain SEQ ID NO: 128
319-9-75
CDRs SEQ ID NO: 11-16
Heavy chain SEQ ID NO: 9
Light chain SEQ ID NO: 10
CDRs SEQ ID NO: 71-76
319-9-27
CDRs SEQ ID NO: 27-32
Heavy chain SEQ ID NO: 25
Light chain SEQ ID NO: 26
CDRs SEQ ID NO: 41-46
Heavy chain SEQ ID NO: 7
Light chain SEQ ID NO: 8
397-27-93
CDRs SEQ ID NO: 35-40
Heavy chain SEQ ID NO: 33
Light chain SEQ ID NO: 34
Heavy chain SEQ ID NO: 9
Light chain SEQ ID NO: 10
319-9-34
CDRs SEQ ID NO: 43-48
Heavy chain SEQ ID NO: 41
Light chain SEQ ID NO: 42
CDRs SEQ ID NO: 53-58
Heavy chain SEQ ID NO: 11
Light chain SEQ ID NO: 12
319-9-17
CDRs SEQ ID NO: 51-56
Heavy chain SEQ ID NO: 49
Light chain SEQ ID NO: 50
Heavy chain SEQ ID NO: 3
Light chain SEQ ID NO: 4
319-9-53
CDRs SEQ ID NO: 59-64
Heavy chain SEQ ID NO: 57
Light chain SEQ ID NO: 58
CDRs SEQ ID NO:35-40
Heavy chain SEQ ID NO: 5
Light chain SEQ ID NO: 6
397-27-23
CDRs SEQ ID NO: 67-72
Heavy chain SEQ ID NO: 65
Light chain SEQ ID NO: 66
Heavy chain SEQ ID NO: 13
Light chain SEQ ID NO: 14
397-27-3
CDRs SEQ ID NO: 75-80
Heavy chain SEQ ID NO: 73
Light chain SEQ ID NO: 74
Heavy chain SEQ ID NO: 15
Light chain SEQ ID NO: 16
Regarding newly added claim 69, wherein the antibody, antibody reagent, antigen-binding portion thereof, or CAR of claim 17 further comprises a conservative substitution in a sequence not comprised by a CDR, Alt discloses wherein the antibody, antibody reagent, antigen-binding portion thereof, or CAR of claim 1 further comprises a conservative substitution in a sequence not comprised by a CDR (Pg. 92, claim 13).
Regarding newly added claim 70, wherein the antibody, antibody reagent, or antigen-binding portion thereof of claim 17 is fully humanized except for the CDR sequences, Alt discloses the antibody, antibody reagent, antigen-binding portion thereof, or CAR is fully humanized except for the CDR sequences (Pg. 92, claims 14 and 15).
Regarding newly added claim 71, wherein the antibody, antibody reagent, or antigen-binding portion thereof of claim 17 is selected from the group consisting of: an immunoglobulin molecule, a monoclonal antibody, a chimeric antibody, a CDR- grafted antibody, a humanized antibody, a Fab, a Fab', a F(ab')2, a Fv, a disulfide linked Fv, a scFv, a diabody, a multispecific antibody, a dual specific antibody, and a bispecific antibody, Alt discloses wherein the antibody is an immunoglobulin molecule, a monoclonal antibody, a chimeric antibody, a CDR grafted antibody, a humanized antibody, a Fab, a Fab', a F(ab')2, a Fv, a disulfide linked Fv, a scFv, a diabody, a multispecific antibody, a dual specific antibody, an anti-idiotypic antibody, and a bispecific antibody (Pg. 92, claim 16).
Claim Rejections - 35 USC § 103
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.
Claims 17-18, 27-29, 33, and newly added 69-71 remain/are rejected under 35 U.S.C. 103 as being unpatentable over Alt (WO2018/204303A1, published 11/08/2018, IDS filed 10/28/2024) as applied to claims 17 and 69-71 above, and further in view of Shibayama (US2014/0220021A1, published 08/07/2014, IDS filed 10/28/2024).
As described in the 35 USC § 102 rejection above, Alt discloses the instant antibodies comprising the variable regions of instant claim 1. Alt teaches coadministration with an immunosuppressive agent interferon alpha ([00142], Line 7) and that the antibody can be used in an antibody drug conjugate [0069].
Alt does not teach (1) the immunosuppressive agent is conjugated to the antibody (claim 18) or (2) administration of the anti-PD1 antibody for the treatment of an autoimmune disorder or for suppressing an immune response (claims 27-29 and 33).
These deficiencies are taught by Shibayama.
The disclosure of Shibayama is directed to anti-PD1 agonists as therapeutic agents for autoimmune disease ([0009]-[0010]).
Regarding claim 18, wherein the antibody, antibody reagent, or antigen-binding portion thereof of the composition, kit or combination of claim 17 is conjugated to the immunosuppressive agent, Alt teaches an antibody-drug conjugate and Shibayama teaches coadministration of the antibody with steroids and other immunosuppressive agents ([0244]-[0245]).
Regarding claims 27-29 and 33, pertaining to a method of treating an autoimmune disorder, wherein the autoimmune disorder is a T cell-mediated disorder selected from the group disclosed in claim 29 (claim 27-29) and a method of suppressing an immune response in a subject (claim 33) comprising administration of an antibody of the disclosure, Shibayama teaches the use of a PD-1 agonist for the treatment of an autoimmune disease, wherein the autoimmune disease is selected from a group comprising type 1 diabetes mellitus ([0012] and [0020]).
It would have been obvious to one having ordinary skill in the art to (1) conjugate an immunosuppressive agent to the antibody and (2) use the anti-PD1 antibody of Alt in a method to treat an autoimmune disorder or to suppress an immune response. One would have been motivated to do so because (1) Alt teaches conjugation of drugs to the anti-PD1 antibody, a known method of targeted drug delivery and (2) Shibayama teaches that agonist PD1 antibodies can be used to treat autoimmune diseases. The disclosure of Alt does not specifically disclose which anti-PD1 antibodies are inherently agonist, however Alt provides the anti-PD1 antibodies for which the agonist mechanism of action could readily be determined pointing to their use in reducing inflammatory conditions. There would be an expectation of success in combining the teachings of Alt and Shibayama because Alt provides antibodies that can readily be used in treatment methods.
Response to Applicant’s Arguments
Applicant's arguments filed 03/05/2026 have been fully considered but they are not persuasive.
The applicant traverses the 35 U.S.C. §102 rejection as being novel over the cited art. The remarks state: Claim 17 recites "an immunosuppressive agent." The Office alleges that Alt's disclosure of "interferon-alpha" reads on "an immunosuppressive agent." Applicant disagrees. The instant specification is clear that interferons are "pro-inflammatory". (Remarks, Pg. 2).
The applicant traverses the 35 U.S.C. §103 rejection because Shibayama teaches conjugation of agents to anti-PD1 antibodies generally. The applicant states that no combination of Alt and Shibayama can render the claimed invention obvious (Remarks, Pg. 3).
In response, the art teaches that interferon alpha is dual pro-inflammatory and anti-inflammatory cytokine depending on context, concentration, and duration of exposure. To this end, the following references are provided below:
Tilg (Gastroenterology. 1997 Mar;112(3):1017-21) reviews multiple studies demonstrating anti-inflammatory effects of IFN-α, including reduction of IL-1 and induction of IL-10 in human PBMCs (Table 1).
Billiau (Antiviral Res. 2006 Sep;71(2-3):108-16) reviews the pleiotropic nature of type I interferons (IFN-α/β) and teaches for example, that IFN-α inhibits production of the pro-inflammatory TNF-α production by mitogen-activated human PBMC (Pg. 112, Right column, 4.5 Mononuclear phagocytes).
Chalise (Arthritis Res Ther. 2013 Oct 3;15(5):R143) teaches IFN-α both enhances and prevents inflammation, with their disclosure showing that administration of IFN-α in a mouse model of rheumatoid arthritis protected mice from arthritis in a dose-dependent manner by inhibiting the production of pro-inflammatory cytokines (Abstract).
Razzuoli (J Interferon Cytokine Res. 2013 Oct;33(10):597-605) teaches that high doses of IFN-α is anti-proliferative, anti-viral, and pro-inflammatory, whereas low doses have shown preferential immunomodulatory and anti-inflammatory activity (Pg. 601, Right column, Discussion, first full paragraph). Their disclosure showed pretreatment of a porcine intestinal epithelial cell line with recombinant IFN-α reduced IL-8 release under conditions of oxidative stress (Fig. 1) and reduced the production of pro-inflammatory cytokines in response to LPS exposure (Fig. 5).
Ribon (Abstract Number: 52. 2018 ACR/ARHP Annual Meeting) teaches in transgenic mice that induction of IFN-α1 in transgenic mice that overexpress IFN-α1 resulted in CIA protection and reduced pain. Transgenic IFN-α1 mice also had reduced anti-collagen antibodies and reduced IL-6 production as well as decreased polarization to Th17 cells and increased polarization to Th2 cells.
In all, the art teaches IFN-α is anti-inflammatory in certain contexts and falls under the broad, but reasonable interpretation of “an immunosuppressive agent” which would include agents that have anti-inflammatory properties. Therefore the 35 U.S.C. §102 rejection is appropriate and is maintained.
In acknowledgement of the pleiotropic nature of IFN-α wherein it is pro-inflammatory in many contexts, the Shibayama disclosure also teaches that it would be obvious to co-administer an agonist anti-PD1 antibody with a more canonical “immunosuppressive agent” such as a steroid as discussed in the 35 U.S.C. §103 rejection above. For this reason, the 35 U.S.C. §103 is also maintained.
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.
US11427636B2
Claims 17-18, 27-29, 33, and newly added 69-71 remain/are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 11,427,636 B2 in view of Alt (WO2018/204303A1, published 11/08/2018, IDS filed 10/28/2024) and Shibayama (US2014/0220021A1, published 08/07/2014, IDS filed 10/28/2024).
Regarding instant claim 17, pertaining to a composition comprising the antibody, antibody reagent, antigen-binding portion thereof, or CAR of claim 1 or additionally disclosed antibody and (ii) an immunosuppressive agent, ‘636 discloses four of the instant antibodies shown below:
Clone Name
Instant
US11427636B2
319-9-75
CDRs SEQ ID NO: 11-16
Heavy chain SEQ ID NO: 9
Light chain SEQ ID NO: 10
CDRs SEQ ID NO: 71-76
319-9-27
CDRs SEQ ID NO: 27-32
Heavy chain SEQ ID NO: 25
Light chain SEQ ID NO: 26
CDRs SEQ ID NO: 41-46
Heavy chain SEQ ID NO: 7
Light chain SEQ ID NO: 8
319-9-34
CDRs SEQ ID NO: 43-48
Heavy chain SEQ ID NO: 41
Light chain SEQ ID NO: 42
CDRs SEQ ID NO: 53-58
Heavy chain SEQ ID NO: 11
Light chain SEQ ID NO: 12
319-9-53
CDRs SEQ ID NO: 59-64
Heavy chain SEQ ID NO: 57
Light chain SEQ ID NO: 58
CDRs SEQ ID NO:35-40
Heavy chain SEQ ID NO: 5
Light chain SEQ ID NO: 6
Regarding newly added claim 69, wherein the antibody, antibody reagent, antigen-binding portion thereof, or CAR of claim 17 further comprises a conservative substitution in a sequence not comprised by a CDR, ‘636 claim 5 discloses wherein the antibody, antibody reagent, antigen-binding portion thereof, or CAR of claim 1 further comprises a conservative substitution in a sequence not comprised by a CDR.
Regarding newly added claim 70, wherein the antibody, antibody reagent, or antigen-binding portion thereof of claim 17 is fully humanized except for the CDR sequences, ‘636 claim 6 discloses the antibody, antibody reagent, antigen-binding portion thereof, or CAR is fully humanized except for the CDR sequences.
Regarding newly added claim 71, wherein the antibody, antibody reagent, or antigen-binding portion thereof of claim 17 is selected from the group consisting of: an immunoglobulin molecule, a monoclonal antibody, a chimeric antibody, a CDR- grafted antibody, a humanized antibody, a Fab, a Fab', a F(ab')2, a Fv, a disulfide linked Fv, a scFv, a diabody, a multispecific antibody, a dual specific antibody, and a bispecific antibody, ‘636 claim 8 discloses wherein the antibody is an immunoglobulin molecule, a monoclonal antibody, a chimeric antibody, a CDR grafted antibody, a humanized antibody, a Fab, a Fab', a F(ab')2, a Fv, a disulfide linked Fv, a scFv, a diabody, a multispecific antibody, a dual specific antibody, an anti-idiotypic antibody, and a bispecific antibody.
‘636 does not teach (1) the immunosuppressive agent is conjugated to the antibody (claim 18) or (2) administration of the anti-PD1 antibody for the treatment of an autoimmune disorder or for suppressing an immune response (claims 27-29 and 33).
These deficiencies are taught by Alt and Shibayama.
Regarding claim 18, wherein the antibody, antibody reagent, or antigen-binding portion thereof of the composition, kit or combination of claim 17 is conjugated to the immunosuppressive agent, Alt teaches an antibody-drug conjugate and Shibayama teaches coadministration of the antibody with steroids and other immunosuppressive agents ([0244]-[0245]).
Regarding claims 27-29 and 33, pertaining to a method of treating an autoimmune disorder, wherein the autoimmune disorder is a T cell-mediated disorder selected from the group disclosed in claim 29 (claim 27-29) and a method of suppressing an immune response in a subject (claim 33) comprising administration of an antibody of the disclosure, Shibayama teaches the use of a PD-1 agonist for the treatment of an autoimmune disease, wherein the autoimmune disease is selected from a group comprising type 1 diabetes mellitus ([0012] and [0020]).
It would have been obvious to one having ordinary skill in the art to (1) conjugate an immunosuppressive agent to the antibody of ‘636 and (2) use the anti-PD1 antibody of ‘636 in a method to treat an autoimmune disorder or to suppress an immune response. One would have been motivated to do so because (1) Alt teaches conjugation of drugs to the anti-PD1 antibody, a known method of targeted drug delivery and (2) Shibayama teaches that agonist PD1 antibodies can be used to treat autoimmune diseases. The disclosure of Alt does not specifically disclose which anti-PD1 antibodies are inherently agonist, however Alt provides the anti-PD1 antibodies for which the agonist mechanism of action could readily be determined pointing to their use in reducing inflammatory conditions. There would be an expectation of success in combining the teachings of ‘636 with Alt and Shibayama because ‘636 provides antibodies that can readily be used in treatment methods.
U.S. Application No. 17/870, 010 Notice of Allowance Mailed 05/30/2025
Claims 17-18, 27-29, 33, and newly added 69-71 remain/are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13, and 15-16 of copending Application No. 17/870, 010 in view of Alt (WO2018/204303A1, published 11/08/2018, IDS filed 10/28/2024) and Shibayama (US2014/0220021A1, published 08/07/2014, IDS filed 10/28/2024).
Application 17/870, 010 is a DIV of U.S. Pat. No. 11,427,636 B2 directed to the nucleic acids encoding the instant anti-PD1 antibody. The rejection of U.S. Pat. No. 11,427,636 B2 outlined above is incorporated herein.
This is a provisional nonstatutory double patenting rejection.
U.S. Application No. 19/264,986
Claims 17-18, 27-29, 33, and newly added 69-71 remain/are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of copending Application No. 19/264,986 in view of Alt (WO2018/204303A1, published 11/08/2018, IDS filed 10/28/2024) and Shibayama (US2014/0220021A1, published 08/07/2014, IDS filed 10/28/2024).
Application 19/264,98 is a DIV of U.S. Pat. No. 11,427,636 B2 directed to the nucleic acids encoding the instant anti-PD1 antibody. The rejection of U.S. Pat. No. 11,427,636 B2 outlined above is incorporated herein.
This is a provisional nonstatutory double patenting rejection.
Response to Applicant’s Arguments
The applicant traverses the nonstatutory double patenting rejections because the '636 patent, the ‘010 application and the ‘986 application claim priority to Alt and therefore fail to disclose an "immunosuppressive agent" for at least the reasons given above. Accordingly, the '636 patent does not disclose, teach, or suggest the subject matter of instant claim 17. Alt and Shibayama cannot repair this deficiency for at least the reasons given above. (Remarks, Pgs. 3-4)
In response, the examiner reaffirms that Shibayama does indeed render conjugation of an agonist anti-PD-1 antibody to an immunosuppressive agent as obvious. For this reason, the nonstatutory double patenting rejection are maintained.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. 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 CAROL ANN CHASE whose telephone number is (571)270-0934. The examiner can normally be reached Monday-Friday 9:00am-6:00pm.
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/CAROL ANN CHASE/Examiner, Art Unit 1646
/HONG SANG/Primary Examiner, Art Unit 1646
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