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 .
Election/Restrictions
Applicant's reply to the Restriction Requirement, dated July 20, 2026, has been received. By way of this submission, Applicant has elected, without traverse, Group I, claims 1, 4, 7-8, 15, 21, 26-27, 30-31, 34, 41-42 and 51, drawn to methods for treating cancer, IDO1 as the species of first immune checkpoint polypeptide, PD-L1 as the species of second immune checkpoint polypeptide, an anti-PD-1 antibody as the species of immune checkpoint inhibitor, administering the IDO1 polypeptide and the PD-L1 polypeptide as a first composition and the anti-PD-1 antibody as a second composition, and metastatic melanoma as the species of cancer.
Claims 1, 4, 7-8, 15, 21, 26-27, 30-31, 34-36, 41-44, 47-49 and 51 are pending in the application. Claims 35-36, 43-44, and 47-49 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on July 20, 2026.
Claims 1, 4, 7-8, 15, 21, 26-27, 30-31, 34, 41-42 and 51 are therefore under examination before the Office.
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.
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.
Claims 1, 4, 7-8, 15, 21, 26-27, 31, and 51 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Clinical Trial NCT03047928 (version V4 (2018-10-30), retrieved from the Internet at https://clinicaltrials.gov/study/NCT03047928?tab=history&a=4#version-content-panel).
Clinical Trial NCT03047928 teaches a method of treating metastatic melanoma, comprising administering the anti-PD-1 antibody nivolumab and a peptide vaccine consisting of programmed death ligand 1 (PD-L1) and Indoleamine 2,3-dioxygenase (IDO) peptides (page 6, brief summary), which is pertinent to claims 1, 7-8, 15, 21, 27, and 31.
Clinical Trial NCT03047928 further teaches that the patient may be anti PD-1/PD-L1 naïve (page 11), which is pertinent to claim 4.
Clinical Trial NCT03047928 further teaches that the PD-L1 peptide and IDO peptides are administered as a vaccine (i.e., a first composition), and nivolumab is administered separately (i.e., as a second composition) (pages 8-9), which is pertinent to claim 21.
Clinical Trial NCT03047928 further teaches that this method may result in progression-free treatment for up to 24 months (i.e., 2 years) (page 10), which is pertinent to claims 26 and 51.
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.
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.
Claims 30, 34, and 41-42 are rejected under 35 U.S.C. 103 as being unpatentable over Clinical Trial NCT03047928 as applied to claim 1 above, and further in view of Gambichler (Br J Dermatol. 2020 May;182(5):1214-1220).
The teachings of Clinical Trial NCT03047928 have been discussed supra. However, Clinical Trial NCT03047928 does not teach an immune profile.
Gambichler teaches that the frequency of CD4+ regulator T cells significantly decreases after the first cycle of immunotherapy with nivolumab, and this decrease is associated with better clinical outcomes in patients with melanoma (page 1214: "Results").
Gambichler further teaches that the cell populations are determined by FACS sorting on peripheral blood (page 1215: "Blood cells and flow cytometry for lymphocyte subsets").
It would have been prima facie obvious for a person of ordinary skill in the art as of the effective filing date to combine the teachings of Clinical Trial NCT03047928 and Gambichler to arrive at the claimed invention. An ordinary artisan would have been motivated to do so, and have a reasonable expectation of success, since both Clinical Trial NCT03047928 and Gambichler are concerned with cancer immunotherapy for melanoma. As Clinical Trial NCT03047928 teaches, methods of treating metastatic melanoma with combinations of nivolumab and PD-L1/IDO peptide vaccines were known in the art. Gambichler teaches that decreases in CD4+ Tregs are indicative of responsiveness to nivolumab in patients with melanoma. One of ordinary skill would therefore be motivated to perform the immune profiling of Gambichler in order to select suitable patients for the method of Clinical Trial NCT03047928. Each component would perform its known, usual function, and the combination would yield nothing more that predictable results.
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, 7-8, 15, 21, 26-27, 30-31, 34, 41-42 and 51 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 11 and 12 of U.S. Patent No. 9,669,078 in view of Clinical Trial NCT03047928 and Gambichler.
The '078 patent claims a method of treating cancer, comprising administering a PD-L1 polypeptide (claim 11).
However, the '078 patent does not claim a second polypeptide or an immune checkpoint inhibitor.
Clinical Trial NCT03047928 teaches a method of treating metastatic melanoma, comprising administering the anti-PD-1 antibody nivolumab and a peptide vaccine consisting of programmed death ligand 1 (PD-L1) and Indoleamine 2,3-dioxygenase (IDO) peptides (page 6, brief summary), which is pertinent to claims 1, 7-8, 15, 21, 27, and 31.
Clinical Trial NCT03047928 further teaches that the patient may be anti PD-1/PD-L1 naïve (page 11), which is pertinent to claim 4.
Clinical Trial NCT03047928 further teaches that the PD-L1 peptide and IDO peptides are administered as a vaccine (i.e., a first composition), and nivolumab is administered separately (i.e., as a second composition) (pages 8-9), which is pertinent to claim 21.
Clinical Trial NCT03047928 further teaches that this method may result in progression-free treatment for up to 24 months (i.e., 2 years) (page 10), which is pertinent to claims 26 and 51.
Gambichler teaches that the frequency of CD4+ regulator T cells significantly decreases after the first cycle of immunotherapy with nivolumab, and this decrease is associated with better clinical outcomes in patients with melanoma (page 1214: "Results").
Gambichler further teaches that the cell populations are determined by FACS sorting on peripheral blood (page 1215: "Blood cells and flow cytometry for lymphocyte subsets").
It would have been prima facie obvious for a person of ordinary skill in the art as of the effective filing date to combine the claims of the '078 patent teachings of Clinical Trial NCT03047928 and Gambichler to arrive at the claimed invention. As Clinical Trial NCT03047928 teaches, methods of treating metastatic melanoma with combinations of nivolumab and PD-L1/IDO peptide vaccines were known in the art. One such PD-L1 peptide vaccine is claimed by the '078 patent. Gambichler teaches that decreases in CD4+ Tregs are indicative of responsiveness to nivolumab in patients with melanoma. One of ordinary skill would therefore be motivated to perform the immune profiling of Gambichler in order to select suitable patients for the method of Clinical Trial NCT03047928, and using the peptide of the '078 patent. Each component would perform its known, usual function, and the combination would yield nothing more that predictable results.
Conclusion
No claim is allowed.
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/PETER JOHANSEN/Primary Examiner, Art Unit 1642
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