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 .
DETAILED ACTION
Applicant's election with traverse of Group I, claims 1-16, 21 and 22, as well as species: (a) a specific non-small cell lung cancer: non-squamous cell carcinoma NSCLC; (b) a specific first line chemotherapeutic agent: pemetrexed and cisplatin, in the reply filed on August 18, 2026 is acknowledged.
Claims 19 and 20 were previously canceled.
Claim 5, 9, and 10 have been canceled by the amendment of August 18, 2026.
Claims 1, 2, 6 and 17 have been amended.
Claims 1-4, 6-8, 11-18, 21 and 22 are pending.
The traversal is mainly on the ground(s):
As a preliminary matter, independent claims 1 and 17 have been amended to include, inter alia, the following two features:
1. Specific CDR sequences of the anti-PD-I antibody, namely light chain CD Rs of SEQ ID NOs: 1, 2, 3 and heavy chain CDRs of SEQ ID NOs: 4, 5, 6 (these are the CDRs of toripalimab); and
2. Specific patient population of the advanced non-small cell lung cancer not accompanied by EGFR-sensitive mutations and ALK fusions.
Thus, the common technical feature shared by all pending claims (both method and pharmaceutical combination) is the use of an anti-PD-1 antibody having the specific CDRs of
toripalimab (SEQ ID NOs:1-6) in combination with a first-line chemotherapeutic agent for
the treatment of advanced NSCLC that does not harbor EGFR-sensitive mutations or ALK
fusions.
Applicant respectfully submits that Ren does not disclose or suggest this common
technical feature. Specifically, Ren relates to a Phase n study in advanced NSCLC patients with
EGFR mutations who were refractory to TKI therapies, a distinctly different patient
population. See, e.g., Ren at Title. Importantly, Ren does not involve patients lacking
EG:FR-sensitive mutations and ALK fusions, nor does it suggest that the combination therapy
would be effective in such a population. This claimed patient subgroup is expressly excluded
from the scope of Ren' s study.
This is not found persuasive. Although the amended claim 1 and claim 17 recite specific anti-PD1 antibody and specific NSCLC, claim 17 is drawn to a composition and the intended use for a composition does not change the structure of the composition. Thus, the combination taught by Ren still reads on the combination of claim 17 (see Office Action of 05/19/2026). In addition, as shown in the 103 rejection below, the prior art suggests the method of amended claim 1. Therefore, even with the newly added limitations to claims 1 and 17, the technical feature linking the inventions of Group I and II does not define a contribution over the prior art.
The requirement is still deemed proper and is therefore made FINAL.
Claims 17 and 18 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions or species, there being no allowable generic or linking claim.
Claims 1-4, 6-8, 11-16, 21 and 22 are pending and under consideration.
Priority
It is acknowledged that this application is a 371 of International Application: PCT/CN2022/088257 filed April 21, 2022, which claims the benefit of priority to a foreign application: CN202110436365.9, filed April 22, 2021
Certified copies of foreign priority applications have been received as required by 37 CFR 1.55.
The priority date has been established as April 21, 2022 for the pending claims.
It is noted that the Examiner has established a priority date of April 21, 2022 for claims 1-4, 6-8, 11-16, 21 and 22 of the instant application because the priority of the instantly claimed invention is based on the prior filed applications PCT/CN2022/088257 and CN202110436365.9, which are written Chinese. The prior filed applications have not been translated and the Examiner is unable to determine the information in the document.
If Applicant disagrees with any rejection set forth in this action based on examiner's establishment of a priority date of April 21, 2022 for claims 1-4, 6-8, 11-16, 21 and 22, then Applicant is invited to submit a proper translation of the priority document and to point to page and line where support can be found establishing an earlier priority date. If Applicants choose to file a translation, then the translation must be filed together with a statement that the translation of the certified copy is accurate. See 35 U.S.C. 119 (b)(3), 37 C.F.R. 1.55(g)(3)(4), 37 C.F.R. 1.78(d)(7), and MPEP 1895.01.
Information Disclosure Statement
The Information Disclosure Statements filed on 10/23/2023 and 06/24/2025 have been considered and entered by examiner.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - The Incorporation by Reference paragraph required by 37 CFR 1.821(c)(1) is missing or incomplete. See item 1) a) or 1) b) above.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Drawings
The drawings are objected to because some legends in Figs. 1a-1d, 2a-2c, 5a, 5b, 6a, 6b, 10, 11, 12, and 13 are illegible. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claim 8 is objected to because of the following informalities: “toripallimab” should be “toripalimab”. Appropriate correction is required.
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 1-4, 6-8, 11-16, 21 and 22 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 1 recites “EGFR-sensitive mutations” which renders the claim indefinite. It is unclear whether the term refers to mutations making EGFR sensitive to EGFR inhibitors or ligands; or refers to mutations affecting EGFR structure or function in some other ways. For examination purpose, any mutation in EGFR would read on the limitation.
Regarding claim 12, the phrase "e.g.," renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 12 recites “AUC 5”, “AUC 6” and “AUC 7”, which renders the claim indefinite. Paragraphs of [0171]-[0173] teach that AUC 5 dose can be calculated by the Calvert formula. However, it is unclear whether “AUC 5”, “AUC 6” and “AUC 7” (recited by claim 12) are limited to the calculating method, or whether this calculation applies to “AUC 6” and “AUC 7”.
Claim 15 recites “administered in an administration cycle of one week, two weeks, three weeks, one month,…” which renders the claim indefinite. Because claim 15 depends on claim 14 which recites administering agents once every three weeks, it is unclear, for example, how to administer an agent every three weeks in an administration cycle of one week.
Claim 2-4, 6-8, 11, 13, 14, 16, 21 and 22 are is also rejected because it depends on the rejected claims.
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.
Claims 1-4, 6-8, and 11-16 are rejected under 35 U.S.C. 103 as being unpatentable over Melosky (Melosky et al., The Oncologist, 2020, 25, 64-77, Publication Date: 05/28/2019, cited in IDS of 06/24/2025) in view of Ren (Ren et al., Journal of Clinical Oncology, 38 (15): e21618-e21618, Publication Date: 05/20/2020, cited in IDS of 06/24/2025, of record).
Melosky teaches that immunotherapy using checkpoint inhibitors has become standard of care in advanced non-small cell lung cancer (NSCLC) (Abstract).
Melosky teaches that four first-line trials reported outcomes for checkpoint inhibitor combinations in nonsquamous NSCLC (the elected species). Pembrolizumab-chemotherapy, atezolizumab-chemotherapy, and atezolizumab-bevacizumab-chemotherapy showed significantly improved overall survival compared with controls in patients with advanced nonsquamous epidermal growth factor receptor-negative (EGFR-)/ anaplastic lymphoma kinase gene (ALK)- NSCLC (EGFR-/ALK- NSCLC, which would read on the limitation “not accompanied by EGFR-sensitive mutations and ALK fusion”). Two trials reported outcomes for squamous NSCLC, with pembrolizumab-chemotherapy reporting significantly improved overall survival (OS) compared with chemotherapy (Abstract).
Melosky teaches KEYNOTE-189 phase III trial in which patients with stage IV (advanced) nonsquamous EGFR-/ALK- NSCLC to receive pembrolizumab 200mg plus pemetrexed 500 mg/m2 and (cisplatin 75 mg/m2 or carboplatin AUC 6), q3w x 4 or 6 (Table 1, and page 69, col. 1, para. 1). It is noted that pemetrexed + cisplatin is the elected first line chemotherapeutic agent.
Melosky teaches that in KEYNOTE-189 trial, significant improvements were seen for the coprimary endpoints of median PFS (8.8 vs. 4.9 months; HR, 0.52; 95% CI, 0.43-0.64; p< 0.001) and median OS (not yet reached vs. 11.3 months; HR, 0.49; 95% CI, 0.38-0.64; p< 0.001) for the combination treatment versus control arms, respectively (Table 1, and page 69, col. 1, para. 1).
Melosky teaches phase III IMpower-132 trial in which patients with stage IV (advanced) nonsquamous EGFR-/ALK- NSCLC to receive atezolizumab 1200 mg plus pemetrexed 500 mg/m2 and (cisplatin 75 mg/m2 or carboplatin AUC 6), q3w x 4 or 6 (Table 1, and page 69, the bridging paragraph of cols 1-2).
Melosky teaches that in in IMpower-132 trial, significant improvements were seen for the coprimary endpoints of median PFS (7.6 vs. 5.2 months; HR, 0.60; 95% CI, 0.49-0.72; p< 0.001) for the combination treatment versus control arms, respectively (Table 1, and page 69, the bridging paragraph of cols 1-2).
Melosky teaches that first-line checkpoint inhibitors added to standard therapies improve overall survival for nonsquamous EGFR-/ALK- and squamous advanced NSCLC (§ Abstract-Conclusion).
Melosky teaches as set forth above. However, Melosky does not teach the anti-PD-1 antibody as recited by the instant claims.
Ren discloses a combination of 500 mg/m2 pemetrexed, AUC 5 carboplatin and 240 or 360 mg toripalimab (an anti-PD1 antibody), q3w for up to 6 cycles, for the treatment of advanced NSCLC with EGFR mutations refractory to tyrosine kinase inhibitors (TKIs), i.e. they are not EGFR sensitive mutations.
Ren teaches that the combination showed promising anti-tumor activity with a manageable safety profile for advance NSCLC patients (conclusion).
As evidenced by claim 8 and paragraph [0142] of the instant publication US 2024/0218066 A1, toripalimab comprising a light chain of SEQ ID NO: 9 and a heavy chain of SEQ ID NO: 10 would read on the antibody of claims 1, 7 and 8. As shown below, SEQ ID NO: 9 comprises SEQ ID NO: 7 and SEQ ID NO: 10 comprise SEQ ID NO: 8, thus, toripalimab also reads on claim 6.
SEQ ID NO: 7 and SEQ ID NO: 9 alignment:
Qy 1 DVVMTQSPLSLPVTLGQPASISCRSSQSIVHSNGNTYLEWYLQKPGQSPQLLIYKVSNRF 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DVVMTQSPLSLPVTLGQPASISCRSSQSIVHSNGNTYLEWYLQKPGQSPQLLIYKVSNRF 60
Qy 61 SGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCFQGSHVPLTFGQGTKLEIK 112
||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 SGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCFQGSHVPLTFGQGTKLEIK 112
SEQ ID NO: 8 and SEQ ID NO: 10 alignment:
Qy 1 QGQLVQSGAEVKKPGASVKVSCKASGYTFTDYEMHWVRQAPIHGLEWIGVIESETGGTAY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QGQLVQSGAEVKKPGASVKVSCKASGYTFTDYEMHWVRQAPIHGLEWIGVIESETGGTAY 60
Qy 61 NQKFKGRVTITADKSTSTAYMELSSLRSEDTAVYYCAREGITTVATTYYWYFDVWGQGTT 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 NQKFKGRVTITADKSTSTAYMELSSLRSEDTAVYYCAREGITTVATTYYWYFDVWGQGTT 120
Qy 121 VTVSS 125
|||||
Db 121 VTVSS 125
It would have prima facie been obvious to one of ordinarily skilled in the art
before the effective filing date of the claimed invention to treat advanced EGFR-/ALK- NSCLC with a combination of pembrolizumab + pemetrexed + cisplatin or atezolizumab + pemetrexed + cisplatin as taught by Melosky, and to substitute anti-PD-1 antibody pembrolizumab (or atezolizumab) with another anti-PD-1 antibody toripallimab taught by Ren. One of ordinary skill in the art would have had a reasonable expectation that toripallimab would also be efficacious to advanced EGFR-/ALK- NSCLC, because Melosky teaches that different anti-PD-1 antibodies are more effective when combined with pemetrexed + cisplatin and checkpoint inhibitors added to standard therapies improve overall survival for nonsquamous EGFR-/ALK- advanced NSCLC; Ren teaches that toripallimab and chemotherapeutic agent combinations can be used to treat advanced NSCLC with manageable safety profile. The motivation would have been to develop new treatments for advanced NSCLC and to expand applications of toripallimab.
Regarding claim 2, Melosky teaches that first-line checkpoint inhibitors added to standard therapies improve overall survival for nonsquamous EGFR-/ALK- and squamous advanced NSCLC (§ Abstract-Conclusion). Checkpoint inhibitor combinations are therefore an important new treatment option for first-line NSCLC (§ Implication for Practice, on page 64). It would have prima facie been obvious to one of ordinarily skilled in the art to use the combination taught by Melosky and Ren as the first-line treatment for an untreated advanced NSCLC.
Regarding claim 4, Melosky teaches PD-L1 negative (PD-L1< 1%) or low PD-L1 expression population show good responses to the combination therapy (Table 3, the bridging paragraph of cols. 1-2 on page 72). It would have prima facie been obvious to one of ordinarily skilled in the art to use the combination taught by Melosky and Ren to treat patient population recited by claim 4. In addition, by reciting “PD-L1 expression of ≥ 1% or PD-L1 expression < 1%” would encompass individuals with all possible PD-L1 expression levels, because any non-small cell lung cancer can have either PD-L1 expression of ≥ 1% or PD-L1 expression < 1% in immunohistochemical staining analysis of a tumor tissue section.
Regarding claims 12-16, Melosky teaches treating advanced EGFR-/ALK- NSCLC with pembrolizumab 200mg plus pemetrexed 500 mg/m2 and (cisplatin 75 mg/m2 or carboplatin AUC 6), q3w x 4 or 6 cycles (Table 1, and page 69, col. 1, para. 1). Ren teaches the dosage of torillimab (240mg or 360 mg) and administration method (patients received toripallimab intravenously (read on injection of claim 16) combined with carboplatin and premetrexed). In addition, one of ordinary skill in the art could modify the dose, route of administration, and the like to reach the specific regimens as claimed through routine and conventional practices.
Claims 21 and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Melosky (Melosky et al., The Oncologist, 2020, 25, 64-77, Publication Date: 05/28/2019, cited in IDS of 06/24/2025) in view of Ren (Ren et al., Journal of Clinical Oncology, 38 (15): e21618-e21618, Publication Date: 05/20/2020, cited in IDS of 06/24/2025, of record), as applied to claims 1-4, 6-8,11-16 above, and further in view of Gorgisen (Gorgisen et al., Genetics and Molecular Biology, 42, 1, 15-25, Publication Year: 2019).
Melosky and Ren teach the method of claim 1 as set forth above. However, Melosky and Ren do not teach that the NSCLC accompanied by mutations recited by claims 21 and 22.
Gorgisen teaches that 9 of 42 tested NSCLC patients have IRS1 mutation (S668T) from tumor samples, 4 of 9 have an additional IRS mutation (D674H) (Abstract). Gorgisen teaches that NSCLC cells (H1299 cell line) with different versions of IDS1 (wild-type, single mutant or double mutant) all show responses to cisplatin (Fig. 6a).
It is noted that an IRS1 mutation would read on gene mutation of an IL-7 signaling pathway, as evidenced by paragraph [0011] of the instant publication US 2024/0218066 A1.
It would have prima facie been obvious to one of ordinarily skilled in the art before the effective filing date of the claimed invention to combine teachings of Melosky, Ren and Gorgisen to treat advanced EGFR-/ALK- NSCLC with a combination of toripalimab + pemetrexed + cisplatin and to apply the treatment to individuals also have mutations in IRS1. One ordinary skill in the art would have had a reasonable expectation that the combination would also be efficacious to individuals having mutations in IRS1 because Gorgisen teaches that NSCLC cancer cells carrying different IRS1 mutations respond to cisplatin and the combination would enhance the anti-tumor activity because the combination provides multiple anti-tumor mode of actions. The motivation would have been to treat a suitable population with the claimed combination.
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.
Patent No. 10,066,013
Claims 1-4, 6-8, 11-16, 21 and 22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No. 10,066,013 B2 (reference patent, corresponding to Appl. No. 14/392,360) in view of Melosky (Melosky et al., The Oncologist, 2020, 25, 64-77, Publication Date: 05/28/2019, cited in IDS of 06/24/2025) and Ren (Ren et al., Journal of Clinical Oncology, 38 (15): e21618-e21618, Publication Date: 05/20/2020, cited in IDS of 06/24/2025, of record) for claims 1-4, 6-8,11-16, and further in view of Gorgisen (Gorgisen et al., Genetics and Molecular Biology, 42, 1, 15-25, Publication Year: 2019) for claims 21 and 22.
Claims 1-4, 6-8, 11-16, 21 and 22 are rendered obvious by the combined teachings of the prior art above as discussed in the 103 rejection, the 103 being incorporated here.
Claim 1 of reference patent teaches a monoclonal antibody or functional fragment thereof that binds to a programmed cell death 1 (PD-1) protein comprising the amino acid sequence of SEQ ID NO: 43, comprising a heavy chain variable region comprising SEQ ID NO: 33 and a light chain variable region comprising SEQ ID NO: 34.
Claim 7 of reference patent teaches a pharmaceutical composition comprising the antibody or functional fragment thereof according to claim 1 and a pharmaceutical carrier. It is noted that SEQ ID NO: 34 of reference patent comprises SEQ ID NO: 7 of instant application; SEQ ID NO: 33 of reference patent comprises SEQ ID NO: 8 of instant application. Alignments are shown below:
SEQ ID NO: 34 vs SEQ ID NO: 7:
Qy 1 DVVMTQSPLSLPVTLGQPASISCRSSQSIVHSNGNTYLEWYLQKPGQSPQLLIYKVSNRF 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DVVMTQSPLSLPVTLGQPASISCRSSQSIVHSNGNTYLEWYLQKPGQSPQLLIYKVSNRF 60
Qy 61 SGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCFQGSHVPLTFGQGTKLEIK 112
||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 SGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCFQGSHVPLTFGQGTKLEIK 112
SEQ ID NO: 33 vs SEQ ID NO: 8:
Qy 1 QGQLVQSGAEVKKPGASVKVSCKASGYTFTDYEMHWVRQAPIHGLEWIGVIESETGGTAY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QGQLVQSGAEVKKPGASVKVSCKASGYTFTDYEMHWVRQAPIHGLEWIGVIESETGGTAY 60
Qy 61 NQKFKGRVTITADKSTSTAYMELSSLRSEDTAVYYCAREGITTVATTYYWYFDVWGQGTT 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 NQKFKGRVTITADKSTSTAYMELSSLRSEDTAVYYCAREGITTVATTYYWYFDVWGQGTT 120
Qy 121 VTVSS 125
|||||
Db 121 VTVSS 125
Thus, the claims of the reference patent teach anti-PD-1 antibodies read on the antibody of instant claims 1 and 6. However, the claims of the reference patent do not teach the method as instantly claimed, or the antibody of instant claim 7 or claim 8. These deficiencies are addressed by the cited references, as provided by the teachings specified in the 103 section.
The claims of reference patent, Melosky and Reb are in the same field of anti-PD-1 antibodies and treating cancers with the antibodies. Regarding claims 1-4, 6-8,11-16, it would have prima facie been obvious to one of ordinarily skilled in the art before the effective filing date of the claimed invention to treat advanced EGFR-/ALK- NSCLC with a combination of pembrolizumab + pemetrexed + cisplatin or atezolizumab + pemetrexed + cisplatin as taught by Melosky, and to substitute anti-PD-1 antibody pembrolizumab (or atezolizumab) with another anti-PD-1 antibody of reference patent (e.g. toripallimab) taught by the claims of reference patent and Ren. One of ordinary skill in the art would have had a reasonable expectation that toripallimab would also be efficacious to advanced EGFR-/ALK- NSCLC, because Melosky teaches that different anti-PD-1 antibodies are more effective when combined with pemetrexed + cisplatin and checkpoint inhibitors added to standard therapies improve overall survival for nonsquamous EGFR-/ALK- advanced NSCLC; Ren teaches that toripallimab and chemotherapeutic agent combinations can be used to treat advanced NSCLC with manageable safety profile. One of ordinary skill in the art would be motivated to use the antibodies of the reference patent based on the teachings of Melosky and Ren, to arrive the instantly claimed method.
Regarding claims 21 and 22, Gorgisen teaches that NSCLC cells (H1299 cell line) with different versions of IDS1 (wild-type, single mutant or double mutant) all show responses to cisplatin (Fig. 6a). It would have prima facie been obvious to one of ordinarily skilled in the art before the effective filing date of the claimed invention to combine teachings of the claims of reference patent, Melosky, Ren and Gorgisen to treat advanced EGFR-/ALK- NSCLC with a combination of toripalimab + pemetrexed + cisplatin and to apply the treatment to individuals also have mutations in IRS1. One ordinary skill in the art would have had a reasonable expectation that the combination would also be efficacious to individuals having mutations in IRS1 because Gorgisen teaches that NSCLC cancer cells carrying different IRS1 mutations respond to cisplatin and the combination would enhance the anti-tumor activity because the combination provides multiple anti-tumor mode of actions. The motivation would have been to treat a suitable population with the claimed combination.
Patent No. 10,815,302
Claims 1-4, 6-8, 11-16, 21 and 22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 10,815,302 B2 (reference patent, corresponding to Appl. No. 16/045,363) in view of Melosky (Melosky et al., The Oncologist, 2020, 25, 64-77, Publication Date: 05/28/2019, cited in IDS of 06/24/2025) and Ren (Ren et al., Journal of Clinical Oncology, 38 (15): e21618-e21618, Publication Date: 05/20/2020, cited in IDS of 06/24/2025, of record) for claims 1-4, 6-8,11-16, and further in view of Gorgisen (Gorgisen et al., Genetics and Molecular Biology, 42, 1, 15-25, Publication Year: 2019) for claims 21 and 22.
Claims 1-4, 6-8, 11-16, 21 and 22 are rendered obvious by the combined teachings of the prior art above as discussed in the 103 rejection, the 103 being incorporated here.
Claim 1 of reference patent teaches an antibody or a functional fragment thereof that can bind to the programmed cell death 1 (PD-1) protein having an amino acid sequence of SEQ ID NO: 43, wherein the antibody or a functional fragment thereof comprises:
i) a heavy chain CDR1 having the amino acid sequence of Asp Tyr Glu Met His (SEQ ID NO: 1),
ii) a heavy chain CDR2 having the amino acid sequence of Val Ile Glu Ser Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe Lys Gly (SEQ ID NO: 2),
iii) a heavy chain CDR3 having the amino acid sequence of Glu Gly Ile Thr Thr Val Ala Thr Thr Tyr Tyr Trp Tyr Phe Asp Val (SEQ ID NO: 3),
iv) a light chain CDR1 having the amino acid sequence of Arg Ser Ser Gln Ser Ile Val His Ser Asn Gly Asn Thr Tyr Leu Glu (SEQ ID NO: 10),
v) a light chain CDR2 having the amino acid sequence of Lys Val Ser Asn Arg Phe Ser (SEQ ID NO: 11), and
vi) a light chain CDR3 having the amino acid sequence of Phe Gln Gly Ser His Val Pro Leu Thr (SEQ ID NO: 12).
Claim 11 of reference patent teaches a pharmaceutical composition comprising the antibody or functional fragment thereof according to claim 1 and a pharmaceutical carrier.
Claim 7 of reference patent teaches the antibody or functional fragment according to claim 1, comprising a heavy chain variable region comprising SEQ ID NO: 35 or an amino acid sequence that has at least 95% sequence identity with SEQ ID NO: 35 and a light chain variable region comprising SEQ ID NO: 37 or an amino acid sequence that has at least 95% sequence identity with SEQ ID NOs: 37. It is noted that SEQ ID NO: 37 of reference patent comprises SEQ ID NOs: 1-2-3 of instant application; SEQ ID NO: 35 of reference patent comprises SEQ ID NO: 4-5-6 of instant application. Alignments are shown below:
SEQ ID NO: 37 vs SEQ ID NOs: 1-2-3:
Qy 1 RSSQSIVHSNGNTYLE---------------KVSNRFS---------------------- 23
|||||||||||||||| |||||||
Db 24 RSSQSIVHSNGNTYLEWYLQKPGQSPRLLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRV 83
Qy 24 ----------FQGSHVPLT 32
|||||||||
Db 84 EAEDVGVYYCFQGSHVPLT 102
SEQ ID NO: 35 vs SEQ ID NOs: 4-5-6:
Qy 1 DYEMH--------------VIESETGGTAYNQKFKG------------------------ 22
||||| |||||||||||||||||
Db 31 DYEMHWVRQAPGQGLEWMGVIESETGGTAYNQKFKGRAKITADKSTSTAYMELSSLRSED 90
Qy 23 --------EGITTVATTYYWYFDV 38
||||||||||||||||
Db 91 TAVYYCTREGITTVATTYYWYFDV 114
Thus, the claims of the reference patent teach anti-PD-1 antibodies read on the antibody of instant claims 1 and 6. However, the claims of the reference patent do not teach the method as instantly claimed, or the antibody of instant claim 6, claim 7 or claim 8. These deficiencies are addressed by the cited references, as provided by the teachings specified in the 103 section.
The claims of reference patent, Melosky and Reb are in the same field of anti-PD-1 antibodies and treating cancers with the antibodies. Regarding claims 1-4, 6-8,11-16, it would have prima facie been obvious to one of ordinarily skilled in the art before the effective filing date of the claimed invention to treat advanced EGFR-/ALK- NSCLC with a combination of pembrolizumab + pemetrexed + cisplatin or atezolizumab + pemetrexed + cisplatin as taught by Melosky, and to substitute anti-PD-1 antibody pembrolizumab (or atezolizumab) with another anti-PD-1 antibody of reference patent (e.g. toripallimab) taught by the claims of reference patent and Ren. One of ordinary skill in the art would have had a reasonable expectation that toripallimab would also be efficacious to advanced EGFR-/ALK- NSCLC, because Melosky teaches that different anti-PD-1 antibodies are more effective when combined with pemetrexed + cisplatin and checkpoint inhibitors added to standard therapies improve overall survival for nonsquamous EGFR-/ALK- advanced NSCLC; Ren teaches that toripallimab and chemotherapeutic agent combinations can be used to treat advanced NSCLC with manageable safety profile. One of ordinary skill in the art would be motivated to use the antibodies of the reference patent based on the teachings of Melosky and Ren, to arrive the instantly claimed method.
Regarding claims 21 and 22, Gorgisen teaches that NSCLC cells (H1299 cell line) with different versions of IDS1 (wild-type, single mutant or double mutant) all show responses to cisplatin (Fig. 6a). It would have prima facie been obvious to one of ordinarily skilled in the art before the effective filing date of the claimed invention to combine teachings of the claims of reference patent, Melosky, Ren and Gorgisen to treat advanced EGFR-/ALK- NSCLC with a combination of toripalimab + pemetrexed + cisplatin and to apply the treatment to individuals also have mutations in IRS1. One ordinary skill in the art would have had a reasonable expectation that the combination would also be efficacious to individuals having mutations in IRS1 because Gorgisen teaches that NSCLC cancer cells carrying different IRS1 mutations respond to cisplatin and the combination would enhance the anti-tumor activity because the combination provides multiple anti-tumor mode of actions. The motivation would have been to treat a suitable population with the claimed combination.
Conclusion
No claims are allowed.
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/CHENG LU/Examiner, Art Unit 1642
/PETER J REDDIG/Primary Examiner, Art Unit 1646
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