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 .
Priority
This application 17/997,905 filed on 11/03/2022 is a 371 national phase of PCT/EP2021/061638, filed 05/04/2021, and claims the benefit of EP Application No. 20172842.5 filed on 05/05/2020.
The priority date of independent claim 1 and its dependent claims 5-21 is determined to be 05/05/2020, the filing date of EP Application No. 20172842.5.
Status of Claims
Applicant’s amendments to claims filed 01/30/2026 in response to the Non-Final Rejection mailed 08/18/2025 are acknowledged.
Claims 1, 17, and 21 are amended.
Claims 3 and 4 have been canceled.
Claims 1 and 5-21 are pending and under examination.
Response to Remarks filed 01/30/2026
The amendments and arguments presented in the papers filed 01/30/2026 ("Remarks”) have been thoroughly considered. The issues raised in the Office action dated 08/18/2025 listed below have been reconsidered as indicated.
The objection to a lack of sequence listing in XML format is withdrawn in view of the applicant’s response pointing out the national stage status permitting submission of an ASCII version.
The objections to the specification regarding the use of hyperlinks and an incorporation by reference paragraph for the sequence listing are withdrawn in view of the amendments to the specification.
Objections to claims, 17, and 21 for informalities are withdrawn in view of amendments to the claims.
The 35 USC 112(b) indefiniteness rejections of claims 5 and 6 have been withdrawn in view of the amendments to claims.
The 35 USC 112(d) rejection of claim 3 is moot in view of the cancellation of the claim.
The rejection of claim 4 under 35 U.S.C. 101 is moot in view of the cancellation of the claim.
The rejection of claims 1 and 3-21 under 135 U.S.C. 103 as being unpatentable over Klein et al. (WO2018055145) in view of Campesato et al. (Oncotarget 6(33):34221-7 (2015)) and Bikeye et al. (Cancer Cell Int' l. 10: 1-9 (2010) is withdrawn in view of the amendments to the claims and the cancellation of claims 3 and 4.
The obviousness-type double patenting rejection of claims 1 and 3-21 over claims 1-3 of U.S. Patent 11,513,122 in view of Klein, Campesato and Bikeye is withdrawn in view of the amendments to the claims and the cancellation of claims 3 and 4
New and modified grounds of rejection necessitated by amendment are detailed below and this action is made FINAL.
Claim Rejections - 35 USC § 103 - New
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.
Claims 1, 5-18, and 20-21 are rejected under 35 U.S.C. 103 as being unpatentable over Wong (US PGPub 20170130271).
The following are new rejections necessitated by amendments.
Regarding claim 1, Wong teaches identification of biomarkers predictive of responsiveness to anti-immune checkpoint inhibitor therapies. Wong teaches anti-immune checkpoint inhibitor therapies include inhibitors of PD-1, PD-L1, and PD-L2 (para 18), which reads on PD-1 axis inhibitor therapy. Wong teaches administering to the individual a therapeutically effective amount of an immune checkpoint inhibitor therapy (para 323). Wong teaches obtaining a biological sample from a subject afflicted with cancer; determining the presence or amount (i.e. abundance) of biomarkers in the sample; and determining if the cancer would benefit from anti-immune checkpoint inhibitor therapy (para 13). Wong teaches analyzing gene expression using U133A Affymetrix arrays (para 373) which include the genes ASPM, CNOT3, LRP5 and PBX1, thus satisfying the requirements of characterizing the abundance of stem cell maintenance-related genes by detecting the expression level of the genes ASPM, CNOT3, LRP5 and PBX1.
Wong teaches stem cell markers are markers of interest (paras 8, 298, 408) but does not teach the genes ASPM, CNOT3, LRP5 and PBX1 as stem cell maintenance-related genes.
However, It would have been prima facie obvious to a person of ordinary skill in the art to arrive at the instantly claimed invention before the effective filing date from the teachings of Wong. The genes ASPM, CNOT3, LRP5 and PBX1 are all measured by Wong, and Wong teaches the importance of stem cell markers in the context of responsiveness to anti-immune checkpoint inhibitor therapies. One would have been motivated to identify additional stem cell maintenance-related genes as known in the art. Further, a person of ordinary skill in the art would understand that any given gene can be related to stem cell maintenance by direct or indirect action, thus Wong teaches elements encompassed by the requirements of the claim that “the abundance of stem cell maintenance-related genes is characterized by detecting the expression level of the genes ASPM, CNOT3, LRP5 and PBX1”. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding claim 5, Wong teaches detecting the level of a biomarker protein (para 235).
Regarding claim 6, Wong teaches detecting the level of mRNA (para 18)
Regarding claim 7, Wong teaches detecting the level of a biomarker by Western blotting (para 235).
Regarding claim 8, Wong teaches the cancer is non-small cell lung cancer (NSCLC) (para 56).
Regarding claim 9, Wong teaches the cancer is non-small cell lung cancer (para 56). Wong further teaches the importance of tumor propagating cells (i.e. cancer stem cells) in non-small cell lung cancer (SCC) in propagating cancer (i.e. metastasizing) (para 9) but does not explicitly teach the non-small cell lung cancer is advanced or metastatic.
Wong does not explicitly teach the non-small cell lung cancer is advanced or metastatic.
However, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Wong to arrive at the instantly claimed invention. The modification would have entailed selecting a tumor sample from a patient with tumor propagating cells (metastatic) for the method. Wong taught the importance of tumor propagating cells and further characterized secondary and tertiary tumor cells from lunch cancer tumors (paras 30 and 410). Wong taught the challenge of developing targeted therapies for SCC (para 3) and identifying the propagating cells in SCC (i.e. metastatic non-small cell lung cancer) (para 9). One of skill in the art would have been motivated to select patients with metastatic non-small cell lung cancer for the method in order to identify therapies that would be effective in treating a subject afflicted with cancer (a stated desire) at risk for spreading of the disease. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding claim 10, Wong teaches using anti-PD-1 antibodies alone (para 68), i.e., as a monotherapy.
Regarding claim 11, Wong teaches combination therapies including anti-immune checkpoint inhibitor therapy and chemotherapeutic agents (para 276).
Regarding claim 12, Wong teaches the anti-immune checkpoint inhibitor therapy is nivolumab (para 419), a PD-1 binding antagonist.
Regarding claim 13, Wong teaches the anti-immune checkpoint inhibitor therapy is nivolumab (para 419), which inhibits the binding of PD-1 to PD-L1.
Regarding claim 14, Wong teaches the anti-immune checkpoint inhibitor therapy includes anti-PD-1 antibodies (para 68).
Regarding claim 15, Wong teaches blocking antibodies (para 54) and the anti-immune checkpoint inhibitor therapy includes anti-PD-L1 antibodies (para 68), which reads on a PD-L1 binding antagonist.
Regarding claim 16, Wong teaches anti-immune checkpoint inhibitor agents include anti-PD-L1 antibodies that block PD-L1 binding to PD-1 (para 328).
Regarding claim 17, Wong teaches the anti-immune checkpoint inhibitor therapy includes anti-PD-L1 antibodies (para 68).
Regarding claim 18, Wong teaches agents useful for inhibiting immune checkpoint inhibitors include fragments of antibodies (para 68), including Fab or Fv fragments (para 48).
Regarding claim 20, Wong teaches determining biomarker measurements prior to administration of anti-immune checkpoint inhibitor therapy (para 300),
Regarding claim 21, Wong teaches administering anti-immune checkpoint inhibitor therapy if the cancer is determined to benefit from anti-immune checkpoint inhibitor therapy (para 13).
Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over Wong (US PGPub 20170130271) as applied to claims 1, 5-18 and 20-21 above, and further in view of Klein et al. (WO2018055145, published 03/29/2018).
The following are new rejections necessitated by amendments.
Regarding claim 19, Wong does not teach the anti-PD-L1 antibody is atezolizumab.
Klein teaches a method of predicting response to pd-1 axis inhibitors. Klein further teaches the PD-1 axis inhibitor is a PD-L1 binding antagonist (claim 13) that is an anti-PD-L1 antibody (claim 15) and embodiments where the anti-PD-LI=1 antibody is atezolizumab (p. 30, line 6).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Wong and Klein to arrive at the instantly claimed invention. The modification would have entailed using the anti-PD-LI antibody of Klein in the method of Wong. One would have been motivated to use the antibody of Klein because it meets the criteria of anti-immune checkpoint inhibitor therapies taught by Wong and Klein teaches the use of the antibody in a similar method directed towards predicting response to pd-a axis inhibitors. One of skill in the art would have been motivated to select an anti-PD-L1 antibody that was well-known in the art and routine and conventional to use. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Double Patenting -New
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, and 5-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of U.S. Patent No. 11,513,122 in view of Wong (US PGPub 20170130271).
The following are new rejections necessitated by amendments.
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant application and the ‘122 patent are drawn to a method comprising determining a gene signature expression level in a tumor tissue sample from a patient with cancer, comparing the expression level to a reference gene signature, and treating with an effective amount of a PD-1 axis inhibitor.
Regarding instant claim 1, claim 1 step (i) of the ‘122 patent requires a method for treating a patient with NSCLC, the method comprising: (i) determining in vitro a DC-related gene signature expression level in a tumor tissue sample obtained from the patient, wherein the DC-related gene signature expression level is characterized by an expression level of a group of genes consisting of XCR1, IRF8, BATF3 and FLT3.
The ’122 patent does not require detecting the expression level of the genes ASPM, CNOT3, LRP5 and PBX1.
The teachings of Wong as they relate to instant claim 1 is given previously in this office action and are fully incorporated here.
Regarding instant claim 6, claim 2 of the ‘122 patent requires gene signature expression level is determined in the sample by RNA sequencing.
Regarding instant claim 8, claim 1 of the ‘122 patent requires a patient with NSCLC (non-small cell lung cancer).
Regarding instant claim 15, claim 1 step (iii) of the ‘122 patent requires treating the patient with a therapy comprising an effective amount of atezolizumab (a PD-L1 binding antagonist).
Regarding instant claim 16, claim 1 step (iii) of the ‘122 patent requires treating the patient with a therapy comprising an effective amount of atezolizumab (a PD-L1 binding antagonist that inhibits the binding of PD-L1 to PD-1).
Regarding instant claim 17, claim 1 step (iii) of the ‘122 patent requires treating the patient with a therapy comprising an effective amount of atezolizumab.
Regarding instant claim 19, claim 1 step (iii) of the ‘122 patent requires treating the patient with a therapy comprising an effective amount of atezolizumab (i.e. an anti-PD-L1 antibody).
Regarding instant claim 20, claim 1 step (iii) of the ‘122 patent requires the tumor tissue sample is obtained from the patient before the therapy.
Regarding instant claims 5, 7, 9-14, 18, and 21, the claims of the ‘122 patent do not require the expression level is detected in the sample by protein expression (instant claim 5), the expression level is detected using a method selected from the group recited in instant claim 7, the cancer is locally advanced or metastatic non-small cell lung cancer or urothelial bladder cancer (instant claim 9), the therapy comprises an effective amount of a PD-1 axis inhibitor as monotherapy (instant claim 10), the therapy comprises an effective amount of a PD-1 axis inhibitor and an effective amount of a second agent selected from the group recited in instant claim 11, the PD-1 axis inhibitor is a PD-1 binding antagonist (instant claim 12), the PD-1 binding antagonist inhibits the binding of PD-1 to PD-L1 (instant claim 13), the PD-1 binding antagonist is an anti-PD-1 antibody (instant claim 14),the anti-PD-L1 antibody is an antibody fragment selected from the group consisting of Fab, Fab'-SH, Fv, scFv, and (Fab')2 (instant claim 18), or a method of treating a patient having a cancer, comprising administering to the patient an effective amount of a PD-1 axis inhibitor, wherein the patient is determined to be responsive to a therapy comprising an effective amount of the PD-1 axis inhibitor in accordance with the in vitro method of claim 1 (instant claim 21).
The teachings of Wong as they relate to these claims are given previously in this office action and are fully incorporated here.
Conclusion
Applicant's amendment necessitated the new ground(s) 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 JESSICA GRAY whose telephone number is (571)272-0116. The examiner can normally be reached Monday-Friday 8-5 with second Fridays off.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, WINSTON SHEN can be reached at (571)272-3157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JESSICA GRAY/Examiner, Art Unit 1682
/WU CHENG W SHEN/Supervisory Patent Examiner, Art Unit 1682
Prosecution Insights