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 amendments received 27JUL2026 are acknowledged.
Claims 9-11 and 35-36 have been canceled.
Claims 1, 8, 12-21, 25-26, 30-31, and 34 have been amended.
Claims 1-8 and 12-34 are pending in the instant application and examined on the merits (i.e., Claim 1 is independent).
Priority
The present application is a 371 National Stage of PCT International Application No. PCT/US2022/017247 filed February 22, 2022, which claims the benefit of priority to
U.S. Provisional Patent Application No. 63/276,006 filed 05NOV2021,
U.S. Provisional Patent Application No. 63/238,309 filed 30AUG2021,
U.S. Provisional Patent Application No. 63/182,454 filed 30APR2021,
U.S. Provisional Patent Application No. 63/174,480 filed 13APR2021, and
U.S. Provisional Patent Application No. 63/152,608 filed 23FEB2021. Applicant’s claim for the benefit of prior-filed application is acknowledged.
Specification
Applicant’s arguments, see p 11, Objections to the specification section, filed 27JUL2026, with respect to objections to the specification for minor informalities have been fully considered and said objections to the specification have been withdrawn in view of amendments to the specification filed as part of said response.
Claim Objections
Applicant’s arguments, see p 11-12, Objections to claims section, filed 27JUL2026, with respect to objections to of claim(s) 8, 10, 14, 25-26, and 30-31 (i.e., objection to claim 10 is moot because claims have been cancelled) for informalities have been fully considered and said objections to claim(s) 8, 14, 25-26, and 30-31 have been withdrawn in view of claim amendments filed as part of said response.
Withdrawn Rejections
Indefiniteness
Applicant’s arguments, see p 12-13, Rejections under 35 USC §112(b) section, filed 27JUL2026, with respect to the rejection(s) of claim(s) 1-34 and 36 (i.e., rejection of claim(s) 9-11 and 36 are moot because claims have been cancelled) under 35 USC §112(b) have been fully considered and said rejections of claim(s) 1-8 and 12-34 have been withdrawn in view of the claim amendments filed as part of said response.
Written Description
Applicant’s arguments, see 13-14, Rejections under 35 USC §112(a) section, filed 27JUL2026, with respect to the rejection(s) of claim(s) 1-34 and 36 (i.e., rejection of claim(s) 9-11 and 36 are moot because claims have been cancelled) under 35 USC §112(a) – written description have been fully considered and said rejections of claim(s) 1-8 and 12-34 have been withdrawn in view of the claim amendments filed as part of said response.
Double Patenting
Applicant’s arguments, see p 15, Double patenting rejection section, filed 27JUL2026, with respect to the rejection(s) of claim(s) 1-8, 10-28, and 30-34 (i.e., rejection of claim(s) 10-11 are moot because claims have been cancelled) under non-statutory double patenting have been fully considered and are fully persuasive because of the claim amendments which add limitations not taught in the cited art. As such, said rejection of claim(s) 1-8, 12-28, and 30-34 have been withdrawn in view of the claim amendments filed as part of said response.
35 USC §102
Applicant’s arguments, see p 15-16, Rejections under 35 USC §102 section, filed 27UL2026, with respect to the rejection(s) of claim(s) 1-34 and 36 (i.e., rejection of claim(s) 9-11 and 36 are moot because claims have been cancelled) under 35 USC §102 have been fully considered and are fully persuasive because of the claim amendments which add limitations not taught in the cited art. As such, said rejection of claim(s) 1-34 and 36 under 35 USC §102 have been withdrawn.
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 1-8 and 12-34 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-29 of U.S. Patent No. 11,292,842 B2 (Rietschel, et al.,), herein referred to as “‘842” in view of WO 2018/156494 A1 (Regeneron Pharmaceuticals, Inc., et al., 30AUG2018), herein referred to as “’494.” Although the claims at issue are not identical, the methods of treating metastatic NSCLC (i.e., lung cancer with secondary lesions in other organs) in a patient, comprising selecting a specific patient population (i.e., a patient with NSCLC, wherein the patient expresses PDL1 in > 50% of tumor cells and has not tested positive for EGFR, ALK, or ROS1 aberrations) and administering one or more doses of cemiplimab of claims 1, 11, and 24-25 or 26 and 29 of the issued ‘842 patent are an obvious variant of the method of treating a tumor, comprising selecting a specific patient population (i.e., lung cancer with brain metastasis, the patient is neurologically stable for at least two weeks, and the tumor has no EGFR, ALK, or ROS1 aberrations) and administering cemiplimab of the instant application.
The claims of the issued ‘842 patent and the claims of the instant application are compared in the table below:
Issued claims of the ‘842 patent:
Instant Application patent claims, underline corresponds to direct mapping to claim 1 of the ‘842 patent and italics corresponds to the additional claim limitations.
PNG
media_image1.png
2
402
media_image1.png
Greyscale
PNG
media_image1.png
2
402
media_image1.png
Greyscale
PNG
media_image2.png
40
287
media_image2.png
Greyscale
PNG
media_image1.png
2
402
media_image1.png
Greyscale
PNG
media_image3.png
812
399
media_image3.png
Greyscale
A method of treating or inhibiting the growth of a tumor, comprising:(a) selecting a patient with lung cancer and brain metastasis, wherein the patient is neurologically stable for at least two weeks and the tumor has no EGFR, ALK, or ROS1 aberrations; and (b) administering to the patient a programmed death-1 (PD-1) inhibitor, wherein the PD-1 inhibitor is a human antibody that binds specifically to PD- 1, wherein the antibody is an Ig molecule comprising two HCs and two LCs interconnected by disulfide bonds, wherein each HC comprises a HCVR comprising three heavy chain complementarity determining regions (CDRs) (HCDR1, HCDR2 and HCDR3) comprising the amino acid sequences of SEQ ID NOs: 3, 4, and 5, respectively; and each LC comprises a LCVR comprising three light chain CDRs (LCDR1, LCDR2, and LCDR3) comprising SEQ ID NOs: 6, 7, and 8, respectively. (see OA.APPENDIX for sequence alignments)
The method according to claim 1, wherein the lung cancer is non-small cell lung cancer.
The method according to claim 1, wherein the lung cancer is locally advanced or metastatic non-small cell lung cancer.
The method according to claim 1, wherein the lung cancer is locally advanced non-small cell lung cancer.
The method according to claim 4, wherein the patient is not a candidate for surgical resection or definitive chemoradiation.
The method according to claim 1, wherein the lung cancer is metastatic.
The method according to claim 1, wherein the patient has squamous or non-squamous lung cancer.
The method according to claim 1, wherein the tumor tissue in the patient expresses PD-L1 in >50% of tumor cells.
12. The method according to claim 1, wherein the HCVR comprises the amino acid sequence of SEQ ID NO: 1.
13. The method according to claim 1, wherein the LCVR comprises the amino acid sequence of SEQ ID NO: 2.
14. The method according to claim 1, wherein the HCVR and LCVR comprise the amino acid sequences of SEQ ID NO: 1 and 2, respectively.
15. The method according to claim 1, wherein the heavy chain has an amino acid sequence of SEQ ID NO: 9.
16. The method according to claim 1, wherein the light chain has an amino acid sequence of SEQ ID NO: 10.
17. The method according to claim 1, wherein the heavy chain has an amino acid sequence of SEQ ID NO: 9 and the light chain has an amino acid sequence of SEQ ID NO: 10.
18. The method according to claim 1, wherein the antibody is cemiplimab.
19. The method according to claim 11, wherein the HCVR comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 1.
20. The method according to claim 11, wherein the LCVR comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 2.
21. The method according to claim 11, wherein the HCVR comprises an amino acid sequence with at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 1 and the LCVR comprises an amino acid sequence with at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 2.
22. The method according to claim 1, wherein the method promotes tumor regression, reduces tumor cell load, reduces tumor burden, and/or prevents tumor recurrence in the patient.
23. The method according to claim 1, wherein the method leads to at least one effect selected from increase in progression-free survival, increase in overall survival, complete response, partial response, and stable disease.
24. The method of claim 1, wherein the method leads to increase in at least one of progression-free survival, overall survival, and objective response rate, as compared to chemotherapy.
25. The method according to claim 1, wherein the method leads to improved functioning and quality of life of the patient, as measured by EORTC QLQ-C30 and QLQ-LCi3, as compared to a patient treated with chemotherapy alone.
26. The method according to claim 1, herein the method delays the time to definitive deterioration in GHS/QoL of the patient, as measured by EORTC QLQ-C30 and QLQ-LCi3, as compared to a patient treated with chemotherapy alone.
27. The method according to claim 1, further comprising administering to the patient an additional therapeutic agent or therapy selected from one or more of: surgery, radiation, an anti-viral therapy, photodynamic therapy, a programmed death ligand 1 (PD-L1) inhibitor, a lymphocyte activation gene 3 (LAG3) inhibitor, a cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor, a glucocorticoid-induced tumor necrosis factor receptor (GITR) agonist, a T-cell immunoglobulin and mucin containing -3 (TIM3) inhibitor, a B- and T-lymphocyte attenuator (BTLA) inhibitor, a T-cell immunoreceptor with Ig and ITIM domains (TIGIT) inhibitor, a CD38 inhibitor, a CD47 inhibitor, an antagonist of another T-cell co-inhibitor or ligand, a CD20 inhibitor, an indoleamine-2,3-dioxygenase (IDO) inhibitor, a CD28 activator, a vascular endothelial growth factor (VEGF) antagonist, an angiopoietin-2 (Ang2) inhibitor, a transforming growth factor beta (TGF3) inhibitor, an epidermal growth factor receptor (EGFR) inhibitor, an agonist to a co-stimulatory receptor, an antibody to a tumor-specific antigen, a vaccine, an adjuvant to increase antigen presentation, an oncolytic virus, a cytotoxin, a chemotherapeutic agent, platinum-based chemotherapy, a tyrosine kinase inhibitor, an IL-6R inhibitor, an IL-4R inhibitor, an IL-10 inhibitor, a cytokine, an antibody drug conjugate (ADC), chimeric antigen receptor T cells, an anti-inflammatory drug, and a dietary supplement.
28. The method of claim 1, wherein the PD-1 inhibitor is administered as one or more doses, wherein each dose is administered two weeks, three weeks, four weeks, five weeks or six weeks after the immediately preceding dose.
29. The method of claim 1, wherein the PD-1 inhibitor is administered as two or more doses, wherein each dose is administered three weeks after the immediately preceding dose.
30. The method of claim 1, wherein the PD-1 inhibitor is administered at a dose of 5 mg to 800 mg.
31. The method of claim 1, wherein the PD-1 inhibitor is administered at a dose of 200 mg, 250 mg, or 350 mg.
32. The method of claim 1, wherein the PD-1 inhibitor is administered at a dose of 1 mg/kg to 20 mg/kg of the patient's body weight.
33. The method of claim 1, wherein the PD-1 inhibitor is administered at a dose of 1 mg/kg, 3 mg/kg or 10 mg/kg of the patient's body weight.
34. The method of claim 1, wherein the PD-1 inhibitor is administered intravenously, or subcutaneously.
Issued claims of the ‘842 patent:
Instant Application patent claims, underline corresponds to direct mapping to claim 26 of the ‘842 patent and italics corresponds to the additional claim limitations.
PNG
media_image4.png
384
410
media_image4.png
Greyscale
PNG
media_image5.png
409
398
media_image5.png
Greyscale
A method of treating or inhibiting the growth of a tumor, comprising:(a) selecting a patient with lung cancer and brain metastasis, wherein the patient is neurologically stable for at least two weeks and the tumor has no EGFR, ALK, or ROS1 aberrations; and (b) administering to the patient a programmed death-1 (PD-1) inhibitor, wherein the PD-1 inhibitor is a human antibody that binds specifically to PD- 1, wherein the antibody is an Ig molecule comprising two HCs and two LCs interconnected by disulfide bonds, wherein each HC comprises a HCVR comprising three heavy chain complementarity determining regions (CDRs) (HCDR1, HCDR2 and HCDR3) comprising the amino acid sequences of SEQ ID NOs: 3, 4, and 5, respectively; and each LC comprises a LCVR comprising three light chain CDRs (LCDR1, LCDR2, and LCDR3) comprising SEQ ID NOs: 6, 7, and 8, respectively. (see OA.APPENDIX for sequence alignments)
However, they do not claim: selecting a patient with lung cancer and brain metastasis, wherein the patient is neurologically stable for at least two weeks.
Nevertheless, ‘494 teaches methods of treating (i.e., tumor regression, abscopal effect inhibition of tumor metastasis, reduction in metastatic lesions over time, reduced use of chemotherapeutic or cytotoxic agents, reduction in tumor burden, increase in progression-free survival, increase in overall survival, complete response, partial response, and stable disease), reducing severity, or inhibiting growth of lung cancer comprising administering anti-PD1 antibodies (i.e., REGN2810, fully human antibody, also known as cemiplimab) wherein the cancer tissue expresses PDL1 (see entire document, specifically see abstract section, ¶0017, and ¶00221). Furthermore, in addition to the inclusion criteria, patients are also eligible if CNS metastases (i.e., brain metastases) are adequately treated and patients have neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least two weeks prior to enrollment (i.e., neurologically stable) (¶00276). ‘494 also teaches other objectives of the methods of treatment studies is to improve QoL and mental status (¶00220).
It would have been obvious to artisans to modify the issued methods of treating NSCLC comprising selecting the patient population and administering cemiplimab as claimed by the ‘842 patent to include selecting a patient population, wherein the patient has NSCLC with brain metastases, the patient is neurologically stable for at least two weeks, and the tumor has no EGFR, ALK, or ROS1 aberrations, as taught by ‘494. This is because ‘494 teaches additional inclusion criteria regarding treating patients with CNS metastases, wherein the patients must have returned to baseline neurologically (i.e., neurologically stable for the patient) prior to enrollment in the study (i.e., treatment with cemiplimab). One would have been motivated to do so, given the direction by the ‘842 patent that cemiplimab can be used to treat metastatic NSCLC, which is generally understood to include NSCLC which has spread from the lungs (i.e., primary tumor) to other organs, such as the brain, liver, or bones (i.e., secondary tumor) and by already limiting the patient population to those that have not tested positive for EGFR, ALK, or ROS1 aberrations, further limiting the patient population to include neurological stability would ensure clinical safety. There would have been a reasonable expectation of success, given the knowledge that by modifying the selected metastatic NSCLC patient population having no EGFR, ALK, or ROS aberrations taught by the ‘842 patent to patients having NSCLC with brain metastases, which have no EGFR, ALK, or ROS aberrations and are neurologically stable for at least two weeks results in methods of treating NSCLC with brain metastasis, wherein the safety of the patient is further taken into consideration by requiring neurological stability prior to treatment with cemiplimab, as taught by ‘494.
Although the ‘842 patent and ‘494 are silent with regard to the anti-PD1 antibody comprising the HCDRs1-3 and LCDRs1-3 of the VH and VL of cemiplimab delaying time to definitive deterioration in the patient upon administration of the anti-PD1 antibody, in claim 26, it is noted that a compound and all of its properties are inseparable; they are one and the same thing (see In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990) and MPEP §2112.01). Therefore, in the absence of evidence to the contrary, the cemiplimab antibody taught by the ‘842 patent and ‘494 would have the claimed properties recited in 26.
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 1-8 and 12-34 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO 2018/156494 A1 (Regeneron Pharmaceuticals, Inc., et al., 30AUG2018, International Application No. PCT/US2018/018747), herein referred to as “’494.”
‘494 teaches methods of treating (i.e., tumor regression, abscopal effect inhibition of tumor metastasis, reduction in metastatic lesions over time, reduced use of chemotherapeutic or cytotoxic agents, reduction in tumor burden, increase in progression-free survival, increase in overall survival, complete response, partial response, and stable disease), reducing severity, or inhibiting growth of lung cancer comprising administering anti-PD1 antibodies (i.e., REGN2810, fully human antibody, also known as cemiplimab, comprising HCDRs1-3 and LCDRs1-3 of SEQ ID NOs: 3-5 and 6-8, respectively; VH and VL of SEQ ID NOs: 1 and 2, respectively; or HC and LC of SEQ ID NOs: 9 and 10, respectively, which are 100% query match to SEQ ID NOs: 1-10 of the instant application) wherein the cancer tissue expresses PDL1 and may further comprise administration of an additional therapy of anti-CLTA4 antibody (see entire document, specifically see abstract section, claim 33, ¶0017, ¶0087, ¶00221, ¶0016) (see OA.APPENDIX for list of sequences and sequence alignments). Specifically, cemiplimab is administered to patients having squamous or non-squamous NSCLC with stage IIIB or stage IV disease or metastatic NSCLC, having tumor cells expressing PDL1 in > 50% of tumor cells, wherein patients with CNS metastases (i.e., brain metastases) have adequately been treated and patients have neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least two weeks prior to enrollment (i.e., neurologically stable) and have not tested positive for EGFR, ALK, or ROS aberrations (¶00275-00276 and ¶00289). Furthermore, ‘494 teaches that cemiplimab is administered to patients having locally advanced or metastatic NSCLC, wherein the tumors are unresectable wherein patients with CNS metastases (i.e., brain metastases) have adequately been treated and patients have neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least two weeks prior to enrollment (i.e., neurologically stable) and have not tested positive for EGFR, ALK, or ROS aberrations (Example 9, ¶00275-00276, and ¶00289). ‘494 also teaches other objectives of the methods of treatment studies is to improve QoL and mental status (¶00220). Furthermore, regarding doses of cemiplimab and dosing regimens thereof, ‘494 teaches that one or more doses are administered, wherein each dose (i.e., at least two doses) comprising 350 mg of cemiplimab is administered three weeks after the immediately preceding dose, or each dose comprises 1, 3, 4, 5, 6, or 10 mg/kg of the patient’s body weight (see claims 18 and 20). Additionally, cemiplimab is administered as an intravenous infusion to the patient or subcutaneously (claim 22 and ¶0098).
Therefore, the prior art anticipates the invention as presently claimed.
Conclusion
No claims are allowed.
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 SAMANTHA L. HOPKINS whose telephone number is (703)756-4666. The examiner can normally be reached Mon-Thurs 6:00 AM to 4:00 PM EST.
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, Misook Yu can be reached at (571)272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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.
/SAMANTHA LAKE HOPKINS/Examiner, Art Unit 1641
/MISOOK YU/Supervisory Patent Examiner, Art Unit 1641
Prosecution Insights