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 preliminary amendments received 02APR2024 are acknowledged.
Claim 35 has been canceled.
Claims 3-4, 6-34, and 36 have been amended.
Claims 1-34 and 36 are pending in the instant application (i.e., Claim(s) 1 and 36 is/are 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.
Information Disclosure Statement
The information disclosure statement(s) (IDS) submitted on 21AUG2023 (2x), 18NOV2025, and 04MAAR2026 is/are acknowledged and the references cited therein have been considered.
Specification
The disclosure is objected to because of the following informalities:
Examiner notes that the specification contains a list of references at the end of the specification. Unless said references are included in the IDS or PTO-892 they have not been considered.
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (see p 47 and p 49). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Appropriate correction is required.
Claim Objections
Claims 8, 10, 14, 25-26, and 30-31 are objected to because of the following informalities:
Claim 8 contains a typographical error and should include “the” between “wherein” and “tumor” in the first line of the claim.
Claim 14 contains “/” and instead should include “and” in two places in line two of the claim.
Claims 10 and 25-26 contain the acronyms. While acronyms are permissible as shorthand in the claims, the first recitation of the term should include the full recitation followed by the acronym in parentheses.
Claims 30-31 contain a typographical error, as a space is necessary between the numbers and units in line 2 of the claims.
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.
Claim 1-34 and 36 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.
In this instance, claim 1 recites the term “bioequivalent thereof” which renders the claim indefinite. The term “bioequivalent thereof” is not defined by the claim, the specification does not provide a standard for ascertaining a bioequivalent of cemiplimab, especially when broadly defined in the specification as referring to anti-PD1 antibodies or PD1 binding proteins or fragments thereof that are pharmaceutical equivalents or alternatives whose rate and/or extent of absorption do not show a significant difference with that of cemiplimab (¶0037) without providing a definitive cemiplimab bioequivalent structure, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Furthermore, a PD1 binding protein is primarily known as a PD1 ligand and generally not considered a bioequivalent of an anti-PD1 antibody. Claims 2-34 are also rejected since they depend on claim 1 but do not remedy this deficiency.
Claims 1 and 36 recite, “…comprises HCDRs1-3 contained in a HCVR of SEQ ID NO: 1 and LCDRs1-3 contained in LCVR of SEQ ID NO: 2” and does not provide the SEQ ID NOs for the HCDRs1-3 and LCDRs1-3, which makes the claims indefinite for failing to particularly point out and distinctly claim the structure of the anti-PD1 antibody. Claims 2-10, 12-17, and 19-34 are also rejected since they depend on claim 1 but do not remedy this deficiency. In this instance, claim 11 distinctly claims six nondegenerate CDRs and their amino acid sequences of specific SEQ ID NOs and claim 18 distinctly claims the structure of cemiplimab.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Written Description
Claims 1-34 and 36 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. A “representative number of species” means that the species which are adequately described are representative of the entire genus. See, e.g., AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number” of species. The “structural features common to the members of the genus” needed for one of skill in the art to ‘visualize or recognize’ the members of the genus takes into account the state of the art at the time of the invention.
Applicant has broadly claimed a method of treating or inhibiting the growth of essentially any tumor, comprising i) selecting a patient with essentially any lung cancer and essentially any brain metastasis, and ii) administering to the patient a therapeutically effective amount of a PD1 inhibitor, wherein the PD1 inhibitor is an antibody that binds specifically to PD1 and comprises HCDRs1-3 of the VH of SEQ ID NO: 1 and LCDRs1-3 of the VL of SEQ ID NO: 2 or a bioequivalent thereof (i.e., the HCDRs1-3 and LCDRs1-3 of cemiplimab, but not necessarily cemiplimab). Claims 2-34 are also rejected since they depend from claim 1, but do not remedy this deficiency.
In this instance, the specification provides support for: a method of treating patients with advanced NSCLC and brain metastases comprising administering 350 mg every 3 weeks of cemiplimab for up to 108 weeks or until disease progression, wherein the advanced NSCLC is squamous or non-squamous NSCLC, with PDL1 expression ≥ 50%, and no EGFR, ALK, or ROS1 mutations; wherein the brain metastases are stable at baseline; and wherein cemiplimab comprises the HCDR1-3 and the LCDR1-3 amino acid sequences of SEQ ID NOs: 3-5 and 6-8, respectively. Furthermore, the specification teaches that the methods include administering a therapeutically effective amount of a PD1 inhibitor, wherein the PD1 inhibitor is cemiplimab or a bioequivalent thereof, wherein bioequivalent refers to anti-PD1 antibodies or PD1 binding proteins or fragments thereof that are pharmaceutical equivalents or pharmaceutical alternatives whose rate and/or extent of adsorption do not show a significant difference with that of cemiplimab when administered at the same molar dose under similar experimental conditions, either single dose or multiple dose and includes antigen-binding proteins that bind to PD-1 and do not have clinically meaningful differences with cemiplimab with respect to safety, purity and/or potency, but fails to provide specific examples of said bioequivalents. Per the discussion supra, the written description does not provide a definitive bioequivalent structure and is unclear on the definition of a PD1 binding protein within the bioequivalent definition. Therefore, the specification only provides support for the administration of cemiplimab, which in this instance the structure must comprise the six nondegenerate CDRs comprising the amino acid sequences set forth in SEQ ID NOs: 3-8 to function (i.e., treat lung cancer and stable brain metastases) upon administration and furthermore, the specification provides no other alternatives or bioequivalents for administration. The art supports that cemiplimab monotherapy (i.e., 350 mg every 3 weeks) provided significant survival benefit versus chemotherapy in patients with advanced NSCLC with PDL1 ≥ 50% and with brain metastases at baseline (Kilickap, et al., Cancer, 2025, 131, 1-14, see abstract section). Therefore, the prior art supports the method of treating patients with advanced NSCLC with PDL1 ≥ 50% and with brain metastases at baseline comprising administering 350 mg every 3 weeks of cemiplimab. As presently written, the claims recite that the six nondegenerate CDRs of a VH and VL of SEQ ID NOs: 1 and 2, respectively without reciting the specific CDR SEQ ID NOs or a bioequivalent thereof would upon administration treat or inhibit any tumor growth in a patient with lung cancer and brain metastasis. However, the specification fails to disclose the breadth of structures of an anti-PD1 antibody or bioequivalent thereof of cemiplimab and therefore, one of ordinary skill in the art would reasonably conclude that the applicant was not in possession of the full breadth of the claimed genus of any anti-PD1 antibody comprising the HCDRs and LCDRs in the VH and VL of SEQ ID NOs: 1 and 2 or any bioequivalent thereof, other than cemiplimab that treats or inhibits any tumor growth in a patient with any lung cancer and brain metastasis, at the time the instant application was filed.
Furthermore, the kit of claim 36 which comprises a PD1 inhibitor and written instructions, wherein the PD1 inhibitor comprises the HCDRs and LCDRs in the VH and VL of SEQ ID NOs: 1 and 2 is not fully supported in the specification because the specification only mentions a kit which includes a PD1 inhibitor (e.g., cemiplimab or a bioequivalent thereof) for therapeutic uses as described herein and typically includes a label indicating the intended use of the contents of the kit and instructions for use (¶0057); however, there are no working examples which support the kit itself or what the instructions of use would include. Thus, one of ordinary skill in the art would reasonably conclude that the applicant was not in possession of the full breadth of the claimed genus of a kit comprising a PD1 inhibitor and written instructions for use, at the time the instant application was filed.
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, 10-28, and 30-34 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 Zhou, et al., (Cancer Letters, Avail online 21JAN2021, 502, 166-179, included in IDS), herein referred to as “Zhou.” Although the claims at issue are not identical, the method of treating metastatic NSCLC patients (i.e., lung cancer with secondary lesions in other organs) comprising administering cemiplimab of specifically claim 1 and 5 of the issued ‘842 patent is an obvious variant of the method of treatment of a specific sub-population of lung cancer patients (i.e., lung cancer with brain metastasis) comprising 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.
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A method of treating or inhibiting the growth of a tumor, comprising:(a) selecting a patient with lung cancer and brain metastasis; and (b) administering to the patient a therapeutically effective amount of a programmed death-1 (PD-1) inhibitor, wherein the PD-1 inhibitor is an antibody that binds specifically to PD- 1 and comprises three heavy chain complementarity determining regions (CDRs) (HCDR1, HCDR2 and HCDR3) contained in a heavy chain variable region (HCVR) of SEQ ID NO: 1 and three light chain CDRs (LCDR1, LCDR2 and LCDR3) contained in a light chain variable region (LCVR) of SEQ ID NO: 2, or a bioequivalent thereof. (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.
11. The method according to claim 1, wherein the anti-PD-1 antibody comprises HCDR1 having an amino acid sequence of SEQ ID NO: 3; HCDR2 having an amino acid sequence of SEQ ID NO: 4; HCDR3 having an amino acid sequence of SEQ ID NO: 5; LCDR1 having an amino acid sequence of SEQ ID NO: 6; LCDR2 having an amino acid sequence of SEQ ID NO: 7; and LCDR3 having an amino acid sequence of SEQ ID NO: 8. (see OA.APPENDIX for sequence alignments)
12. The method according to claim 1, wherein the anti-PD-1 antibody comprises a HCVR comprising an amino acid sequence of SEQ ID NO: 1.
13. The method according to claim 1, wherein the anti-PD-1 antibody comprises a LCVR comprising an amino acid sequence of SEQ ID NO: 2.
14. The method according to claim 1, wherein the anti-PD-1 antibody comprises a HCVR/LCVR amino acid sequence pair of SEQ ID NO: 1/2.
15. The method according to claim 1, wherein the anti-PD-1 antibody comprises a heavy chain and a light chain, wherein the heavy chain has an amino acid sequence of SEQ ID NO: 9.
16. The method according to claim 1, wherein the anti-PD-1 antibody comprises a heavy chain and a light chain, wherein the light chain has an amino acid sequence of SEQ ID NO: 10.
17. The method according to claim 1, wherein the anti-PD-1 antibody comprises a heavy chain and a light chain, 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 anti-PD-1 inhibitor is an antibody comprising a HCVR with at least 90% sequence identity to SEQ ID NO: 1.
20. The method according to claim 11, wherein the anti-PD-1 inhibitor is an antibody comprising a LCVR with at least 90% sequence identity to SEQ ID NO: 2.
21. The method according to claim 11, wherein the anti-PD-1 inhibitor is an antibody comprising a HCVR with at least 90% sequence identity to SEQ ID NO: 1 and a LCVR with at least 90% sequence identity to 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.
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.
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A method of treating or inhibiting the growth of a tumor, comprising:(a) selecting a patient with lung cancer and brain metastasis; and (b) administering to the patient a therapeutically effective amount of a programmed death-1 (PD-1) inhibitor, wherein the PD-1 inhibitor is an antibody that binds specifically to PD- 1 and comprises three heavy chain complementarity determining regions (CDRs) (HCDR1, HCDR2 and HCDR3) contained in a heavy chain variable region (HCVR) of SEQ ID NO: 1 and three light chain CDRs (LCDR1, LCDR2 and LCDR3) contained in a light chain variable region (LCVR) of SEQ ID NO: 2, or a bioequivalent thereof.
The method according to claim 1, wherein the patient has no EGFR, ALK, or ROS1 aberrations.
However, they do not claim: selecting a patient with lung cancer and brain metastasis.
Nevertheless, Zhou teaches PD(L)1 inhibitors (e.g., pembrolizumab, nivolumab, atezolizumab, and cemiplimab) for the use in NSCLC patients with brain metastases (see entire document, specifically see Table 1). Specifically, Zhou teaches that the results from a phase 3 EMPOWER-Lung 1 study demonstrated that cemiplimab monotherapy significantly improved OS and PFS compared with chemotherapy in advanced NSCLC patients with PD-L1 expression of ≥ 50%, while superior PFS and OS were also observed in a subgroup of patients with brain metastases (see entire document, specifically see section 4.4.1). Furthermore, Zhou teaches that NSCLC comprises ~85% of all lung cancer cases and the brain is one of the most frequent sites of distant relapse in NSCLC, which is associated with extremely poor prognosis and limited treatment options due to the necessity for local control (i.e., surgery poses high-risk and radiotherapy suffers from cancer resistance) and/or lack of efficacy (i.e., systemic treatments such as chemotherapy suffers from cancer resistance and lack of BBB permeability) (see Introduction section).
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 treating NSCLC with brain metastases, as taught by Zhou. This is because Zhou teaches that NSCLC comprises ~85% of all lung cancer cases and the brain is one of the most frequent sites of distant relapse in NSCLC, which is associated with extremely poor prognosis and limited treatment options due to the necessity for local control (i.e., surgery poses high-risk and radiotherapy suffers from cancer resistance) and/or lack of efficacy (i.e., systemic treatments such as chemotherapy suffers from cancer resistance and lack of BBB permeability). 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). There would have been a reasonable expectation of success, given the knowledge that by modifying the metastatic NSCLC patient population taught by the ‘842 patent to specific metastases of the brain which would result in exemplary outcomes for treating NSCLC with brain metastasis, as taught by Zhou.
Although the ‘842 patent and Zhou are silent with regard to the anti-PD1 antibody comprising the HCDRs1-3 and LCDRs1-3 of the VH and VL of cemiplimab, promoting tumor regression, reducing tumor load, reducing tumor burden, preventing tumor recurrence, improving function and quality of life, or delaying time to definitive deterioration in the patient upon administration of the anti-PD1 antibody, in claims 22 and 25-26, 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 Zhou would have the claimed properties recited in claims 22 and 25-26.
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 1-3, 5-6, 9, 11-23, 27-30, 32-34, and 36 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by U.S. patent 9987500 B2 (Papadopoulos, et al., 05JUN2018), herein referred to as “’500.”
‘500 teaches the anti-PD1 antibody comprising the HC and LC of SEQ ID NOs: 330 and 331 (i.e., cemiplimab, 100% query match to SEQ ID NOs: 9 and 10 of the instant application and therefore 100% query match to SEQ ID NOs: 3-5 and 6-8 or SEQ ID NOs: 1 and 2) for the use in the treatment of early or late stage (i.e., metastatic) NSCLC cancer, wherein the antibody treatment reduces, inhibits, or shrinks the tumor growth, or leads to more than 50% regression of a tumor in a subject, or prevents relapse, or extends overall survival (see entire document, specifically see abstract, claim 7, and col 35, lines 35-60, see OA.APPENDIX for sequence alignments). Additionally, ‘500 teaches that the target study population comprises patients with advanced malignancies who are not candidates for standard therapy (col 75, lines 35-37) and may include patients with previously treated brain metastases provided they are stable (i.e., without evidence of progression by imaging for at least 4 weeks prior to the first dose of study treatment and any neurologic symptoms have returned to baseline (col 76, lines 9-13). Furthermore, ‘500 teaches that the antibodies of the present invention may be combined synergistically with one or more anti-cancer drugs or therapy used to treat cancer, including immunostimulatory or immunosuppressive therapies to inhibit tumor growth and/or enhance survival of cancer patients (col 36, lines 52-67), radiation, chemotherapy, anti-angiogenic agents, and surgery and one or more antibodies may be used in combination, such as a LAG3 inhibitor, a CTLA4 inhibitor, TIM3 inhibitor, etc. (col 37, lines 1-55). ‘500 further teaches that the anti-PD1 antibodies of the present invention may be administered as a single initial dose, followed by one or more secondary doses of the anti-PD1 antibody, and optionally followed by one or more tertiary doses wherein the dose administered is between 0.1 to about 60 mg/kg (col 33, lines 14-15) with 1.0, 3.0, or 10.0 mg/kg of patient weight is administered in the monotherapy study (col 76, lines 55-64) or 0.1 mg to about 800 mg (col 33, line 22-23) and wherein the secondary and tertiary doses 1 to 26 weeks (e.g., …2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, etc. weeks) after the immediately preceding dose (col 40, lines 48-54). Dosage forms may include intravenous, subcutaneous, intracutaneous, etc. (col 34, lines 8-11). Additionally, ‘500 teaches that the study treatment comprises the anti-PD1 monoclonal antibody comprising a vial of sterile liquid comprising 10 mL of the antibody at a concentration of 25 mg/mL as well as instructions on dose preparation for administration to a patient (i.e., a kit) (col 76, lines 44-50).
Although the ‘500 patent is silent with regard to the anti-PD1 antibody comprising SEQ ID NOs: 330/331 (i.e., HC/LC) being cemiplimab in claim 18, 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 antibody taught by the ‘500 patent would be equivalent to cemiplimab taught in claim 18.
Therefore, the prior art anticipates the invention as presently claimed.
Claims 1-4, 8, and 11-26 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zhou, et al., (Cancer Letters, Avail online 21JAN2021, 502, 166-179, included in IDS), herein referred to as “Zhou” and as evidenced by KEGG DRUG: Cemiplimab, accessed on 09APR2026, herein referred to as “KEGG.”
Zhou teaches PD(L)1 inhibitors (e.g., pembrolizumab, nivolumab, atezolizumab, and cemiplimab) for the use in NSCLC patients with brain metastases (see entire document, specifically see Table 1) and PD(L)1 inhibitors in combination with other therapeutic modalities (e.g., radiotherapy, chemotherapy, other ICIs) (see Table 2). Specifically, Zhou teaches that the results from a phase 3 EMPOWER-Lung 1 study demonstrated that cemiplimab monotherapy (see OA.APPENDIX for HC and LC sequence alignments between SEQ ID NOs: 9 and 10 of the instant application and cemiplimab as evidenced by KEGG) significantly improved OS and PFS compared with chemotherapy in advanced NSCLC patients with PD-L1 expression of ≥ 50%, while superior PFS and OS were also observed in a subgroup of patients with brain metastases (see entire document, specifically see section 4.4.1). Furthermore, Zhou teaches that NSCLC comprises ~85% of all lung cancer cases and the brain is one of the most frequent sites of distant relapse in NSCLC, which is associated with extremely poor prognosis and limited treatment options due to the necessity for local control (i.e., surgery poses high-risk and radiotherapy suffers from cancer resistance) and/or lack of efficacy (i.e., systemic treatments such as chemotherapy suffers from cancer resistance and lack of BBB permeability) (see Introduction section). In recent years, PD1 and PDL1 ICI have become the most promising first-line treatments for advanced NSCLC patients with positive PDL1 expression and although it has been proposed that ICI are unable to cross the BBB, several promising studies have suggested that anti-PD(L)1 immunotherapies have shown promising results in NSCLC with brain metastases (see Introduction section). Zhou further teaches that activated cytotoxic T cells that are mainly derived from the primary tumor and deep cervical lymph nodes are critical for the intracranial response to anti-PD(L)1 immunotherapy, which is driven by IFNγ (see Abstract section, Section 3, and Fig 1).
Although Zhou is silent with regard to the anti-PD1 antibody comprising the HCDRs1-3 and LCDRs1-3 of the VH and VL of cemiplimab, promoting tumor regression, reducing tumor load, reducing tumor burden, preventing tumor recurrence, improving function and quality of life, or delaying time to definitive deterioration in the patient upon administration of the anti-PD1 antibody, in claims 22 and 25-26, 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 Zhou would have the claimed properties recited in claims 22 and 25-26.
Therefore, the prior art anticipates the invention as presently claimed.
Conclusion
No claims are allowed.
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/SAMANTHA LAKE HOPKINS/Examiner, Art Unit 1641
/MISOOK YU/Supervisory Patent Examiner, Art Unit 1641
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