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
Claims 1-17 are pending and under examination.
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 – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings. A sequence identifier for the human LAG-3 protein in Fig. 1 is not provided in the drawings or the specification.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, 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.
Claim Rejections - 35 USC § 112(b)
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 3-6 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.
Regarding claims 3, 4, and 6, the phrase "preferably" 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).
Regarding claim 5, the phrase "for example" 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 Rejections - 35 USC § 112(a)
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 1-9 and 14 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.
The teachings of the specification and the claimed invention
The instant invention is directed to methods of preventing, treating or ameliorating cancer in a subject, the method comprising administering (a) A LAG-3 protein, or a derivative thereof that is able to bind to MHC class II molecules, (b) a PD-pathway inhibitor, and (c) a chemotherapy agent.
According to the claims, the LAG-3 derivative has to have the function of binding to MHC class II molecules, but the claims do not provide a minimal structure required for any LAG-3 derivative to have this function.
The specification teaches IMP321 (eftilagimod alpha) is a soluble dimeric recombinant form of LAG-3, which is an APC activator that has shown anti-cancer T cell response alone and in combination with chemotherapy (Specification, Pg. 29-33). Pertaining to “derivatives” of LAG-3, the specification teaches several derivatives are known in the art, with some mutants having reduced binding to MHC class II and some with increased affinity to MHC class II (Specification, Pg. 8, Lines 4-10). The specification further teaches the residues and structure required for binding LAG-3 to MHC class II are clustered in a loop structure of the D1 of human LAG-3. The specification teaches that in an embodiment of the invention, the derivative of LAG-3 comprises SEQ ID NO: 2 (GPPAAAPGHPLAPGPHPAAPSSWGPRPRRY) pertaining to the amino acid loop structure of the D1 domain of human LAG-3 with amino acid substitutions, however, the specification does not teach that any polypeptide comprising SEQ ID NO:2 would have the secondary structure required to bind MHC class II and activate APCs. Importantly, the specification does not provide any therapeutically relevant variants of LAG-3 other than IMP321.
The state of the prior art
The art teaches that LAG-3 is an immune checkpoint molecule comprising four Ig-like domains, and the interaction of T cell-expressed LAG-3 with its ligands leads to down-regulation of CD4+ T cell clone activation (Huard et al. Proc Natl Acad Sci U S A. 1997 May 27;94(11):5744-9; Pg. 5744, Right column, first full paragraph, Lines 1-7). However, US2011/0008331A1 teaches some forms of soluble LAG-3 can bind to MHC class II molecules and can induce dendritic cells to mature and migrate to secondary lymphoid organs where they can prime naïve CD4 and CD8 T cells leading to an anti-tumor response ([0006], Lines 1-12). US2011/0008331A1 also discloses a recombinant LAG-3 Ig fusion, IMP321, which was shown to activate a large range of effector cells, in particular activating monocyte/macrophages to secrete cytokines and chemokines ([0006], Lines 12-16).
Ming (Nat Commun. 2024 Aug 29;15(1):7513) characterizes the nature of LAG-3-MHC-II binding through resolving the crystal structure of the binding pair (see Fig. 1a). Ming importantly teaches that the binding requires both critical amino acid residues and critical secondary protein structures, teaching the following: (1) D1 of LAG3 engages the membrane-proximal α2 and β2 subdomains of I-Ab, (2) - interactions with α2 are largely mediated by inter-strand loops at the tip of mLAG3 D1, and (3) LAG-3 interactions with β2 are mediated by residues along the edge of the D1 β-sheet (Fig. 2a). A
cluster of polar residues in two D1 loops, N54, R57, R121, Q124 and R125, are located opposite a charge-complementary surface of MHC-II α2 (Fig. 2b, structure described Pg. 2, right column, full paragraph 1, entire paragraph). To this end, any variants of LAG-3 that are capable of binding MHC class II molecules must possess the critical binding residues and secondary protein structures.
Importantly, Huard (supra) describes several LAG-3 variants which can bind MHC class II molecules but also states “Unexpectedly, some mutations were able to reduce class II binding while other mutations increased the affinity of LAG-3 for class II molecules” (see page 5747, 1st column, paragraph 3). Given this unpredictability, wherein not all variants of LAG-3 can bind MHC class II and initiate antitumorigenic effects, one skilled in the art would not have recognized that mutants disclosed in the specification are representative to the claimed genus. Furthermore, there is no correlation between structure and the recited functions. Thus, one skilled in the art cannot predict the structures of other derivatives based on the disclosure of the instant specification and prior art.
Claim analysis
In view of the teachings of the disclosure and the state of the prior art, the claims have the following written description issues:
Claims 1 and 2 are directed to methods of treating or ameliorating cancer in a subject comprising administering a LAG-3 protein or a derivative thereof (emphasis added) that is able to bind MHC class II molecules, but this language allows for fragments, mutations, deletions in the LAG-3 protein without defining the minimum structure required for this function.
Claims 3 and 4 claim that the derivative of the LAG-3 protein comprises an amino acid sequence that has at least 70% identity with D1-D4 LAG-3 domains, but this language allows for fragments, mutations, deletions in the LAG-3 protein without defining the minimum structure required for this function.
The LAG-3 protein of the claims is undefined and uncharacterized, as not all variants of a LAG-3 protein would be capable of binding MHC class II molecules. Applicant’s specification does not make clear they are in possession of all possible LAG-3 proteins or derivatives thereof to establish possession. The examples from the specification are not representative of the full breadth of the term “LAG-3 derivative” and the claim does not provide evidence for one to identify what falls under this term.
That is, the specification provides neither a representative number of the encompassed LAG-3 proteins, nor does it provide a descriptive of structural features that are common to the encompassed LAG-3 proteins.
Since the disclosure fails to describe the common attributes or characteristics that identify members of the genus, and because the genus is highly variant, the artisan cannot envision the detailed structure of the encompassed LAG-3 proteins and therefore Applicant was not in possession of the instant claimed invention.
Dependent claims 5-9, and 14 are rejected for being dependent on claim 10 and not providing limitations that overcome the 35 U.S.C. 112(a) rejection.
SCOPE OF ENABLEMENT
Claims 1-17 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of treating or ameliorating a cancer in a subject comprising administering the LAG-3 Ig fusion protein IMP321, does not reasonably provide enablement for (1) treating or ameliorating a cancer in a subject by administering any LAG-3 protein derivative or (2) preventing cancer in a subject using any of the claimed methods. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The factors to be considered in determining whether a disclosure would require undue experimentation include:
A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
In re Wands, 8 USPQ2d, 1400 (CAFC 1988) and MPEP 2164.01.
The breadth of the claims and the nature of the invention
With respect to claim breadth, the standard under 35 U.S.C. §112, first paragraph, entails the determination of what the claims recite and what the claims mean as a whole. As such, the broadest reasonable interpretation of the claimed method is that: (1) any LAG-3 protein derivative can treat or ameliorate cancer in a subject and (2) a triple combination comprising a LAG-3 protein can prevent cancer. A skilled artisan would not know how to use the method with a reasonable expectation of success based solely on what is disclosed in the specification.
The state of the relevant art and level of predictability in the art
Pertaining to cancer treatment comprising LAG-3 variants:
Multiple references teach the administration of recombinant LAG-3 Ig fusion, IMP321, alone and in combination with other therapeutics for the treatment of cancer. IMP321 is described in WO 2009/044273 (IDS 12/15/2023) which describes the use of IMP321 alone and in combination with a chemotherapy agent for the treatment of cancer (Pg. 15-16, claims 1-8). In addition, WO2016/110593 describes the use of IMP321 in combination with a PD-1 pathway inhibitor for the treatment of cancer and infectious disease.
In a post-filing review, Chocarro (Immunooncol Technol. 2022 Mar 17;14:100079) describes three classes of clinically relevant LAG-3 targeted therapies which are anti-LAG-3 monoclonal antibodies, LAG-3-Ig fusion proteins and anti-LAG-3 bispecific molecules (Fig. 1). Within the category of LAG-3-Ig fusion proteins, only one clinically relevant pharmaceutical IMP321 was provided, teaching the that soluble LAG-3 IMP321 is associated with protective resistance to both infectious and malignant disease (Pg. 4, Right column, Soluble LAG-3 fusion proteins, entire section).
Importantly, as reviewed in the above written description rejection, Huard (Proc Natl Acad Sci U S A. 1997 May 27;94(11):5744-9) describes several LAG-3 variants which can bind MHC class II molecules but also states “Unexpectedly, some mutations were able to reduce class II binding while other mutations increased the affinity of LAG-3 for class II molecules” (see page 5747, 1st column, paragraph 3).
Pertaining to the prevention of cancer:
The art does not provide compensatory teachings regarding the prevention of cancer. Cancer has a wide variety of causes, from environmental and/or developmental exposure to ionizing radiation and/or chemical exposure in addition to some types viral and bacterial exposure (Lichtman MA et al. The Oncologist 2017; 22(5); 542–548). Even though cancer is characterized by cell proliferation, its pathogenesis is extremely complex and related to many mechanisms. In general, the hallmarks of cancer consist of ten biological capabilities during the development of cancers, namely sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, tumor-promoting inflammation, genome instability and mutation, evading immune destruction and reprogramming energy metabolism (Hanahan D et al. Cell 2011 144(5) p646-674, Figures 1 and 3). More than 100 types of cancer have been identified which are typically termed for the organs or tissues where they occur. Hanahan taught over the past decade, tumors have increasingly been recognized as organs whose complexity approaches and may even exceed that of normal healthy tissues (page 661, right column second to last paragraph). Hanahan taught many human tumors are histopathologically diverse, containing regions demarcated by various degrees of differentiation, proliferation, vascularity, inflammation, and/or invasiveness (page 662, left column, first paragraph).
The art pertaining to the prevention of cancer focuses mostly on health promoting primary prevention methods that mitigate known risk factors through behavior modification such as reducing of tobacco usage, reducing exposure to occupational carcinogens and managing obesity (Vineis, P. Lancet. 2014 Feb 8;383(9916):549-57)
There is no evidence of the use of immunotherapy as described in the instant claims in undiagnosed individuals for the prevention of cancer. Clinical trials aimed at proving preventative cancer activity attributable to a specific intervention are largely infeasible, due to the impossibly large number of subjects and an equally impossible long timeframe. Although cancer is a common disease, specific types of cancer are still relatively infrequent events in an otherwise healthy population. Therefore, trials with cancer incidence as endpoints would necessarily involve several thousands of subjects followed for several decades. Such logistic difficulties have precluded trials with cancer incidence prevention as an endpoint.
The specification as filed does not provide enabling guidance that overcomes this unpredictability within the art.
The amount of direction provided by the inventor and the existence of working examples
What is enabled by the working examples is narrow in comparison to the breadth of the claims.
The disclosure describes treatment of patients with NSCLC comprising administration of IMP321 in parallel with pemetrexed, carboplatin, and pembrolizumab (Example 1, Pg. 22, Lines 13-17). The specification describes results of the therapy in a single patient, showing the treatment resulted in shrinkage of target tumor lesions (Pg. 22, Lines 20-29).
The quantity of experimentation needed to make or use the invention
The instant specification is not enabling because one cannot follow the guidance presented therein, or within the art at the time of filing, and practice the claimed method without first making a substantial inventive contribution. Given that the nature of the invention is in vivo prevention and treatment of disease, a person having ordinary skill in the art would have to perform multiple further in vivo experiments, in human clinical trials, or in animal models that are predictive of cancer prevention of the broadly recited diseases with a reasonable expectation of success. The amount of experimentation required for enabling guidance, commensurate in scope with what is claimed, goes beyond what is considered ‘routine' within the art, and constitutes undue further experimentation in order to use the method with a reasonable expectation of successfully treating and preventing the disclosed diseases and conditions.
In view of the lack of predictability of the art to which the invention pertains, the lack of guidance and direction provided by applicant, and the absence of appropriate working examples commensurate with the scope of the claims, undue experimentation would be required to use the claimed invention.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-14 and 17 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Srivastava (WO2020/023707A1, published 01/30/2020, effectively filed 07/25/2019) as evidenced by Triebel (US2011/0008331A1, published 01/13/2011).
The disclosure of Srivastava is directed to a medicament for the treatment of tumors in a human patient comprising a LAG-3 antagonist, wherein the LAG-3 antagonist is defined in the disclosure as an anti-LAG-3 antibody or a soluble LAG-3 protein, in combination with PD-1 pathway inhibitor and one or more chemotherapeutic agents (Abstract).
Regarding claims 1 and 2, pertaining to a method of treating or ameliorating a cancer in subject, the method comprising administering to the subject (a) a LAG-3 protein, or a derivative thereof that is able to bind to MHC class II molecules, (b) a programmed cell death protein (PD-1) pathway inhibitor and (c) a chemotherapy agent (claim 1), and wherein the LAG-3 protein is administered simultaneously or sequentially with the PD-1 pathway inhibitor and chemotherapy agent (claim 2), Srivastava discloses a method of inhibiting the growth of a malignant tumor and a method of treating cancer in human patient, comprising administering to the patient an effective amount of each of (a) a LAG-3 antagonist, (b) a PD-1 pathway inhibitor, and (c) one or more chemotherapeutic agents (Pg. 79, claims 1 and 2). Srivastava defines the LAG-3 antagonist as comprising soluble LAG-3 polypeptides ([0128], Lines 2-3) and discloses the use of IMP321 (Pg. 81, claim 15). As evidenced by the instant specification, IMP321 stimulates APCs through binding MHC class II molecules (Pg. 1, Lines 29-31).
Regarding claims 3 and 4, wherein the derivative of LAG-3 protein comprises an amino acid sequence that has at least 70% amino acid sequence identity with domain D1, optionally D2 (claim 3) or at least 70% amino acid identity with domains D1, D2, and D3, optionally domain D4 (claim 4), IMP321 comprises the extracellular domains of human LAG-3 linked to human IgG1 Fc as evidenced by Triebel ([0040]-[0041]).
Regarding claims 5 and 6, wherein the cancer according to the method of claim 1 is selected from the disclosed list (claim 5), and wherein the cancer is lung cancer (claim 6), Srivastava discloses the tumor treated by the method of disclosure is a lung cancer (Pg. 79, claim 5).
Regarding claims 7 and 8, wherein the PD-1 pathway inhibitor according to the method of claim 1 is selected from the disclosed group (claim 7), and wherein the PD-1 pathway inhibitor is pembrolizumab (claim 8), Srivastava discloses the anti-PD-1 antibody is pembrolizumab (Pg. 82, claim 21).
Regarding claim 9, wherein the chemotherapy agent according to the method of claim 1 is combination of two or more chemotherapy agents, Srivastava discloses the use of one or more chemotherapeutic agents (Pg. 79, claims 1-4) and provides multiple chemotherapy treatment combinations comprising two or more chemotherapeutic agents, for example XELOX treatment comprising oxaliplatin and capecitabine (Pg. 83, claim 28) and others in claims 29, 32, 33.
Regarding claim 10, wherein the LAG-3 derivative is IMP321, the PD-1 pathway inhibitor is pembrolizumab, the chemotherapy agent comprises a combination of two chemotherapy agents, and the cancer is NSLC, Srivastava discloses the LAG-3 antagonist is IMP321 (Pg. 81, claim 15), the PD-1 pathway inhibitor is pembrolizumab (Pg. 82, claim 21), and the treatment comprises one or more chemotherapeutic agents and provides an exemplary combination of two chemotherapeutics oxaliplatin and capecitabine (Pg. 83, claim 28).
Regarding claims 11-13, wherein the PD-L1 expression level of the subject is <50% (claim 11), 1-49% (claim 12), <1% (claim 13), Srivastava teaches embodiments wherein the patient has a “PD-L1 positive tumor” ([0085], Lines 1-5) and defines PD-L1 positive is at least 0.01% and up to at least 30% ([0058], Lines 1-9).
Regarding claim 14, wherein the subject according to the method according to claim 1 is a human, Srivastava discloses the method of inhibiting tumor growth and treating cancer are in a human patient (Pg. 79, claims 1-4).
Regarding claim 17, wherein the subject according to the method of claim 10 is treated without regard to their PD-L1 status, Srivastava teaches the criteria for their claimed treatment methods are that the patient’s tumor associated immune cells express LAG-3 (Pg. 79) and are silent to PD-L1 status of the patient.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-15 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Srivastava (WO2020/023707A1, published 01/30/2020) as applied to claims 1-14 and 17 above, and further in view of Langer (Lancet Oncol. 2016 Nov;17(11):1497-1508, IDS filed 12/15/2023).
The disclosure of Srivastava teaches a method of treating a cancer in a human patient comprising administering LAG-3 polypeptide IMP321, pembrolizumab, and one or more chemotherapeutic agents. Srivastava teaches the use of platinum agents such as cisplatin, oxaliplatin, and carboplatin (Pg. 58, Line 26).
The disclosure of Srivastava does not teach the one or more chemotherapeutic agents is a combination of pemetrexed and a platinum chemotherapy agent selected from the group consisting of carboplatin, cisplatin, and oxaliplatin.
The disclosure of Langer is directed to a clinical trial assessing the addition of pembrolizumab to platinum doublet chemotherapy comprising carboplatin and pemetrexed for the treatment of non-small-cell lung cancer (NSCLC). Langer teaches 55% of patients who received pembrolizumab plus chemotherapy achieved an objective response compared with 29% of the patients in the chemotherapy alone group (Abstract, Findings).
Regarding claim 15, wherein the combination of two chemotherapy agents according to the method of claim 10 is a combination of pemetrexed and a platinum chemotherapy agent selected from the group consisting of carboplatin, cisplatin, and oxaliplatin, Langer teaches co-administration of pembrolizumab plus carboplatin and pemetrexed (response to treatment shown in Table 2).
It would have been prima facie obvious to one having ordinary skill in the art at the time of filing to modify the treatment method of Srivastava comprising IMP321, pembrolizumab and one or more chemotherapy agents, by using carboplatin and pemetrexed as the chemotherapeutic agents. One would have been motivated to do so because Langer teaches their clinical trial data suggests the combination of pembrolizumab, carboplatin and pemetrexed provides a significant and clinically relevant improvement in antitumor activity compared to single therapy treatment. There would be an expectation of success of using carboplatin and pemetrexed in Srivastava’s method because the method requires the use of chemotherapeutic agents and Langer teaches favorable antitumorigenic results from a combination of carboplatin and pemetrexed and pembrolizumab.
Claims 1-14 and 16-17 are rejected under 35 U.S.C. 103 as being unpatentable over Srivastava (WO2020/023707A1, published 01/30/2020) as applied to claims 1-14 and 17 above, and further in view of Paz-Ares (N Engl J Med. 2018 Nov 22;379(21):2040-2051).
The disclosure of Srivastava teaches a method of treating a cancer in a human patient comprising administering LAG-3 polypeptide IMP321, pembrolizumab, and one or more chemotherapeutic agents. Srivastava teaches the use of platinum agents such as cisplatin, oxaliplatin, and carboplatin (Pg. 58, Line 26).
The disclosure of Srivastava does not teach the one or more chemotherapeutic agents is a combination of carboplatin and a taxane selected from the group consisting of paclitaxel and nab-paclitaxel.
This deficiency is taught by Paz-Ares.
The disclosure of Paz-Ares is directed to a clinical trial of pembrolizumab and chemotherapy comprising carboplatin plus paclitaxel or nab-paclitaxel for the treatment of NSCLC. The median overall survival was 15.9 months (95% confidence interval [CI], 13.2 to not reached) in the pembrolizumab-combination group and 11.3 months (95% CI, 9.5 to 14.8) in the placebo-combination group (Abstract, Results). In patients with previously untreated metastatic, squamous NSCLC, Paz-Ares teaches the addition of pembrolizumab to standard chemotherapy with carboplatin and either paclitaxel or nab-paclitaxel prolonged median overall survival by 4.6 months and median progression-free survival by 1.6 months (Pg. 2047, Data shown in Fig. 1 and Fig. 2).
Regarding claim 16, wherein the combination of two chemotherapy agents according to the method of claim 10 is a combination of carboplatin and a taxane selected from the group consisting of paclitaxel and nab-paclitaxel, Paz-Ares teaches the addition of pembrolizumab to standard chemotherapy with carboplatin and either paclitaxel or nab-paclitaxel (Pg. 2047, Data shown in Fig. 1 and Fig. 2).
It would have been prima facie obvious to one having ordinary skill in the art at the time of filing to modify the treatment method of Srivastava comprising IMP321, pembrolizumab and one or more chemotherapy agents, by using carboplatin plus paclitaxel or nab-paclitaxel as the chemotherapeutic agents. One would have been motivated to do so because Paz-Ares teaches that in patients with previously untreated metastatic, squamous NSCLC, the addition of pembrolizumab to chemotherapy with carboplatin plus paclitaxel or nab-paclitaxel resulted in significantly longer overall survival and progression-free survival than chemotherapy alone (Abstract, Conclusions). There would be an expectation of success of using carboplatin plus paclitaxel or nab-paclitaxel in Srivastava’s method because the method requires the use of chemotherapeutic agents and Paz-Ares teaches favorable antitumorigenic results from a combination of carboplatin plus paclitaxel or nab-paclitaxel and pemroblizumab.
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.
U.S. Pat. No. 10,736,940
Claims 1-14 and 17 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-40 of U.S. Patent No. 10,736,940 in view of Srivastava (WO2020/023707A1, published 01/30/2020, effectively filed 07/25/2019) as evidenced by Triebel (US2011/0008331A1, published 01/13/2011).
Regarding claims 1-4, pertaining to a method of treating or ameliorating a cancer in subject, the method comprising administering to the subject (a) a LAG-3 protein, or a derivative thereof that is able to bind to MHC class II molecules, (b) a programmed cell death protein (PD-1) pathway inhibitor and (c) a chemotherapy agent (claim 1), and wherein the LAG-3 protein is administered simultaneously or sequentially with the PD-1 pathway inhibitor and chemotherapy agent (claim 2), ‘940 teaches a method of treating or ameliorating cancer comprising administering IMP321 and a platinum-based chemotherapy comprising oxaliplatin or carboplatin (claims 1 and 10).
‘940 does not teach (1) administration of a PD-1 pathway inhibitor, (2) the cancer treated is lung cancer, specifically NSCLC, or (3) treatment based on PD-L1 status.
These limitations are taught by Srivastava.
Regarding the limitation of claims 1-2 and claims 7-8, wherein the combination therapy comprises a PD-1 pathway inhibitor (claims 1-2), wherein the PD-1 pathway inhibitor according to the method of claim 1 is selected from the disclosed group (claim 7), and wherein the PD-1 pathway inhibitor is pembrolizumab (claim 8), Srivastava discloses the anti-PD-1 antibody is pembrolizumab (Pg. 82, claim 21).
Regarding claims 5 and 6, wherein the cancer according to the method of claim 1 is selected from the disclosed list (claim 5), and wherein the cancer is lung cancer (claim 6), Srivastava discloses the tumor treated by the method of disclosure is a lung cancer, specifically NSCLC (Pg. 79, claim 5).
Regarding claim 9, wherein the chemotherapy agent according to the method of claim 1 is combination of two or more chemotherapy agents, Srivastava discloses the use of one or more chemotherapeutic agents (Pg. 79, claims 1-4) and provides multiple chemotherapy treatment combinations comprising two or more chemotherapeutic agents, for example XELOX treatment comprising oxaliplatin and capecitabine (Pg. 83, claim 28) and others in claims 29, 32, 33.
Regarding claim 10, wherein the LAG-3 derivative is IMP321, the PD-1 pathway inhibitor is pembrolizumab, the chemotherapy agent comprises a combination of two chemotherapy agents, and the cancer is NSLC, Srivastava discloses the LAG-3 antagonist is IMP321 (Pg. 81, claim 15), the PD-1 pathway inhibitor is pembrolizumab (Pg. 82, claim 21), and the treatment comprises one or more chemotherapeutic agents and provides an exemplary combination of two chemotherapeutics oxaliplatin and capecitabine (Pg. 83, claim 28).
Regarding claims 11-13, wherein the PD-L1 expression level of the subject is <50% (claim 11), 1-49% (claim 12), <1% (claim 13), Srivastava teaches embodiments wherein the patient has a “PD-L1 positive tumor” ([0085], Lines 1-5) and defines PD-L1 positive is at least 0.01% and up to at least 30% ([0058], Lines 1-9).
Regarding claim 14, wherein the subject according to the method according to claim 1 is a human, Srivastava discloses the method of inhibiting tumor growth and treating cancer are in a human patient (Pg. 79, claims 1-4).
Regarding claim 17, wherein the subject according to the method of claim 10 is treated without regard to their PD-L1 status, Srivastava teaches the criteria for their claimed treatment methods are that the patient’s tumor associated immune cells express LAG-3 (Pg. 79) and are silent to PD-L1 status of the patient.
It would have been prima facie obvious to one having ordinary skill in the art at the time of filing to modify the combination therapy of ‘940 comprising IMP321 and chemotherapy with the addition of pembrolizumab because Srivastava teaches a triple combination cancer therapy comprising a LAG-3 polypeptide, pembrolizumab and chemotherapeutic agents. One would have been motivated to do because Srivastava teaches the efficacy of LAG-3 targeted therapy in addition to standard treatment for NSCLC comprising pembrolizumab and chemotherapy. This modification to the method constitutes combining prior art elements according to known methods to yield predictable results. There would be an expectation of success in modifying the combination therapy of ‘940 with the teaching of Srivastava because combination therapies comprising different means of targeting cancer is standard in the field.
Claims 1-15 and 17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-40 of U.S. Patent No. 10,736,940 in view of Srivastava (WO2020/023707A1, published 01/30/2020, effectively filed 07/25/2019) as applied to claims 1-14 and 17 above and further in view of Langer (Lancet Oncol. 2016 Nov;17(11):1497-1508).
The combined teachings of Pat. No. ‘940 and Srivastava teach a triple combination therapy comprising adminstering LAG-3 polypeptide IMP321, pembrolizumab, and one or more chemotherapeutic agents.
‘940 does not teach the one or more chemotherapeutic agents is a combination of pemetrexed and a platinum chemotherapy agent selected from the group consisting of carboplatin, cisplatin, and oxaliplatin.
The disclosure of Langer is directed to a clinical trial assessing the addition of pembrolizumab to platinum doublet chemotherapy comprising carboplatin and pemetrexed for the treatment of non-small-cell lung cancer (NSCLC). Langer teaches 55% of patients who received pembrolizumab plus chemotherapy achieved an objective response compared with 29% of the patients in the chemotherapy alone group (Abstract, Findings).
Regarding claim 15, wherein the combination of two chemotherapy agents according to the method of claim 10 is a combination of pemetrexed and a platinum chemotherapy agent selected from the group consisting of carboplatin, cisplatin, and oxaliplatin, Langer teaches co-administration of pembrolizumab plus carboplatin and pemetrexed (response to treatment shown in Table 2).
It would have been prima facie obvious to one having ordinary skill in the art at the time of filing to modify the treatment method of ‘940 comprising IMP321, pembrolizumab and one or more chemotherapy agents, by using carboplatin and pemetrexed as the chemotherapeutic agents. One would have been motivated to do so because Langer teaches their clinical trial data suggests the combination of pembrolizumab, carboplatin and pemetrexed provides a significant and clinically relevant improvement in antitumor activity compared to single therapy treatment. There would be an expectation of success of using carboplatin and pemetrexed in ‘940 method because the method requires the use of chemotherapeutic agents and Langer teaches favorable antitumorigenic results from a combination of carboplatin and pemetrexed and pemroblizumab.
Claims 1-14 and 16-17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-40 of U.S. Patent No. 10,736,940 in view of Srivastava (WO2020/023707A1, published 01/30/2020, effectively filed 07/25/2019) as applied to claims 1-14 and 17 above and further in view of Paz-Ares (N Engl J Med. 2018 Nov 22;379(21):2040-2051).
The combined teachings of Pat. No. ‘940 and Srivastava teach a triple combination therapy comprising adminstering LAG-3 polypeptide IMP321, pembrolizumab, and one or more chemotherapeutic agents.
‘940 does not teach the one or more chemotherapeutic agents is a combination of carboplatin and a taxane selected from the group consisting of paclitaxel and nab-paclitaxel.
This deficiency is taught by Paz-Ares.
The disclosure of Paz-Ares is directed to a clinical trial of pembrolizumab and chemotherapy comprising carboplatin plus paclitaxel or nab-paclitaxel. The median overall survival was 15.9 months
(95% confidence interval [CI], 13.2 to not reached) in the pembrolizumab-combination group and 11.3 months (95% CI, 9.5 to 14.8) in the placebo-combination group (Abstract, Results). In patients with previously untreated metastatic, squamous NSCLC, Paz-Ares teaches the addition of pembrolizumab to standard chemotherapy with carboplatin and either paclitaxel or nab-paclitaxel prolonged median overall survival by 4.6 months and median progression-free survival by 1.6 months (Pg. 2047, Data shown in Fig. 1 and Fig. 2).
Regarding claim 16, wherein the combination of two chemotherapy agents according to the method of claim 10 is a combination of carboplatin and a taxane selected from the group consisting of paclitaxel and nab-paclitaxel, Paz-Ares teaches the addition of pembrolizumab to standard chemotherapy with carboplatin and either paclitaxel or nab-paclitaxel (Pg. 2047, Data shown in Fig. 1 and Fig. 2).
It would have been prima facie obvious to one having ordinary skill in the art at the time of filing to modify the treatment method of ‘940 comprising IMP321, pembrolizumab and one or more chemotherapy agents, by using carboplatin plus paclitaxel or nab-paclitaxel as the chemotherapeutic agents. One would have been motivated to do so because Paz-Ares teaches that in patients with previously untreated metastatic, squamous NSCLC, the addition of pembrolizumab to chemotherapy with carboplatin plus paclitaxel or nab-paclitaxel resulted in significantly longer overall survival and progression-free survival than chemotherapy alone (Abstract, Conclusions). There would be an expectation of success of using carboplatin plus paclitaxel or nab-paclitaxel in ‘940 method because the method requires the use of chemotherapeutic agents and Paz-Ares teaches favorable antitumorigenic results from a combination of carboplatin plus paclitaxel or nab-paclitaxel and pemroblizumab.
Additional Nonprovisional and Provisional Rejections from the US Pat. No. 10,736,940 patent family
Claims 1-17 are rejected on the ground of nonstatutory double patenting as being unpatentable over the U.S. patents and co-pending applications listed below pertaining to the same patent family in view of Srivastava (WO2020/023707A1), Langer (Lancet Oncol. 2016 Nov;17(11):1497-1508), and Paz-Ares (N Engl J Med. 2018 Nov 22;379(21):2040-2051).
Nonprovisional
US 12,214,012 – claims 1-12
Provisional
19/000,820 – claims 30-37
U.S. Pat. No. 10,874,713
Claims 1-14 and 17 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 10,874,713 in view of Srivastava (WO2020/023707A1, published 01/30/2020, effectively filed 07/25/2019) as evidenced by Triebel (US2011/0008331A1, published 01/13/2011).
Regarding claims 1-4, 7-8, and 10, pertaining to a method of treating or ameliorating a cancer in subject, the method comprising administering to the subject (a) a LAG-3 protein, or a derivative thereof that is able to bind to MHC class II molecules, (b) a programmed cell death protein (PD-1) pathway inhibitor and (c) a chemotherapy agent (claim 1), ‘713 teaches a method of treating or ameliorating cancer comprising administering IMP321 and pembrolizumab (claim 1).
‘713 does not teach (1) administration of a chemotherapy agent, (2) the cancer treated is lung cancer, specifically NSCLC, or (3) treatment based on PD-L1 status.
These limitations are taught by Srivastava.
Regarding the limitation of claim 1 and claim 9, wherein the combination therapy comprisies a chemotherapy agent (claim 1), the chemotherapy agent is combination of two or more chemotherapy agents (claim 9), Srivastava discloses the use of one or more chemotherapeutic agents (Pg. 79, claims 1-4) and provides multiple chemotherapy treatment combinations comprising two or more chemotherapeutic agents, for example XELOX treatment comprising oxaliplatin and capecitabine (Pg. 83, claim 28) and others in claims 29, 32, 33.
Regarding claims 5 and 6, wherein the cancer according to the method of claim 1 is selected from the disclosed list (claim 5), and wherein the cancer is lung cancer (claim 6), Srivastava discloses the tumor treated by the method of disclosure is a lung cancer, specifically NSCLC (Pg. 79, claim 5).
Regarding claim 9, wherein the chemotherapy agent according to the method of claim 1 is combination of two or more chemotherapy agents, Srivastava discloses the use of one or more chemotherapeutic agents (Pg. 79, claims 1-4) and provides multiple chemotherapy treatment combinations comprising two or more chemotherapeutic agents, for example XELOX treatment comprising oxaliplatin and capecitabine (Pg. 83, claim 28) and others in claims 29, 32, 33.
Regarding claims 11-13, wherein the PD-L1 expression level of the subject is <50% (claim 11), 1-49% (claim 12), <1% (claim 13), Srivastava teaches embodiments wherein the patient has a “PD-L1 positive tumor” ([0085], Lines 1-5) and defines PD-L1 positive is at least 0.01% and up to at least 30% ([0058], Lines 1-9).
Regarding claim 14, wherein the subject according to the method according to claim 1 is a human, Srivastava discloses the method of inhibiting tumor growth and treating cancer are in a human patient (Pg. 79, claims 1-4).
Regarding claim 17, wherein the subject according to the method of claim 10 is treated without regard to their PD-L1 status, Srivastava teaches the criteria for their claimed treatment methods are that the patient’s tumor associated immune cells express LAG-3 (Pg. 79) and are silent to PD-L1 status of the patient.
It would have been prima facie obvious to one having ordinary skill in the art at the time of filing to modify the combination therapy of ‘713 comprising IMP321 and pembrolizumab with the addition of chemotherapy because Srivastava teaches a triple combination cancer therapy comprising a LAG-3 polypeptide, pembrolizumab and chemotherapeutic agents. One would have been motivated to do because Srivastava teaches the efficacy of LAG-3 targeted therapy in addition to standard treatment for NSCLC comprising pembrolizumab and chemotherapy. This modification to the method constitutes combining prior art elements according to known methods to yield predictable results. There would be an expectation of success in modifying the combination therapy of ‘713 with the teaching of Srivastava because combination therapies comprising different means of targeting cancer is standard in the field.
Claims 1-15 and 17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 10,874,713 in view of Srivastava (WO2020/023707A1, published 01/30/2020, effectively filed 07/25/2019) as applied to claims 1-14 and 17 above and further in view of Langer (Lancet Oncol. 2016 Nov;17(11):1497-1508).
The combined teachings of Pat. No. ‘713 and Srivastava teach a triple combination therapy comprising adminstering LAG-3 polypeptide IMP321, pembrolizumab, and one or more chemotherapeutic agents.
‘713 does not teach the one or more chemotherapeutic agents is a combination of pemetrexed and a platinum chemotherapy agent selected from the group consisting of carboplatin, cisplatin, and oxaliplatin.
The disclosure of Langer is directed to a clinical trial assessing the addition of pembrolizumab to platinum doublet chemotherapy comprising carboplatin and pemetrexed for the treatment of non-small-cell lung cancer (NSCLC). Langer teaches 55% of patients who received pembrolizumab plus chemotherapy achieved an objective response compared with 29% of the patients in the chemotherapy alone group (Abstract, Findings).
Regarding claim 15, wherein the combination of two chemotherapy agents according to the method of claim 10 is a combination of pemetrexed and a platinum chemotherapy agent selected from the group consisting of carboplatin, cisplatin, and oxaliplatin, Langer teaches co-administration of pembrolizumab plus carboplatin and pemetrexed (response to treatment shown in Table 2).
It would have been prima facie obvious to one having ordinary skill in the art at the time of filing to modify the treatment method of ‘713 comprising IMP321, pembrolizumab and one or more chemotherapy agents, by using carboplatin and pemetrexed as the chemotherapeutic agents. One would have been motivated to do so because Langer teaches their clinical trial data suggests the combination of pembrolizumab, carboplatin and pemetrexed provides a significant and clinically relevant improvement in antitumor activity compared to single therapy treatment. There would be an expectation of success of using carboplatin and pemetrexed in ‘713 method because the method requires the use of chemotherapeutic agents and Langer teaches favorable antitumorigenic results from a combination of carboplatin and pemetrexed and pemroblizumab.
Claims 1-14 and 16-17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 10,874,713 in view of Srivastava (WO2020/023707A1, published 01/30/2020, effectively filed 07/25/2019) as applied to claims 1-14 and 17 above and further in view of Paz-Ares (N Engl J Med. 2018 Nov 22;379(21):2040-2051).
The combined teachings of Pat. No. ‘713 and Srivastava teach a triple combination therapy comprising adminstering LAG-3 polypeptide IMP321, pembrolizumab, and one or more chemotherapeutic agents.
‘713 does not teach the one or more chemotherapeutic agents is a combination of carboplatin and a taxane selected from the group consisting of paclitaxel and nab-paclitaxel.
This deficiency is taught by Paz-Ares.
The disclosure of Paz-Ares is directed to a clinical trial of pembrolizumab and chemotherapy comprising carboplatin plus paclitaxel or nab-paclitaxel. The median overall survival was 15.9 months
(95% confidence interval [CI], 13.2 to not reached) in the pembrolizumab-combination group and 11.3 months (95% CI, 9.5 to 14.8) in the placebo-combination group (Abstract, Results). In patients with previously untreated metastatic, squamous NSCLC, Paz-Ares teaches the addition of pembrolizumab to standard chemotherapy with carboplatin and either paclitaxel or nab-paclitaxel prolonged median overall survival by 4.6 months and median progression-free survival by 1.6 months (Pg. 2047, Data shown in Fig. 1 and Fig. 2).
Regarding claim 16, wherein the combination of two chemotherapy agents according to the method of claim 10 is a combination of carboplatin and a taxane selected from the group consisting of paclitaxel and nab-paclitaxel, Paz-Ares teaches the addition of pembrolizumab to standard chemotherapy with carboplatin and either paclitaxel or nab-paclitaxel (Pg. 2047, Data shown in Fig. 1 and Fig. 2).
It would have been prima facie obvious to one having ordinary skill in the art at the time of filing to modify the treatment method of ‘713 comprising IMP321, pembrolizumab and one or more chemotherapy agents, by using carboplatin plus paclitaxel or nab-paclitaxel as the chemotherapeutic agents. One would have been motivated to do so because Paz-Ares teaches that in patients with previously untreated metastatic, squamous NSCLC, the addition of pembrolizumab to chemotherapy with carboplatin plus paclitaxel or nab-paclitaxel resulted in significantly longer overall survival and progression-free survival than chemotherapy alone (Abstract, Conclusions). There would be an expectation of success of using carboplatin plus paclitaxel or nab-paclitaxel in ‘713 method because the method requires the use of chemotherapeutic agents and Paz-Ares teaches favorable antitumorigenic results from a combination of carboplatin plus paclitaxel or nab-paclitaxel and pemroblizumab.
Additional Nonprovisional and Provisional Rejections from the US Pat. No. 10,874,713 patent family
Claims 1-17 are rejected on the ground of nonstatutory double patenting as being unpatentable over the U.S. patents listed below pertaining to the same patent family in view of Srivastava (WO2020/023707A1), Langer (Lancet Oncol. 2016 Nov;17(11):1497-1508), and Paz-Ares (N Engl J Med. 2018 Nov 22;379(21):2040-2051).
Nonprovisional
US 10,940,181 – claims 1-9
US 11,684,654 – claims 1-10
US 12,673,088 – claims 1-15
Provisional
18/312,626 – claims 64-74
Conclusion
No claims are allowed.
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/CAROL ANN CHASE/Examiner, Art Unit 1646
/HONG SANG/Primary Examiner, Art Unit 1646
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