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 .
Election/Restrictions
Applicant's election with traverse of Claims 1-7 and 10-14 in the reply filed on 04 Feb 2026 is acknowledged. The traversal is on the ground(s) that the “patent classifications of Groups I and II are similar, therefore a single search can cover these inventions without imposing a heavy burden on the examiner.” This argument is not found persuasive: the inventions of Groups I and II do not relate to a single general inventive concept under PCT Rule 13.1 because, under PCT Rule 13.2, they lack the same or corresponding special technical features. Moreover, the inventions would require a different field of search including the use of different search queries that is not likely to result in finding art pertinent to the other inventions. Therefore, restriction for examination purposes as indicated is proper.
With regard to the requirement for election of species, Applicant “submits that all the species have a common property or activity and belong to a recognized class of chemical compounds.”
With regard to the requirement for election of species between the PD-1 antibody species and the PD-L1 antibody species, the species will be rejoined and examined together in the interest of compact prosecution.
However, with regard to the requirement for election of species between disclosed multi-kinase inhibitors, the species do not relate to a single general inventive concept under PCT Rule 13.1 because, under PCT Rule 13.2, they lack the same or corresponding special technical features. Moreover, the species are independent or distinct because each species may exhibit significantly different properties—such as solubility, stability, or reactivity—that are not predictable from one another. In addition, these species are not obvious variants of each other based on the current record. There is a serious search and/or examination burden for the patentably distinct species as set forth above because at least the following reason(s) apply: because each species may exhibit significantly different properties—such as solubility, stability, or reactivity—that are not predictable from one another, searching the species will require different, non-overlapping search queries. As such, the requirement for election of species between disclosed multi-kinase inhibitors is maintained.
Applicant is reminded that, upon the allowance of a generic claim, applicant will be entitled to consideration of claims to additional species which are written in dependent form or otherwise require all the limitations of an allowed generic claim.
The requirement is still deemed proper and is therefore made FINAL.
Claims 8-9 and 15-16 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 04 Feb 2026.
Status of Claims
Claims 1-16 are pending. Claims 8-9 and 15-16, which are drawn to non-elected invention(s), are withdrawn from consideration.
Priority
Instant application claims priority as follows:
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Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
All references from IDS(s) received 27 Sep 2023, 11 Feb 2025, and 03 Sep 2025 have been considered unless marked with a strikethrough.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 3-7 and 14 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 7 and 14, each claim includes the phrase "can further comprise" (emphasis added), which phrase renders each claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claims 1 and 3-6, claim 1 (and claims 3-6 through dependency) fails to include a transitional phrase. Transitional phrases (such as “comprising”, “consisting essentially of” and “consisting of”) define the scope of a claim with respect to what unrecited additional components, if any, are excluded from the scope of the claim. See MPEP § 2111.03. As such, in the absence of a transitional phrase, the claims are indefinite because it is unclear what unrecited additional components, if any, are excluded from the scope of the claim.
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.
Claims 1-7 and 10-14 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 claims contain 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. This is a written description rejection.
“[T]he purpose of the written description requirement is to ‘ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent specification.’” Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353-54 (Fed. Cir. 2010) (en banc) (quoting Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920 (Fed. Cir. 2004)). To satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163.04.
For a claim to a genus, a generic statement that defines a genus of substances by only their functional activity does not provide an adequate written description of the genus. Reagents of the University of California v. Eli Lilly, 43 USPQ2d 1398 (CAFC 1997). The recitation of a functional property alone, which must be shared by the members of the genus, is merely descriptive of what the members of the genus must be capable of doing, not of the substance and structure of the members. The Federal Circuit has cautioned that, for claims reciting a genus of antibodies with particular functional properties (e.g., binding to antigen, high affinity, neutralization activity, competing with a reference antibody for binding), “[c]laiming antibodies with specific properties, e.g., an antibody that binds to human TNF-α with A2 specificity, can result in a claim that does not meet written description even if the human TNF-α protein is disclosed because antibodies with those properties have not been adequately described." Centocor Ortho Biotech Inc. v. Abbott Labs., 97 USPQ2d 1870, 1875, 1877-78 (Fed. Cir. 2011).
“[A] sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus.” Ariad, 598 F.3d at 1350 (quoting Eli Lilly, 119 F.3d at 1568-69). A “representative number of species” means that those species that are adequately described are representative of the entire genus. AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (“The ’128 and ’485 patents, however, only describe species of structurally similar antibodies that were derived from Joe-9. Although the number of the described species appears high quantitatively, the described species are all of the similar type and do not qualitatively represent other types of antibodies encompassed by the genus.”). 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. For antibodies, the Federal Circuit has found that possession of a mouse antibody heavy and light chain variable regions provides a structural "stepping stone" to the corresponding chimeric antibody, but not to human antibodies. Centocor, 97 USPQ2d at 1875 (“[T]he application only provides amino acid sequence information (a molecular description of the antibody) for a single mouse variable region, i.e., the variable region that the mouse A2 antibody and the chimeric antibody have in common. However, the mouse variable region sequence does not serve as a stepping stone to identifying a human variable region within the scope of the claims.”). A chimeric antibody shares the full heavy and light chain variable regions with the corresponding mouse antibody; that is, the structure shared between a mouse and chimeric antibody would generally be expected to conserve the antigen binding activity.
Even if a selection procedure is disclosed that was, at the time of the invention, sufficient to enable the skilled artisan to identify antibodies with the recited functional properties, the written description provision of 35 U.S.C § 112 is severable from its enablement provision. Ariad, 94 USPQ2d at 1167; Centocor at 1876 (“The fact that a fully-human antibody could be made does not suffice to show that the inventors of the '775 patent possessed such an antibody.”)
Additionally, “An adequate written description must contain enough information about the actual makeup of the claimed products—“a precise definition, such as by structure, formula, chemical name, physical properties, or other properties, of species falling within the genus sufficient to distinguish the genus from other materials,” which may be present in “functional” terminology “when the art has established a correlation between structure and function.” Ariad, 598 F.3d at 1350. But both in this case and in our previous cases, it has been, at the least, hotly disputed that knowledge of the chemical structure of an antigen gives the required kind of structure-identifying information about the corresponding antibodies.” Amgen Inc v. Sanofi 124 USPQ2d 1354, 1361 (Fed. Cir. 2017). “Further, the “newly characterized antigen” test flouts basic legal principles of the written description requirement. Section 112 requires a “written description of the invention.” But this test allows patentees to claim antibodies by describing something that is not the invention, i.e., the antigen. The test thus contradicts the statutory “quid pro quo” of the patent system where “one describes an invention, and, if the law's other requirements are met, one obtains a patent.” Ariad, 598 F.3d at 1345.” Amgen at 1362.
Applicants’ specification at paragraph [0107] recites the following: “The ‘antibody’ of the present invention refers to any form of an antibody that exhibits the desired biological or binding activity. Thus, it is used in the broadest sense and specifically covers, but is not limited to, a monoclonal antibody (including a full-length monoclonal antibody), a polyclonal antibody, a multispecific antibody (for example, a bispecific antibody), a humanized and primatized antibody, a fully human antibody, a chimeric antibody, a murine antibody, and a camelized single-domain antibody.”
With regard to the characteristics of a PD-1 antibody, Applicants’ specification at paragraph [0114] recites the following: “The term ‘PD-1 antibody’ refers to any antibody that specifically binds to programmed cell death protein 1 (PD-1) or a soluble fragment thereof and blocks the binding of a ligand to PD-1, thereby causing competitive inhibition of PD-1 and inhibition of PD-1-mediated T cell activation.”
The specification provides only a single working example of a PD-1 antibody, namely InVivoMAb anti-mouse PD-1 with a clone number of RMP1-14. However, this single PD-1 antibody does not provide a precise definition, such as by structure, formula, chemical name, physical properties, or other properties, of a representative number of species falling within the genus sufficient to distinguish the genus from other materials. Merely describing the antigen does not provide sufficient information about the PD-1 antibody.
With regard to the characteristics of a PD-L1 antibody, Applicants’ specification at paragraph [0116] recites the following: “The term ‘PD-L1 antibody’ refers to an antibody that specifically binds to programmed cell death protein 1 ligand 1 (PD-L1) or a soluble fragment thereof and blocks the binding of a ligand to PD-1, thereby causing competitive inhibition of PD-1 and inhibition of PD-1-mediated T cell activity.” As such, the genus of PD-L1 antibodies is defined solely in terms of function—i.e. antagonizing PD-L1.
The specification provides only a single working example of a PD-L1 antibody, namely InVivoMAb anti-mouse PD-L1 (B7-H1), clone number: 10F.9G2 (IgG2b). However, this single PD-L1 antibody does not provide a precise definition, such as by structure, formula, chemical name, physical properties, or other properties, of a representative number of species falling within the genus sufficient to distinguish the genus from other materials. Merely describing the antigen does not provide sufficient information about the PD-L1 antibody.
It is well established in the art that the formation of an intact antigen-binding site of all antibodies requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three CDRs or hypervariable regions, which provide the majority of the contact residues for the binding of the antibody to its target epitope (Paul, Fundamental Immunology, 3rd Edition, 1993, pp. 292-295, under the heading “Fv Structure and Diversity in Three Dimensions”) (cited on PTO-892). The amino acid sequences and conformations of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity, which is characteristic of the parent immunoglobulin. It is expected that all of the heavy and light chain CDRs in their proper order and in the context of framework sequences which maintain their required conformation, are required in order to produce a protein having antigen-binding function and that proper association of heavy and light chain variable regions is required in order to form functional antigen binding sites (Paul, page 293, first column, lines 3-8 and line 31 to column 2, line 9 and lines 27-30). It was well established in the art that the formation of an intact antigen-binding site in an antibody usually required the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three “complementarity determining regions” (“CDRs”) which provide the majority of the contact residues for the binding of the antibody to its target epitope. E.g., Almagro & Fransson, Frontiers in Bioscience 2008; 13:1619-33 (see Section 3 “Antibody Structure and the Antigen Binding Site” and Figure 1) (cited on PTO-892). Chimeric antibodies comprise the heavy and light chain variable regions of a rodent antibody linked to human constant regions and preserve the entirety of the VH and VL of the parent antibody. Id. at 1619-20. Humanized antibodies comprise only the CDRs, or in some cases an abbreviated subset of residues within the CDRs, of a parental rodent antibody in the context of human framework sequences. Id. at Section 4. All of the CDRs of the heavy and light chain, in their proper order of CDR1, then 2, then 3, and in the context of framework sequences which maintain their required conformation are generally required to produce a humanized antibody in which the heavy and light chains associate to form an antigen-binding region that binds the same antigen as the parental rodent antibody. Id. at Section 4. Almagro provides a detailed discussion regarding various methods of humanization, including rationale design approaches and empirical approaches based on random screening. Almagro, Sections 4 and 5. It has long been established that even minor changes in the amino acid sequences of the heavy and light variable regions, particularly in the CDRs, may dramatically affect antigen-binding function. In 1982, Rudikoff et al. (Proc. Natl. Acad. Sci. USA 1982 Vol. 79: page 1979) (cited on PTO-892) teach that the alteration of a single amino acid in the CDR of a phosphocholine-binding myeloma protein resulted in the loss of antigen-binding function. Pascalis et al. (The Journal of Immunology (2002) 169, 3076-3084) (cited on PTO-892) demonstrate that grafting of the CDRs into a human framework was performed by grafting CDR residues and maintaining framework residues that were deemed essential for preserving the structural integrity of the antigen binding site (see page 3079, right col.). Although abbreviated CDR residues were used in the constructs, some residues in all 6 CDRs were used for the constructs (see page 3080, left col.). The fact that not just one CDR is essential for antigen binding or maintaining the conformation of the antigen binding site, is underscored by Casset et al. (2003) BBRC 307, 198-205, (cited on PTO-892) which constructed a peptide mimetic of an anti-CD4 monoclonal antibody binding site by rational design and the peptide was designed with 27 residues formed by residues from 5 CDRs (see entire document). Casset et al. also states that although CDR H3 is at the center of most if not all antigen interactions, clearly other CDRs play an important role in the recognition process (page 199, left col.) and this is demonstrated in this work by using all CDRs except L2 and additionally using a framework residue located just before the H3 (see page 202, left col.). More recently, D’Angelo et al., Frontiers in Immunology vol. 9 p. 1 (2018) (cited on PTO-892) shows that antibodies bind their targets using diversified loops (CDRs) and, of the 6CDRs, HCDR3 is the most diverse. D’Angelo et al examined one CDR in depth and concluded that HCDR3 generated many different VDJ rearrangements (abstract and entire reference). They conclude “that a specific HCDR3 will only define a particular binding specificity within a very narrow structurally appropriate context: i.e. HCDRs is necessary, but is insufficient to define specific anti-binding properties unless combined with appropriate VL and VL germline genes” (page 8, second column). Thus, binding is highly specific to HCDR3 and VH and VL combinations. A generic disclosure of “antibody” with only one example, does not provide a representative number of examples to show that applicant had possession of the claimed invention at the time of filing.
In view of the aforementioned case law, the state of the art and in view of the lack of a representative number of examples representing the genus of PD1 antibodies and/or PD-L1 antibodies, the skilled artisan would not recognize that applicants were in possession of the invention as broadly claimed at the time the application was filed.
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.
The framework for the objective analysis for determining obviousness under 35 U.S.C. 103 is stated in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966). Obviousness is a question of law based on underlying factual inquiries. The factual inquiries enunciated by the Supreme Court in Graham are summarized as follows:
(A) Determining the scope and content of the prior art;
(B) Ascertaining the differences between the claimed invention and the prior art; and
(C) Resolving the level of ordinary skill in the pertinent art.
Objective evidence relevant to the issue of obviousness must be evaluated by Office personnel. Id. at 17-18, 148 USPQ at 467. The evidence may be included in the specification as filed, accompany the application on filing, or be provided in a timely manner at some other point during the prosecution. The weight to be given any objective evidence is determined on a case-by-case basis. The mere fact that an applicant has presented evidence does not mean that the evidence is dispositive of the issue of obviousness.
The Supreme Court in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper "functional approach" to the determination of obviousness as laid down in Graham. See MPEP 2143.
Examples of rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) "Obvious to try" – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation (TSM) in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Claims 1 and 3-7 (drawn to pharmaceutical compositions) and Claims 2 and 10-14 (drawn to kits for treating a cancer) are rejected under 35 U.S.C. 103 as being unpatentable over Denker (US-20180092901-A1; published 05 April 2018) in view of Wu ‘042 (US-10208042-B1; granted 02 February 2019).
With regard to claims 1 and 3-7, Denker teaches a pharmaceutical composition comprising: (a) lenvatinib mesylate, which is compound having inhibitory activity against a variety of kinases; and (b) pembrolizumab, which is a programmed cell death protein 1 (PD-1) antibody. See Denker at paragraph [0205], items 31 and 32. See also Denker at paragraphs [0192], [0194], and [0203] for additional context.
With regard to Claims 2 and 10-14, Denker teaches a kit for treating a cancer, comprising: (a) lenvatinib mesylate, which is compound having inhibitory activity against a variety of kinases; (b) pembrolizumab, which is a programmed cell death protein 1 (PD-1) antibody; and (c) a package insert. See Denker at [0205], items 26 and 28. See also Denker at paragraphs [0203] for additional context.
Relevant to claims 7 and 14, Denker teaches that a combination therapy may further comprise an additional chemotherapeutic agent, which is an anti-cancer agent. See Denker at paragraphs [0173] and [0174].
Denker does not teach a multi-kinase inhibitor having a structure that falls within the scope of the multi-kinase element recited in claims 1-7 and 10-14.
Wu ‘042 teaches a multi-kinase inhibitor compound, namely Compound 29, that falls within the scope of the multi-kinase element recited in claims 1-7 and 10-14. See Wu ‘042 at Column 16, lines 38-50. Indeed, Compound 29 taught by Wu ‘042 is identical in structure compared to the species that Applicant elected in response to the requirement for election of species between multi-kinase inhibitors. The elected species and Compound 29 taught by Wu ‘042 each have the following structure:
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Applying KSR rationale (B) outlined above, it would have been prima facie obvious to substitute one known element (namely, Compound 29, taught by Wu ‘042) in place of another known element (namely, lenvatinib mesylate, taught by Denker) to obtain pharmaceutical compositions and kits useful for treating cancer.
Denker at paragraph [0007] teaches: “Lenvatinib mesilate, discovered and developed by Eisai Co., Ltd., is an oral receptor tyrosine kinase (RTK) inhibitor that selectively inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors (VEGFR1 (FLT1), VEGFR2 (KDR) and VEGFR3 (FLT4)), and fibroblast growth factor (FGF) receptors FGFR1, 2, 3 and 4 in addition to other proangiogenic and oncogenic pathway-related RTKs (including the platelet-derived growth factor (PDGF) receptor PDGFRα; KIT; and the RET proto-oncogene (RET)) involved in tumor proliferation.” Similarly, Wu ‘042 at column 76, lines 13-20, teaches: “From the experimental results in Table 6, the crystal form I of [Compound 29] of the present invention has good inhibitory activity against a variety of kinases, indicating the compounds of the present invention have a good clinical application potential in the treatment of diseases mediated by abnormal expression of various kinases, such as Aurora, VEGFR2 (KDR), FGFR, FLT, and JAK.” That is, before the effective filing date of the claimed invention, as one of ordinary skill in the art would have recognized that lenvatinib mesylate and Compound 29 share substantial overlap in inhibitory activity against a variety of kinases.
Given that as one of ordinary skill in the art would have recognized that lenvatinib mesylate and Compound 29 share substantial overlap in inhibitory activity against a variety of kinases, one of ordinary skill in the art would have had an expectation that substituting Compound 29 (taught by Wu ‘042) in place of lenvatinib mesylate, (taught by Denker) would result in pharmaceutical compositions and kits useful for treating cancer.
Therefore, applying KSR rationale (B) outlined above, 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.
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. Patent No. 10,208,042
Claims 1-7 and 10-14 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 2 of U.S. Patent No. 10,208,042 (reference patent) in view of Denker (US-20180092901-A1; published 05 April 2018).
Claim 2 of the ‘042 patent claims a pharmaceutical composition comprising a multi-kinase inhibitor having the following structure:
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The compound recited in claim 2 of the ‘042 patent falls within the scope of the multi-kinase element recited in claims 1-7 and 10-14 of the instant application. Indeed, Compound 29 recited in claim 2 of the ‘042 patent is identical in structure compared to the species that Applicant elected in response to the requirement for election of species between multi-kinase inhibitors.
Claim 2 of the ‘042 patent (reference patent) fails to recite an element that corresponds to the PD-1 antibody element of claims 1-7 and 10-14.
Claim 2 of the ‘042 patent (reference patent) fails to recite elements that correspond to the kit and package insert elements of claims 2 and 10-14.
Claim 2 of the ‘042 patent (reference patent) fails to recite an element that corresponds to the additional anti-cancer agent element of claims 7 and 14.
With regard to claims 1-7 and 10-14, Denker teaches a pharmaceutical composition comprising: (a) lenvatinib mesylate, which is a compound having inhibitory activity against a variety of kinases; and (b) pembrolizumab, which is a programmed cell death protein 1 (PD-1) antibody. See Denker at paragraph [0205], items 31 and 32. See also Denker at paragraphs [0192], [0194], and [0203] for additional context. As such, Denker teaches an element corresponding to the PD-1 antibody element recited in claims 1-7 and 10-14 of the instant application.
With regard to Claims 2 and 10-14, Denker teaches a kit for treating a cancer, comprising: (a) lenvatinib mesylate, which a is compound having inhibitory activity against a variety of kinases; (b) pembrolizumab, which is a programmed cell death protein 1 (PD-1) antibody; and (c) a package insert. See Denker at [0205], items 26 and 28. See also Denker at paragraphs [0203] for additional context. As such, Denker teaches elements that correspond to the kit and package insert elements recited in claims 2 and 10-14 of the instant application.
Relevant to claims 7 and 14, Denker teaches that a combination therapy may further comprise an additional chemotherapeutic agent, which is an anti-cancer agent. See Denker at paragraphs [0173] and [0174]. As such, Denker teaches an element that corresponds to the additional anti-cancer agent element recited in instant claims 7 and 14 of the instant application.
Applying KSR rationale (G) outlined above, the teachings of Denker would have led one of ordinary skill to modify claim 2 of the ‘042 patent (reference patent) to arrive at the invention of claims 1-7 and 10-14 of the instant application. Motivation to do so, and a reasonable expectation of success, is provided by Denker at paragraph [0220], which teaches that “the combination of lenvatinib and anti-PD-1 demonstrates a synergistic effect between the two. Unexpectedly, the administration of lenvatinib only for 7 days followed by administration of lenvatinib and anti-PD-1 showed an even greater effect on reducing tumor volume that the combined administration of lenvatinib and anti-PD-1.”
Therefore, applying KSR rationale (G) outlined above, 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.
U.S. Patent No. 10,889,586
Claims 1-7 and 10-14 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 9 of U.S. Patent No. 10,889,586 (reference patent) in view of Denker (US-20180092901-A1; published 05 April 2018).
Claim 9 of the ‘586 patent claims a crystal form of a multi-kinase inhibitor having the following structure:
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The compound recited in claim 9 of the ‘586 patent falls within the scope of the multi-kinase element recited in claims 1-7 and 10-14 of the instant application. Indeed, Compound 29 recited in claim 9 of the ‘586 patent is identical in structure compared to the species that Applicant elected in response to the requirement for election of species between multi-kinase inhibitors.
Claim 9 of the ‘586 patent (reference patent) fails to recite an element that corresponds to the PD-1 antibody element of claims 1-7 and 10-14.
Claim 9 of the ‘586 patent (reference patent) fails to recite elements that correspond to the kit and package insert elements of claims 2 and 10-14.
Claim 9 of the ‘586 patent (reference patent) fails to recite an element that corresponds to the additional anti-cancer agent element of claims 7 and 14.
With regard to claims 1-7 and 10-14, Denker teaches a pharmaceutical composition comprising: (a) lenvatinib mesylate, which is compound having inhibitory activity against a variety of kinases; and (b) pembrolizumab, which is a programmed cell death protein 1 (PD-1) antibody. See Denker at paragraph [0205], items 31 and 32. See also Denker at paragraphs [0192], [0194], and [0203] for additional context. As such, Denker teaches an element corresponding to the PD-1 antibody element recited in claims 1-7 and 10-14 of the instant application.
With regard to Claims 2 and 10-14, Denker teaches a kit for treating a cancer, comprising: (a) lenvatinib mesylate, which a is compound having inhibitory activity against a variety of kinases; (b) pembrolizumab, which is a programmed cell death protein 1 (PD-1) antibody; and (c) a package insert. See Denker at [0205], items 26 and 28. See also Denker at paragraphs [0203] for additional context. As such, Denker teaches elements that correspond to the kit and package insert elements recited in claims 2 and 10-14 of the instant application.
Relevant to claims 7 and 14, Denker teaches that a combination therapy may further comprise an additional chemotherapeutic agent, which is an anti-cancer agent. See Denker at paragraphs [0173] and [0174]. As such, Denker teaches an element that corresponds to the additional anti-cancer agent element recited in instant claims 7 and 14 of the instant application.
Applying KSR rationale (G) outlined above, the teachings of Denker would have led one of ordinary skill to modify Claim 9 of the ‘586 patent (reference patent) to arrive at the invention of claims 1-7 and 10-14 of the instant application. Motivation to do so, and a reasonable expectation of success, is provided by Denker at paragraph [0220], which teaches that “the combination of lenvatinib and anti-PD-1 demonstrates a synergistic effect between the two. Unexpectedly, the administration of lenvatinib only for 7 days followed by administration of lenvatinib and anti-PD-1 showed an even greater effect on reducing tumor volume that the combined administration of lenvatinib and anti-PD-1.”
Therefore, applying KSR rationale (G) outlined above, 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.
Conclusion
Claims 1-7 and 10-14 are rejected.
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/BSM/Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621