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/Restriction
Claims 1-30 are generic to the following disclosed patentably distinct species:
Species A: a single and specific immunogenic composition including a single and specific polynucleotide encoding a single and specific amino acid sequence or combination thereof (i.e., one, two, or a single and specific combination) indicating the heteroclitic modifications including the KRAS mutation (please see claims 1, 4-8, 11-16, 19-23, and 26-30).
The species are independent or distinct because as disclosed the different species have mutually exclusive characteristics for each identified species. In addition, these species are not obvious variants of each other based on the current record.
Applicant is required under 35 U.S.C. 121 to elect a single disclosed species, or a single grouping of patentably indistinct species, for prosecution on the merits to which the claims shall be restricted if no generic claim is finally held to be allowable.
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:
(a) the species or groupings of patentably indistinct species have acquired a separate status in the art in view of their different classification;
(b) the species or groupings of patentably indistinct species have acquired a separate status in the art due to their recognized divergent subject matter;
(c) the species or groupings require a different field of search (for example, searching different classes/subclasses or electronic resources, or employing different search queries); and/or
(d) the species may raise different non-prior art issues under 35 U.S.C. 101 and/or 35 U.S.C. 112, first paragraph.
There is a serious search and/or examination burden because the species may raise different non-prior art issues under 35 U.S.C. 101 and/or 35 U.S.C. 112, first paragraph.
Applicant is advised that the reply to this requirement to be complete must include (i) an election of a species or a grouping of patentably indistinct species to be examined even though the requirement may be traversed (37 CFR 1.143) and (ii) identification of the claims encompassing the elected species or grouping of patentably indistinct species, including any claims subsequently added. An argument that a claim is allowable or that all claims are generic is considered nonresponsive unless accompanied by an election.
The election may be made with or without traverse. To preserve a right to petition, the election must be made with traverse. If the reply does not distinctly and specifically point out supposed errors in the election of species requirement, the election shall be treated as an election without traverse. Traversal must be presented at the time of election in order to be considered timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are added after the election, applicant must indicate which of these claims are readable on the elected species or grouping of patentably indistinct species.
Should applicant traverse on the ground that the species, or groupings of patentably indistinct species from which election is required, are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the species to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the species unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other species.
Upon the allowance of a generic claim, applicant will be entitled to consideration of claims to additional species which depend from or otherwise require all the limitations of an allowable generic claim as provided by 37 CFR 1.141.
During a telephone conversation with Anastasia Greenberg (Applicant’s representative) on May 6, 2025, a provisional election was made to elect an immunogenic composition comprising a polynucleotide that encodes one amino acid sequence of SEQ ID NO: 158, claims 1-3 and 5-7. Affirmation of this election must be made by applicant in replying to this Office action. Claims 4 and 8-30 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected species. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Applicant is reminded that upon the cancelation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
Status of Claims
Claims 1-30 were originally filed on March 12, 2024.
The amendment received on May 30, 2025, canceled claims 3 and 10; and amended claims 1-2, 5, and 12; and added new claims 31-32. The amendment received on September 16, 2025, canceled claims 20-21; amended claims 1 and 31; and added new claims 32-34. The amendment received on January 29, 2026, canceled claims 31 and 33; and amended claims 1 and 34.
Claims 1-2, 4-9, 11-19, 22-30, 32, and 34 are currently pending and claims 1-2, 5-7, 32, and 34 are under consideration as claims 4, 8-9, 11-19, and 22-30 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse telephonically on May 6, 2025.
Priority
The present application is a divisional of US Non-Provisional Application No. 18/170,994, filed on February 17, 2023, now issued as US Patent No. 12,064,475 B2, which is a continuation of US Non-Provisional Application No. 17/729,290, filed on April 26, 2022, now issued as US Patent No. 11,672,850 B2, which is a continuation of US Non-Provisional Application No. 17/243,096, filed on April 28, 2021, now issued as US Patent No. 11,464,842 B2.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on October 31, 2025; and January 29, 2026, are being considered by the examiner.
Claim Interpretation
For purposes of applying prior art, the claim scope has been interpreted as set forth below per the guidance set forth at MPEP § 2111. If Applicant disputes any interpretation set forth below, Applicant is invited to unambiguously identify any alleged misinterpretations or specialized definitions in the subsequent response to the instant action. Applicant is advised that a specialized definition should be properly supported and specifically identified (see, e.g., MPEP § 2111.01(IV), describing how Applicant may act as their own lexicographer).
For claim 1, with respect to a complete chain of a MHC molecule, the instant specification does not define what constitutes a complete chain of a MHC molecule. Pursuant to MPEP 2111.01, under a broadest reasonable interpretation, words of the claim must be given their plain meaning, unless such meaning is inconsistent with the specification. The plain meaning of a term means the ordinary and customary meaning given to the term by those of ordinary skill in the art at the time of the invention. MHC molecules are glycoproteins encoded in a large cluster of genes located on chromosome 6 (See Intl. Union of Immunological Societies, “MHC & Antigen Presentation,” Immunopaedia.org, available online at https://www.immunopaedia.org.za/immunology/basics/4-mhc-antigen-presentation/, 8 pages (accessed on 10/28/25) at pg. 1, 1st paragraph). Although there are three types of MHCs; namely, MHC-1, MHC-II, and MHC-III, typically when referring to MHC, reference is to either MHC-I or MHC-II (See Immunopaedia reference, pg. 2, 2nd and 6th paragraph). As such, the MHC molecule referred to in claim 1 encompasses either the MHC-I or -II. MHC-I molecules consist of two polypeptide chains, i.e., a larger alpha chain, and a smaller beta-2 microglobulin (See Immunopaedia reference, pg. 3, 1st paragraph; Table 1). The class I alpha chains consist of a single polypeptide composed of three extracellular domains named alpha-1, alpha-2, and alpha-3, a transmembrane region that anchors it in the plasma membrane, and a short intracytoplasmic tail as depicted in Figure 2 (See Immunopaedia reference, pg. 3, 2nd paragraph). The beta-2 microglobulin consists of a single non-polymorphic molecule noncovalently bound to the alpha chain (See Immunopaedia reference, pg. 3, 3rd paragraph). MHC-II molecules consist of two polypeptide chains, alpha and beta, which are noncovalently linked to one another as depicted in Figure 2 (See Immunopaedia reference, pg. 3, 5th paragraph; Table 1). The alpha and beta chains each consist of two extracellular domains referred to as alpha-1 and alpha-2, and beta-1 and beta-2 (See Immunopaedia reference, pg. 3, 6th paragraph). The alpha and beta chains also contain a transmembrane segment and a cytoplasmic tail as depicted in Figure 2 (See Immunopaedia reference, pg. 3, 6th paragraph). As such, each MHC molecule contains two individual complete chains, i.e., a heavy alpha chain and a beta-2 microglobulin chain for MHC-I molecules, and an alpha chain and beta chain for MHC-II molecules. Alternatively, MHC-I molecules can be engineered as a single-chain in which the beta-2 microglobulin and heavy alpha chain are all joined together via flexible linkers (See Kotsiou et al., Antioxidants & Redox Signaling 15:635-644 (2011) at abstract). These single-chain molecules exhibit improved stability (See Kotsiou, abstract). As such, MHC molecules also can be engineered such that both chains are linked to form one complete chain. Thus, as further discussed in the 112(b) rejection below, it is unclear if a “complete chain” of a MHC molecule refers to a complete alpha chain or a complete beta chain, i.e., any polynucleotide encoding at least one amino acid sequence, e.g., elected SEQ ID NO: 158 linked to a complete heavy alpha chain or a complete beta-2 microglobulin chain of a MHC-I molecule; or if a “complete chain” of a MHC molecule refers to a single complete chain having both the heavy alpha chain and beta chain.
Sequence Interpretation
Please note that the Examiner is interpreting the scope of claims 1 and 7 as open-ended requiring 100% identity to at least one of the claimed sequences but where each sequence encompasses any N-/C-terminal additions.
Response to Arguments
Applicant’s arguments, see Response, filed 1/29/26, with respect to the 112(a), new matter, rejection have been fully considered and are persuasive. The rejection of claims 1-2, 5-7, and 31-34 as failing to comply with the written description requirement has been withdrawn. Please note that claim 1 no longer recites that a complete chain of a MHC molecule is encoded by the administered polynucleotide.
Applicant’s arguments, see Response, filed 1/29/26, with respect to 112(b) rejection have been fully considered and are persuasive. The rejection of claims 1-2, 5-7, and 31-34 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 has been withdrawn.
Response to Amendment
The Declaration under 37 CFR 1.132 filed 1/29/26 is insufficient to overcome the rejection of claims 1-2, 5-7, 32, and 34 based upon Seidel et al. WO 2021/055594 A1 published on March 25, 2021 (cited in the IDS received on 3/27/24), in view of Betts et al., “Chap. 14: Amino Acid Properties and Consequences of Substitutions,” Bioinformatics for Geneticists, Barnes et al., eds., John Wiley & Sons, Ltd., pgs. 297-316 (2003) (cited in the IDS received on 3/27/24) as set forth in the last Office action for the following reasons.
Declarant asserts that the claimed invention is nonobvious over the cited references because: (1) there is no teaching or suggestion in Seidel that would motivate an ordinary skilled artisan to modify Seidel’s KRAS peptide with amino acid substitutions to improve binding of the peptide to an HLA allele to achieve a binding affinity of less than about 100 nM; (2) there is no teaching or suggestion in Seidel that would direct an ordinary skilled artisan to make the specific amino acid substitutions posited by the Examiner; and (3) even if an ordinary skilled artisan were motivated to make these substitutions, they would have no reasonable expectation of success that doing so would result in the peptide-HLA binding affinity as recited in instant claim 1 in view of the teachings of the cited references.
The Examiner thanks the Declarant for describing binding affinity and how it is measured. The Examiner does not dispute this description. However, based on the MPEP and current case law, a structure that is encompassed by the claims would necessarily exhibit the same properties as claimed. As an initial matter, the Examiner would like to address the broadest reasonable interpretation of claim 1. Pursuant to MPEP 2111, the pending claims must be "given their broadest reasonable interpretation consistent with the specification." The Federal Circuit’s en banc decision in Phillips v. AWH Corp., 415 F.3d 1303, 1316, 75 USPQ2d 1321, 1329 (Fed. Cir. 2005) expressly recognized that the USPTO employs the "broadest reasonable interpretation" standard:
The Patent and Trademark Office ("PTO") determines the scope of claims in patent applications not solely on the basis of the claim language, but upon giving claims their broadest reasonable construction "in light of the specification as it would be interpreted by one of ordinary skill in the art." In re Am. Acad. of Sci. Tech. Ctr., 367 F.3d 1359, 1364[, 70 USPQ2d 1827, 1830] (Fed. Cir. 2004). Indeed, the rules of the PTO require that application claims must "conform to the invention as set forth in the remainder of the specification and the terms and phrases used in the claims must find clear support or antecedent basis in the description so that the meaning of the terms in the claims may be ascertainable by reference to the description." 37 CFR 1.75(d)(1).
Claim 1 is directed to a method of promoting an immune response against a case or treating the case in a human subject by administering an effective amount of an immunogenic composition comprising a polynucleotide encoding SEQ ID NO: 158, where the cancer is associated with a KRAS G12C mutation and where administering the effective amount of the immunogenic composition causes SEQ ID NO: 158 to be displayed by an HLA class I molecule in the human subject with a peptide-HLA binding affinity value of less than 100 nM, and causes an immune response against or treatment of the cancer. As such, claim 1 requires one manipulative step, i.e., administering an effective amount of an immunogenic composition comprising a polynucleotide encoding SEQ ID NO: 158 to a subject in order to promote an immune response against a cancer or treat the cancer in the subject. Claim 1 also requires the structural limitations of (1) an effective amount of a composition comprising a polynucleotide encoding SEQ ID NO: 158, (2) the subject being a human subject, and (3) the cancer to be treated is associated with a KRAS G12C mutation in the human subject. As such, a reference or combination of references need to teach or suggest this manipulative step and these structural limitations. The composition being an immunogenic composition, and SEQ ID NO: 158 encoded by the polynucleotide being displayed by an HLA class I molecule with a peptide-HLA binding affinity value of less than about 100 nM are functional properties of the composition and SEQ ID NO: 158, respectively. As such, a reference or combination of references do not need to expressly teach or suggest these functional properties. Rather, if the reference or combination of references teach or suggest the required structure, then that structure would necessarily exhibit the claimed function. Furthermore, it is further noted that the claim utilizes the transitional phrase, “comprising”. Pursuant to MPEP 2113.03(I), the transitional term "comprising" is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. Thus, with respect to the structural limitations as indicated in the “Sequence Interpretation” section supra, the scope of the claimed peptide requires 100% identity to one of the recited sequences but with any N- and/or C-terminal additions. With respect to the manipulative step, claim 1 encompasses any number of additional steps and/or agents as long as the unrecited steps/agents do not negate the intended use of promoting an immune response against a cancer or treating the cancer.
Turning to the cited references, as discussed in the rejection below, Seidel expressly teaches the required manipulative step and the required structural limitations except for one residue of SEQ ID NO: 158, i.e., a C-terminal R instead of a C-terminal K as taught by Seidel. As such, Seidel’s TMP fusion protein is encompassed by the BRI of the structural limitations. Thus, the question is then whether an ordinary skilled artisan would be motivated with a reasonable expectation of success to substitute the C-terminal K in Seidel’s sequence with an R residue. The Examiner maintains that the answer to this question is yes in light of the teachings of Betts. Betts expressly suggests that substituting lysine for arginine would result in similar properties. This expectation is due to the similar properties of the side chains of both residues, and as will be further discussed below, due to the finite number of possible substitutions at the C-terminus.
Notably, the question is NOT whether an ordinary skilled artisan would be motivated to substitute the C-terminal K in Seidel’s sequence with an R residue in order to improve binding of the peptide to an HLA allele to achieve a binding affinity of less than about 100 nM as asserted by the Declarant. There is no claimed requirement that the HLA-binding affinity is improved. Plus, it begs the question, improved relative to what? Does SEQ ID NO: 158 exhibit improved HLA-binding affinity when compared to Seidel’s sequence with the C-terminal K? If this is the case, such evidence would likely constitute unexpected results thereby overcoming the pending 103 rejection. However, such evidence is not presented in the instant specification. Nor has the Declarant provided such evidence. In fact, as discussed in the 112(a) rejection below, the instant specification does not support or identify the HLA-binding affinity of SEQ ID NO: 158 or any other immunogenic peptide. As such, there is no support that SEQ ID NO: 158 even exhibits a HLA-binding affinity value of less than about 100 nM or 50 nM. The fact that the specification refers to selecting a desired HLA-binding affinity value when generating an immunogenic peptide (See instant, [0672]), does not per se support that SEQ ID NO: 158 exhibits a HLA-binding affinity value of less than about 100 nM or less than about 50 nM. Since the specification refers to varying HLA-binding affinity values, e.g., less than about 1000 nM or less than about 500 nM, would inherently imply that the described peptides exhibit varying HLA-binding affinities. Applicants are invited to provide evidence that Seidel’s KRAS peptide, i.e., without the K to R substitution (note: closest prior art), does not exhibit a HLA binding affinity within the claimed range as compared to instant SEQ ID NO: 158, which does exhibit a HLA biding affinity within the claimed range. Thus, without evidence comparing the HLA-binding affinity value of Seidel’s sequence to instant SEQ ID NO: 158, a determination of nonobviousness based upon the functional property of the claimed peptide cannot be made.
Therefore, as long as there is a motivation with a reasonable expectation of success to make the substitution where such motivation is based upon any rationale (i.e., does not need to be based upon HLA binding affinity), the modified amino acid sequence will necessarily exhibit the functional property of a peptide-HLA binding affinity of less than about 100 nM. Pursuant to MPEP 2112.01(II), “[p]roducts of identical chemical composition cannot have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id. Furthermore, the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of invention, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003). Here, the Examiner maintains that whether Seidel’s peptide sequence (since Seidel’s sequence is the closest prior art), exhibits this functional property is dependent upon the structure of the peptide. Since the BRI of claim 1 encompasses where a polynucleotide encodes SEQ ID NO: 158 with any N- and/or C-terminal additions thereby encompassing Seidel’s fusion protein, the suggested amino acid sequence would necessarily exhibit the claimed functional property. Therefore, the Examiner maintains that an ordinary skilled artisan would have the requisite motivation to modify Seidel’s KRAS peptide such that the C-terminal K residue is substituted with a C-terminal R residue where such modification would necessarily result in the modified KRAS peptide exhibiting a HLA-binding affinity value of less than about 100 nM.
In response to the Declarant’s argument that there is no teaching or suggestion in Seidel that would direct an ordinary skilled artisan to make the specific amino acid substitutions posited by the Examiner, it is found unpersuasive. The examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). Here, it is acknowledged that Seidel does not teach or suggest which specific substitutions at which residue positions can be made. However, Seidel broadly teaches that the KRAS peptides contain one or more substitutions relative to a wild type KRAS peptide. As stated in the Action mailed on 11/4/25, given the finite number of residues in Seidel’s SEQ ID NO: 181, i.e., 10 residues, where 8 of the 10 residues are hydrophobic aliphatic amino acids thereby encompassing the same potential conservative substitutions, two hydrophilic residues, one of which is the C-terminal Lys residue, and given the finite number of potential conservative substitutions of Lys, i.e., Arg, an ordinary skilled artisan would be motivated, at a minimum, to try with a reasonable expectation of success to substitute the C-terminal Lys residue with Arg (See MPEP 2145(X)(B) stating: an "obvious to try" rationale may support a conclusion that a claim would have been obvious where one skilled in the art is choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success. " [A] person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely that product [was] not of innovation but of ordinary skill and common sense. In that instance the fact that a combination was obvious to try might show that it was obvious under § 103." KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 421, 82 USPQ2d 1385, 1397 (2007). Although an obvious-to-try rationale should not be utilized when the prior art gives either no indication of which parameters were critical or no direction as to which of many possible choices is likely to be successful (See MPEP 2145(X)(B)), this is not the case in the instant application. An ordinary skilled artisan would not be testing every possible substitution with each residue, as asserted by the Declarant. Rather, an ordinary skilled artisan would be substituting a residue of a specific amino acid sequence with a finite number of substitutions known to result in similar properties.
Furthermore, it is acknowledged that Betts does not teach any immunogenic compositions or amino acid substitutions relevant for treating cancer. However, the teachings of Seidel et al. teach immunogenic compositions relevant for treating cancer, and thus, when Betts is combined with Seidel, the combination of both references suggest modifying Seidel’s immunogenic peptide in light of Bett’s teachings. Thus, contrary to the Declarant’s argument, an ordinary skilled artisan would, at a minimum, be motivated to try to make the specific amino acid substitution of Seidel’s KRAS peptide to arrive at instant SEQ ID NO: 158.
In response to the Declarant’s argument that even if an ordinary skilled artisan were motivated to make these substitutions, they would have no reasonable expectation of success that doing so would result in the peptide-HLA binding affinity as recited in instant claim 1 in view of the teachings of the cited references, it is found unpersuasive. Pursuant to MPEP 2143.02(II), obviousness does not require absolute predictability, however, at least some degree of predictability is required. Evidence showing there was no reasonable expectation of success may support a conclusion of nonobviousness. In re Rinehart, 531 F.2d 1048, 189 USPQ 143 (CCPA 1976). Here, as discussed supra, Betts expressly suggests that substituting lysine for arginine would result in similar properties. This expectation is due to the similar properties of the side chains of both residues. Thus, Betts demonstrates that an ordinary skilled artisan would have the requisite motivation with the requisite expectation of success in substituting the C-terminal Lys residue of Seidel’s SEQ ID NO: 181 with an Arg residue.
Furthermore, the references cited and relied upon by the Declarant to demonstrate the unpredictability in the art are acknowledged. However, it is not readily apparent how immunogenic peptides that are not structurally related to the claimed KRAS peptides can support a finding of unpredictability, and thus, nonobviousness. As stated by the Declarant, “it was understood that even a single amino acid substitution could have extreme impact on binding affinity” (See Declaration, paragraph 17). Thus, even if there is evidence to suggest that peptides that are not structurally related to the instant KRAS peptides, and in particular to SEQ ID NO: 158, exhibit varying HLA binding affinities when there is a substitution, e.g., Wang’s TRP peptide having a R to K substitution resulted in one identical binding affinity to a specific HLA allele (See Wang, Table II) (cited in the IDS received on 1/29/26), such evidence does not per se support that a single conservative substitution of Seidel’s KRAS peptide would dramatically impact the peptide’s HLA-binding affinity, especially when the instant specification does not identify the binding affinity for any claimed sequence including SEQ ID NO: 158, as discussed supra. Therefore, contrary Declarant’s argument, since the standard for predictability is one of reasonableness and not absolute predictability, and the Declarant has not provided evidence that a C-terminal K substitution to a C-terminal R in Seidel’s KRAS peptide would significantly impact it’s HLA-binding affinity, the Examiner maintains that an ordinary skilled artisan has the requisite expectation of success to arrive at the claimed method.
Accordingly, the Declaration is found unpersuasive.
New Rejections NOT Necessitated by Amendment
Claim Rejections - 35 USC § 112
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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 1-2, 5-7, and 31-34 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
In the instant case, claim 1 was amended (cf. amendment filed 1/29/2026) to further limit the peptides encoded by the at least one isolated polynucleotide to be displayed by an HLA class I molecule in the human subject with a peptide-HLA binding affinity value of less than about 100 nM (note: italicized portion was added as new claim 31 (cf. amendment filed 5/30/25)). Claim 32 was added (cf. amendment filed 5/30/25) to recite where the peptide-HLA binding affinity value is less than about 50 nM. Applicants stated in their remarks received on 5/30/25 that “no new matter has been introduced.” (See pg. 10 of the Remarks filed on 5/30/2025). Applicants also stated in their remarks received on 9/16/25 that support for new claim 33, which also was directed to where a peptide-HLA binding affinity value of less than about 100 nM and now is canceled, is found “throughout the as-filed application including, for example, at paragraphs [0672] and [0678] of the instant application.” (See pg. 11 of the Remarks filed on 9/16/2025). Turning to the original claims and specification-as-filed, there is no expressed and/or inherent support for the claim limitations where the specifically claimed peptides in claim 1 will exhibit a peptide-HLA binding affinity value of less than about 100 nM or less than about 50 nM including the cited support, i.e., [0672], [0678]. [0672] teaches evaluating a base set of vaccine peptides’ HLA-binding affinities. Although [0672] indicates that various affinity criteria may be used such as a 50 nM, less than about 1000 nM or less than about 500 nM, there is no indication which peptides would exhibit which peptide-HLA binding affinity amount or range. [0678] discusses modifying the immunogenic peptides, in particular, anchor residue modifications, to create a new heteroclitic base set, where the heteroclitic peptide can then be evaluated in experimental assays. Therefore, [0672] and [0678] does not provide support that SEQ ID NO: 158, for example, would exhibit a HLA-binding affinity value of less than about 100 nM or less than about 50 nM.
Lack of Ipsis Verbis Support
The specification is void of support that would clearly support the instant amendment. The specification does not teach the specifically claimed method where the one or more peptides such as SEQ ID NO: 158 encoded by the at least one isolated polynucleotide to be displayed by an HLA class I molecule with a peptide-HLA binding affinity value of less than about 100 nM or at least about 50 nM. Examination of the instant support refers generally to setting up varying peptide-HLA binding criteria where the criteria can accommodate different goals during the base set selection and vaccine design phases (See instant, [0672]). For example, a target peptide with peptide-HLA binding affinities of 500 nM may be displayed by an individual that is diseased, but at a lower frequency than a target peptide with a 50 nM peptide-HLA binding affinity (See instant, [0672]). In some embodiments, a relatively less constrained threshold (e.g., less than about 1000 nM or less than about 500 nM) of peptide-HLA immunogenicity or peptide-HLA binding is used for filtering candidate peptides and a relatively more constrained threshold (e.g., a less than about 50 nM) is used for filtering expanded set peptides (See instant, [0672]). As such, the specification refers generally to select any criteria with respect to peptide-HLA binding affinity dependent upon the goals during the base set selection and vaccine design phases. However, this support does not demonstrate the HLA binding affinity for any specific peptides. For example, there is no support that elected SEQ ID NO: 158 exhibits a peptide-HLA binding affinity value of less than about 100 nM or less than about 50 nM. Thus, the claimed subgenus encompassing where peptide-HLA binding affinity values are less than about 100 nM or less than about 50 nM is not expressly described. In In re Ruschig, 379 F.2d 990, 154 USPQ 118 (CCPA 1967), the Court rejected a claim species that fell within a large genus. The Court analogized the genus of the compounds to a forest and the species to a tree. The Court stated “[i]t is an old custom in the woods to mark trails by making blaze marks on the trees. It is no help in finding a trail… to be confronted simply by a large number of unmarked trees. Appellants are pointing to trees. We are looking for blaze marks which single out particular trees. We see none.” Ruschig, 154 USPQ at 122. Similarly, in Fujikawa v. Wattanasin, 93 F.3d 1559, 39 USPQ2d 1895, the Federal Circuit declined to find support for a subgenus based on the discloser of a genus because the application did not contain "blazemarks" to support the subgenus. In justification for denying support, the Court stated that “just because a moiety is listed as one possible choice for one position does not mean there is ipsis verbis support for every species or sub-genus that chooses that moiety.” Fujikawa, 39 USPQ2d at 1905. Thus it is clear from these decisions that the specification must provide blazemarks to the new sub-genus or species.
Lack of Inherent Support
“While there is no in haec verba requirement, newly added claim limitations must be supported in the specification through express, implicit, or inherent disclosure.” MPEP 2105 states that “A lack of adequate written description issue also arises if the knowledge and level of skill in the art would not permit one skilled in the art to immediately envisage the product claimed from the disclosed process. See, e.g., Fujikawa v. Wattanasin, 93 F.3d 1559, 1571, 39 USPQ2d 1895, 1905 (Fed. Cir. 1996) (a "laundry list” disclosure of every possible moiety does not constitute a written description of every species in a genus because it would not “reasonable lead” those skilled in the art to any particular species); In re Ruschig, 379 F.2d 990, 995, 154 USPQ 118, 123 (CCPA 1967). In the instant case, as set forth above, the disclosure describes selecting HLA binding affinity values to accommodate the desired goals during the base set selection and vaccine design phases where the HLA binding affinity values may be set at less than about 1000 nM, less than about 500 nM, or less than about 50 nM. However, the instantly carved subgenus encompassing where the specific peptide sequences exhibit a HLA binding affinity value of less than about 100 nM or less than about 50 nM has not been adequately supported.
Maintained/Modified Rejections Necessitated by Amendment
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 factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
103 - KSR Examples of 'Rationales' Supporting a Conclusion of Obviousness(Consistent with the "Functional Approach" of Graham)
Further regarding 35 USC 103(a) rejections, the Supreme Court in KSR International Co. v. Teleflex Inc., 550 U.S. 398, 127 S. Ct. 1727, 82 USPQ2d 1385, 1395-97 (2007) (KSR) 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. The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. The Supreme Court in KSR noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit.
Exemplary 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 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.
Note that the list of rationales provided is not intended to be an all-inclusive list. Other rationales to support a conclusion of obviousness may be relied upon by Office personnel.
Also, a reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings. (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976).
Claims 1-2, 5-7, 32, and 34 are rejected under 35 U.S.C. 103 as being unpatentable over Seidel et al. WO 2021/055594 A1 published on March 25, 2021 (cited in the IDS received on 3/27/24), in view of Betts et al., “Chap. 14: Amino Acid Properties and Consequences of Substitutions,” Bioinformatics for Geneticists, Barnes et al., eds., John Wiley & Sons, Ltd., pgs. 297-316 (2003) (cited in the IDS received on 3/27/24). Please note that the rejection has been updated in light of Applicants’ amendments.
Determination of the Scope and Content of the Prior Art (MPEP §2141.01)
For claims 1, 5, and 7, with respect to a method of treating cancer associated with KRAS G12C expression comprising administering an effective amount to a human subject of a composition comprising a nucleic acid sequence encoding the amino acid sequence of SEQ ID NO: 158 as recited in instant claims 1 and 7; and with respect to where the at least one amino acid sequence comprises two heteroclitic modifications of a fragment of a KRAS protein containing a KRAS G12C mutation as recited in instant claim 5:
Seidel et al. teaches compositions comprising a nucleic acid or a recombinant expression vector (i.e., same as a construct) (See Seidel specification, paragraph [00277], [00282]) where the recombinant expression vector comprises nucleic acids encoding a heterodimeric and single-chain T-cell modulatory polypeptides (TMPs) and dimers thereof (See Seidel specification, paragraph [0003], [00264]-[00265], [00270]). The TMPs comprise an immunomodulatory polypeptide, class I HLA polypeptides (a class I HLA heavy chain polypeptide and a β2 microglobulin polypeptide), and a KRAS peptide (e.g., a KRAS peptide comprising a cancer-associated mutation) that presents an epitope to a T-cell receptor (See Seidel specification, paragraph [0003], [00282]). Mutated forms of KRAS associated with certain cancers include a substitution of G12 such as G12C where the G12C mutation is known to be associated with lung cancer, e.g., non-small cell lung cancer (See Seidel specification, paragraph [0056], [0058]). The KRAS peptide can have one or more amino acid substitutions relative to the wild-type, non-cancer associated KRAS peptide (See Seidel specification, paragraph [0056]) where the mutated KRAS peptide with one or more amino acid substitutions includes SEQ ID NO: 181 (See Seidel specification, paragraph [0092] and [0099]). When comparing Seidel’s SEQ ID NO: 181 with instant SEQ ID NO: 158, there is 100% identity except for where the lysine residue at position 10 is arginine in instant SEQ ID NO: 158.
Furthermore, Seidel et al. teaches a method of treatment of an individual by administering to the individual an amount of a TMP, or one or more nucleic acids encoding the TMP, effective to treat the individual (See Seidel specification, paragraph [00288], [00293]). Conditions to be treated include cancer such as a cancer that expresses a KRAS polypeptide, e.g., a mutant KRAS polypeptide (See Seidel specification, paragraph [00288], [00293]). Seidel et al. also defines “an individual” as referring to any mammalian subject (See Seidel specification, paragraph [0039]). Mammals include humans (See Seidel specification, paragraph [0039]). As such, since Seidel et al. teaches that a KRAS G12C mutation is associated with lung cancer, the teachings of Seidel et al. suggest a method of treating lung cancer as a cancer associated with KRAS G12C expression by administering to a human subject an effective amount of a composition comprising a nucleic acid encoding a TMP containing instant SEQ ID NO: 158 as recited in instant claims 1, 5, and 7.
Regarding instant SEQ ID NO: 158, it is noted that the amino acid at position 10 has been substituted from lysine to arginine.
Betts et al. teaches that valine can be substituted by other hydrophobic, particularly, aliphatic amino acids such as isoleucine and leucine (See Betts article, pg. 298, 4th paragraph; pg. 300, 5th to last paragraph to pg. 301, 1st to 5th paragraph). As such, substituting valine with leucine is a conservative substitution. Furthermore, Betts et al. teaches that lysine can be substituted by arginine or other polar amino acids (See Betts article, pg. 303, last paragraph to pg. 305, 2nd paragraph). As such, substituting lysine with arginine is a conservative substitution. Thus, the lysine residue at position 10 of Seidel’s SEQ ID NO: 158 can be substituted with arginine because these two amino acids exhibit similar properties. Therefore, when considering the teachings of Seidel et al. as a whole in combination with the teachings of Betts et al., the combined references suggest a composition comprising nucleic acid sequences encoding TMP dimers where each TMP is a heterodimer comprising a KRAS peptide and where the KRAS peptides encompass mutated polypeptides such as instant SEQ ID NO: 158 as recited in instant claims 1 and 7.
For claim 1, with respect to where the composition is an immunogenic composition:
Seidel et al. teaches that the compositions comprising the heterodimeric TMPs are useful for modulating the activity of a T-cell and for modulating an immune response (See Seidel specification, paragraph [0003]). As such, Seidel et al. teaches that the compositions exhibit immunogenic properties.
Additionally and/or alternatively, even if Seidel et al. did not expressly teach that the composition comprising heterodimeric TMPs are immunogenic, since Seidel et al. teaches a composition comprising nucleic acid sequences encoding a TMP where each TMP comprising a KRAS peptide and where the KRAS peptides encompass a mutated polypeptide such as instant SEQ ID NO: 158 thereby constituting a well-known composition, the functional property (i.e., being immunogenic) of the composition as claimed and the known composition would necessarily read upon the same. The discovery of a previously unappreciated property of a prior art composition, or a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer. Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus, the claiming of a new functional property (i.e., being immunogenic) which would necessarily read upon the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 4333 (CCPA 1977). Therefore, the teachings of Seidel et al. satisfy the claim limitation with respect to where the composition is immunogenic as recited in instant claim 1.
For claims 1-2, with respect to where the effective amount of the immunogenic composition causes the one or more peptides encoded by the at least one isolated polynucleotide to be displayed by an HLA class I molecule in the human subject as recited in instant claim 1; and with respect to where the at least one isolated polynucleotide is contained in a construct for expression in vivo of one or more peptides encoded by the at least one isolated polynucleotide as recited in instant claim 2:
As discussed supra for claim 1, Seidel et al. teaches compositions comprising a nucleic acid or a recombinant expression vector (i.e., same as a construct) (See Seidel specification, paragraph [00277], [00282]). As such, the teachings of Seidel et al. satisfy the claim limitation with respect to where to the nucleic acid sequence encoding the peptide is part of a construct as recited in instant claim 2. Since Seidel et al. teaches the claimed structure of the nucleic acid sequence being a component in a recombinant expression vector thereby satisfying the claimed structure recited in instant claim 2, it would necessarily follow nucleic acid being in the construct results in in vivo expression of the peptide that is encoded. Properties are the same when the structure and composition are the same. Thus, burden shifts to applicant to show unexpected results, by declaration or otherwise. In re Fitzgerald, 205 USPQ 594. In the alternative, the claimed properties would have been present once the composition was employed in its intended use. In re Best, 195 USPQ 433. Therefore, the teachings of Seidel et al. satisfy the claim limitation as recited in instant claim 2.
Regarding the effective amount, it is noted that the instant specification does not define what constitutes an effective amount. It is further noted that no specific amount or range is recited. However, the effective amount as recited in instant claim 1 must be an amount that causes the one or more peptides encoded by the at least one isolated polynucleotide to be displayed by an HLA class I molecule in the human subject. Seidel et al. teaches that an effective amount can be an amount that, when administered in one or more doses to an individual in need thereof, reduces the number of cancer cells in the individual, reduces the tumor mass in the individual, tumor volume in the individual, or increases survival time of the individual (See Seidel specification, paragraph [00293]-[00294]).
Furthermore, as discussed supra, Seidel et al. teaches that the TMPs comprise an immunomodulatory polypeptide, class I HLA polypeptides (a class I HLA heavy chain polypeptide an a β2 microglobulin polypeptide), and a KRAS peptide (e.g., a KRAS peptide comprising a cancer-associated mutation) that presents an epitope to a T-cell receptor (See Seidel specification, paragraph [0003], [00282]). As such, a nucleic acid sequence that encodes the heterodimeric TMPs are configured to present the KRAS peptide (e.g., instant SEQ ID NO: 158) as an epitope to a T-cell receptor. Thus, the teachings of Seidel et al. satisfy the claim limitation with respect to where the effective amount of the composition causes one or more peptides encoded by the at least one isolated polynucleotide to be displayed by an HLA class I molecule to be expressed in a subject as recited in instant claim 1.
Additionally and/or alternatively, since Seidel et al. in of Betts et al. teaches the claimed structure of an effective amount of the composition thereby satisfying the claimed structure recited in instant claim 1, it would necessarily follow the effective amount of the composition causes one or more peptides encoded by the at least one isolated polynucleotide to be displayed by an HLA class I molecule to be expressed in a subject. Properties are the same when the structure and composition are the same. Thus, burden shifts to applicant to show unexpected results, by declaration or otherwise. In re Fitzgerald, 205 USPQ 594. In the alternative, the claimed properties would have been present once the composition was employed in its intended use. In re Best, 195 USPQ 433. Therefore, the teachings of Seidel et al. satisfy the claim limitation as recited in instant claim 1.
For claims 1 and 32, with respect to where the one or more peptides encoded by the at least one isolated polynucleotide to be displayed by an HLA class I molecule with a peptide-HLA binding affinity value of less than about 100 nM as recited in instant claim 1; with respect to where the peptide-HLA binding affinity value of less than about 50 nM as recited in instant claim 32:
As discussed supra, Seidel et al. teaches a method of treatment of an individual by administering to the individual an amount of a TMP, or one or more nucleic acids encoding the TMP, effective to treat the individual where the treatment is based on a disease associated KRAS mutation such as G12C such as non-small cell lung cancer (See Seidel specification, paragraph [0056], [0058], [00288], [00293]). The TMP comprises an immunomodulatory polypeptide, class I HLA polypeptides (a class I HLA heavy chain polypeptide and a β2 microglobulin polypeptide), and a KRAS peptide (e.g., a KRAS peptide comprising a cancer-associated mutation) that presents an epitope to a T-cell receptor (See Seidel specification, paragraph [0003], [00282]). Seidel et al. teaches that the binding affinity of the KRAS peptide/MHC complex binds to a T-cell receptor (TCR) on a T cell with an affinity of from about 1 nM to about 100 µM (See Seidel specification, paragraph [0040]). Seidel et al. also teaches that whether a given peptide, e.g., a KRAS peptide that comprises a KRAS epitope) binds a class I HLA (comprising an HLA heavy chain and a β2M polypeptide), and when bound to the HLA complex, can effectively present an epitope to a T-cell receptor (TCR), can be determined using any number of well-known methods, e.g., biochemical binding assays or T-cell activation assays (See Seidel specification, paragraph [00197]). However, Seidel does not expressly teach the binding affinity between the KRAS peptide and HLA class I molecule.
Since Seidel et al. in view of Betts et al. teaches the claimed structure of an effective amount of the composition comprising the KRAS peptide thereby satisfying the claimed structure recited in instant claim 1, it would necessarily follow the KRAS peptide in the composition would exhibit a peptide-HLA binding affinity value of less than about 100 nM/50 nM. Properties are the same when the structure and composition are the same. Thus, burden shifts to applicant to show unexpected results, by declaration or otherwise. In re Fitzgerald, 205 USPQ 594. In the alternative, the claimed properties would have been present once the composition was employed in its intended use. In re Best, 195 USPQ 433. Therefore, the teachings of Seidel et al. in view of Betts et al. satisfy the claim limitation as recited in instant claims 1 and 32.
For claim 6, with respect to selecting for administration the at least one isolated polynucleotide encoding the at least one amino acid sequence based on a HLA class I allele that is expressed in the human subject:
As discussed supra for claim 1, Seidel et al. teaches a method of treatment of an individual by administering an amount of a TMP or one or more nucleic acids encoding the TMP, effective to treat the individual where the conditions that can be treated include cancer such as a cancer that expresses a KRAS polypeptide (See Seidel specification, paragraph [00288]). Moreover, as discussed supra, Seidel et al. teaches where the administered TMP contains mutated KRAS polypeptides. Seidel et al. also teaches that cancers that can be treated with a method of the present disclosures include cancers in which the cancer cells express a mutated form of KRAS such as adenocarcinomas and hematological malignancies including multiple myeloma, breast cancer, lunger cancer, etc. (See Seidel specification, paragraph [00295], [00297]). As such, Seidel et al. teaches where the KRAS polypeptide in the TMP is are selected based on the mutated RAS protein that is expressed in the subject. Thus, it would necessarily follow that the mutated KRAS polypeptides selected to be part of the administered TMP would correspond to/based on a HLA class I allele that expresses the mutated KRAS peptide in the human subject.
Plus, Seidel et al. teaches that the MHC polypeptide in the TMP (also referred to as a HLA polypeptide) can be a Class I HLA polypeptide including a Class I HLA heavy chain polypeptide such as HLA-A, HLA-B, HLA-C, HLA-E, HLA-F, HLA-G, and variant forms thereof (See Seidel specification, paragraph [00104]-[00148]; Table 1). Seidel et al. also teaches a method of selectively modulating the activity of an epitope-specific T cell, e.g., a KRAS peptide comprising a cancer-associated mutation, by contacting the T cell with a TMP that selectively modulates the activity of the epitope-specific T cell (See Seidel specification, paragraph [00283]). Similarly, Seidel et al. teaches a method of modulating an immune response in an individual by administering to the individual an effective amount of a TMP where the TMP induces an epitope-specific T-cell response, e.g., cancer epitope-specific T-cell response, and an epitope-non-specific T cell response at a ratio of at least 2:1 (See Seidel specification, paragraph [00285]). In some case, the modulating increases cytotoxic T cell response to a cancer cell, e.g., a cancer cell expressing an antigen that displays the same epitope displayed by the KRAS epitope present in the TMP and/or increases the number of T cells specific for the KRAS epitope (See Seidel specification, paragraph [00285]). As such, it would necessarily follow that the Class I HLA polypeptide included in the TMP would be based on the HLA polypeptide that contains the specific epitope for the KRAS mutation that is expressed in the individual. Thus, the teachings of Seidel et al. satisfy the claim limitation with respect to selection of the at least one polynucleotide encoding the at least one amino acid sequence based on a HLA class I allele that is expressed in the human subject as recited in instant claim 6.
For claim 34, with respect to where the at least one isolated polynucleotide encodes an MHC signal peptide or a MHC trafficking signal:
Seidel et al. teaches that in some cases, the MHC class I heavy chain present in a TMP does not include a signal peptide, a transmembrane domain, or an intracellular domain (cytoplasmic tail) associated with a native MHC class I heavy chain (See Seidel specification, paragraph [00103]). As such, if a signal peptide is not included in some cases, that would necessarily correlate to embodiments where a MHC signal peptide is included. Thus, the nucleic acid encoding the TMP by Seidel encompasses both embodiments where a MHC signal peptide is or is not encoded. Therefore, the teachings of Seidel et al. satisfy the claim limitation as recited in instant claim 34.
Ascertainment of the Difference Between Scope of the Prior Art and the Claims (MPEP §2141.012)
Seidel et al. does not expressly teach in a method of treating cancer associated with KRAS G12C expression comprising administering an effective amount to a human subject of a composition comprising a nucleic acid sequence encoding the amino acid sequence of SEQ ID NO: 158 as recited in instant claims 1 and 7. However, the teachings of Betts et al. cure this deficiency by constituting some teaching, suggestion, or motivation 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 and/or utilizing an "Obvious to try" rationale - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success pursuant under KSR.
Finding of Prima Facie Obviousness Rationale and Motivation (MPEP §2142-4143)
With respect to a method of treating cancer associated with KRAS G12C expression comprising administering an effective amount to a human subject of a composition comprising a nucleic acid sequence encoding the amino acid sequence of SEQ ID NO: 158 but not encoding a complete chain of a MHC molecule as recited in instant claims 1 and 7, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to modify the teachings of Seidel et al. and administer to a human subject an effective amount of an immunogenic composition comprising a nucleic acid sequence encoding a TMP comprising an immunomodulatory polypeptide, class I HLA polypeptides (a class I HLA heavy chain polypeptide with or without a signal peptide) and/or a β2 microglobulin polypeptide), and a KRAS peptide (e.g., a KRAS peptide comprising a cancer-associated mutation) wherein the KRAS peptide is instant SEQ ID NO: 158 in order to treat lung cancer associated with KRAS G12C expression in the human subject. One of ordinary skill in the art at the time the invention was made would have been motivated to do so because conservative substitutions were known to include the substitution between arginine and lysine such that the substitution of these amino acid residues results in similar properties as taught by Betts et al. thereby constituting a finite number of potential substitutions given that there are a finite number of residues that can be substituted and a finite number of substitutions considered conservative substitutions. One of ordinary skill in the art at the time the invention was made would have had a reasonable expectation of success given that the immunogenic compositions of Seidel et al. were administered to a human subject in an amount effective to treat lung cancer based on a specific KRAS mutation such as KRAS G12C and comprised a nucleic acid sequence encoding a TMP comprising an immunomodulatory polypeptide, class I HLA polypeptides (a class I HLA heavy chain polypeptide with or without a signal peptide and/or a β2 microglobulin polypeptide, and a KRAS peptide (e.g., a KRAS peptide comprising a cancer-associated mutation), and therefore, utilizing Seidel’s KRAS polypeptide SEQ ID NO: 181 as the KRAS polypeptide of the TMP where the lysine residue at position 10 of Seidel’s SEQ ID NO: 181 is conservatively substituted to arginine would support the treatment of lung cancer associated with KRAS G12C expression in a subject by constituting some teaching, suggestion, or motivation 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 and/or utilizing an "Obvious to try" rationale - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success pursuant under KSR.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant's arguments filed 1/29/26 for claims 1-2, 5-7, 32 and 34 have been fully considered but they are not persuasive. It is noted that Applicants’ arguments mirror those in the Declaration. Thus, Applicant’s attention is directed to the “Response to Amendments” section supra, which is incorporated herewith.
Conclusion
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/THEA D' AMBROSIO/Primary Examiner, Art Unit 1654