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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 02/04/2026 has been entered.
Priority
This application is a 371 of PCT/US2018/051280 filed 09/17/2018. PCT/US2018/051280 has PRO 62/565,464 filed 09/29/2017.
Claim Status
Claims 1-15, 18-21, and 23 are pending. Claims 7, 12-15, 18-21 are withdrawn.
Claims 1, 3 are amended. claims 16-17, and 22 are canceled.
Claims 1-6, 8-11, and 23 are being examined on the merits in this office action.
Claim Rejections - Withdrawn
The rejection of claims 1-2, 4-5, 8-11, and 23 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in view of the claim amendments.
Claim Rejections - 35 USC § 112 - New
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 1-6, 8-11 and 23 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a NEW MATTER rejection.
The response filed 02/04/2026 has introduced NEW MATTER into the claims. The newly added/amended Claim(s) 1 recites “no more than 25 amino acids in length”. The response did not specifically and adequately point out where support for newly added/amended Claim(s) 1 could be found in the originally filed disclosure.
Although the PTO has the initial burden of presenting evidence or reasons why persons skilled in the art would not recognize in the disclosure a description of the invention defined by the claims, when filing an amendment an applicant should show support in the original disclosure for new or amended claims. See MPEP 714.02 and 2163.06 (“Applicant should therefore specifically point out the support for any amendments made to the disclosure.”).
The amended claims now recites limitations, which were not clearly disclosed in the specification as filed, and now change the scope of the instant disclosure as filed. Such limitations recited in newly amended claim, which did not appear in the specification, as filed, introduce new concepts and violate the description requirement of the first paragraph of 35 U.S.C 112. “no more than 25 amino acids in length” is not found at al in the disclosure. Examiner notes that the paragraphs cited for support for the new amendments disclose that the peptide is 25 amino acid long. However, some of the peptide such SEQ ID NO: 599 is 15 amino acids long. Applicant is required to provide sufficient written support for the limitations recited in the present claims in the specification, or claims as-filed, or remove these limitations from the claims in response to this Office Action.
Claim Rejections - 35 USC § 103 - Maintained
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-6, 8-11 and 23 remain rejected under 35 U.S.C. 103 as being unpatentable over WO 2016/053339 A1 (hereinafter “the ‘339 publication”, cited and enclosed in the previous office action) in view of Shamalov et al. (Oncoimmunology. 2017; 6(4): e1285990, cited and enclosed in the previous office action), and Fersht et al. (WO 2008017863A2 – hereinafter “Fersht - cited and enclosed in the previous office action).
‘339 teaches a method of isolating T cells having antigenic specificity for a mutated amino acid sequence encoded by a cancer-specific mutation, the method comprising: identifying one or more genes in the nucleic acid of a cancer cell of a patient, each gene containing a cancer-specific mutation that encodes a mutated amino acid sequence; inducing autologous antigen presenting cells (APCs) of the patient to present the mutated amino acid sequence; co-culturing autologous T cells of the patient with the autologous APCs that present the mutated amino acid sequence; and selecting the autologous T cells that (a) were co-cultured with the autologous APCs that present the mutated amino acid sequence and (b) have antigenic specificity for the mutated amino acid sequence presented in the context of a major histocompatability complex (MHC) molecule expressed by the patient to provide isolated T cells having antigenic specificity for the mutated amino acid sequence encoded by the cancer-specific mutation (claim 1). ‘339 teaches that the method can identify one or more genes (See Abstract; claim 1, 10; [0003, 0004, 0029]). Examiner notes that one of ordinary skill in the art who has read the ‘339 reference has a choice of focusing on a number of genes or mutations in only one gene. ‘339 further teaches that cancer-specific mutation may be any mutation in any gene which encodes a mutated amino acid sequence and includes missense mutations [0032]. ‘339 further teaches that the autologous T cells have antigenic specificity for the mutated amino acid sequence (See Page 13, line 1-2). Examiner notes that this particular teaching clearly indicates that the isolating of T cells having antigenic specificity for a single mutated amino acid sequence. See also [0044-0046]. ‘339 further identifies a single specific mutated amino acid sequence, ERBB2IP, and using the sequence to generate APC, co-culturing them in T cells see [0071-0092]. ‘339 teaches the method wherein inducing autologous APCs of the patient to present the mutated amino acid sequence comprises pulsing APCs with peptides comprising the mutated amino acid sequence or a pool of peptides, each peptide in the pool comprising a different mutated amino acid sequence (claim 2 and [0036]). Examiner notes that this teaching reads on “at least two mutated amino acid sequence..”. ‘339 teaches the mutated amino acid sequences of SEQ ID NO: 73, 31-38, 53, 57 [0010, 0018], all of which have no more than 25 amino acids.
The difference between ‘339 and the instant application is that ‘339 does not teach that the mutated amino acid sequence encoded by a cancer-specific mutation is p53. The specific mutated p53 amino acid sequence that Applicant elected is the Y220C mutation in SEQ ID NO: 12.
Shamalov teaches that p53 is an attractive immunotherapy target because it is mutated in approximately half of human cancers, resulting in its inactivation and often accumulation in tumor cells and that peptides derived from p53 are presented by class I MHC molecules and may act as tumor-associated epitopes which could be targeted by p53-specific T cells (abstract). Shamalov teaches that selected p53 mutations altering protein stability can modulate p53 presentation to T cells, leading to a differential immune reactivity inversely correlated with measured p53 protein levels (abstract). Shamalov teaches that 86% of p53 mutations are found in p53 DNA binding domain (DBD) located between aa 102-292, most of them being missense mutations encoding a stable full-length protein (Page 1, left col., line 6-9; Page 2, left col., 3rd paragraph, line 10-11). Shamalov further teaches that a p53 construct that comprises the instant Y220C mutation (see Fig. 1) and teaches that p53 mutants can be divided into several groups based on their recognition by T cells, by means of cytokine secretion and activation marker level and that the mutant comprising Y220C triggered higher IFNγ, TNF-α and CD69 levels than wt p53 or G245S (up to 2.2-fold more than wt p53). (Page 2, right col., line 1-3). Even though Shamalov discloses constructs with the instant Y220C mutation, Shamalov does not explicitly disclose the sequence. The sequence is however disclosed by the ‘863 publication.
Fersht teaches p53 mutants such as P53Y220C (claim 10) and that the construct comprises p53-Y220C protein comprises residues 104-287 of SEQ ID NO:1 (claim 21). The sequence of ‘863 comprises the instant SEQ ID NO: 12 which is no more than 25 amino acids in length. ‘863 teaches the mutants help to identify ligands that bind in order to stabilize the proteins (Abstract). Further, Fersht teaches P53 mutants such as Y220C with the sequence of SEQ ID NO: 1 which comprises the instant SEQ ID NO: 512 (See Table 4 on Page 36), which is no more than 25 amino acids in length. Fersht teaches that the p53 mutants includes fragments (Page 3, line 26-30).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of ‘339, Shamalov, and Fersht and use a mutated p53 amino acid sequence as taught by Shamalov and Fersht because Shamalov teaches that mutated p53 is an attractive immunotherapy target for treatment of human cancers and teaches isolation of the T cells (Abstract) and ‘863 teaches the mutants help to identify ligands that bind in order to stabilize the proteins (Abstract). One of ordinary skill in the art would be motivated and would have had a reasonable expectation of success in using the method of ‘339 to isolate T cells having antigenic specificity for a mutated p53 amino acid sequence since Shamlov teaches p53 peptide is presented by class I MHC molecules and may act as tumor-associated epitopes which could be targeted by p53-specific T cells (Abstract) and ‘339 teaches a specific cancer specific mutation for the isolation of T cells [0071]. It would be obvious to specifically choose p53 since Shamalov teaches that p53 is an attractive immunotherapy target because it is mutated in approximately half of human cancers and that 86% of p53 mutations are found in p53 DNA binding domain (DBD) located between aa 102-292, most of them being missense mutations encoding a stable full-length protein (Page 1, left col., line 6-9; Page 2, left col., 3rd paragraph, line 10-11). Additionally, it would have been obvious to specifically use a fragment of the mutated p53 peptide taught by Fersht that is not more than 25 amino acids, since all the peptides of ‘339 are no more than 25 amino acids. The teachings of the cited references render obvious claim 1.
Regarding claim 2, ‘339 teaches the method wherein inducing autologous APCs of the patient to present the mutated amino acid sequence comprises pulsing APCs with peptides comprising the mutated amino acid sequence or a pool of peptides, each peptide in the pool comprising a different mutated amino acid sequence (claim 2 and [0036]). It would have been obvious for one of ordinary skill in the art to similarly use a mutated p53 of Shamalov and ‘863 in the method of ‘339.
Regarding claim 3, both Shamalov and ‘863 teach the p53 construct with the instant mutation (abstract and claim 21). Specifically, ‘863 teaches p53 mutants such as P53Y220C (claim 10) and that the construct comprises p53-Y220C protein comprises residues 104-287 of SEQ ID NO:1 (claim 21). The sequence of ‘863 comprises the instant SEQ ID NO: 12. Further, Fersht teaches P53 mutants such as Y220C with the sequence of SEQ ID NO: 1 (See Table 4 on Page 36). Examiner notes that the sequence of Fersht is identical and comprises the instant SEQ ID NO: 512. Examiner further notes that the disclosed sequence is no more than 25 amino acids in length. It would have been obvious to modify ‘339 and use a fragment the mutated p53 sequence of Fersht.
Regarding claim 4, ‘339 teaches the method wherein inducing autologous APCs of the patient to present the mutated amino acid sequence comprises introducing a nucleotide sequence encoding the mutated amino acid sequence into the APCs (claim 3 and [0037]). One of ordinary skill in the art would be motivated to use another mutated amino acid sequence such as mutated p53 of Shamalov and ‘863.
Regarding claim 5, ‘339 teaches the method wherein the nucleotide sequence introduced into the autologous APCs is a tandem minigene (TMG) construct, each minigene comprising a different gene, each gene including a cancer-specific mutation that encodes a mutated amino acid sequence (claim 4 and [0038]). ‘339 further teaches that cancer-specific mutation may be any mutation in any gene which encodes a mutated amino acid sequence and includes missense mutations [0032]. One of ordinary skill in the art would be motivated to use another mutated amino acid sequence such as mutated p53 of Shamalov and ‘863 in the method of ‘339.
Regarding claim 6, ‘339 teaches that the nucleotide sequence introduced into the autologous APCs is a tandem minigene (TMG) construct, each minigene comprising a different gene, each gene including a cancer-specific mutation that encodes a mutated amino acid sequence (claim 4). It would be obvious to use the mutated amino acid sequence such as p53 since both Shamalov and ‘863 teach the p53 construct with the instant mutation (abstract and claim 21). Specifically, ‘863 teaches p53 mutants such as P53Y220C (claim 10) and that the construct comprises p53-Y220C protein comprises residues 104-287 of SEQ ID NO:1 (claim 21). The sequence of ‘863 comprises the instant SEQ ID NO: 12. Further, Fersht teaches P53 mutants such as Y220C with the sequence of SEQ ID NO: 1 (See Table 4 on Page 36). Examiner notes that the sequence of Fersht is identical and comprises the instant SEQ ID NO: 512. Examiner further notes that the disclosed sequence is no more than 25 amino acids in length. It would have been obvious to modify ‘339 and use the sequence of ‘863 and Fersht.
Regarding claim 8, ‘339 teaches the method wherein selecting the autologous T cells that have antigenic specificity for the mutated amino acid sequence comprises selectively growing the autologous T cells that have antigenic specificity for the mutated amino acid sequence (claim 6 and [0040]). One of ordinary skill in the art would be motivated to use the mutated p53 amino acid sequence of Shamalov and ‘863.
Regarding claim 9, ‘339 teaches the method wherein selecting the autologous T cells that have antigenic specificity for the mutated amino acid sequence comprises selecting the T cells that express any one or more of programmed cell death 1 (PD-1), lymphocyte-activation gene 3 (LAG-3), T cell immunoglobulin and mucin domain 3 (TIM-3), 4- IBB, OX40, and CD 107a (claim 7 and [0041]). One of ordinary skill in the art would be motivated to use the mutated p53 amino acid sequence of Shamalov and ‘863.
Regarding claim 10, ‘339 teaches the method wherein selecting the autologous T cells that have antigenic specificity for the mutated amino acid sequence comprises selecting the T cells (i) that secrete a greater amount of one or more cytokines upon co-culture with APCs that present the mutated amino acid sequence as compared to the amount of the one or more cytokines secreted by a negative control or (ii) in which at least twice as many of the numbers of T cells secrete one or more cytokines upon co-culture with APCs that present the mutated amino acid sequence as compared to the numbers of negative control T cells that secrete the one or more cytokines (claim 8 and [0042]). One of ordinary skill in the art would be motivated to try and use the mutated p53 amino acid sequence of Shamalov and ‘863 to isolate the T cells.
Regarding claim 11, ‘339 teaches the method wherein the one or more cytokines comprise interferon (IFN)-y, interleukin (IL)-2, tumor necrosis factor alpha (TNF-a), granulocyte/monocyte colony stimulating factor (GM-CSF), IL-4, IL-5, IL-9, IL-10, IL-17, and IL-22 (claim 9 and [0042]).
Regarding claim 23, ‘339 teaches a method of isolating T cells having antigenic specificity for a mutated amino acid sequence encoded by a cancer-specific mutation, the method comprising inducing autologous antigen presenting cells (APCs) of the patient to present the mutated amino acid sequence; co-culturing autologous T cells of the patient with the autologous APCs that present the mutated amino acid sequence; and selecting the autologous T cells that (a) were co-cultured with the autologous APCs that present the mutated amino acid sequence and (b) have antigenic specificity for the mutated amino acid sequence presented in the context of a major histocompatability complex (MHC) molecule expressed by the patient to provide isolated T cells having antigenic specificity for the mutated amino acid sequence encoded by the cancer- specific mutation (claim 1). ‘339 further teaches that the autologous T cells have antigenic specificity for the mutated amino acid sequence (See Page 13, line 1-2). Examiner notes that this particular teaching clearly indicates that the isolating of T cells having antigenic specificity is for a single mutated amino acid sequence. See also [0044-0046]. ‘339 further identifies a single specific mutated amino acid sequence, ERBB2IP, and using the sequence to generate APC, co-culturing them in T cells see [0071-0092]. One of ordinary skill in the art would be motivated to try and use the mutated p53 amino acid sequence of Shamalov and ‘863 to isolate the T cells.
Response to Arguments
Applicant's arguments filed 12/03/2025 have been fully considered but they are not persuasive.
Applicant argues that the claims have been amended to recite "each mutated p53 amino acid sequence is no more than 25 amino acids in length” (Arguments page 8-15).
The arguments presented have been fully considered but are unpersuasive. Examiner further notes that ‘339 teaches the mutated amino acid sequences of SEQ ID NO: 73, 31-38, 53, 57 [0010, 0018], all of which have no more than 25 amino acids. Further, Fersht teaches that the p53 mutants includes fragments (Page 3, line 26-30). Additionally, Examiner notes that the instant claims (e.g. claim 2) still recite comprising language, thus the sequence can be part of a larger sequence. The arguments are unpersuasive and the rejection is maintained.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Mercy H. Sabila whose telephone number is (571)272-2562. The examiner can normally be reached Monday - Friday 5:00 am - 3:00 pm.
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/MERCY H SABILA/Examiner, Art Unit 1654