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 .
Information Disclosure Statement
The information disclosure statement filed 12/23/2025 fails to comply with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609 because the Foreign Document 1 is not attached. It has been placed in the application file, but the information referred to therein has not been considered as to the merits. Applicant is advised that the date of any re-submission of any item of information contained in this information disclosure statement or the submission of any missing element(s) will be the date of submission for purposes of determining compliance with the requirements based on the time of filing the statement, including all certification requirements for statements under 37 CFR 1.97(e). See MPEP § 609.05(a).
Claim Status
Claims 1-4, 8-9, and 22-29 are cancelled. Claims 5-7, 10-21, and 30-43 as filed on 13 May 2026 are pending. Claims 21 is withdrawn. Claims 5-7, 10-20, and 30-43 are under examination.
As previously noted in office actions: applicant’s Elected Species of SEQ ID NO: 2 was found to be free of the art.
The following sequences have been rejoined for prosecution and appeared to be free of the art: SEQ ID NOs: 1-14,17-32, 35-40, 45-46,51-52, 60-61, 102, 107-110, 113-114, 117-118, 121-122, 125-126, 289-290, 303-304, and 355-356.
The following species has been rejoined for prosecution: A polypeptide comprising the amino acid sequences of 41 and 57; and a polypeptide comprising the amino acid sequences of SEQ ID NOs: 401 and 402.
Rejections Withdrawn
Rejection of claims 30-43 under 35 U.S.C. 112(b) is withdrawn with applicant amendment of claims.
Rejections Maintained
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 for establishing a background for determining obviousness under 35 U.S.C. 103 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.
Claims 5-7, 10, 12-15, and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Pereira & Cornel. Discovery Medicine. 20(109):111-119 (2015) (Of Record), Dullaers & Thielmans. J Gene Med. 8:3-17 (2006) (Of Record), and Zhuo (US20170009304A1 (Of Record).
Pereira teaches viral vectors that target dendritic cells (DCs) to induce immunity to tumor associated antigens (abstract and page 2 in pars 4-8). Pereira teaches an adenovirus vector that encoded multiple genes for induction of a T cell response to a specific disease (page 2 in pars 7-8).
Regarding claims 10 and 13-15, Pereira teaches the use of viral vectors including adenovirus or poxvirus vectors (page 2 in par 5), or self-replicating RNA vector of lentiviral (page 3 in par 1).
Regarding claim 12, Pereira teaches the use of vaccinia virus vector comprising cancer specific antigens (page 4 in par 8).
Regarding claim 20, Pereira teaches the use of the vectors as pharmaceuticals which would be pharmaceutical compositions as they are administered to patients (abstract).
Pereira does not teach the neoantigens comprising the sequence that is the same as instant SEQ ID NO:41 or 57. This deficiency is filled by Dullaers and Zhuo.
Dullaers teaches the capacity of DCs for efficient activation of naïve T cells through viral and non-viral delivery methods including viral vector delivery of tumor associated antigens both in vitro and in vivo (Summary). Dullaers teaches the use of DC activation in the treatment of human diseases including cancer (page 6 in col 2 in par 1-2). Dullaers teaches the use of modifying DCs to present multiple TAA-derived peptides (page 5 in col 1 in last paragraph).
Zhuo teaches SEQ ID NO: 250048 which matches instant SEQ ID NO: 42 which encodes instant SEQ ID NO: 41 and SEQ ID NO: 49236 which matches instant SEQ ID NO: 58 which encodes instant SEQ ID NO: 57.
Zhuo teaches the sequences are fusion sequences found in human cancer and other diseases ([0006]).
It would have been obvious at the time the application was filed to combine the DC stimulating vectors comprising neoantigens for use in the treatment of cancer taught by Pereira with the neoantigens of instant SEQ ID NO: 42 and 58 taught by Zhuo. One of skill in the art would have been motivated by the teachings of Pereira and Dullaers teaching vectors encoding one or more neoantigens known to be associated with cancer for use with other known in the art neoantigens associated with cancer. There would have been a reasonable expectation of success as Pereira and Dullaers teach the use of the vectors with varying neoantigens for use in the treatment of cancer.
Applicant Arguments
Applicant argues the office failed to provide a motivation for one of skill in the art to combine the teachings of the prior art or that one with skill in the art would have a reasonable expectation of success.
Applicant argues Pereira and Dullaers do not teach the sequences of the neoantigens of the claims. Applicant argues one of skill in the art would not have used the neoantigens of Zhuo in the vectors of Pereira and Dullaers. Applicant points to the teachings of Zhuo which are to a kit and method for detecting at least one KANSARL fusion transcript from a biological sample from a subject.” (Zhuo abstract). Applicant argues Zhuo is silent on viral vectors and does not disclose a single use for any of its discloses sequences. Applicant argues there is no reason to combine the many sequences of Zhuo with Pereira with a reasonable expectation of success and applicant argues there is no teaching towards the specific sequences of the instant claims. Applicant argues sequences have been cherry picked from Zhuo based on hindsight combination of teachings in the art.
Response to Arguments
Applicant's arguments filed 05/13/2026 have been fully considered but they are not persuasive.
Pereira and Dullaers are not relied upon to teach the sequences of the claims. Pereira and Dullaers are relied upon to teach the routine use of tumor associated antigens (TAA) in vectors for use in cancer research and specifically cancer therapies. Dullaers specifically teaches TAA from varying genes and cancers and teaches the focus on antigens that are unique to tumors so vaccines can provide an immune response that distinguishes between cancer cells from normal cells based on the expression of TAA (page 3 in “Immunotherapy of Cancer” and page 4 in col 1 in par 2). Pereira also teaches the use of the use of antigens from varying tissue sources (page 2 in pars 4 and 7). Zhuo is then relied upon to teach fusion transcripts that Zhuo states they are novel and found in human cancer and disease ([0006]). Zhuo teaches these sequences as disease related. The teachings of Pereira and Dullaers would point one of skill in the art to known antigens that are markers of disease as Pereira and Dullaers teaches the use of their vectors for use with TAAs from various tissues and cancers.
Pereira and Dullaers teach one of skill in the art to use TAAs in the vectors of their invention. It would have been equally obvious to one of skill in the art to select any of the 866,543 sequences taught by Zhuo as identifies them as unique antigens for diseased cells as Pereira and Dullaers teaches the use of unique antigens for the ability to target disease cells and not normal cells in patients.
Claims 5, 10-12, and 16-18 are rejected under 35 U.S.C. 103 as being unpatentable over Pereira & Cornel. Discovery Medicine. 20(109):111-119 (2015) (OF RECORD), Dullaers & Thielmans. J Gene Med. 8:3-17 (2006) (OF RECORD), and Zhuo (US20170009304A1) (Of Record) as applied to claims 5-7, 10, 12-15, and 20 above, and further in view of and Bachman (US 2020/0222478 A1) (Of Record).
The teachings of Pereira from the previous 103 rejection are incorporated here in full.
Pereira in view of Dullaers and Zhao teach vectors including adenovirus and poxvirus vectors comprising two or more neoantigens in a vector as described in the rejection of claims 5, and 10-12.
Pereira in view of Dullaers and Zhao does not teach the use of the poxvirus vector of MVA or the specific adenovirus vectors of hAd26 or Gad20.
This deficiency is filled by Bachman.
Bachman teaches the use of cancer neoantigens in vectors encoding them as polynucleotides for use in methods of making and using the neoantigens (Abstract). Bachman teaches vaccines and pharmaceutical compositions comprising RNA or DNA encoding polypeptides for neoantigens ([0016]-0029] and [4416]).
Regarding claims 10-12 and 14-19, Bachman teaches adenovirus vectors of poxvirus MVA ([4431]), ChAd20 ([4432]), an RNA of self-replicating RNA ([4425]-[[4426]), Gad20, and hAd26 ([4642]).
Thus Bachman teaches a number of successful vectors for encoding gene sequences of interest for us in pharmaceutical compositions.
It would have been obvious at the time the application was filed to substitute the generic adenovirus vectors and poxvirus vectors of Pereira in view of Dullaers and Zhao with the vectors of MVA, Gad20, and hAd26 taught by Bachman. The substitution of generic adeno or pox viral vectors for the specific species of vectors taught by Bachman would be obvious to one of skill in the art. Further, Bachman teaches vectors that are art equivalents used for expressing neoantigens. There would have been a reasonable expectation of success as Pereira, Dullaers, and Bachman all teach the successful use of multiple vector types for use in vectors expressing neoantigens.
Applicant Arguments
Applicant argues Bachman does not cure the deficiencies of Pereira in view of Dullaers and Zhao.
Response to Arguments
Applicant's arguments filed 05/13/2026 have been fully considered but they are not persuasive.
The previous rejection was maintained so there are no deficiencies to fill. Bachman is relied upon to teach additional vectors for expression of antigens known in the art.
Claims 30-33, 35-38, and 43 are rejected under 35 U.S.C. 103 as being unpatentable over Pereira & Cornel. Discovery Medicine. 20(109):111-119 (2015) (OF RECORD), Dullaers & Thielmans. J Gene Med. 8:3-17 (2006) (OF RECORD), Goldsmith (WO 2007/005635 A2)(Of Record), and Ethell (WO 2017/147139 A1) (Of Record).
Pereira teaches viral vectors that target dendritic cells (DCs) to induce immunity to tumor associated antigens (abstract and page 2 in pars 4-8). Pereira teaches an adenovirus vector that encored multiple genes for induction of a T cell response to a specific disease (page 2 in pars 7-8).
Regarding claims 32-33 and 36-38, Pereira teaches the use of viral vectors including adenovirus or poxvirus vectors (page 2 in par 5), or self-replicating RNA vector of lentiviral (page 3 in par 1).
Regarding claim 35, Pereira teaches the use of vaccinia virus vector comprising cancer specific antigens (page 4 in par 8).
Regarding claim 43, Pereira teaches the use of the vectors as pharmaceuticals which would be pharmaceutical compositions as they are administered to patients (abstract).
Pereira does not teach the neoantigens of the sequences that is the same as instant SEQ ID NOs: 401 and 402. This deficiency is filled by Dullaers, Goldsmith, and Ethell.
Dullaers teaches the capacity of DCs for efficient activation of naïve T cells through viral and non-viral delivery methods including viral vector delivery of tumor associated antigens both in vitro and in vivo (Summary). Dullaers teaches the use of DC activation in the treatment of human diseases including cancer (page 6 in col 2 in par 1-2). Dullaers teaches the use of modifying DCs to present multiple TAA-derived peptides (page 5 in col 1 in last paragraph).
Goldsmith teaches diagnostic and therapeutic methods and compositions featuring Abnormal Spindle-like Microcephaly (ASPM) proteins and nucleic acids whose expression is increased in neoplastic tissues (Abstract). Instant SEQ ID NO: 115 matches ASPM splice variant 2 of Goldsmith as shown in Figure 8E from amino acid 1366 to 1389. Goldsmith teaches the use of neoantigens of its inventions in multiple tissues including pancreas, brain, breast, and lung (claim 8), colon and thyroid (Example 1).
Regarding claims 30-32, Goldsmith teaches a vector comprising a polynucleotide expressing a polypeptide of the ASPM (claims 1 and 29-30).
Regarding claim 33 and 36-37, Goldsmith teaches self-replicating viral vectors (page 13 in lines 19-28). Goldsmith further teaches a variety of vectors including retroviral vectors, pox viruses, and adenovirus vectors (page 23 in lines 16-22).
Regarding claim 43, Goldsmith teaches recombinant viral vectors (page 15 in line 19, page 16 in lines 22-24). Goldsmith further teaches pharmaceutical compositions (page 37 in lines 7-15 and claims 47-50).
Instant SEQ ID NO: 401 is a KRAS neoantigen named M7 by the applicant (Table 11 top of page 259 of specification) which is encoded by instant SEQ ID NO: 402 (bottom of page 259 of specification).
Regarding claims 30-32, Ethell teaches neoantigen proteins and nucleic acids that encode them (Abstract). Ethell teaches SEQ ID NO: 14 which matches instant SEQ ID NO: 402 and SEQ ID NO: 15 which matches instant SEQ ID NO: 402 which is identified in Ethell as KNRAS-61K (page 11 at the bottom). Ethell teaches the neoantigen of SEQ ID NO: 14 as an exemplary neoantigen ([0044]). Ethell teaches the NRAS mutation Q61K as occurring in melanoma, NSCLC, AML, colorectal cancer, and Thyroid cancer (Table below [0043]). Ethell teaches the NRAS-Q61K mutation as a driver mutation to be used in an expression vector comprising CD4 (Example 3).
Regarding claims 33 and 36, Ethell teaches viral vectors including adenoviruses ([0049]).
Ethell teaches the treatment of many cancers including pancreatic cancer ([0066], [0038]).
Regarding claim 43, Ethell teaches pharmaceutical compositions (Abstract, [0008], and claim 20).
It would have been obvious at the time the application was filed to combine the DC stimulating vectors comprising neoantigens for use in the treatment of cancer taught by Pereira with the neoantigens of colon cancer taught by Goldsmith and Ethell. One of skill in the art would have been motivated by the teachings of Pereira and Dullaers teaching vectors encoding one or more neoantigens known to be associated with cancer for use with other known in the art neoantigens associated with cancer and Ethell and Goldsmith teach neoantigens of colon cancer. There would have been a reasonable expectation of success as Pereira and Dullaers teach the use of the vectors with varying neoantigens for use in the treatment of cancer.
Applicant Arguments
Applicant argues Pereira and Dullaers do not teach the sequences of the neoantigens of the claims.
Applicant argues that there is no provided rational for combining the sequence of Goldsmith and Ethell of ASPM splice variant and SEQ ID NO: 14, respectively.
Applicant argues the combination of elements are only combined based on their presence in the art.
Response to Arguments
Applicant's arguments filed 05/13/2026 have been fully considered but they are not persuasive.
Pereira and Dullaers are not relied upon to teach the sequences of the claims. Pereira and Dullaers are relied upon to teach the routine use of tumor associated antigens (TAA) in vectors for use in cancer research and specifically cancer therapies. Dullaers specifically teaches TAA from varying genes and cancers and teaches the focus on antigens that are unique to tumors so vaccines can provide an immune response that distinguishes between cancer cells from normal cells based on the expression of TAA (page 3 in “Immunotherapy of Cancer” and page 4 in col 1 in par 2). Pereira also teaches the use of the use of antigens from varying tissue sources (page 2 in pars 4 and 7).
Pereira and Dullaers then teach the use of vectors that comprise one or more antigen sequences for use in directing immune response to disease cells while not directing a response to healthy cells.
Goldsmith and Ethell are relied upon as they each teach an antigen to colon cancer. Goldsmith and Ethell both teach vectors for use in cancer therapeutics where a single antigen to colon cancer is used in their vectors (Goldsmith Example 1 and Ethell Example 3). Pereira and Dullaers combined with Goldsmith and Ethell then teach the combination into one vector. One of skill in the art would see both Goldsmith and Ethell teaching antigens to colon cancer.
Claims 30, 33-35, and 39-42 are rejected under 35 U.S.C. 103 as being unpatentable over Pereira & Cornel. Discovery Medicine. 20(109):111-119 (2015) (OF RECORD), Dullaers & Thielmans. J Gene Med. 8:3-17 (2006) (OF RECORD), Goldsmith (WO 2007/005635 A2)(Of Record), and Ethell (WO 2017/147139 A1) (Of Record) as applied to claims 30-33, 35-38, and 43 above, and further in view of and Bachman (US 2020/0222478 A1) (Of Record).
The teachings of Pereira from the previous 103 rejection are incorporated here in full.
Pereira in view of Dullaers, Goldsmith, and Ethell teach vectors including adenovirus and poxvirus vectors comprising two or more neoantigens in a vector as described in the rejection of claims 30 and 33-35.
Pereira in view of Dullaers, Goldsmith, and Ethell does not teach the use of the poxvirus vector of MVA or the specific adenovirus vectors of hAd26 or Gad20.
This deficiency is filled by Bachman.
Bachman teaches the use of cancer neoantigens in vectors encoding them as polynucleotides for use in methods of making and using the neoantigens (Abstract). Bachman teaches vaccines and pharmaceutical compositions comprising RNA or DNA encoding polypeptides for neoantigens ([0016]-0029] and [4416]).
Bachman teaches adenovirus vectors of poxvirus MVA ([4431]), ChAd20 ([4432]), an RNA of self-replicating RNA ([4425]-[[4426]), Gad20, and hAd26 ([4642]).
Thus Bachman teaches a number of successful vectors for encoding gene sequences of interest for us in pharmaceutical compositions.
It would have been obvious at the time the application was filed to substitute the generic adenovirus vectors and poxvirus vectors of Pereira in view of Dullaers Goldsmith, and Ethell with the vectors of MVA, Gad20, and hAd26 taught by Bachman. The substitution of generic adeno or pox viral vectors for the specific species of vectors taught by Bachman would be obvious to one of skill in the art. Further, Bachman teaches vectors that are art equivalents used for expressing neoantigens. There would have been a reasonable expectation of success as Pereira, Dullaers, and Bachman all teach the successful use of multiple vector types for use in vectors expressing neoantigens.
Applicant Arguments
Applicant argues Bachman does not cure the deficiencies of Pereira in view of Dullaers, Goldsmith, and Ethell.
Response to Arguments
Applicant's arguments filed 05/13/2026 have been fully considered but they are not persuasive.
The previous rejection was maintained so there are no deficiencies to fill. Bachman is relied upon to teach additional vectors for expression of antigens known in the art.
Conclusion
No Claims allowable.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/F.E./Examiner, Art Unit 1643
/JULIE WU/Supervisory Patent Examiner, Art Unit 1643
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