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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 29 September 2025 has been entered.
Claim Status
Claims 1-4, 8-9, and 22-29 are cancelled. Claims 5-7, 10-21, and 30-43 as filed on 29 September 2025 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 Claims 21 is withdrawn.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 search has been expanded with sequence searches reviewed until a sequence was found in the art.
The following sequences appear free of the art: 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.
Rejections Withdrawn
Rejection of claims 5-7, 10-20, and 30-43 under 35 U.S.C. 102 and 35 U.S.C. 103 are withdrawn with applicant amendment to claims requiring the vector encodes two or more neoantigens. New Examination of claims was performed and new rejections are made below based on new scope of the claims.
New Rejections Necessitated by Applicant Amendment of Claims.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 30-43 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 30 requires two or more polypeptides selected from the listed sequences. SEQ ID NO: 199 is listed twice. The claim is then unclear on whether a vector encoded 199 alone would fall within the metes and bounds of the claims.
For the purposes of prosecution the examiner has searched claim 30 and the depending claims as a vector comprising two or more polypeptides wherein the vector encodes SEQ ID NO: 199 with an additional sequence from the ones listed.
New Rejections Necessitated by Applicant Amendment of Claims.
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) (PTO-892), Dullaers & Thielmans. J Gene Med. 8:3-17 (2006) (PTO-892), 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 of the sequences of the claims. 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.
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) (PTO-892), Dullaers & Thielmans. J Gene Med. 8:3-17 (2006) (PTO-892), 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.
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) (PTO-892), Dullaers & Thielmans. J Gene Med. 8:3-17 (2006) (PTO-892), 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 of the claims. 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.
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) (PTO-892), Dullaers & Thielmans. J Gene Med. 8:3-17 (2006) (PTO-892), 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, Goldsmtih, 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, Goldsmtih, 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 Goldsmtih, 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.
Conclusion
No claims allowable.
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/F.E./Examiner, Art Unit 1643
/Meera Natarajan/Primary Examiner, Art Unit 1643