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 .
Priority
Acknowledgment is made of applicant’s claim for priority based on a provisional application filed as 62/869,877 on 07/02/2019.
All claims are given the priority date of 07/02/2019.
Application Status
Receipt is acknowledged of amendment, filed 03/04/2026. Claims 1-4, 10, 11, 22, 23, 39, 50, 99, 105, 107, 112 and 190 are currently pending.
Election/Restriction
Applicant’s election without traverse of Group I, claims 1-4, 10, 11, 22, 23, 39, 50, 99, 105, 107, 112 and 190, in the reply filed on 03/04/2026 is acknowledged.
Applicant’s election without traverse of SEQ ID NO: 5610 and delivery of an antigen expression system in the reply filed on 03/04/2026 is acknowledged.
The previous claims 113, 114, 131 and 206-208 were canceled by Applicant along with the election of invention remarks filed on 03/04/2026.
Claims 1-4, 10, 11, 22, 23, 39, 50, 99, 105, 107, 112 and 190 are currently under examination.
Information Disclosure Statement
Receipt of acknowledgment of the information disclosure statements filed on 12/23/2022 and 03/04/2026 have been received and all references have been considered.
Claim Objections
Claim 1 is objected to because of the following informalities:
Claim 1 comprises abbreviations of HIV and MHC. The first occurrence of any abbreviation must be spelled out with the abbreviation in the parenthesis. For example, Human Immunodeficiency Virus (HIV).
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 4, 10, 11, 22, 99, 107 and 112 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.
Claims 1, 10, 11, 22, 99, 107 and 112 are vague and indefinite in that the metes and bounds of the phrase “optionally” are unclear. The phrase is unclear in that it is used multiple times within the claims and therefore it is unclear which limitations are required and which are optional.
Claim 4 is dependent upon a claim that is not in the claim set (i.e., “claim 0”) and is therefore “incomplete.” See MPEP § 608.01(n)(V).
Improper Markush
Claims 1-4, 10, 11, 22, 23, 39, 50, 99, 105, 107, 112 and 190 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of HIV epitopes is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: The HIV epitopes all have different amino acid sequences which confer different levels of function in targeting specificity. Specifically, the instant specification teaches that the decision to focus on the specific HIV epitopes chosen in instant claim 2 was due to the specific level of functionality in targeting a particular HIV subtype [00358]. The instant specification teaches that each HIV epitope is specific to each HLA allele such as if an antigen-based vaccine is developed for the A2501 HLA allele, then the epitope sequence "DTIAIA VAGW (SEQ ID NO: 756)" can be selected for inclusion [00249].
Berger et al (JOURNAL OF VIROLOGY, Sept. 2011, Vol. 85, No. 18; p. 9334–9345) teaches the effectiveness of HIV-specific cytotoxic T lymphocyte (CTL) responses is highly dependent on epitope specificity, with certain epitopes providing superior viral control and others being easily escaped by the virus (Page 9334, Abstract).
Therefore, each epitope sequence confers different levels of specificity to a target and would not be capable of targeting all of the HLA allele targets with the same specificity.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Claim Rejections - 35 USC § 103
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 (i.e., changing from AIA to pre-AIA ) 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.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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 1-4, 10, 11, 22, 23, 39, 50, 99, 105, 107, 112 and 190 are rejected under 35 U.S.C. 103 as being unpatentable over Blair et al (WO 2018/098362 A1) in view of Llano et al (HIV Molecular Immunology 2013; pgs. 3-25).
Regarding claims 1 and 190, Blair teaches chimpanzee adenovirus vector comprising a neoantigen cassette, the neoantigen cassette comprising: a plurality of neoantigen-encoding nucleic acid sequences derived from a tumor present within a subject, the plurality comprising: at least two subject-specific MHC class I neoantigen-encoding nucleic acid sequences each comprising: a MHC class I epitope encoding nucleic acid sequence with at least one alteration that makes the encoded peptide sequence distinct from the corresponding peptide sequence encoded by a wild-type nucleic acid sequence [0011].
Blair does not teach the specific epitope sequence, such as SEQ ID NO: 5610, for targeting HIV MHC-I.
Llano teaches a list of specific epitopes by determining the HLA restriction and optimal epitope length for the most efficient epitopes for successful HIV vaccine selection (Page 5, Column 1 and Column 2). Llano teaches one of the optimal epitopes found with high specificity was HLA Cw5 (HIV protein p24) corresponding to epitope sequence AEQASQEVKNWM which is 100% identical to SEQ ID NO: 5610 (Page 13, Table I-A-1; See Appendix I).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the general subject-specific MHC class I neoantigen-encoding nucleic acid of Blair for the specific HIV MHC-I epitope such as HLA Cw5 (HIV protein p24) corresponding to epitope sequence AEQASQEVKNWM as taught by Llano because Blair teaches it is within the ordinary skill in the art to use chimpanzee adenovirus vector comprising a neoantigen cassette for vaccine delivery and Llano teaches specific HIV MHC-I epitope sequence shown to have improved function in due to the HLA restriction and epitope length properties.
One would have been motivated to make such a modification in order to receive the expected benefit of improved HIC MHC-I epitope function for HIV vaccines as taught by Llano.
Regarding claims 2-4, Blair teaches chimpanzee adenovirus vector comprising a neoantigen cassette, the neoantigen cassette comprising: a plurality of neoantigen-encoding nucleic acid sequences derived from a tumor present within a subject, the plurality comprising: at least two subject-specific MHC class I neoantigen-encoding nucleic acid sequences each comprising: a MHC class I epitope encoding nucleic acid sequence with at least one alteration that makes the encoded peptide sequence distinct from the corresponding peptide sequence encoded by a wild-type nucleic acid sequence [0011].
Blair does not teach the specific epitope sequence, such as SEQ ID NO: 5610, for targeting HIV MHC-I.
Llano teaches a list of specific epitopes by determining the HLA restriction and optimal epitope length for the most efficient epitopes for successful HIV vaccine selection (Page 5, Column 1 and Column 2). Llano teaches one of the optimal epitopes found with high specificity was HLA Cw5 (HIV protein p24) corresponding to epitope sequence AEQASQEVKNWM which is 100% identical to SEQ ID NO: 5610 (Page 13, Table I-A-1; See Appendix I).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the general subject-specific MHC class I neoantigen-encoding nucleic acid of Blair for the specific HIV MHC-I epitope such as HLA Cw5 (HIV protein p24) corresponding to epitope sequence AEQASQEVKNWM as taught by Llano because Blair teaches it is within the ordinary skill in the art to use chimpanzee adenovirus vector comprising a neoantigen cassette for vaccine delivery and Llano teaches specific HIV MHC-I epitope sequence shown to have improved function in due to the HLA restriction and epitope length properties.
One would have been motivated to make such a modification in order to receive the expected benefit of improved HIC MHC-I epitope function for HIV vaccines as taught by Llano.
Regarding claims 10 and 11, Blair teaches chimpanzee adenovirus vector comprising a neoantigen cassette, the neoantigen cassette comprising: a plurality of neoantigen-encoding nucleic acid sequences, the plurality comprising: at least 20 subject-specific MHC class I neoantigen-encoding nucleic acid sequences linearly linked to each other and each comprising: (A) an MHC class I epitope encoding nucleic acid sequence, wherein the MHC I epitope encoding nucleic acid sequence encodes an MHC class I epitope 7-15 amino acids in length, (B) a 5' linker sequence, wherein the 5' linker sequence is a native 5' nucleic acid sequence of the MHC I epitope, and wherein the 5' linker sequence encodes a peptide that are at least 5 amino acids in length; and (2) at least two MHC class II antigen-encoding nucleic acid sequences comprising: (A) a PADRE MHC class II sequence, (B) a Tetanus toxoid MHC class II sequence, (C) a first GPGPG linker sequence linking the PADRE MHC class II sequence and the Tetanus toxoid MHC class II sequence, (D) a second GPGPG linker sequence linking the 5' end of the at least two MHC class II antigen-encoding nucleic acid sequences to the plurality of neoantigen-encoding nucleic acid sequences and (E) a third GPGPG linker sequence linking the 3' end of the at least two MHC class II antigen encoding nucleic acid sequences to the SV40 polyadenylation signal nucleotide sequence [0012].
Blair does not teach the specific epitope sequence, such as SEQ ID NO: 5610, for targeting HIV MHC-I.
Llano teaches a list of specific epitopes by determining the HLA restriction and optimal epitope length for the most efficient epitopes for successful HIV vaccine selection (Page 5, Column 1 and Column 2). Llano teaches one of the optimal epitopes found with high specificity was HLA Cw5 (HIV protein p24) corresponding to epitope sequence AEQASQEVKNWM which is 100% identical to SEQ ID NO: 5610 (Page 13, Table I-A-1; See Appendix I).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the general subject-specific MHC class I neoantigen-encoding nucleic acid of Blair for the specific HIV MHC-I epitope such as HLA Cw5 (HIV protein p24) corresponding to epitope sequence AEQASQEVKNWM as taught by Llano because Blair teaches it is within the ordinary skill in the art to use chimpanzee adenovirus vector comprising a neoantigen cassette for vaccine delivery and Llano teaches specific HIV MHC-I epitope sequence shown to have improved function in due to the HLA restriction and epitope length properties.
One would have been motivated to make such a modification in order to receive the expected benefit of improved HIC MHC-I epitope function for HIV vaccines as taught by Llano.
Regarding claim 22, Blair teaches a chimpanzee adenovirus vector comprising: a. a
modified ChAdV68 sequence comprising the sequence of SEQ ID NO: 1 with an El (nt 577 to
3403) deletion and an E3 (nt 27, 125-31,825) deletion wherein SEQ ID NO: 1 of Blair is 100% identical to instant SEQ ID NO: 1 (See Appendix II); b. a CMV promoter sequence; c. an SV 40 polyadenylation signal nucleotide sequence; and d. a neoantigen cassette, the neoantigen cassette comprising: (1) a plurality of neoantigen-encoding nucleic acid sequences, the plurality comprising: at least 20 subject-specific MHC class I neoantigen-encoding nucleic acid sequences linearly linked to each other and each comprising: (A) an MHC class I epitope encoding nucleic acid sequence with at least one alteration that makes the encoded peptide sequence distinct from the corresponding peptide sequence encoded by a wild-type nucleic acid sequence, wherein the MHC I epitope encoding nucleic acid sequence encodes an MHC class I epitope 7-15 amino acids in length, (B) a 5' linker sequence, wherein the 5' linker sequence is a native 5' nucleic acid sequence of the MHC I epitope, and wherein the 5' linker sequence encodes a peptide that are at least 5 amino acids in length, (C) a 3' linker sequence, wherein the 3' linker sequence is a native 3' nucleic acid sequence of the MHC I epitope, and wherein the 3' linker sequence encodes a peptide that is at least 5 amino acids in length, and wherein each of the MHC class I neoantigen-encoding nucleic acid sequences encodes a polypeptide that is 25 amino acids in length, and wherein each 3' end of each MHC class I neoantigen-encoding nucleic acid sequence is linked to the 5' end of the following MHC class I neoantigen-encoding nucleic acid sequence with the exception of the final MHC class I neoantigen-encoding nucleic acid sequence in the plurality; and (2) at least two MHC class II antigen-encoding nucleic acid sequences comprising: (A) a PADRE MHC class II sequence, (B) a Tetanus toxoid MHC class II sequence, (C) a first GPGPG linker sequence linking the PADRE MHC class II sequence and the Tetanus toxoid MHC class II sequence, (D) a second GPGPG linker sequence linking the 5' end of the at least two MHC class II antigen-encoding nucleic acid sequences to the plurality of neoantigen-encoding nucleic acid sequences, (E) a third GPGPG linker sequence linking the 3' end of the at least two MHC class II antigen encoding nucleic acid sequences to the SV 40 polyadenylation signal nucleotide sequence; and wherein the neoantigen cassette is inserted within the E 1 deletion and the CMV promoter sequence is operably linked to the neoantigen cassette [0012, 0074 and 0076] and (Page 301, Fig. 16B and Page 304, Fig. 19A). Blair teaches the chimpanzee adenovirus vector can be substituted for the alphavirus Venezuelan equine encephalitis vector backbone and the CMV promoter for the 26S promoter [00151-00152].
Blair does not teach the specific epitope sequence, such as SEQ ID NO: 5610, for targeting HIV MHC-I.
Llano teaches a list of specific epitopes by determining the HLA restriction and optimal epitope length for the most efficient epitopes for successful HIV vaccine selection (Page 5, Column 1 and Column 2). Llano teaches one of the optimal epitopes found with high specificity was HLA Cw5 (HIV protein p24) corresponding to epitope sequence AEQASQEVKNWM which is 100% identical to SEQ ID NO: 5610 (Page 13, Table I-A-1; See Appendix I).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the general subject-specific MHC class I neoantigen-encoding nucleic acid of Blair for the specific HIV MHC-I epitope such as HLA Cw5 (HIV protein p24) corresponding to epitope sequence AEQASQEVKNWM as taught by Llano because Blair teaches it is within the ordinary skill in the art to use chimpanzee adenovirus vector comprising a neoantigen cassette for vaccine delivery and Llano teaches specific HIV MHC-I epitope sequence shown to have improved function in due to the HLA restriction and epitope length properties.
One would have been motivated to make such a modification in order to receive the expected benefit of improved HIC MHC-I epitope function for HIV vaccines as taught by Llano.
Regarding claim 23, Blair teaches the vector has an ordered sequence of each element of the vector is described in the formula, from 5' to 3', comprising: Pa-(L5b-Nc-L3d)x-(G5e-Uf)y-G3g-Ah; wherein P comprises the at least one promoter sequence operably linked to at least one
sequence of the plurality, where a chimpanzee adenovirus vector, optionally= 1, N comprises
one of the MHC class I epitope encoding nucleic acid sequence with at least one alteration that
makes the encoded peptide sequence distinct from the corresponding peptide sequence encoded
by the wild-type nucleic acid sequence, where c = 1, L5 comprises the 5' linker sequence,
where b = 0 or 1, L3 comprises the 3' linker sequence, where d = 0 or 1, G5 comprises one of
the at least one GPGPG linker sequences, where e = 0 or 1, G3 comprises one of the at least
one GPGPG linker sequences, where g = 0 or 1, U comprises one of the at least one MHC class
II antigen-encoding nucleic acid sequence, where f = 1, A comprises the at least one
polyadenylation sequence, where h = 0 or 1, X = 2 to 400, where for each X the corresponding
Nc is a C68distinct MHC class I epitope encoding nucleic acid sequence, and Y = 0-2, where
for each Y the corresponding Uf MHC class II antigen-encoding nucleic acid sequence. In a
particular aspect, b = 1, d = 1, e = 1, g = 1, h = 1, X = 20, Y = 2 [0013].
Regarding claim 39, Blair teaches an RNA alphavirus backbone for the neoantigen expression system was generated from a Venezuelan Equine Encephalitis (VEE) based self-replicating RNA (srRNA) vector (wherein the sequence of the VEE is SEQ ID NO: 5 without the deleted sequence which is 100% identical to instant SEQ ID NO: 5) wherein the sequences encoding the structural proteins of VEE located 3' of the 26S subgenomic promoter were deleted (VEE sequences 7544 to 11,175 deleted; SEQ ID NO:6 which is 100% identical to instant SEQ ID NO: 6 with the deleted sequences) and replaced by antigen sequences or a luciferase reporter (e.g., VEE-Luciferase) (Page 311, Fig. 24 and [00702]; See Appendix III and IV).
Regarding claim 50, Blair teaches a chimpanzee adenovirus vector comprising: a. a
modified ChAdV68 sequence comprising the sequence of SEQ ID NO: 1 with an El (nt 577 to
3403) deletion and an E3 (nt 27, 125-31,825) deletion wherein SEQ ID NO: 1 of Blair is 100% identical to instant SEQ ID NO: 1 ([0012, 00671 and 00672]; See Appendix III).
Regarding claim 99, Blair teaches the neoantigen cassette comprises junctional epitope sequences formed by adjacent sequences in the neoantigen cassette wherein the at least one or each junctional epitope sequence has an affinity of greater than 500 nM for MHC [0038].
Regarding claim 105, Blair teaches a pharmaceutical composition comprising a vector disclosed herein (such as a ChAd-based vector disclosed) and a pharmaceutically acceptable carrier [0039].
Regarding claims 107 and 112, Blair teaches an RNA alphavirus backbone for the neoantigen expression system was generated from a Venezuelan Equine Encephalitis (VEE) based self-replicating RNA (srRNA) vector (wherein the sequence of the VEE is SEQ ID NO: 5 without the deleted sequence which is 100% identical to instant SEQ ID NO: 5) wherein the sequences encoding the structural proteins of VEE located 3' of the 26S subgenomic promoter were deleted (VEE sequences 7544 to 11,175 deleted; SEQ ID NO:6 which is 100% identical to instant SEQ ID NO: 6 with the deleted sequences) and replaced by antigen sequences or a luciferase reporter (e.g., VEE-Luciferase) (Page 311, Fig. 24 and [00702]; See Appendix III and IV). Blair teaches the genomic RNA, which is in a plus-strand orientation and comprises a 5' methylguanylate cap and 3' poly A tail, is translated to produce non-structural proteins nsPl-4 that form the replication complex [00310]. Blair teaches RNA was transcribed from the srRNA DNA vector in vitro, transfected into HEK293A cell [00702].
Conclusion
No claims are allowed.
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/ALEXANDRA ROSE LIPPOLIS/Examiner, Art Unit 1637
/CELINE X QIAN/Primary Examiner, Art Unit 1637
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