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 .
Examiner prosecuting this application has changed.
Claims Status
Claims 1-167, 169, 171-172, 174, 176, 178-179, 181-187 is/are cancelled and claims 188-199 is/are newly added. Claims 168, 170, 173, 175, 177, 180, 188-199 is/are currently pending and under examination.
Claim Interpretation
The claims contain limitations preceded by the term “optional”. All claim limitations recited as “optional” are interpreted as not required. As such, prior art can be applied to teach these limitations, but does not need to be applied.
Information Disclosure Statement
The information disclosure statements filed 07/25/2025 and 11/19/2021 fail to comply with 37 CFR 1.98(a)(2), which requires a legible copy of each cited foreign patent document; each non-patent literature publication or that portion which caused it to be listed; and all other information or that portion which caused it to be listed. It has been placed in the application file, but the information referred to therein has not been considered. No copy was provided of FOR #6 of the IDS filed 07/25/2025. No copies were provided of all struck-through references of the IDS filed 11/19/2021.
The information disclosure statement filed 11/19/2021 fails to comply with 37 CFR 1.98(a)(1), which requires the following: (1) a list of all patents, publications, applications, or other information submitted for consideration by the Office; (2) U.S. patents and U.S. patent application publications listed in a section separately from citations of other documents; (3) the application number of the application in which the information disclosure statement is being submitted on each page of the list; (4) a column that provides a blank space next to each document to be considered, for the examiner’s initials; and (5) a heading that clearly indicates that the list is an information disclosure statement. The information disclosure statement has been placed in the application file, but the information referred to therein has not been considered. Trail, 2010 (doi:10.3390/antib2010113) was provided with the IDS filed 11/19/2021 but was not listed in the IDS.
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. Hyperlinks were found in paragraph [00237]. Applicant is advised to review the specification in order to ensure that all hyperlinks are identified and appropriately removed.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Figs. 2B, 5B, 6B show amino acid sequences with no corresponding SEQ ID NOs in the drawings or description of the drawings in the specification.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 168, 173, 188-190 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Rooney (WO 2017173321 A1).
Regarding claim 168, Rooney teaches a vector comprising a promoter sequence (claims 78, 87-92; paragraphs [0166]-[0167], [0486]), at least on polyadenylation sequence (paragraphs [0280], [0486]), and nucleic acid sequences encoding multiple antigen epitopes (claims 1, 87-92). These multiple epitopes encompass a KRAS G12C epitope, a KRAS G12D epitope, a KRAS G12V epitope, and KRAS Q61H epitope (paragraph [0609]; Table 3). One KRAS G12C epitope sequence is VVVGACGVGK (100% identical to instant SEQ ID NO:19850). One KRAS G12V epitope sequence is VVGAVGVGK (100% identical to instant SEQ ID NO:19779) (page 181). One KRAS Q61H epitope sequence is ILDTAGHEEY (100% identical to instant SEQ ID NO:14409) (page 181). Rooney paragraph [0609] teaches that “The neonantigenic [sic] peptide can be a peptide comprising 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15…amino acid residues of the protein, e.g., KRAS including the substitution”. While the KRAS G12D epitopes taught in Tables 2 and 3 are KLVVVGADGV and LVVVGADGV, any 5 or more consecutive amino acids of the “mutation sequence context” which comprise the G12D substitution (underlined in Table 2) may be used in the invention of Rooney. As such, Rooney teaches epitopes encompassing instant SEQ ID NOs:19749 and 19865 (9 and 10 consecutive amino acids, respectively, of the “mutation sequence context” of KRAS G12D as listed in Rooney Table 2.
Regarding claim 173, Rooney teaches that the vector is comprised in a vaccine (a pharmaceutical composition), which comprises a pharmaceutically acceptable carrier (paragraphs [0099], [0137], [0352], [0384]).
Regarding claim 188, Rooney teaches that the antigenic polynucleotides are linked (claims 94-95).
Regarding claim 189, Rooney teaches that the epitopes may comprise two additional amino acids at the N- or C-termini (see Table 2; paragraph [0609] teaches that “The neonantigenic [sic] peptide can be a peptide comprising 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15…amino acid residues of the protein, e.g., KRAS including the substitution”). Table 2 of Rooney provides the “mutation sequence context” of KRAS G12C, G12D, G12V, and Q61H (page 164). While the particular epitope example sequences provided in Tables 2 and 3 do not comprise two or more additional N- or C-terminal amino acids relative to the instant recited sequences of claim 168, the teachings of Rooney state that the epitope may consist of any 5-100 consecutive amino acids from a fragment of the protein sequence comprising the substitution [paragraph [0609]). The neoantigenic peptides of Rooney thus encompass epitopes comprising two or more additional N- and/or C-terminal amino acids relative to the instant sequences recited in claim 168.
Regarding claim 190, the epitopes taught by Rooney are 9, 10 or more amino acids long (see Tables 2 and 3; paragraphs [0174], [0609]).
Claim(s) 175, 180, 194-196 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Mleczek (WO2017182634A1).
Regarding claim 175, Mleczek teaches a composition for delivery of an antigen expression system, comprising one or more vectors comprising: a vector backbone comprising at least one promoter sequence and at least one polyA sequence; and an antigen cassette comprising any combination of nucleic acid sequences encoding any of the following antigens: MAGE-A1, MAGE-A4, MAGE-B2, MAGE-A11, MAGE-A3, MAGE-A6, and CT83 (claims 1-2, 16, 29; Table 1; page 16 line 25-page 17 line 5; page 3 lines 9-15; page 12 lines 15-30). SEQ ID NO:267 of Mleczek comprises sequences 100% identical to instant SEQ ID NOs:4750, 4818, and 4864; Mleczek SEQ ID NO:270 comprises sequences 100% identical to instant SEQ ID NO:5880, 5784, and 5785; Mleczek SEQ ID NO:281 comprises a sequence 100% identical to instant SEQ ID NO:6631; Mleczek SEQ ID NO:264 comprises sequences 100% identical to instant SEQ ID NO:5245 and 5206; Mleczek SEQ ID NO:257 comprises sequences 100% identical to instant SEQ ID NOs:1454, 1423, 1446, and 1433; Mleczek SEQ ID NO:269 comprises sequences 100% identical to instant SEQ ID NOs:5483 and 5504; Mleczek SEQ ID NO: (see alignments below; see Table 1).
SEQ ID NO:267 and SEQ ID NO:4750:
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141
617
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SEQ ID NO:267 and SEQ ID NO:4818:
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139
613
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SEQ ID NO:267 and SEQ ID NO:4864:
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140
619
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SEQ ID NO:270 and SEQ ID NO:5880:
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136
613
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SEQ ID NO:270 and SEQ ID NO:5784:
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141
612
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SEQ ID NO:270 and SEQ ID NO:5785:
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138
611
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SEQ ID NO:281 and SEQ ID NO:6631:
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143
619
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SEQ ID NO:264 and SEQ ID NO:5245:
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139
612
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SEQ ID NO:264 and SEQ ID NO:5206:
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138
614
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SEQ ID NO:257 and SEQ ID NO:1454:
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136
614
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SEQ ID NO:257 and SEQ ID NO:1423:
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140
615
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SEQ ID NO:257 and SEQ ID NO:1446:
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139
610
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SEQ ID NO:257 and SEQ ID NO:1433:
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138
616
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SEQ ID NO:269 and SEQ ID NO:5483:
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139
610
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SEQ ID NO:269 and SEQ ID NO:5504:
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614
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Regarding claim 180, Mleczek teaches a pharmaceutical composition comprising the vector system and a pharmaceutically acceptable carrier (claim 30).
Regarding claim 194, Mleczek teaches that in a multicistronic system (encoding multiple coding sequences), all antigen coding sequences are present on one nucleic acid molecule and are thus linked (page 5 lines 6-10).
Regarding claim 195, Mleczek teaches that an “epitope” “refers to a fragment of an antigen or a variant of an antigen” and “typically comprise from about 5 to about 20 amino acids (page 6 lines 17-19). The sequences that Mleczek teaches in Table 1 as being inserted into the expression vector comprise epitopes, or fragments, of 5-20 amino acids within larger native sequences (see Table 1). Thus, the sequences Mleczek teaches in Table 1 comprise epitope sequences flanked by two or more additional amino acids at the N- and/or C- termini.
Regarding claim 196, Mleczek teaches that the antigen fragments are preferably “a sequence of an antigen or of a variant thereof as defined herein, which has a length of about 5 to about 20 or even more amino acids and which is preferably processed and presented by an MHC complex (page 34 lines 1-25).
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 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.
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.
Claim(s) 168, 170, 173, 170, 188-189, 191 is/are rejected under 35 U.S.C. 103 as being unpatentable over Rooney (WO 2017173321 A1), in view of Roshorm (2012).
Regarding claim 168, Rooney teaches a vector comprising a promoter sequence (claims 78, 87-92; paragraphs [0166]-[0167], [0486]), at least on polyadenylation sequence (paragraphs [0280], [0486]), and nucleic acid sequences encoding multiple antigen epitopes (claims 1, 87-92). These multiple epitopes encompass a KRAS G12C epitope, a KRAS G12D epitope, a KRAS G12V epitope, and KRAS Q61H epitope (paragraph [0609]; Table 3). One KRAS G12C epitope sequence is VVVGACGVGK (100% identical to instant SEQ ID NO:19850). One KRAS G12V epitope sequence is VVGAVGVGK (100% identical to instant SEQ ID NO:19779) (page 181). One KRAS Q61H epitope sequence is ILDTAGHEEY (100% identical to instant SEQ ID NO:14409) (page 181). Rooney paragraph [0609] teaches that “The neonantigenic [sic] peptide can be a peptide comprising 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15…amino acid residues of the protein, e.g., KRAS including the substitution”. While the KRAS G12D epitopes taught in Tables 2 and 3 are KLVVVGADGV and LVVVGADGV, any 5 or more consecutive amino acids of the “mutation sequence context” which comprise the G12D substitution (underlined in Table 2) may be used in the invention of Rooney. As such, Rooney teaches epitopes encompassing instant SEQ ID NOs:19749 and 19865 (9 and 10 consecutive amino acids, respectively, of the “mutation sequence context” of KRAS G12D as listed in Rooney Table 2.
Regarding claims 170, 191, Rooney teaches that the vector backbone is an adenovirus backbone (paragraphs [0335], [0337]-[0338]).
Regarding claim 173, Rooney teaches that the vector is comprised in a vaccine (a pharmaceutical composition), which comprises a pharmaceutically acceptable carrier (paragraphs [0099], [0137], [0352], [0384]).
Regarding claim 188, Rooney teaches that the antigenic polynucleotides are linked (claims 94-95).
Regarding claim 189, Rooney teaches that the epitopes may comprise two additional amino acids at the N- or C-termini (see Table 2; paragraph [0609] teaches that “The neonantigenic [sic] peptide can be a peptide comprising 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15…amino acid residues of the protein, e.g., KRAS including the substitution”). Table 2 of Rooney provides the “mutation sequence context” of KRAS G12C, G12D, G12V, and Q61H (page 164). While the particular epitope example sequences provided in Tables 2 and 3 do not comprise two or more additional N- or C-terminal amino acids relative to the instant recited sequences of claim 168, the teachings of Rooney state that the epitope may consist of any 5-100 consecutive amino acids from a fragment of the protein sequence comprising the substitution [paragraph [0609]). The neoantigenic peptides of Rooney thus encompass epitopes comprising two or more additional N- and/or C-terminal amino acids relative to the instant sequences recited in claim 168.
Regarding claim 190, the epitopes taught by Rooney are 9, 10 or more amino acids long (see Tables 2 and 3; paragraphs [0174], [0609]).
However, Rooney does not teach that the viral vector is a chimpanzee adenovirus vector, as required by claims 170 and 191.
Roshorm teaches that ChAdV68 can be used as a vaccine viral vector.
Regarding claims 170 and 191, Roshorm teaches that ChAdV68 can be engineered to encode a heterologous immunogen-coding sequence, wherein administration of the recombinant ChAdV68 vector to T cells induces expression of the heterologous immunogen by the T cells and induces a protective immunogenic response (Abstract; pages 3246, 3252; Fig. 2).
It would have been obvious to an artisan that viral vectors known in the art as useful as vaccine vectors for introducing immunogen- or antigen-coding sequences into immune cells would be useful as viral vectors for delivery of the compositions of Rooney to immune cells. While Rooney teaches that adenoviral vectors may be used for this purpose, Rooney does not teach that ChAdV68 specifically should be used. The teachings of Roshorm regarding the utility of the ChAdV68 vector as a vaccine vector would have rendered obvious to an artisan at the time of filing that the ChAdV68 viral vector was an obvious adenoviral vector species for use in compositions and methods of Rooney.
Claim(s) 168, 170, 173, 170, 188-189, 192-193 is/are rejected under 35 U.S.C. 103 as being unpatentable over Rooney (WO 2017173321 A1), in view of Pushko (1997) and GenBank: L01442.2 (1999).
Regarding claim 168, Rooney teaches a vector comprising a promoter sequence (claims 78, 87-92; paragraphs [0166]-[0167], [0486]), at least on polyadenylation sequence (paragraphs [0280], [0486]), and nucleic acid sequences encoding multiple antigen epitopes (claims 1, 87-92). These multiple epitopes encompass a KRAS G12C epitope, a KRAS G12D epitope, a KRAS G12V epitope, and KRAS Q61H epitope (paragraph [0609]; Table 3). One KRAS G12C epitope sequence is VVVGACGVGK (100% identical to instant SEQ ID NO:19850). One KRAS G12V epitope sequence is VVGAVGVGK (100% identical to instant SEQ ID NO:19779) (page 181). One KRAS Q61H epitope sequence is ILDTAGHEEY (100% identical to instant SEQ ID NO:14409) (page 181). Rooney paragraph [0609] teaches that “The neonantigenic [sic] peptide can be a peptide comprising 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15…amino acid residues of the protein, e.g., KRAS including the substitution”. While the KRAS G12D epitopes taught in Tables 2 and 3 are KLVVVGADGV and LVVVGADGV, any 5 or more consecutive amino acids of the “mutation sequence context” which comprise the G12D substitution (underlined in Table 2) may be used in the invention of Rooney. As such, Rooney teaches epitopes encompassing instant SEQ ID NOs:19749 and 19865 (9 and 10 consecutive amino acids, respectively, of the “mutation sequence context” of KRAS G12D as listed in Rooney Table 2.
Regarding claim 170, Rooney teaches that the vector backbone is a viral backbone (paragraphs [0335], [0337]-[0338]).
Regarding claim 173, Rooney teaches that the vector is comprised in a vaccine (a pharmaceutical composition), which comprises a pharmaceutically acceptable carrier (paragraphs [0099], [0137], [0352], [0384]).
Regarding claim 188, Rooney teaches that the antigenic polynucleotides are linked (claims 94-95).
Regarding claim 189, Rooney teaches that the epitopes may comprise two additional amino acids at the N- or C-termini (see Table 2; paragraph [0609] teaches that “The neonantigenic [sic] peptide can be a peptide comprising 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15…amino acid residues of the protein, e.g., KRAS including the substitution”). Table 2 of Rooney provides the “mutation sequence context” of KRAS G12C, G12D, G12V, and Q61H (page 164). While the particular epitope example sequences provided in Tables 2 and 3 do not comprise two or more additional N- or C-terminal amino acids relative to the instant recited sequences of claim 168, the teachings of Rooney state that the epitope may consist of any 5-100 consecutive amino acids from a fragment of the protein sequence comprising the substitution [paragraph [0609]). The neoantigenic peptides of Rooney thus encompass epitopes comprising two or more additional N- and/or C-terminal amino acids relative to the instant sequences recited in claim 168.
Regarding claim 190, the epitopes taught by Rooney are 9, 10 or more amino acids long (see Tables 2 and 3; paragraphs [0174], [0609]).
However, Rooney does not teach that the viral backbone is an alphavirus backbone, or more specifically, a Venezuelan equine encephalitis (VEE) backbone, as required by claims 170 and 192-193.
Pushko teaches that VEE viral replicon backbones are useful as vaccine vectors.
Regarding claims 170 and 192-193, Pushko teaches that VEE viral replicons have been developed as vaccine vectors, wherein a heterologous protein-coding sequence fully replaces the structural protein-coding VEE sequence between nucleotides 7546 and 11446 (Abstract; page 390; Fig. 1). Pushko indicates the available digestion sites in the VEE genome, with the closest to nucleotide 7546 of the genome being the Tth11I restriction site at nucleotide 7544 (Fig. 1). It would have been obvious to an artisan at the time of filing that the VEE replicon vector could alternatively be created by digesting the VEE genome with Tth11I and NotI and inserting the heterologous sequence therein, thereby inserting the heterologous sequence at position 7544 of the VEE genome. The resultant VEE replicon would have the same protein-coding sequences deleted and the same non-coding sequences and regulatory sequences preserved, and thus would not be functionally distinct from the VEE replicon which contains a heterologous sequence inserted at position 7546 of the VEE genome. Pushko therefore renders obvious a VEE replicon vector comprising a deletion of nucleotides 7544-11175 and comprising a heterologous sequence inserted at position 7544 of the VEE genome, as required by instant claim 193.
Additionally, while Pushko does not provide the full nucleotide sequence of the VEE wild type genome used to create the VEE replicon, this sequence was known in the art prior to the instant filing and was 100% identical to instant SEQ ID NO:3 (see alignment below between GenBank L01442.2 and instant SEQ ID NO:3).
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Pushko teaches that alphavirus replicon vectors “typically express heterologous genes to high levels, suggesting that a relatively low dose of replicon particles would produce a large dose of immunogen in vivo”, “do not contain a complete complement of viral genes, so that…no additional infectious particles would be produced to spread to other tissues”, and allow “the sequential use of these vectors for immunization of the same individual with immunogens of different pathogens” (page 390). Pushko further teaches that “VEE is the only alphavirus for which a live, attenuated vaccine strain (TC-83) has been developed for veterinary and human use” (page 390). Pushko thus teaches that VEE has an ideal viral backbone for use as a vaccine vector, as it exhibits high expression of heterologous sequences and good safety in human and animal use.
As described above, Rooney teaches that viral vectors can be used to deliver antigenic peptides to immune cells, for expression in immune cells (claims 79-80, 82-86). While Rooney does not teach the use of alphaviruses as the viral vectors for use in the invention, the teachings of Pushko render obvious that alphaviruses, and particularly VEE, may be ideal candidates for such viral vectors for delivery of heterologous protein-coding sequences to immune cells, for expression of the heterologous protein by the immune cells. The VEE replicon vector of Pushko would have been, to an artisan at the time of filing, an obvious alternative viral vector for use in the compositions and methods of Rooney.
Claim(s) 175, 177, 180, 194-197 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mleczek (WO2017182634A1), in view of Roshorm (2012).
Claim(s) 175, 180, 194-196 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Mleczek (WO2017182634A1).
Regarding claim 175, Mleczek teaches a composition for delivery of an antigen expression system, comprising one or more vectors comprising: a vector backbone comprising at least one promoter sequence and at least one polyA sequence; and an antigen cassette comprising any combination of nucleic acid sequences encoding any of the following antigens: MAGE-A1, MAGE-A4, MAGE-B2, MAGE-A11, MAGE-A3, MAGE-A6, and CT83 (claims 1-2, 16, 29; Table 1; page 16 line 25-page 17 line 5; page 3 lines 9-15; page 12 lines 15-30). SEQ ID NO:267 of Mleczek comprises sequences 100% identical to instant SEQ ID NOs:4750, 4818, and 4864; Mleczek SEQ ID NO:270 comprises sequences 100% identical to instant SEQ ID NO:5880, 5784, and 5785; Mleczek SEQ ID NO:281 comprises a sequence 100% identical to instant SEQ ID NO:6631; Mleczek SEQ ID NO:264 comprises sequences 100% identical to instant SEQ ID NO:5245 and 5206; Mleczek SEQ ID NO:257 comprises sequences 100% identical to instant SEQ ID NOs:1454, 1423, 1446, and 1433; Mleczek SEQ ID NO:269 comprises sequences 100% identical to instant SEQ ID NOs:5483 and 5504; Mleczek SEQ ID NO: (see alignments below; see Table 1).
SEQ ID NO:267 and SEQ ID NO:4750:
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SEQ ID NO:267 and SEQ ID NO:4818:
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SEQ ID NO:267 and SEQ ID NO:4864:
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SEQ ID NO:270 and SEQ ID NO:5880:
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SEQ ID NO:270 and SEQ ID NO:5784:
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SEQ ID NO:270 and SEQ ID NO:5785:
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SEQ ID NO:281 and SEQ ID NO:6631:
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143
619
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SEQ ID NO:264 and SEQ ID NO:5245:
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139
612
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SEQ ID NO:264 and SEQ ID NO:5206:
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138
614
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SEQ ID NO:257 and SEQ ID NO:1454:
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136
614
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SEQ ID NO:257 and SEQ ID NO:1423:
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140
615
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SEQ ID NO:257 and SEQ ID NO:1446:
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139
610
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SEQ ID NO:257 and SEQ ID NO:1433:
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138
616
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SEQ ID NO:269 and SEQ ID NO:5483:
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139
610
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SEQ ID NO:269 and SEQ ID NO:5504:
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143
614
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Regarding claim 177, Mleczek teaches that the vector may be a viral vector (page 12 lines 25-26).
Regarding claim 180, Mleczek teaches a pharmaceutical composition comprising the vector system and a pharmaceutically acceptable carrier (claim 30).
Regarding claim 194, Mleczek teaches that in a multicistronic system (encoding multiple coding sequences), all antigen coding sequences are present on one nucleic acid molecule and are thus linked (page 5 lines 6-10).
Regarding claim 195, Mleczek teaches that an “epitope” “refers to a fragment of an antigen or a variant of an antigen” and “typically comprise from about 5 to about 20 amino acids (page 6 lines 17-19). The sequences that Mleczek teaches in Table 1 as being inserted into the expression vector comprise epitopes, or fragments, of 5-20 amino acids within larger native sequences (see Table 1). Thus, the sequences Mleczek teaches in Table 1 comprise epitope sequences flanked by two or more additional amino acids at the N- and/or C- termini.
Regarding claim 196, Mleczek teaches that the antigen fragments are preferably “a sequence of an antigen or of a variant thereof as defined herein, which has a length of about 5 to about 20 or even more amino acids and which is preferably processed and presented by an MHC complex (page 34 lines 1-25).
However, Mleczek does not teach that the viral vector is a chimpanzee adenovirus vector, as required by claims 177 and 197.
Roshorm teaches that ChAdV68 can be used as a vaccine viral vector.
Regarding claims 177 and 197, Roshorm teaches that ChAdV68 can be engineered to encode a heterologous immunogen-coding sequence, wherein administration of the recombinant ChAdV68 vector to T cells induces expression of the heterologous immunogen by the T cells and induces a protective immunogenic response (Abstract; pages 3246, 3252; Fig. 2).
It would have been obvious to an artisan that viral vectors known in the art as useful as vaccine vectors for introducing immunogen- or antigen-coding sequences into immune cells would be useful as viral vectors for delivery of the compositions of Mleczek to immune cells. While Mleczek teaches that viral vectors may be used for this purpose, Mleczek does not teach that ChAdV68 specifically should be used. The teachings of Roshorm regarding the utility of the ChAdV68 vector as a vaccine vector would have rendered obvious to an artisan at the time of filing that the ChAdV68 viral vector was an obvious viral vector species for use in compositions and methods of Mleczek.
Claim(s) 175, 177, 180, 194-196, 198-199 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mleczek (WO2017182634A1), in view of Pushko (1997) and GenBank: L01442.2 (1999).
Claim(s) 175, 180, 194-196 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Mleczek (WO2017182634A1).
Regarding claim 175, Mleczek teaches a composition for delivery of an antigen expression system, comprising one or more vectors comprising: a vector backbone comprising at least one promoter sequence and at least one polyA sequence; and an antigen cassette comprising any combination of nucleic acid sequences encoding any of the following antigens: MAGE-A1, MAGE-A4, MAGE-B2, MAGE-A11, MAGE-A3, MAGE-A6, and CT83 (claims 1-2, 16, 29; Table 1; page 16 line 25-page 17 line 5; page 3 lines 9-15; page 12 lines 15-30). SEQ ID NO:267 of Mleczek comprises sequences 100% identical to instant SEQ ID NOs:4750, 4818, and 4864; Mleczek SEQ ID NO:270 comprises sequences 100% identical to instant SEQ ID NO:5880, 5784, and 5785; Mleczek SEQ ID NO:281 comprises a sequence 100% identical to instant SEQ ID NO:6631; Mleczek SEQ ID NO:264 comprises sequences 100% identical to instant SEQ ID NO:5245 and 5206; Mleczek SEQ ID NO:257 comprises sequences 100% identical to instant SEQ ID NOs:1454, 1423, 1446, and 1433; Mleczek SEQ ID NO:269 comprises sequences 100% identical to instant SEQ ID NOs:5483 and 5504; Mleczek SEQ ID NO: (see alignments below; see Table 1).
SEQ ID NO:267 and SEQ ID NO:4750:
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141
617
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SEQ ID NO:267 and SEQ ID NO:4818:
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139
613
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Greyscale
SEQ ID NO:267 and SEQ ID NO:4864:
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140
619
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Greyscale
SEQ ID NO:270 and SEQ ID NO:5880:
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136
613
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Greyscale
SEQ ID NO:270 and SEQ ID NO:5784:
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141
612
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SEQ ID NO:270 and SEQ ID NO:5785:
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138
611
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SEQ ID NO:281 and SEQ ID NO:6631:
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143
619
media_image7.png
Greyscale
SEQ ID NO:264 and SEQ ID NO:5245:
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139
612
media_image8.png
Greyscale
SEQ ID NO:264 and SEQ ID NO:5206:
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138
614
media_image9.png
Greyscale
SEQ ID NO:257 and SEQ ID NO:1454:
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136
614
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Greyscale
SEQ ID NO:257 and SEQ ID NO:1423:
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140
615
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Greyscale
SEQ ID NO:257 and SEQ ID NO:1446:
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139
610
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SEQ ID NO:257 and SEQ ID NO:1433:
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138
616
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Greyscale
SEQ ID NO:269 and SEQ ID NO:5483:
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139
610
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SEQ ID NO:269 and SEQ ID NO:5504:
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143
614
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Greyscale
Regarding claim 177, Mleczek teaches that the vector may be a viral vector (page 12 lines 25-26).
Regarding claim 180, Mleczek teaches a pharmaceutical composition comprising the vector system and a pharmaceutically acceptable carrier (claim 30).
Regarding claim 194, Mleczek teaches that in a multicistronic system (encoding multiple coding sequences), all antigen coding sequences are present on one nucleic acid molecule and are thus linked (page 5 lines 6-10).
Regarding claim 195, Mleczek teaches that an “epitope” “refers to a fragment of an antigen or a variant of an antigen” and “typically comprise from about 5 to about 20 amino acids (page 6 lines 17-19). The sequences that Mleczek teaches in Table 1 as being inserted into the expression vector comprise epitopes, or fragments, of 5-20 amino acids within larger native sequences (see Table 1). Thus, the sequences Mleczek teaches in Table 1 comprise epitope sequences flanked by two or more additional amino acids at the N- and/or C- termini.
Regarding claim 196, Mleczek teaches that the antigen fragments are preferably “a sequence of an antigen or of a variant thereof as defined herein, which has a length of about 5 to about 20 or even more amino acids and which is preferably processed and presented by an MHC complex (page 34 lines 1-25).
However, Mleczek does not teach that the viral backbone is an alphavirus backbone, or more specifically, a Venezuelan equine encephalitis (VEE) backbone, as required by claims 177 and 198-199.
Pushko teaches that VEE viral replicon backbones are useful as vaccine vectors.
Regarding claims 177 and 198-199, Pushko teaches that VEE viral replicons have been developed as vaccine vectors, wherein a heterologous protein-coding sequence fully replaces the structural protein-coding VEE sequence between nucleotides 7546 and 11446 (Abstract; page 390; Fig. 1). Pushko indicates the available digestion sites in the VEE genome, with the closest to nucleotide 7546 of the genome being the Tth11I restriction site at nucleotide 7544 (Fig. 1). It would have been obvious to an artisan at the time of filing that the VEE replicon vector could alternatively be created by digesting the VEE genome with Tth11I and NotI and inserting the heterologous sequence therein, thereby inserting the heterologous sequence at position 7544 of the VEE genome. The resultant VEE replicon would have the same protein-coding sequences deleted and the same non-coding sequences and regulatory sequences preserved, and thus would not be functionally distinct from the VEE replicon which contains a heterologous sequence inserted at position 7546 of the VEE genome. Pushko therefore renders obvious a VEE replicon vector comprising a deletion of nucleotides 7544-11175 and comprising a heterologous sequence inserted at position 7544 of the VEE genome, as required by instant claim 199.
Additionally, while Pushko does not provide the full nucleotide sequence of the VEE wild type genome used to create the VEE replicon, this sequence was known in the art prior to the instant filing and was 100% identical to instant SEQ ID NO:3 (see alignment below between GenBank L01442.2 and instant SEQ ID NO:3).
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369
839
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Pushko teaches that alphavirus replicon vectors “typically express heterologous genes to high levels, suggesting that a relatively low dose of replicon particles would produce a large dose of immunogen in vivo”, “do not contain a complete complement of viral genes, so that…no additional infectious particles would be produced to spread to other tissues”, and allow “the sequential use of these vectors for immunization of the same individual with immunogens of different pathogens” (page 390). Pushko further teaches that “VEE is the only alphavirus for which a live, attenuated vaccine strain (TC-83) has been developed for veterinary and human use” (page 390). Pushko thus teaches that VEE has an ideal viral backbone for use as a vaccine vector, as it exhibits high expression of heterologous sequences and good safety in human and animal use.
As described above, Mleczek teaches that viral vectors can be used as delivery vehicles to cells. While Mleczek does not teach the use of alphaviruses as the viral vectors for use in the invention, the teachings of Pushko render obvious that alphaviruses, and particularly VEE, may be ideal candidates for such viral vectors for delivery of heterologous protein-coding sequences to immune cells, for expression of the heterologous protein by the immune cells. The VEE replicon vector of Pushko would have been, to an artisan at the time of filing, an obvious viral vector species for use in the compositions and methods of Mleczek.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
17838114:
Claims 168, 170, 173, 175, 177, 180, 188, 190-194, 196-199 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 21, 40, 96, 187, 198, 202-204 of copending Application No. 17838114 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other. The copending claims recite methods using compositions which are identical to the compositions of the instant claims (see copending claims 21, 40, 96, 187, 198, 202, 203, 204; the viral vectors, antigen expression systems, and antigen sequences are identical). The copending application recites sequences that are identical in SEQ ID NO and sequence as those of the instant application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
18272087:
Claims 168, 170, 173, 175, 177, 180, 188-197 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2, 31, 44, 58, 62, 69, 72, 76, 81, 122, 124, 128-129, 131 of copending Application No. 18272087 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other. The copending claims recite methods of using compositions which are identical to the compositions of the instant claims (see copending claims 31, 44, 58, 62, 69, 72, 76, 81, 122, 124, 128-129, 131; the viral vectors, antigen expression systems, and antigen sequences are identical). The copending application recites sequences that are identical in SEQ ID NO and sequence as those of the instant application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
18607061:
Claims 168, 170, 173, 188-191 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2-3, 6, 8, 24, 26, 29, 33, 35, 44-45, 47 of copending Application No. 18607061 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other. The copending claims recite methods of using compositions identical to the compositions of the instant claims (see copending claims 2-3, 6, 8, 24, 26, 29, 33, 35, 44-45, 47; the viral vectors, antigen expression systems, and antigen sequences are identical). The broad recitation in the copending claims of a ChAdV vector encompasses the ChAdV68 serotype (see claim 44). Copending claim 24 recites KRAS G12C, KRAS G12D, KRAS G12V, and KRAS Q61H epitope sequences identical to those recited in the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
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/AFRICA M MCLEOD/ Examiner, Art Unit 1635
/KIMBERLY CHONG/ Primary Examiner, Art Unit 1636
Prosecution Insights