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 .
Detailed Action
This action is in response to the papers filed August 14, 2025.
Amendments
Applicant's response and amendments, filed August 14, 2025, is acknowledged. Applicant has cancelled Claims 2, 5-6, 8-15, 17-89, 91-92, 99-112, 114-132, 134-178, 181-184, 186-188, 190-195, and 198-434, and amended Claims 1, 90, 113, 133, and 196.
Claims 1, 3-4, 7, 16, 90, 93-98, 113, 133, 179-180, 185, 189, and 196-197 are pending.
Election/Restrictions
Applicant has elected the following species, wherein:
i) the alternative disease is colon cancer, more specifically microsatellite-stable colorectal cancer (MSS-CRC), as recited in Claims 98 and 133; and
ii) the alternative epitope and corresponding SEQ ID NO is KRAS_G12V MHC class I epitope SEQ ID NO:19,779 (VVGAVGVGK).
The prior alternative ChAdv vector structure species election is rendered moot in light of Applicant’s amendment to Claim 113 to require all three deletions.
Claims 1, 3-4, 7, 16, 90, 93-98, 113, 133, 179-180, 185, 189, and 196-197 are pending and under examination.
Priority
This application is a continuation of PCT/US2020/058983 filed on November 4, 2020. Applicant’s claim for the benefit of a prior-filed application provisional applications:
63/051,227 filed on July 13, 2020;
62/959,798 filed on January 10, 2020;
62/946,956 filed on December 11, 2019; and
62/930,460 filed on November 4, 2019,
under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged.
Information Disclosure Statement
Applicant has filed Information Disclosure Statements on September 24, 2025 that have been considered.
The information disclosure statement filed September 24, 2025 fails to comply with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609 because 37 CFR 1.98(b) requires that each item of information in an IDS be identified properly. Each publication must be identified by publisher, author (if any), title, relevant pages of the publication, and date and place of publication. The date of publication supplied must include at least the month and year of publication, except that the year of publication (without the month) will be accepted if the applicant points out in the information disclosure statement that the year of publication is sufficiently earlier than the effective U.S. filing date and any foreign priority date so that the particular month of publication is not in issue.
See also MPEP 707.05(e) for electronic documents, including, but not limited to:
(D) reference to the unique Digital Object Identifier (DOI) number, or other unique identification number, if known.
Bibliographic information provided must be at least enough to identify the publication. author, title and date. For books, minimal information includes the author, title, and date. For periodicals, at least the title of the periodical, the volume number, date, and pages should be given.
NPL citations have been lined through for being defective of one or more requirements.
The signed and initialed PTO Forms 1449 are mailed with this action.
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.
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.
1. Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the specification are not identified by sequence identifiers in accordance with 37 CFR 1.821(d).
See [00354], Tables 32A, 32B, 47A, 47B, 55A, and 55B.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, 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.
Specification
2. The prior objection to the disclosure is withdrawn in light of Applicant’s amendment to the specification, which the Examiner finds persuasive.
Claim Objections
3. The prior objections to Claims 1, 90, 113, 133, and 196 are withdrawn in light of Applicant’s amendment to the claims, which the Examiner finds persuasive.
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.
4. Claim(s) 90 and 93-95 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Blair et al (WO 18/098362; Applicant’s own work; of record in IDS).
With respect to Claim 90, Blair et al is considered relevant prior art for having disclosed a composition comprising 1x10^12 or less ChAdV virus particles (e.g. [00387]) whose genome encodes at least one promoter and at least one polyA sequence operably linked to an expression cassette encoding an antigen (e.g. [0013]).
With respect to Claims 93-95, Blair et al disclosed a composition comprises at least 1x10^11 ChAdV virus particles, to wit, not more than a total dose of 1x10^12 ChAdV virus particles (e.g. [00387-388]).
Thus, Blair et al anticipate the claims.
5. Claim(s) 1, 3-4, 7, 16, 97-98, 133, and 179-180 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Blair et al (WO 18/098362; Applicant’s own work; of record in IDS).
With respect to Claim 1, Blair et al disclosed a composition comprising at least 10ug of lipid nanoparticles (LNP) encapsulating a self-amplifying alphavirus (e.g. [00704]) whose genome encodes at least one promoter and at least one polyA sequence operably linked to an expression cassette encoding an antigen (e.g. [0013]).
With respect to Claim 179, Blair et al disclosed the composition is formulated with a pharmaceutically acceptable carrier (e.g. [00375]).
With respect to Claim 180, Blair et al disclosed a kit comprising the composition and instructions for use (e.g. claim 76).
With respect to Claims 3-4 and 7, Blair et al disclosed a composition comprises at least at least 30ug or 100ug, or 300ug of lipid nanoparticles (LNP) encapsulating a self-amplifying alphavirus (e.g. [00387-388]; Table 23).
With respect to Claim 16, Blair et al disclosed a composition comprises the self-amplifying alphavirus virus particles at a concentration of 1mg/ml (syn. 10ug srRNA vaccine/0.1ml; [00698]).
With respect to Claims 97-98 and 133, Blair et al disclosed wherein the tumor is colon cancer (e.g. [0019, 705]), and wherein the colon cancer tumor is microsatellite-stable colorectal cancer (MSS-CRC), to wit, CT26 xenograft tumor model (e.g. [00705]), whereby CT26 is an art-recognized microsatellite-stable colorectal cancer (MSS-CRC), and wherein the antigen encodes an epitope known or suspected to be presented by MHC class I on the surface of a tumor cell, e.g. KRAS [00214].
Thus, Blair et al anticipate the claims.
6. Claim(s) 196-197 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Blair et al (WO 18/098362; Applicant’s own work; of record in IDS).
With respect to Claim 197, Blair et al disclosed a method for stimulating an immune response in a subject, the method comprising the step(s) of:
i) administering to the subject 1x10^12 or less of the ChAdV expression system; and
ii) administering to the subject at least 10ug of the alphavirus expression system (e.g. Table 15, Groups 3-4; Table 23, Groups 4-6).
With respect to Claim 198, Blair et al disclosed wherein:
i) the ChAdV is the priming dose (syn. admin first); and
ii) the alphavirus is the boosting dose (syn. admin second) (e.g. Table 15, Groups 3-4; Table 23, Groups 4-6).
Thus, Blair et al anticipate the claims.
7. Claim(s) 90 and 93-95, and 113 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Binder et al (U.S. 2015/0125465).
With respect to Claim 90, Binder et al is considered relevant prior art for having disclosed a composition comprising 1x10^12 or less adenovirus particles (e.g. Example 10, 1x10^11 adenovirus particles), wherein the adenovirus is ChAdV whose genome encodes at least one promoter and at least one polyA sequence operably linked to an expression cassette encoding an antigen (e.g. Example 11, [0295]).
With respect to Claims 93-95, Binder et al disclosed a composition comprises at least 1x10^11 ChAdV virus particles, to wit, not more than a total dose of 1x10^12 ChAdV virus particles (e.g. Example 10, 1x10^11 adenovirus particles).
With respect to Claim 113, Binder et al disclosed wherein the ChAdv expression vector genome lacks each of:
i) nucleotides 577 to 3403 of the sequence shown in SEQ ID NO:1 corresponding to an El deletion (e.g. [0299]);
ii) nucleotides 27,125 to 31,825 of the sequence shown in SEQ ID NO:1 corresponding to an E3 deletion (e.g. [0299]); and
iii) nucleotides 34,916 to 35,642 of the sequence shown in SEQ ID NO:1 corresponding to a partial E4 deletion (Table 13), as the ChAdvC68 vector ends at 34819, and thus does not comprise nucleotides 34,916 to 35,642 of the sequence shown in SEQ ID NO:1 corresponding to a partial E4 deletion.
Thus, Binder et al anticipate the claims.
8. Claim(s) 90 and 113 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Colloca et al (U.S. 2012/0027788).
With respect to Claim 90, Colloca et al is considered relevant prior art for having disclosed a composition comprising 1x10^12 or less adenovirus particles (e.g. [0221]; Example 3, 1x10^8 adenovirus particles; Example 4, 1x10^7, 1x10^8, or 1x10^9 adenovirus particles), wherein the adenovirus is a chimpanzee adenovirus (e.g. [0038]; Table 1; Examples 3-4) whose genome encodes at least one promoter and at least one polyA sequence operably linked to an expression cassette encoding an antigen (e.g. [0042, 174, 251]).
With respect to Claim 113, Colloca et al disclosed wherein the ChAdv expression vector genome lacks each of:
i) nucleotides 577 to 3403 of the sequence shown in SEQ ID NO:1 corresponding to an El deletion (e.g. [0252]);
ii) nucleotides 27,125 to 31,825 of the sequence shown in SEQ ID NO:1 corresponding to an E3 deletion (e.g. [0253]); and
iii) nucleotides 34,916 to 35,642 of the sequence shown in SEQ ID NO:1 corresponding to a partial E4 deletion (e.g. [0254-255]), as the vector retains the E4 native promoter and polyA signal.
Thus, Colloca et al anticipate the claims.
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 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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103(a) 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.
9. Claims 90 and 93-96 are rejected under AIA 35 U.S.C. 103 as being unpatentable over Blair et al (WO 18/098362; Applicant’s own work; of record in IDS).
Determining the scope and contents of the prior art, and Ascertaining the differences between the prior art and the claims at issue.
With respect to Claim 90, Blair et al is considered relevant prior art for having disclosed a composition comprising 1x10^12 or less ChAdV virus particles (e.g. [00387]) whose genome encodes at least one promoter and at least one polyA sequence operably linked to an expression cassette encoding an antigen (e.g. [0013]).
Blair et al do not disclose ipsis verbis wherein the composition comprises the ChAdV virus particles at a concentration of 5x10^11 vp/ml.
However, Blair et al disclosed administering 5x10^11 particles of said virus to a subject ([00722]) at a concentration of 1x10^11 virus particles/0.1ml (e.g. [00711]), which is equivalent to about 5x10^11 virus particles/0.5ml.
Resolving the level of ordinary skill in the pertinent art.
People of the ordinary skill in the art will be highly educated individuals such as medical doctors, scientists, or engineers possessing advanced degrees, including M.D.'s and Ph.D.'s. Thus, these people most likely will be knowledgeable and well-read in the relevant literature and have the practical experience in molecular biology, virology, and immunology. Therefore, the level of ordinary skill in this art is high.
"A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton." KSR International Co. v. Teleflex Inc., 550 U.S. ___, ___, 82 USPQ2d 1385, 1397 (2007). "[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle." Id. Office personnel may also take into account "the inferences and creative steps that a person of ordinary skill in the art would employ." Id. at ___, 82 USPQ2d at 1396.
Considering objective evidence present in the application indicating obviousness or nonobviousness.
The focus when making a determination of obviousness should be on what a person of ordinary skill in the pertinent art would have known at the time of the invention, and on what such a person would have reasonably expected to have been able to do in view of that knowledge. This is so regardless of whether the source of that knowledge and ability was documentary prior art, general knowledge in the art, or common sense. M.P.E.P. §2141.
The rationale to modify or combine the prior art does not have to be expressly stated in the prior art; the rationale may be expressly or impliedly contained in the prior art or it may be reasoned from knowledge generally available to one of ordinary skill in the art, established scientific principles, or legal precedent established by prior case law. In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988); In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992). See also In re Kotzab, 217 F.3d 1365, 1370, 55 USPQ2d 1313, 1317 (Fed. Cir. 2000) (setting forth test for implicit teachings); In re Eli Lilly & Co., 902 F.2d 943, 14 USPQ2d 1741 (Fed. Cir. 1990) (discussion of reliance on legal precedent); In re Nilssen, 851 F.2d 1401, 1403, 7 USPQ2d 1500, 1502 (Fed. Cir. 1988) (references do not have to explicitly suggest combining teachings); and Ex parte Levengood, 28 USPQ2d 1300 (Bd. Pat. App. & Inter. 1993) (reliance on logic and sound scientific reasoning). See MPEP §2144.
In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). It is routine procedure to optimize component amounts to arrive at an optimal product that is superior for its intended use, since it has been held where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are close enough that one skilled in the art would have expected them to have the same properties. See M.P.E.P. §2144.05(I).
Instant specification fails to disclose an element of criticality for a concentration of 5x10^11 virus particles/ml, as opposed to 5x10^11 virus particles/0.5ml or 1x10^12 virus particles/ml, especially when Applicant themselves previously disclosed administering 5x10^11 particles of said virus to a subject ([00722]), and there is no disclosure in the instant specification nor Applicant’s own work that the concentration itself is dispositive and controlling for the claimed composition.
The "mere existence of differences between the prior art and an invention does not establish the invention's nonobviousness." Dann v. Johnston, 425 U.S. 219, 230, 189 USPQ 257, 261 (1976). The gap between the prior art and the claimed invention may not be "so great as to render the [claim] nonobvious to one reasonably skilled in the art."Id.
It is proper to "take account of the inferences and creative steps that a person of ordinary skill in the art would employ." KSR Int'l Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741,82 USPQ2d 1385, 1396 (2007). See also Id. At 1742, 82 USPQ2d 1397 ("A person of ordinary skill is also a person of ordinary creativity, not an automaton.").
It should be noted that the KSR case forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness. See the recent Board decision Ex parte Smith, —USPQ2d—, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d at 1396) (available at http: www. uspto.gov/web/offices/dcom/bpai/prec/fd071925 .pdf).
With respect to Claims 93-95, Blair et al disclosed a composition comprises at least 1x10^11 ChAdV virus particles, to wit, not more than a total dose of 1x10^12 ChAdV virus particles (e.g. [00387-388]).
In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). It is routine procedure to optimize component amounts to arrive at an optimal product that is superior for its intended use, since it has been held where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are close enough that one skilled in the art would have expected them to have the same properties. See M.P.E.P. §2144.05(I).
The cited prior art meets the criteria set forth in both Graham and KSR, and the teachings of the cited prior art provide the requisite teachings and motivations with a clear, reasonable expectation of success. Thus, the invention as a whole is prima facie obvious.
10. Claims 90, 93-96, and 113 are rejected under AIA 35 U.S.C. 103 as being unpatentable over Blair et al (WO 18/098362; Applicant’s own work; of record in IDS), as applied to Claims 90 and 93-96 above, and in further view of Binder et al (U.S. 2015/0125465) and Colloca et al (U.S. 2012/0027788).
Determining the scope and contents of the prior art, and Ascertaining the differences between the prior art and the claims at issue.
With respect to Claim 113, Blair et al disclosed wherein the ChAdv expression vector genome lacks each of:
i) nucleotides 577 to 3403 of the sequence shown in SEQ ID NO:1 corresponding to an El deletion (e.g. [0012, 671]);
ii) nucleotides 27,125 to 31,825 of the sequence shown in SEQ ID NO:1 corresponding to an E3 deletion (e.g. [0012, 671]); and
iii) nucleotides corresponding to an E4 can be deleted (e.g. [00322, 347]).
Blair et al do not disclose wherein nucleotides 34,916 to 35,642 of the sequence shown in SEQ ID NO:1 corresponding to a partial E4 deletion.
However, prior to the effective filing date of the instantly claimed invention, and with respect to Claims 90 and 113, Binder et al is considered relevant prior art for having disclosed a composition comprising 1x10^12 or less adenovirus particles (e.g. Example 10, 1x10^11 adenovirus particles), wherein the adenovirus is ChAdV whose genome encodes at least one promoter and at least one polyA sequence operably linked to an expression cassette encoding an antigen (e.g. Example 11, [0295]).
Binder et al disclosed wherein the ChAdv expression vector genome lacks each of:
i) nucleotides 577 to 3403 of the sequence shown in SEQ ID NO:1 corresponding to an El deletion (e.g. [0299]);
ii) nucleotides 27,125 to 31,825 of the sequence shown in SEQ ID NO:1 corresponding to an E3 deletion (e.g. [0299]); and
iii) nucleotides 34,916 to 35,642 of the sequence shown in SEQ ID NO:1 corresponding to a partial E4 deletion (Table 13), as the ChAdvC68 vector ends at 34819, and thus does not comprise nucleotides 34,916 to 35,642 of the sequence shown in SEQ ID NO:1 corresponding to a partial E4 deletion.
Similarly, Colloca et al is considered relevant prior art for having disclosed a composition comprising 1x10^12 or less adenovirus particles (e.g. [0221]; Example 3, 1x10^8 adenovirus particles; Example 4, 1x10^7, 1x10^8, or 1x10^9 adenovirus particles), wherein the adenovirus is a chimpanzee adenovirus (e.g. [0038]; Table 1; Examples 3-4) whose genome encodes at least one promoter and at least one polyA sequence operably linked to an expression cassette encoding an antigen (e.g. [0042, 174, 251]).
Colloca et al disclosed wherein the ChAdv expression vector genome lacks each of:
i) nucleotides 577 to 3403 of the sequence shown in SEQ ID NO:1 corresponding to an El deletion (e.g. [0252]);
ii) nucleotides 27,125 to 31,825 of the sequence shown in SEQ ID NO:1 corresponding to an E3 deletion (e.g. [0253]); and
iii) nucleotides 34,916 to 35,642 of the sequence shown in SEQ ID NO:1 corresponding to a partial E4 deletion (e.g. [0254-255]), as the vector retains the E4 native promoter and polyA signal.
Considering objective evidence present in the application indicating obviousness or nonobviousness.
The focus when making a determination of obviousness should be on what a person of ordinary skill in the pertinent art would have known at the time of the invention, and on what such a person would have reasonably expected to have been able to do in view of that knowledge. This is so regardless of whether the source of that knowledge and ability was documentary prior art, general knowledge in the art, or common sense. M.P.E.P. §2141.
The rationale to modify or combine the prior art does not have to be expressly stated in the prior art; the rationale may be expressly or impliedly contained in the prior art or it may be reasoned from knowledge generally available to one of ordinary skill in the art, established scientific principles, or legal precedent established by prior case law. In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988); In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992). See also In re Kotzab, 217 F.3d 1365, 1370, 55 USPQ2d 1313, 1317 (Fed. Cir. 2000) (setting forth test for implicit teachings); In re Eli Lilly & Co., 902 F.2d 943, 14 USPQ2d 1741 (Fed. Cir. 1990) (discussion of reliance on legal precedent); In re Nilssen, 851 F.2d 1401, 1403, 7 USPQ2d 1500, 1502 (Fed. Cir. 1988) (references do not have to explicitly suggest combining teachings); and Ex parte Levengood, 28 USPQ2d 1300 (Bd. Pat. App. & Inter. 1993) (reliance on logic and sound scientific reasoning). See MPEP §2144.
Prior to the effective filing date of the instantly claimed invention, it would have been obvious to one of ordinary skill in the art to substitute a first E4 deletion mutation with a second E4 deletion mutation that is a partial E4 deletion and removes nucleotides 34,916 to 35,642 of the sequence shown in SEQ ID NO:1 with a reasonable expectation of success because the simple substitution of one known element for another would have yielded predictable results to one of ordinary skill in the art at the time of the invention. M.P.E.P. §2144.07 states "The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).” When substituting equivalents known in the prior art for the same purpose, an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982). M.P.E.P. §2144.06.
In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). It is routine procedure to optimize component amounts to arrive at an optimal product that is superior for its intended use, since it has been held where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are close enough that one skilled in the art would have expected them to have the same properties. See M.P.E.P. §2144.05(I).
Instant specification fails to disclose an element of criticality for an E4 deletion mutation that is a partial E4 deletion and removes nucleotides 34,916 to 35,642 of the sequence shown in SEQ ID NO:1 as opposed to a complete or partial E4 deletion disclosed by the prior art, when all such E4 deletion mutations abrogate expression of the adenovirus E4 protein.
The "mere existence of differences between the prior art and an invention does not establish the invention's nonobviousness." Dann v. Johnston, 425 U.S. 219, 230, 189 USPQ 257, 261 (1976). The gap between the prior art and the claimed invention may not be "so great as to render the [claim] nonobvious to one reasonably skilled in the art."Id.
It is proper to "take account of the inferences and creative steps that a person of ordinary skill in the art would employ." KSR Int'l Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741,82 USPQ2d 1385, 1396 (2007). See also Id. At 1742, 82 USPQ2d 1397 ("A person of ordinary skill is also a person of ordinary creativity, not an automaton.").
It should be noted that the KSR case forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness. See the recent Board decision Ex parte Smith, —USPQ2d—, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d at 1396) (available at http: www. uspto.gov/web/offices/dcom/bpai/prec/fd071925 .pdf).
With respect to Claims 93-95, Binder et al disclosed a composition comprises at least 1x10^11 ChAdV virus particles, to wit, not more than a total dose of 1x10^12 ChAdV virus particles (e.g. Example 10, 1x10^11 adenovirus particles).
In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). It is routine procedure to optimize component amounts to arrive at an optimal product that is superior for its intended use, since it has been held where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are close enough that one skilled in the art would have expected them to have the same properties. See M.P.E.P. §2144.05(I).
With respect to Claim 96, Blair et al disclosed administering 5x10^11 particles of said virus to a subject ([00722]) at a concentration of 1x10^11 virus particles/0.1ml (e.g. [00711]), which is equivalent to about 5x10^11 virus particles/0.5ml.
Binder et al disclosed administering 1x10^9, 1x10^10 (Example 11), and 1x10^11 vp (Example 10).
Colloca et al disclosed administering 1x10^9, 5x10^9, 1x10^10, 5x10^10, 1x10^11, or 5x10^11 virus particles (e.g. [0220]).
Thus, per the Blair et al concentration of 1x10^11 virus particles/0.1ml, the prior art disclosed 1x10^9 vp/0.1ml, 5x10^9 vp/0.1ml, 1x10^10 vp/0.1ml, 5x10^10 vp/0.1ml, 1x10^11 vp/0.1ml, or 5x10^11 vp/0.1ml, which is equivalent to 1x10^10 vp/ml, 5x10^10 vp/ml, 1x10^11 vp/ml, 5x10^11 vp/ml, 1x10^12 vp/ml, or 5x10^12 vp/ml.
In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). It is routine procedure to optimize component amounts to arrive at an optimal product that is superior for its intended use, since it has been held where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are close enough that one skilled in the art would have expected them to have the same properties. See M.P.E.P. §2144.05(I).
Instant specification fails to disclose an element of criticality for a concentration of 5x10^11 virus particles/ml, as opposed to 1x10^10 vp/ml, 5x10^10 vp/ml, 1x10^11 vp/ml, 5x10^11 vp/ml, 1x10^12 vp/ml, or 5x10^12 vp/ml, especially when Applicant themselves previously disclosed administering 5x10^11 particles of said virus to a subject ([00722]), and there is no disclosure in the instant specification nor Applicant’s own work that the concentration itself is dispositive and controlling for the claimed composition.
The "mere existence of differences between the prior art and an invention does not establish the invention's nonobviousness." Dann v. Johnston, 425 U.S. 219, 230, 189 USPQ 257, 261 (1976). The gap between the prior art and the claimed invention may not be "so great as to render the [claim] nonobvious to one reasonably skilled in the art."Id.
The cited prior art meets the criteria set forth in both Graham and KSR, and the teachings of the cited prior art provide the requisite teachings and motivations with a clear, reasonable expectation of success. Thus, the invention as a whole is prima facie obvious.
11. Claims 97-98, 133, 185, and 189 are rejected under AIA 35 U.S.C. 103 as being unpatentable over Blair et al (WO 18/098362; Applicant’s own work; of record in IDS), as applied to Claims 1, 3-4, 7, 16, 97-98, 133, and 179-180 above, and in further view of Rooney (WO 17/173321; of record in IDS).
Determining the scope and contents of the prior art, and Ascertaining the differences between the prior art and the claims at issue.
With respect to Claim 1, Blair et al disclosed a composition comprising at least 10ug of lipid nanoparticles (LNP) encapsulating a self-amplifying alphavirus (e.g. [00704]) whose genome encodes at least one promoter and at least one polyA sequence operably linked to an expression cassette encoding an antigen (e.g. [0013]).
With respect to Claims 97-98 and 133, Blair et al disclosed wherein the tumor is colon cancer (e.g. [0019, 705]), and wherein the colon cancer tumor is microsatellite-stable colorectal cancer (MSS-CRC), to wit, CT26 xenograft tumor model (e.g. [00705]), whereby CT26 is an art-recognized microsatellite-stable colorectal cancer (MSS-CRC), and wherein the antigen encodes an epitope known or suspected to be presented by MHC class I on the surface of a tumor cell, e.g. KRAS [00214].
Blair et al do not disclose wherein the antigen encodes the KRAS_G12V MHC class I epitope SEQ ID NO:19,779 (VVGAVGVGK).
However, prior to the effective filing date of the instantly claimed invention, and with respect to Claims 185 and 189, Rooney is considered relevant prior art for having disclosed a vector comprising a promoter and a polyA sequence operably linked to a polynucleotide encoding MHC class I neoantigenic peptides (e.g. [0009, 284, 332, 486, 581]), wherein said vector may be a self-replicating RNA (e.g. [0014]), and wherein the neoantigenic peptide may be a KRAS G12V MHC class I neoantigen (pg 164, Table 2) comprising the epitopes of VVGAVGVGK (instant SEQ ID NO:19,779).
Considering objective evidence present in the application indicating obviousness or nonobviousness.
The focus when making a determination of obviousness should be on what a person of ordinary skill in the pertinent art would have known at the time of the invention, and on what such a person would have reasonably expected to have been able to do in view of that knowledge. This is so regardless of whether the source of that knowledge and ability was documentary prior art, general knowledge in the art, or common sense. M.P.E.P. §2141.
The rationale to modify or combine the prior art does not have to be expressly stated in the prior art; the rationale may be expressly or impliedly contained in the prior art or it may be reasoned from knowledge generally available to one of ordinary skill in the art, established scientific principles, or legal precedent established by prior case law. In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988); In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992). See also In re Kotzab, 217 F.3d 1365, 1370, 55 USPQ2d 1313, 1317 (Fed. Cir. 2000) (setting forth test for implicit teachings); In re Eli Lilly & Co., 902 F.2d 943, 14 USPQ2d 1741 (Fed. Cir. 1990) (discussion of reliance on legal precedent); In re Nilssen, 851 F.2d 1401, 1403, 7 USPQ2d 1500, 1502 (Fed. Cir. 1988) (references do not have to explicitly suggest combining teachings); and Ex parte Levengood, 28 USPQ2d 1300 (Bd. Pat. App. & Inter. 1993) (reliance on logic and sound scientific reasoning). See MPEP §2144.
Prior to the effective filing date of the instantly claimed invention, it would have been obvious to one of ordinary skill in the art to substitute a first KRAS neoantigen epitope with a second KRAS neoantigen epitope comprising SEQ ID NO:19,779 (VVGAVGVGK) in a tumor antigen vaccine expression vector with a reasonable expectation of success because the simple substitution of one known element for another would have yielded predictable results to one of ordinary skill in the art at the time of the invention. M.P.E.P. §2144.07 states "The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).” When substituting equivalents known in the prior art for the same purpose, an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982). M.P.E.P. §2144.06. An artisan would have been motivated to substitute a first KRAS neoantigen epitope with a second KRAS neoantigen epitope comprising SEQ ID NO:19,779 (VVGAVGVGK) in a tumor antigen vaccine expression vector because Rooney disclosed a finite list of known KRAS neoantigen epitopes (e.g., pg 164, Table 2) to be expressed in a tumor antigen vaccine expression vector.
It would have been obvious to one of ordinary skill in the art to choose from a finite number of identified, predictable options because “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipate success, it is likely that product not of innovation but of ordinary skill and common sense.”
It is proper to "take account of the inferences and creative steps that a person of ordinary skill in the art would employ." KSR Int'l Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741,82 USPQ2d 1385, 1396 (2007). See also Id. At 1742, 82 USPQ2d 1397 ("A person of ordinary skill is also a person of ordinary creativity, not an automaton.").
It should be noted that the KSR case forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness. See the recent Board decision Ex parte Smith, —USPQ2d—, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d at 1396) (available at http: www. uspto.gov/web/offices/dcom/bpai/prec/fd071925 .pdf).
With respect to Claim 179, Blair et al disclosed the composition is formulated with a pharmaceutically acceptable carrier (e.g. [00375]).
With respect to Claim 180, Blair et al disclosed a kit comprising the composition and instructions for use (e.g. claim 76).
With respect to Claims 3-4 and 7, Blair et al disclosed a composition comprises at least at least 30ug or 100ug, or 300ug of lipid nanoparticles (LNP) encapsulating a self-amplifying alphavirus (e.g. [00387-388]; Table 23).
In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). It is routine procedure to optimize component amounts to arrive at an optimal product that is superior for its intended use, since it has been held where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are close enough that one skilled in the art would have expected them to have the same properties. See M.P.E.P. §2144.05(I).
Instant specification fails to disclose an element of criticality for at least 10ug, 30ug, 100ug, or 300ug of lipid nanoparticles (LNP) encapsulating a self-amplifying alphavirus, as opposed to the amounts disclosed by Applicant’s own prior art (Blair et al).
The "mere existence of differences between the prior art and an invention does not establish the invention's nonobviousness." Dann v. Johnston, 425 U.S. 219, 230, 189 USPQ 257, 261 (1976). The gap between the prior art and the claimed invention may not be "so great as to render the [claim] nonobvious to one reasonably skilled in the art."Id.
With respect to Claim 16, Blair et al disclosed a composition comprises the self-amplifying alphavirus virus particles at a concentration of 1mg/ml (syn. 10ug srRNA vaccine/0.1ml; [00698]).
The cited prior art meets the criteria set forth in both Graham and KSR, and the teachings of the cited prior art provide the requisite teachings and motivations with a clear, reasonable expectation of success. Thus, the invention as a whole is prima facie obvious.
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.
12. Claim(s) 1, 3-4, 7, 16, 97-98, 133, and 179-180 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-57 of U.S. Patent No. 11,510,973 in view of Blair et al (WO 18/098362; Applicant’s own work; of record in IDS).
Although the claims at issue are not identical, they are not patentably distinct from each other.
With respect to Claim 1, ‘973 claims RNA alphavirus expression vectors encoding an antigen expression cassette, wherein the antigen is presented by an MHC allele, e.g. MHC class I epitope, on the surface of a tumor cell, e.g. colon cancer.
The ‘973 written description of the “alphavirus backbone” comprises elements for self-amplification (e.g. col. 28, lines 42-49).
‘973 does not claim a composition comprising at least 10ug of lipid nanoparticles (LNP) encapsulating a self-amplifying alphavirus.
However, prior to the effective filing date of the instantly claimed invention, Blair et al disclosed a composition comprising at least 10ug of lipid nanoparticles (LNP) encapsulating a self-amplifying alphavirus (e.g. [00704]) whose genome encodes at least one promoter and at least one polyA sequence operably linked to an expression cassette encoding an antigen (e.g. [0013]).
Prior to the effective filing date of the instantly claimed invention, it would have been obvious to one of ordinary skill in the art to modify the pharmaceutical composition of ‘973 comprising an alphavirus expression vector to further comprise lipid nanoparticles (LNP) encapsulating the self-amplifying alphavirus, wherein the composition comprises at least 10ug of said lipid nanoparticles (LNP) encapsulating said self-amplifying alphavirus, with a reasonable expectation of success because Applicant themselves previously disclosed and successfully demonstrated the ability to do so.
It is proper to "take account of the inferences and creative steps that a person of ordinary skill in the art would employ." KSR Int'l Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741,82 USPQ2d 1385, 1396 (2007). See also Id. At 1742, 82 USPQ2d 1397 ("A person of ordinary skill is also a person of ordinary creativity, not an automaton.").
It should be noted that the KSR case forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness. See the recent Board decision Ex parte Smith, —USPQ2d—, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d at 1396) (available at http: www. uspto.gov/web/offices/dcom/bpai/prec/fd071925 .pdf).
With respect to Claim 179, ‘973 claims the composition is formulated with a pharmaceutically acceptable carrier (e.g. claim 10).
Blair et al disclosed the composition is formulated with a pharmaceutically acceptable carrier (e.g. [00375]).
Wi