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 .
Claim Status
Claims 1-17 as filed on 27 February 2024 are pending and under examination.
Priority
This application is a continuation of Application 16/619,500 which is a national stage entry (371) of PCT/US2018/036417, filed 6/7/2018, which claims priority from U.S. provisional application 62516607, filed 6/7/2017.
Application 16/619,500 has a restriction between Group I, an immunological composition comprising a nucleotide sequence encoding a consensus MAGE-E antigen, Group II, a method of treating cancer in a subject by administering a nucleotide sequence encoding a consensus MAGE-A antigen, and Group III, drawn to a protein. Applicant elected without traverse Group I in the reply filed 02/15/2022. The Allowance in Application 16/619,500 dated 11/28/2023 withdrew the restriction and claims to a method of using and the protein of Groups II and III of the restriction of record were rejoined.
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.
Note the hyperlinks on page 142 and page 156 of the instant specification.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-5 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a law of nature (product of nature) without significantly more. The claims recite an immunological composition comprising a nucleic acid molecule comprising a nucleotide sequence encoding a MAGE-A antigen, wherein the antigen comprises an amino acid sequence that is 95% identical or greater to SEQ ID NO: 9.
The claimed immunological composition comprising a nucleic acid molecule encompasses a naturally occurring nucleic acid encoding a mouse MAGE-a5, as the amino acid sequence of mouse MAGE-a5 is greater than 95% identical to instant SEQ ID NO: 9 (See below) as evidenced by Uniprot Accession O89009_MOUSE.
Sequence of Uniprot Accession O89009_MOUSE (Db) against Instant SEQ ID NO: 9 (Qy)
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A nucleic acid molecule comprising a nucleotide sequence encoding an amino acid sequence that is 95% identical or greater to SEQ ID NO: 9 encompasses a product of nature judicial exception.
In regards to claims 2 and 3, cancer antigens are naturally occurring and thus encompass product of nature judicial exceptions.
In regards to claims 4-5, immune checkpoint inhibitors including anti-LAG-3 antibodies are naturally occurring and thus encompass product of nature judicial exceptions (See G. Bratslavsky, I. Tsimafeyeu, 499P - Identification of first-in-class, naturally occurring LAG3 checkpoint inhibitor,
Annals of Oncology, Volume 30, Supplement 5, 2019, Page v188) (IDS).
These judicial exceptions are not integrated into a practical application because their presence in a composition does not add a meaningful limitation as it is merely a nominal component of the claims, and is nothing more than an attempt to general link the products of nature to an environment.
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the products’ presence in a composition is routine and conventional in the art of nucleotide sequence (WO2007026078A2, claim 18 and 21, describing a vector comprising a sequence encoding MAGE-A antigens) (PTO-892).
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-9 and 15-16 rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or it may be satisfied by the disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. “Functional” terminology may be used “when the art has established a correlation between structure and function” but “merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing one has invented a genus and not just a species. Ariad Pharmaceuticals Inc. v. Eli Lilly & Co., 598 F3d 1336, 94 USPQ2d 1161, 1171 (Fed Cir. 2010).
Scope of the Claimed Genus
Claim 1 is drawn to an immunological composition comprising a nucleotide sequence encoding a consensus MAGE-A antigen, wherein the consensus MAGE-A antigen comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO: 11, an amino acid sequence that is 95% identical or greater to SEQ ID NO: 1, an amino acid sequence that is 95% identical or greater to SEQ ID NO:3, an amino acid sequence that is 95% identical or greater to SEQ ID NO:5, an amino acid sequence that is 95% identical or greater to SEQ ID NO:7, an amino acid sequence that is 95% identical or greater to SEQ ID NO:9 and an amino acid sequence that is 95% identical or greater to SEQ ID NO:11.
Claims 6 and 15 are drawn to the immunological composition of claim 1 and a nucleic acid molecule, wherein the nucleotide sequence comprises a nucleotide sequence selected from the group consisting of: SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8 SEQ ID NO: 10, SEQ ID NO: 12, a nucleotide sequence that is 95% identical or greater to SEQ ID NO:2, a nucleotide sequence that is 95% identical or greater to SEQ ID NO:4, a nucleotide sequence that is 95% identical or greater to SEQ ID NO:6, a nucleotide sequence that is 95% identical or greater to SEQ ID NO:8, a nucleotide sequence that is 95% identical or greater to SEQ ID NO: 10, and a nucleotide sequence that is 95% identical or greater to SEQ ID NO:12.
All the other claims either directly or indirectly depend on claims 1 and 15 and do not further limit the sequences of the claims.
Summary of Species Disclosed in the original specification
In the instant specification, Examples 1-2 describe synthetic mouse MAGE-A consensus vaccine constructs, synthetic human MAGE-A consensus #1 vaccine constructs, and synthetic human MAGE-A consensus #2 vaccine constructs (paragraph 00401). These examples are directed to constructs comprising nucleic acid molecules encoding SEQ ID NO: 1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO: 11, not nucleic acid molecules encoding an amino acid sequence that is 95% identical or greater to SEQ ID NO: 1, an amino acid sequence that is 95% identical or greater to SEQ ID NO:3, an amino acid sequence that is 95% identical or greater to SEQ ID NO:5, an amino acid sequence that is 95% identical or greater to SEQ ID NO:7, an amino acid sequence that is 95% identical or greater to SEQ ID NO:9 and an amino acid sequence that is 95% identical or greater to SEQ ID NO:11.
The instant specification discloses nucleic acid sequences SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8 SEQ ID NO: 10, SEQ ID NO: 12 encode amino acid sequences SEQ ID NO: 1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO: 11 (paragraphs 0094-0096). The specification does not disclose any other nucleotide sequence that is 95% identical or greater to SEQ ID NO:2, a nucleotide sequence that is 95% identical or greater to SEQ ID NO:4, a nucleotide sequence that is 95% identical or greater to SEQ ID NO:6, a nucleotide sequence that is 95% identical or greater to SEQ ID NO:8, a nucleotide sequence that is 95% identical or greater to SEQ ID NO: 10, and a nucleotide sequence that is 95% identical or greater to SEQ ID NO:12.
State of the Relevant Art
Protein chemistry is probably one of the most unpredictable areas of biotechnology. It is known in the art that the relationship between the amino acid sequence of a protein (polypeptide) and its tertiary structure (i.e. its binding activity) are not well understood and are not predictable (see Ngo et al., in The Protein Folding Problem and Tertiary Structure Prediction, 1994, Merz, et al., (ed.), Birkhauser, Boston, MA, pp. 433 and 492-495) (IDS). There is no recognition in the art that sequence with identity predicts biological function. It is known in the art that even single amino acid changes or differences in a protein's amino acid sequence can have dramatic effects on the protein's function. For example, conservative replacement of a single “lysine” reside at position 118 of acidic fibroblast growth factor by “glutamic acid” led to the substantial loss of heparin binding, receptor binding and biological activity of the protein (Burgess et al., J of Cell Bio. 111:2129-2138, 1990)(IDS). In transforming growth factor alpha, replacement of aspartic acid at position 47 with alanine or asparagine did not affect biological activity while replacement with serine or glutamic acid sharply reduced the biological activity of the mitogen (Lazar et al. Molecular and Cellular Biology 8:1247-1252, 1988) (IDS). Further, Leninger et al. (Elife. 2019;8:e48909. Published 2019 Oct 22) (IDS) teaches: “a single conservative mutation introduced into an SMR dimer is sufficient to change the resting conformation and function in bacteria…changing a single amino acid (the building blocks that make up proteins) in one of the two subunits to make them minimally different from each other, dramatically modified the transporter’s structure and function”(Abstract). These references demonstrate that even a single amino acid substitution or what appears to be an inconsequential chemical modification will often dramatically affect the biological activity and characteristic of a protein. Furthermore, the specification fails to teach what deletions, truncations, substitutions and mutations of the disclosed sequence can be tolerated that will allow the protein to function as claimed. While it is known that many amino acid substitutions are possible in any given protein, the position within the protein's sequence where such amino acid substitutions can be made with reasonable expectation of success are limited. Certain positions in the sequence are critical to the three-dimensional structure/function relationship, and these regions can tolerate only conservative substitutions or no substitutions. Residues that are directly involved in protein functions such as binding will certainly be among the most conserved (Bowie et al. Science, 247:1306-1310, 1990, p. 1306, col.2) (IDS). It is art known that certain residues are shown to particularly important to the biological or structural properties of a protein or peptide, e.g., residues in active sites and such residues may not be generally be exchanged. Skolnick et al teach that sequence-based methods for function prediction are inadequate and knowing a protein's structure does not tell one its function (Skolnick, et al. Trends in Biotech. 18, 34-39, 2000, see abstract, in particular)(IDS).
Are the disclosed species representative of the claimed genus?
MPEP § 2163 states that a “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
The disclosure fails to describe the common attributes or characteristics that identify members of the genus of MAGE-A antigens having at least 95% sequence identity with of SEQ ID NO: 1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO: 11, wherein the 5% of changes can be anywhere, and because the genus is highly variable, due to the lack of a written description regarding which nucleic acids that encode the MAGE-A antigens can be changed by deletion, addition, substitution and/or combination thereof, the disclosure of the SEQ ID NO: 1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO: 11 are insufficient to describe a highly variant genus. Because the artisan cannot envision the detailed structure of the encompassed MAGE-A antigens outside the specified SEQ ID NO: 1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO: 11 and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation.
Identifying characteristics and structure/function correlation
In the absence of a representative number of species, the written description requirement for a claimed genus may be satisfied by disclosure of relevant, identifying characteristics; i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. To meet this requirement in the instant case, the specification must describe structural features that the skilled artisan as of the effective filing date would have expected to convey the claimed binding activity.
The specification fails to provide a descriptive of structural features that are common to the encompassed composition comprising a nucleotide sequence encoding a consensus MAGE-A antigen. Although the specification discloses a partial structure, i.e. a construct comprising a nucleotide sequence encoding a consensus MAGE-A antigen, wherein the consensus MAGE-A antigen comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO: 11, it does not disclose the structure encompassed by the full scope of the claims wherein the MAGE-A antigen is characterized by an amino acid sequence that shares at least 95% sequence identity with of SEQ ID NO: 1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO: 11, wherein the 5% of changes can be anywhere. The specification does not disclose a representative number of species for the genus of variants. It is unpredictable what and where these 5% of changes can be made in SEQ ID NO: 1, 3, 5, 7, 9 or 11, such that the resulting variants still maintain the recited function of SEQ ID NO:1, 3, 5, 7, 9 or 11 (i.e. having the recited immunological function).
Further, the specification fails to provide a descriptive of structural features that are common to the encompassed composition comprising a nucleotide sequence encoding a consensus MAGE-A antigen. Although the specification discloses a partial structure, i.e. a construct comprising a nucleotide sequence wherein the nucleotide sequence comprises a nucleotide sequence selected from the group consisting of: SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8 SEQ ID NO: 10, SEQ ID NO: 12, it does not disclose the structure feature shared by the variant that is correlated with the immunological function.
Conclusion:
Applicant was only in possession of the following:
An immunological composition comprising a nucleotide sequence encoding a consensus MAGE-A antigen, wherein the consensus MAGE-A antigen comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO: 11.
The immunological composition of claim 1 or nucleic acid molecule, wherein the nucleotide sequence comprises a nucleotide sequence selected from the group consisting of: SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8 SEQ ID NO: 10, SEQ ID NO: 12.
For all of the reasons presented above, one of skill in the art would not know which of the countless other antigens encompassed by the claims that meet the highly general structural requirements of the claims would also possess the required functional activity. Therefore, the skilled artisan would not reasonably conclude that the inventors had full possession of compositions as broadly claimed at the time the application was filed. Given the lack of shared structural properties that provide the claimed binding activity, the limited number of species described, and the fact that the species that were described cannot be considered representative of the broad genus, Applicant was not in possession of the invention as claimed.
Claim Rejections - 35 USC § 102
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.
Claims 1, 2, and 7 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by De Plaen (Genomics. 1999 Jan 15;55(2):176-84.) (IDS).
De Plaen discloses mouse Mage-a5 gene that encodes an amino acid sequence that is greater than 95% identical to instant SEQ ID NO: 9 (See below) as evidenced by Uniprot Accession O89009_MOUSE.
Sequence of Uniprot Accession O89009_MOUSE (Db) against Instant SEQ ID NO: 9 (Qy)
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De Plaen further teaches that the sequence of the polynucleotide was amplified by PCR during RT-PCR assays (Materials and Methods), indicating that the polynucleotide was at least in water. Thus the limitation of a immunological composition is met.
Further, De Plaen teaches the location of MAGE-a1, 2, 3, 5, 6, and 8 genes on the X chromosome in Figure 1. Thus, limitation of the composition further comprising one or more nucleotide sequences encoding one or more additional cancer antigens is also met.
Further, De Plaen teaches the cloning of nucleic acids into plasmids (Materials and Methods). Thus, limitation of the composition further comprising one or more plasmids is met.
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.
Claims 1-17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 11945851. Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding claims 1, 6, and 15, the patent recites an immunological composition comprising a nucleotide sequence encoding a consensus MAGE-A antigen that comprises one of SEQ ID NO: 1, 3, 5, 7, 9, and 11 which match instant SEQ ID NO: 1, 3, 5, 7, 9, and 11 (claim 1).
Regarding claims 2-3, the patent recites the composition further comprises one or more nucleotide sequences encoding one or more additional cancer antigens (claim 2). The patent recites the one or more additional cancer antigens including TYRP1, TYRP2, and gp100 (claim 3).
Regarding claims 4-5, the patent recites the composition further comprises immune checkpoint inhibitors including an anti-PD-1 antibody (claims 4-5).
Regarding claims 7-9 and 16, the patent recites one or more plasmids, the nucleotide sequence encoding an adjuvant including adjuvants of IL-12, IL-15, IL-28, or RANTES (claims 7-9).
Regarding claims 10-14, the patent recites a method of treating cancer in a subject wherein the administration step comprises electroporation, and the composition comprises one or more immune checkpoint inhibitor including an anti-PD-1 antibody (claims 10-14).
Regarding claim 17, the patent recites a protein encoded by sequences of SEQ ID NO: 1, 3, 5, 7, 9, and 11 (claim 17).
Conclusion
No claims allowable.
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/F.E./Examiner, Art Unit 1643
/Meera Natarajan/Primary Examiner, Art Unit 1643