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 .
Applicant’s amendments to the claims dated 9/22/23 are acknowledged. Claims 1-59 are cancelled. Claims 60-79 are new.
Prosecution on the merits commences for claims 60-79.
PRIORITY
The instant application, filed 10/24/2022, which is a 371 National Stage Application of PCT/US2021/028955, filed 4/23/2021, which claims priority to US Provisional Application No. 63/014,960, filed 4/24/2020. Thus, the earliest possible priority for the instant application is 4/24/2020.
SEQUENCE COMPLIANCE
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
37 CFR 1.821(a) requires all sequences longer than ten unbranched nucleotides or four unbranched amino acids explicitly referenced in the specification must include a SEQ ID NO and must be included in the Sequence Listing.
This application is objected to because amino acid sequences within FIGs 2C, 3A, 3B, 5D, 5E, 9A, 13A, 13B, 15A 17B are not associated with a sequence identifier (a SEQ ID NO) in either the figure or the figure legend.
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.
DRAWINGS
The drawings of 10/24/22 are objected to because they are not in compliance with 37 CFR 1.84 (g) Margins:
Each sheet must include a top margin of at least 2.5 cm. (1 inch), a left side margin of at least 2.5 cm. (1 inch), a right side margin of at least 1.5 cm. (5/8 inch), and a bottom margin of at least 1.0 cm. (3/8 inch), thereby leaving a sight no greater than 17.0 cm. by 26.2 cm. on 21.0 cm. by 29.7 cm. (DIN size A4) drawing sheets, and a sight no greater than 17.6 cm. by 24.4 cm. (6 15/16 by 9 5/8 inches) on 21.6 cm. by 27.9 cm. (8 1/2 by 11 inch) drawing sheets.
The Drawings of 10/24/22 have margins smaller than the allowed sizes, and as a result are not properly reproducible for publication due to run off. Applicant is invited to view patent publication No. US2023/0348559.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The disclosure is objected to because of the following informalities:
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.
See paragraph [0198] of the published specification.
The specification of 10/24/22 is also objected to for referencing colors within the figures. The figures are in black and white. Thus, applicant should amend the specification to delete references to any colors in the figures.
See paragraphs [0029], [0030], [0032], [0037]-[0039]. Applicant is requested to review the specification in its entirety and remove any references to colors within the figures.
Appropriate correction is required.
CLAIMS
Independent claim 60 is directed to a construct comprising at least one complementary determining region (CDR) having at least 70% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 1-14, 26-33, and 48-49.
Claim Objections
Claims 60, 65 and 72 are objected to because of the following informalities:
Claim 60 should be amended to recite “A construct” instead of “An construct” in line 1.
Claim 65 recites “wherein the construct further comprising” instead of “further comprises” in line 1.
Claim 72 recites “a pharmaceutically composition” instead of “a pharmaceutical composition” in line 8.
Appropriate correction is required.
Claim Rejections - 35 USC § 112 - Indefinite
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 75 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 75 recites the limitation "the TMEM161A antigen" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim 75, which is directed to method of treating a proliferative disorder, is further rejected for the use of parentheticals at line 2, which recites, "the TMEM161A antigen (TMEM161A-positive cancer)." As not all proliferative disorders are cancers, it is not clear whether the claimed TMEM161A-positive cancer within the parentheticals is structurally required, or if the limitation is exemplary claim language of an example or preference. MPEP2173.05(d).
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 60-79 are 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.
Independent claims 60 and 64 are directed to a construct comprising at least one complementary determining region (CDR) (CDR3β) having at least 70% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 1-14, 26-33, and 48-49.
Claim 61, dependent upon claim 60, requires wherein the construct is capable of binding to an epitope comprising a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 17, 15-16, 18-22 and 44-45.
Claim 66, ultimately dependent upon claim 60, requires wherein the construct further comprises a CDR3α sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 24.
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116.
An applicant shows that the inventor was in possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention. Lockwood v. Amer. Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997). Possession may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was "ready for patenting" such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the inventor was in possession of the claimed invention. See, e.g., Pfaff v. Wells Elecs., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641, 1647 (1998); Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406; Amgen, Inc. v. Chugai Pharm., 927 F.2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991).
For some biomolecules, examples of identifying characteristics include a sequence, structure, binding affinity, binding specificity, molecular weight, and length. Although structural formulas provide a convenient method of demonstrating possession of specific molecules, other identifying characteristics or combinations of characteristics may demonstrate the requisite possession. As explained by the Federal Circuit, "(1) examples are not necessary to support the adequacy of a written description; (2) the written description standard may be met … even where actual reduction to practice of an invention is absent; and (3) there is no per se rule that an adequate written description of an invention that involves a biological macromolecule must contain a recitation of known structure." Falkner v. Inglis, 448 F.3d 1357, 1366, 79 USPQ2d 1001, 1007 (Fed. Cir. 2006); see also Capon v. Eshhar, 418 F.3d at 1358, 76 USPQ2d at 1084 ("The Board erred in holding that the specifications do not meet the written description requirement because they do not reiterate the structure or formula or chemical name for the nucleotide sequences of the claimed chimeric genes" where the genes were novel combinations of known DNA segments.). However, the claimed invention itself must be adequately described in the written disclosure and/or the drawings. For example, disclosure of an antigen fully characterized by its structure, formula, chemical name, physical properties, or deposit in a public depository does not, without more, provide an adequate written description of an antibody claimed by its binding affinity to that antigen, even when preparation of such an antibody is routine and conventional. See Amgen Inc. v. Sanofi, 872 F.3d 1367, 1378, 124 USPQ2d 1354, 1361 (Fed. Cir. 2017)("knowledge of the chemical structure of an antigen [does not give] the required kind of structure-identifying information about the corresponding antibodies"); see also Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341, 1351-52, 97 USPQ2d 1870, 1877 (Fed. Cir. 2011)(patent disclosed the antigen the claimed antibody was supposed to bind, but did not disclose any antibodies with the specific claimed properties).
Describing a composition by its function alone typically will not suffice to sufficiently describe the composition. See Eli Lilly, 119 F.3 at 1568, 43 USPQ2d at 1406 (Holding that description of a gene’s function will not enable claims to the gene "because it is only an indication of what the gene does, rather than what it is."); see also Fiers, 984 F.2d at 1169-71, 25 USPQ2d at 1605-06 (discussing Amgen Inc. v. Chugai Pharm. Co., 927 F.2d 1200, 18 USPQ2d 1016 (Fed. Cir. 1991)). An adequate written description of a chemical invention also requires a precise definition, such as by structure, formula, chemical name, or physical properties, and not merely a wish or plan for obtaining the chemical invention claimed. See, e.g., Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 927, 69 USPQ2d 1886, 1894-95 (Fed. Cir. 2004) (The patent at issue claimed a method of selectively inhibiting PGHS-2 activity by administering a non-steroidal compound that selectively inhibits activity of the PGHS-2 gene product, however the patent did not disclose any compounds that can be used in the claimed methods. While there was a description of assays for screening compounds to identify those that inhibit the expression or activity of the PGHS-2 gene product, there was no disclosure of which peptides, polynucleotides, and small organic molecules selectively inhibit PGHS-2. The court held that "[w]ithout such disclosure, the claimed methods cannot be said to have been described.").
With regard to antibodies specifically, the courts reiterated that functional language is permissible and can fulfill the written description requirement “if a reasonable structure-function correlation is established, whether by the inventor as described in the specification or known in the art at the time of the filing date” (AbbVie Deutschland GmbH v. Janssen Biotechnology, Ltd., 759 F.3d 1285 (Fed. Cir. 2014) at 1298, reiterating Enzo Biochem, Inc., 323 F.3d at 964) (emphasis added). However, In AbbVie, the court determined that genus claims to antibodies that are functionally claimed (such as wherein the antibodies are claimed as achieving a desired result --such as binding an antigen) lack written description when the genus of antibodies is not described by a representative number of examples and/or by common structural features in the specification (AbbVie Deutschland GmbH v. Janssen Biotechnology, Ltd., 759 F.3d 1285 (Fed. Cir. 2014)).
The claims are drawn to, at least, a large genus of complementary determining region (CDR) proteins comprising at least 70% identity to sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 1-14, 26-33, and 48-49, wherein the protein CDRs are capable of binding an epitope comprising a sequence with at least 70% identity to SEQ ID NOs. 15-22, 44-45.
The claims do not limit the variation to the CDR regions to arrive at least 70%, thus, the claims encompass substitutions, deletions and insertions. With regard to generating substitutions, with each CDR3 as the starting structure, there are possibly 19 amino acids substituted at any one of the claimed positions. SEQ ID NOs: 1-14,26-33 and 48-49 are 7, 8, 13, or 14 amino acids in length. Thus, the genus encompasses 19 options for substitutions at each of the 7, 8, 13 or 14 distinct positions. Thus, there is a range of 1.14 x 1016 (for a 7-mer) to 5.97 x 1021 (for a 14-mer) different combinations for each CDR3:
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The scope required for the function of binding, however, is not only dependent upon the amino acid sequences encompassed by of the claimed CDR3s. The scope required for the function of binding is further dependent upon the amino acid sequence of the epitopes of claim 61. The epitopes encompassed by SEQ ID NOs. 15-22 and 44-45 are either 9-mers or 11-mers. There are possibly 19 amino acids substituted at any one of the claimed positions. Thus, the genus encompasses 19 options for substitutions at each residue of the 9-mer or 11-mer. Thus, there is a range of 1.3 x 1018 to 6.1 x 1019 combinations for each epitope:
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The calculations above only take into consideration an amino acid substitution at every position. The scope is actually broader when considering synthetic amino acids, insertions of amino acids, and deletions. Thus, the scope of the claim includes numerous structural variants, and the genus is highly variant because a significant number of structural differences between genus members is permitted.
While claiming a structure by a function is not prohibited, there must be sufficient structure-function relationship described in the specification such that the claimed genus was represented by a representative number of species or the teachings of the specification, or, the prior art can be used support a well-known structure-function relationship. In the instant case, the instant specification does not support the claimed structure-function relationship that any amino acid substitution at the claimed positions, would predictably result in a CDR3 peptide capable of binding the claimed epitopes.
This can be seen, at least, because the claimed SEQ ID NOs 1-14 and 26-33 sequences are CDR3β genes cloned from functional human T-cells, ultimately following clonal expansion and isolation of paired alpha and beta genes (paragraphs [0029]-[0031]; [0033]-[0036], [0041]; [0197]-Examples 1-13, 28 FIGs 2C, 3A, 13A). These clonally expanded TCR CD3 Beta genes were then were then screened against a yeast display library of antigens to identify specific antigens (paragraphs [0057]-[0059]; Examples 14-15). The TCR genes identified as binding specific antigens in the library screen were then subcloned and expressed in Jurkat cells and binding to antigen in vitro was validated ([0042], Example 16-19, 28; FIG 13, 14). Thus, on a high level, the cloned TCR pairs came from functional TCRs.
The Examiner acknowledges that additional analysis and work was performed on the CDR3 sequences. For example, the specification teaches that prior to subjecting the paired TCR alpha and beta genes to yeast library screening, the genes are subjected to predictive software which a) infers antigen specificity motifs shared between patient populations, and b) assigns specificity groups, wherein additional similarities are identified between the T-cells, such as patient population, T-cell tissue source, VB gene usage, numbers of distinct CDR3B sequences, shared antigen specificities, the minimum numbers of patients, and enrichment of clonally expanded CDR3B clonotypes, and HLA type ([0029], [0040], [0053], [0057], [0058]-[0059], [0191]). Such analysis identified single CDR3 peptides with inferred recognition motifs for multiple antigens, epitopes or mimotopes. Motifs for EntS, LMP2, Flu, EBV, TMEM161A (paragraphs [0031], [0041], [0043], Example 28; FIG 3A-C; 5E, 9A; 13A; 14B, 15A; 23).
While such work aided in pooling DNA, the specificity motifs required validation. Validation experiments showed not all CDR3 peptides with the inferred recognition motifs actually recognized the predicted antigens or variants of the antigens ([0197], [0201] fig 13A-13B; 15B-C ). Thus, of the 21 CDR3 sequences whose ligands were identified, these represent a miniscule number of species of the claimed genus. Validation experiments for SEQ ID NOs 48 and 49 showed they were
The fact that not all validation experiments were successful is not sufficient to support this rejection. The issue is that the specification fails to analyze their results in order to establish an actual structure-function relationship between CDR3s and epitope binding, such that when additional peptides with 70% identity to those claimed was subjected to the methods, there would have been a reasonable expectation of success. However, there is little discussion as to why the cut off is 70%, or how the CDR3 sequences differed between sequences, or how ligands differed between sequences. Other than comparing 9mers to 11mers, there were no real rational mutagenesis studies, nothing to establish a structure-function relationship sufficient to support the breadth of the claims and the limited number of species.
The art is also unpredictable. There is no art which recognizes these specific CDR3s, the encompassed motifs, and their mutagenesis of and resulting effects of binding.
There is no teaching in the specification regarding which portion of the claimed peptides can be varied while retaining the ability of the protein to bind. Further, there is no art-recognized correlation these CDR3s and their modification, based on which those of ordinary skill in the art could predict which amino acids can vary while maintaining binding function. Taken together, the skilled artisan would not conclude that Applicant was in possession of the claimed peptides.
Claims 62-63, 65, 67-79 are included in the rejection because they depend from a rejected claim.
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 60-72 are rejected under 35 U.S.C. 102(A)(1) and 102(A)(2) as being anticipated by US Patent No. 5,830,755 to Nishimura.
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With regard to claim 60, Nishimura discloses constructs comprising recombinant T-cell receptor proteins or parts thereof which bind target antigens (Abstract, Col. 2, lines 18-42; Col. 8, lines 27-53; Col. 9, lines 8-24). Nishimura discloses the construct comprise a TCRβ protein comprising SEQ ID NO: 25 therein. SEQ ID NO:25 comprises the CDR3 region of a TCRβ protein from human VDJ junctional sequences (Col. 22, lines 8-19, Col.7, lines 1-55; FIG. 2B). SEQ ID NO: 25 comprises at least 70% identity to instantly claimed SEQ ID NOs: 2, 4-8, 10-11 and 13-14:
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Thus, Nishimura anticipates claim 60.
It is noted that clam 61 does not provide any additional structural features to claim 60. Nishimura discloses constructs which anticipate claim 60. Thus, the constructs of Nishimura anticipate the claimed function.
With regard to claims 62-65, Nishimura discloses the construct is a TCR receptor, comprising TCRβ, TCRα, or TCRα and TCRβ chains or portions thereof, including as a single-chain construct wherein the TCRα and TCRβ chains are covalently linked (Col. 2, lines 33-35, Col. 6, line 17- Col. 7, line 5; Col. 3, lines 59-64; Col. 16, lines 5-17; FIG 5C). SEQ ID NO: 25 comprises at least 70% identity to instantly claimed SEQ ID NOs: 2, 4-8, 10-11 and 13-14, and encodes the TCRβ CDR3 sequence.
With regard to claims 67-70, Nishimura discloses the construct comprising the TCR receptor is encoded on recombinant nucleic acids, transduced into host cells and expressed, thus generating engineered cells expressing the construct (Col. 2, lines 32; Col. 9, lines 25 - Col. 10, line 67; Col. 14, line 49 - Col. 17, line 14).
With regard to claims 71-72, Nishimura discloses the construct comprising the TCR receptor or portion thereof, the nucleic acids encoding the TCR receptor or portions thereof, or an engineered cell expressing the TCR receptor or portions thereof is formulated as a pharmaceutical composition (Col. 17, line 55- Col. 18, line 40). The proteins, nucleic acids encoding, or engineered cells expressing the TCR receptor are administered to a subject to treat or prevent a condition (Col. 14, lines 18-36; Col. 15, line 41 – Col. 16, line 4; Col. 17-54; Col. 19, lines 4-13).
Claims 60-62, 67-72 are rejected under 35 U.S.C. 102(A)(1) and 102(A)(2) as being anticipated by US Application Publication No. 2010/0190163 to Sugiyama.
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With regard to claim 60, Sugiyama discloses constructs comprising recombinant T-cell receptor proteins thereof which bind target antigens (Abstract, paragraphs [0001], [0008], [0010]-[0011], [0090]). Sugiyama discloses the construct comprise TCRβ CDR3 proteins comprising SEQ ID NOs: 1696-3389 therein that has been isolated from TCRs expressed on WT-1 specific T-cells (paragraph [0008]-[0009], [0088]-[0089]). Each of Instantly claimed SEQ ID NOs: 1-11, 13-14, 26-29, 31-33 and 48-49 have 70% or greater identity with one or more TCRβ CDR3 protein SEQ ID NOs: 1752, 1781, 1799, 1946, 2012, 2220, 2224, 2225, 2281, 2379, 2471, 2496, 2522, 2523, 2562, 2563, 2577, 2655, 2776, 2829, 3007, 3239, 3240, 3249, 3250, 3368, and 3371 identified in Sugiyama.
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A single representative alignment for each claimed SEQ ID NO: is provided below:
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Thus, Sugiyama anticipates claim 60.
It is noted that clam 61 does not provide any additional structural features to claim 60. Sugiyama discloses constructs which anticipate claim 60. Thus, the constructs of Sugiyama anticipate the claimed function.
With regard to claim 62, Sugiyama discloses the construct is a TCR receptor, comprising TCRβ chain, or TCRα and TCRβ chains (paragraphs [0093], [0112]).
With regard to claims 67-70, Sugiyama discloses the construct comprising the TCR receptor is encoded on recombinant nucleic acids, transduced into host cells and expressed, thus generating engineered cells expressing the construct (paragraphs [0113]-[0114], [0138]).
With regard to claims 71-72, Sugiyama discloses the construct comprising the TCR receptor, the nucleic acids encoding the TCR receptor, or an engineered cell expressing the TCR receptor is formulated as a pharmaceutical composition (paragraphs [0113]-[0114], [0138]). The proteins, nucleic acids encoding, or engineered cells expressing the TCR receptor are administered to a subject to treat or prevent a condition (paragraphs [0010]-[0011], [0113]-[0114], [0138]).
Claims 60-62, and 67-72 are rejected under 35 U.S.C. 102(A)(1) and 102(A)(2) as being anticipated by US Application Publication No. 2013/0273647 to Sahin.
With regard to claim 60, Sahin discloses constructs comprising a recombinant T-cell receptor protein thereof which bind target antigens (Abstract, paragraphs [0028], [0039]-[0041], [0045], [0234]). Sahin discloses the construct comprises a portion of a TCR receptor, minimally the TCRβ CDR3 proteins identified therein (paragraphs [0040]-[0041], [0057], [0062], [0065]-[0140], [0167], [0254]). SEQ ID NO 67 therein comprises the TCRβ CDR3 sequence underlined (page 50). The TCRβ CDR3 sequence within SEQ ID NO: 67 has 71.7% identity with claimed SEQ ID NO: 6.
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Thus, Sahin anticipates claim 60.
It is noted that clam 61 does not provide any additional structural features to claim 60. Sahin discloses constructs which anticipate claim 60. Thus, the constructs of Sahin anticipate the claimed function.
With regard to claim 62, Sahin discloses the construct comprises a TCR receptor protein, comprising a TCRβ chain, or TCRα and TCRβ chains (paragraphs [0054]-[0060]).
With regard to claims 67-70, Sahin discloses the construct comprising the TCR receptor protein is encoded on recombinant nucleic acids, transduced into host cells and expressed, thus generating engineered cells expressing the construct (paragraphs [0029], [0062]-[0063], [0175], [0200]-[0202], [0229], [0232], [0257]-[0258]).
With regard to claims 71-72, Sahin discloses the construct comprising the TCR receptor, the nucleic acids encoding the TCR receptor, or an engineered cell expressing the TCR receptor is formulated as a pharmaceutical composition (paragraphs [0045]-[0047], [0051], [0065], [0293]-[0300], [0308], [0318]). The proteins, nucleic acids encoding, or engineered cells expressing the TCR receptor are administered to a subject to treat or prevent a condition (paragraphs [0045]-[0047], [0051], [0064]- [0065], [0293]-[0300], [0308], [0318]).
Claims 60-62, and 67-72 are rejected under 35 U.S.C. 102(A)(1) and 102(A)(2) as being anticipated by US Application Publication No. 2014/0255941 to Sugiyama (herein “Sugiyama-2”).
With regard to claim 60, Sugiyama-2 discloses constructs comprising recombinant T-cell receptor proteins thereof which bind target antigens (Abstract, paragraphs [0009]-[0011], [0014], [0038]-[0040]). Sugiyama-2 discloses the construct comprise TCRβ CDR3 proteins comprising SEQ ID NOs: 757-1512 therein that has been isolated from TCRs expressed on WT-1 specific T-cells (paragraphs [0009]-[0011], [0039]-[0040]). Each of Instantly claimed SEQ ID NOs: 1-2, 4-14, and 48 have 70% or greater identity with one or more TCRβ CDR3 protein SEQ ID NOs: 819, 955, 956, 1023, 1031, 1277,
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1321, 2437, 2875, 2902, 2944, and 2968 identified in Sugiyama-2.
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A single representative alignment for each claimed SEQ ID NO is presented below:
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Thus, Sugiyama-2 anticipates claim 60.
It is noted that clam 61 does not provide any additional structural features to claim 60. Sugiyama-2 discloses constructs which anticipate claim 60. Thus, the constructs of Sugiyama-2 anticipate the claimed function.
With regard to claim 62, Sugiyama-2 discloses the construct is a TCR receptor, comprising TCRβ chain, or TCRα and TCRβ chains (paragraphs [0038]-[0039], [0061]).
With regard to claims 67-70, Sugiyama-2 discloses the construct comprising the TCR receptor is encoded on recombinant nucleic acids, transduced into host cells and expressed, thus generating engineered cells expressing the construct (paragraphs [0042], [0061]-[0063]).
With regard to claims 71-72, Sugiyama-2 discloses the construct comprising the TCR receptor, the nucleic acids encoding the TCR receptor, or an engineered cell expressing the TCR receptor is formulated as a composition to treat cancer in vivo, which reads on a “pharmaceutical composition” (paragraphs [0012]-[0014], [0061]-[0064]). The proteins, nucleic acids encoding, or engineered cells expressing the TCR receptor are administered to a subject to treat or prevent a condition (paragraphs [0012], [0061]-[0064]).
Claims 60-72 are rejected under 35 U.S.C. 102(A)(1) and 102(A)(2) as being anticipated by US Application Publication No. 2019/0225692 to Sisson.
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With regard to claim 60, Sisson discloses constructs comprising recombinant T-cell receptor proteins thereof which bind target antigens (Abstract, paragraphs [0003], [0008], [0011], [0048]). Sisson discloses the construct comprise TCRβ CDR3 proteins comprising SEQ ID NOs: 32, 33, 37, 114, 224, 324 and 325 (paragraphs [0009], [0016], [0041], [0042]). Each of Instantly claimed SEQ ID NOs: 7-9, 11, 13-14 have 70% or greater identity with one or more TCRβ CDR3 protein SEQ ID NOs: 32, 33, 37, 114, 224, 324 and 325 identified in Sisson.
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Thus, Sisson anticipates claim 60.
It is noted that clam 61 does not provide any additional structural features to claim 60. Sisson discloses constructs which anticipate claim 60. Thus, the constructs of Sisson anticipate the claimed function.
With regard to claim 62-65, Sisson discloses the construct is a TCR receptor, comprising TCRβ chain, or TCRα and TCRβ chains, including as a single-chain construct wherein the TCRα and TCRβ chains are covalently linked (paragraphs [0009], [0016], [0041], [0042], [0049]).
With regard to claim 66, Sisson discloses the construct comprises a TCRβ chain CDR3 encoded by SEQ ID NO: 32, 33, or 114, and further comprises a TCRα chain CDR3 encoded by SEQ ID NOs: 565, 566 or 569 (paragraphs [0009], [0016], [0041]-[0042]). SEQ ID NOs: 565, 566 or 569 have 76.7 % identity with instantly claimed SEQ ID NO: 24.
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With regard to claims 67-70, Sisson discloses the construct comprising the TCR receptor is encoded on recombinant nucleic acids, transduced into host cells and expressed, thus generating engineered cells expressing the construct (paragraphs [0051]-[0056], [0060]-[0068]).
With regard to claims 71-72, Sisson discloses the construct comprising the TCR receptor, the nucleic acids encoding the TCR receptor, or an engineered cell expressing the TCR receptor is formulated as pharmaceutical composition to treat a subject in vivo (paragraphs [0067]-[0074]). The proteins, nucleic acids encoding, or engineered cells expressing the TCR receptor are administered to a subject to treat or prevent a condition (paragraphs [0067]-[0074]).
Conclusion
No claims are allowed. No claims are free of the prior art.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KIMBERLY A ARON whose telephone number is (571)272-2789. The examiner can normally be reached Monday-Friday 9AM-5PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher Babic can be reached at 571-272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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KAA
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633