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 .
Application Status
Applicant elected Group I (claims 1-23, 26, 27), without traverse, and the following species, SEQ ID NO: 24, with traverse, in the response to the restriction filed on 3/9/2026. The elected species will be used for search purposes. Applicant submits SEQID NO: 13,14,22,23-28,29,32,33,36,37 all relate to TCR IC5.6 and therefore form a similar inventive concept. The species election requirement is withdrawn. The group requirement is still deemed proper and is therefore made FINAL.
The amended claims 1-27, filed on 3/9/26 are under consideration. Claims 24 and 25 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention group, there being no allowable generic or linking claim.
Priority
This application claims priority to NL2026614 (10/2/2020) and is a 371 of PCT/NL2021/050570 (9/22/2021). Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55 for PCT/NL2021/050570 (9/22/2021) but not for NL2026614 (10/2/2020).
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the specification are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Reference must be made to the sequence by use of the sequence identifier (§ 1.823(a)(5)). “SEQ ID NO:”, is necessary before the sequence recited, given that at least four amino acids are enumerated (See MPEP 2412.04; 37 CFR 1.831(a)). See claims 2 and 3.
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.
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
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code on Page 48, final line; Pg 49, lines 4, and 27. 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.
Three hyperlinks identified include:
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Claim Objections
Claims 4, 5, 7, 9, 10, 12, 14, 17, 22, 23 objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim should refer to other claims in the alternative only and cannot depend from any other multiple dependent claim.
See MPEP § 608.01(n). Accordingly, the claims have not been further treated on the merits. Claim 6 depends from claim 5, claim 8 from claim 7, claim 11 from claim 10, claim 13 from claim 12, claims 15 and 16 from claim 14, claims 18-21 from claim 17, and inherit the same issue and are therefore objected to for the same reason.
Applicant is advised that should claim 26 be found allowable, claim 27 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m). Here, claim 27 is a product claim and intended use in therapy does not distinguish scope from claim 26.
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 1-23 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.
MPEP 2163.II.A.3.(a).i) states, “Whether the specification shows that applicant was in possession of the claimed invention is not a single, simple determination, but rather is a factual determination reached by considering a number of factors. Factors to be considered in determining whether there is sufficient evidence of possession include the level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention”.
For claims drawn to a genus, MPEP § 2163 states 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, reduction to drawings, or 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. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
Nature of the Invention:
The application is broadly directed to T cell therapy for human MHC Class I HLA b*35:01 positive patients with disorders such as B cell malignancies or multiple myeloma. Claims include the composition encoding a Bob1 antigen-specific binding protein of claim 1, a vector and cell comprising the composition, and an immunotherapy pharmaceutical composition of these components.
Independent claim 1 further discloses nucleic acid sequences encoding T cell receptor variable domains (Vα and Vβ), each comprising CDR3 amino acid sequences, Vα having at least 80% sequence identity to SEQ ID NO: 12 or a functional fragment thereof, and Vβ, having at least 80% sequence identity to SEQ ID NO: 21, or a functional fragment thereof. Thus, the claims are drawn to two very large genera of sequences, as will be demonstrated below.
First, it is noted that although claim 1 requires that the nucleic acid composition “encodes a Bob1 antigen-specific binding protein having a TCR α chain varilable (Vα) domain and a TCR β chain variable (Vβ) domain” which is a functional limitation of the nucleic acid composition, the claim only specifies a CDR3 amino acid sequence for the Vα and Vβ domains. There is no recitation of the structure for the CDR1 or CDR2 amino acid sequences for each of these Vα and Vβ domains. Accordingly, the claim broadly encompasses a genus of possible nucleic acid compositions that encode a genus of possible a TCR α chain variable (Vα) domain and a TCR β chain variable (Vβ) domain but requires the particular function of binding to Bob1 antigen.
In addition, for the first genus, Vα at least 80% similar to SEQ ID NO: 12. The disclosed sequence is 18 amino acids long, therefore at least 80% similarity allows 3.6 amino acids or fewer, to vary. If, for example, 3 sites vary from SEQ ID NO:12, then (18 AA positions pick any 3 positions) = (18*17*16)/(3*2*1), and results in 816 possible combinations of amino acid sequence. As well, for each position, there are 19 amino acid options that differ from the amino acid found at a given position in SEQ ID NO: 12, so there are, 193 or 6,859 possible amino acid combinations when three positions differ from the SEQ ID. Thus, 816*6,859 = 5,596,944 possible variants in the genus, for just the case when three total sites varying. It is additionally possible that 2 or 1 site(s) could vary, increasing the total possible variants beyond 5,596,944. That these would all be functional as claimed, requires sufficient support in the Specification.
Similarly, the second genus is comprised of all sequences at least 80% similar to SEQ ID NO: 21, which is 14 amino acids long. Therefore, 2.8 sites or less, may vary. If we consider the case of 2 sites varying, (14 sites pick 2) or (14*13/2*1) = 91 possible site combinations, and there are 192 = 361 amino acid alternatives, thus (91*361) is 32,851 possible combinations of any two sites varying from SEQ ID NO: 21, incorporating any of the 19 alternative amino acids, resulting in a second large genus. Additionally, only one site may vary, increasing the total number of species even more.
Further, the claim broadly recites “Bob1 antigen”, which broadly encompasses a large genus of possible epitopes that the TCR α chain varilable (Vα) domain and a TCR β chain variable (Vβ) domain is intended to bind.
Therefore, the Specification must sufficiently demonstrate possession of a representative number of these species for each genus, with the claimed correlated function of being a Bob1 antigen specific binding protein with nucleic acid sequence encoding T cell receptor variable alpha and beta domains, comprising CDR3 amino acid sequence(s). Such representation needs to demonstrate predictability of variant species’ behavior, sufficient to allow one of skill in the art to identify possession of the full scope of the invention.
State of the Art:
Sundberg (Sundberg et al. (2009) Methods in Molecular Biology, Epitope Mapping Protocols, vol 524. Humana Press, New York, pages 23-36) discusses the criticality of all six CDR regions in terms of determining antigen binding specificity. Sundberg explains that CDRs lie in close spatial proximity on the surface of the V domains and determine the conformation of the combining site such that “the CDRs confer specific binding activity to apical regions of the Ig domain” (page 24, paragraph 2). Sundberg reiterates that “The paradigm of antigen recognition is that the three-dimensional structure formed by the six CDRs recognizes and binds a complementary surface (epitope) on the antigen” (page 25, paragraph 1). Accordingly, Sundberg provides evidence of the criticality of having all six CDR regions in order to provide specific antigen-binding activity. In contrast, claim 1 requires that the TCR variable domains bind “Bob1 antigen” but they only refer to CDR3 regions and don’t specify CDR1 or CDR2 sequences for each of the TCR α chain varilable (Vα) domain and a TCR β chain variable (Vβ) domain. Accordingly, given the criticality of all six CDRs in determining antigen binding specificity, one of ordinary skill in the art would conclude that Applicant was not in possession of the genus of possible TCR α chain variable (Vα) domain and a TCR β chain variable (Vβ) domains that bind Bob1 antigen based only on the recitation of two CDR3 sequences.
Regarding the recitation of at least 80% identity to SEQ ID NOs 12, there is unpredictability in the specificity and functioning of the composition of claim 1 encoding a Bob1 antigen-specific binding protein with a TCR variable alpha domain comprising CDR3 amino acid sequence that is at least .80 similar to SEQ ID NO: 12, CAVKVSNAGGTSYGKLTF. This is because the sequence depicted in Burrows, Table 3: CDR3: CAMSSSNAGGTSYGKLTF matches the similarity to SEQ ID NO: 12 required by the instant claim, but instead of Bob1 binding, responds to Epstein Barr Virus (Burrows et al., WO2020/082130 A1; published, 30 April 2020). Burrows discloses a CDR3 alpha chain for TCR for HLA-A*11:01-SSCSSCPLSK, a highly specific HLA class 1 complex used to detect CD8+ T cells reacting to Epstein-Barr virus latent membrane protein 2. The sequence was identified in a donor clone and Burrows indicated HLA detect CD8+ T cells reacting to EVB (Pg 64, Table 3).
The structure: function relationship is also unpredictable in TCR binding of peptides, where sequence similarity alone is insufficient for inferring specificity. Smith (Smith et al., 2014, Nat Comms 5:5233) demonstrated that a few changes in CDR3 regions of the TCRs markedly affected what peptide(s) were bound, and a specificity shift from binding a viral peptide Tax/HLA-A2 to a cancer peptide MART1/HLA-A2 with sequence mutation, was identified with mutational studies (Abstract, Fig 2). Five clones selected with MARTI/HLA-A2, all bound to MART1/HLA-A2; and three were identical in CDR3 sequence and showed specificity for just MARTI; two others also cross-reacted, additionally binding Tax and WT1 (Pg 4 left col, final para), indicative of binding differences related to sequence differences. The cross-reacting sequences binding Tax and WT1 were similar, raising the question how we know what percent sequence variation may occur without altering specificity, since this is unpredictable. Second, does position of mutation alter binding ability? Here, the answer is yes and was not predicted a priori but determined by empirical work, testing functionality, and relating this to when and in what position mutations occurred.
Six clones bound only Tax/HLA-A2, had sequence variants and differential binding. Some residues did not appear free to vary since each sequence retained particular residues at some sites (CDR3beta MSAQ residues at TCRbeta 99-102) that were also present in the high affinitiy A6-X15 TCR (Pg4 left col, para 1). Two particular positions were highly restricted (CDR3alpha W101 and CDR3beta L98) (Pg 4 left col para 1), whereas others were less restricted (CDR1alpha26,28,30, and CDRalpha 98) (Pg 4 left col para 1) indicative that not all positions, but some are free to vary without affecting specificity or binding ability. For restricted residues, position as related to steric hindrance that might prevent binding, was also considered (Pg 10, left col, penult para). Given the unpredictable nature of the relationship between sequence and binding function, empirical work was performed in this study to identify associate sequence and function.
WO2016/071758 A1 (published 5/12/2016) also contributes to the demonstration of unpredictability in Bob1 binding in that the SEQ ID Nos recited differ substantially from those of the instant application, despite the Bob1 polypeptides’ identity between the two cases. ‘758 also considers Bob1 peptides as immunotherapy targets, where Bob1 specific T cell clones were used akin to the instant application, and similarly recognized B cell malignancies and multiple myeloma (Pg 2 lines 3-5). In ‘758, a nucleic acid molecule linked to a polynucleotide encoding a polypeptide comprising the CDR3 region of a TCRα polypeptide, and a second polynucleotide encoding a polypeptide comprising the CDR3 region of a TRC3(β) polypeptide, where the CDR3 region of TCRα and β specifically bind to Bob1 (Pg 6 lines 2-4). The CDR3 region of TCR specifically binds Bob1 polypeptide, comprising AA sequence APAPTAWL, or YALNHTLSV (Pg 6, lines 4-10). The first sequence above (from ‘758) is very similar (or the same, with a typological error) to instant SEQ ID NO: 3 (APAPTAVVL). The second sequence YALNHTLSV is identical to instant SEQ ID NO: 1.
Yet, the first TCRα polypeptide CDR3, of ‘758 comprises the amino acid sequence SEQID: 1 and 25, and the second TCR3 (β) polypeptide CDR3, SEQID 4 and 28. None of these are the same as instant TCRα and β polypeptide CDR3 SEQ ID NOs: 12 and 21 or even closely similar.
‘758 SEQ ID NO: 1 a CDR3 AA is: CAASKGSSNTGKLIFGQGTTLQVKP. This and SEQID NO:25 will be presented in the same format (three letter abbrev.) as the instant amino acid sequence, to show that these are not similar sequences (italics show different amino acids from instant):
Cys Ala Ala Ser Lys Gly Ser Ser Asn Thr Gly Lys Leu Ile Phe (and more)(‘758 SEQ ID NO:1)
Cys Ala Val Lys Val Ser Asn Ala Gly Gly Thr Ser Tyr Gly Lys Leu Thr Phe (‘858 SEQID NO: 12)
Cys Ala Ala Ser Thr Gly Gly Gly Tyr Ser Thr Leu Thr Phe Gly Lys Gly Thr and more (‘758 SEQ ID NO:25).
While CDR3 regions are known to be variable which allows for identification of different antigens, these particular sequences are so dissimilar that it is unreasonable to assume predictability of function from one sequence to another, as related to Bob1 binding.
US10189880B2 (published 1/29/2019; US14/930,572 published 5/12/2016) also discloses an isolated nucleic acid molecule with polynucleotides encoding TCRα and β polypeptides comprising a CDR3 region comprising amino acid SEQ ID Nos: (1 or 25) and (4 or 28), for the respective TCRα chain CDR3:
Cys Ala Ala Ser Lys Gly Ser Ser Asn Thr Gly Lys Leu Ile Phe Gly Gln Gly (and more…Thr Thr Leu Gln Val Lys Pro) (‘572 SEQ ID NO:1)
Cys Ala Val Lys Val Ser Asn Ala Gly Gly Thr Ser Tyr Gly Lys Leu Thr Phe (‘858 SEQ ID NO: 12)
Cys Ala Ala Ser Thr Gly Gly Gly Tyr Ser Thr Leu Thr Phe Gly Lys Gly Thr (and more… Met Leu Val Ser Pro) (572 SEQ ID NO: 25).
For TCR β CDR3,
Cys Ala Ser Ser His Gly Pro Ala Ser Tyr Glu Gln Tyr Phe (and more….Gly Pro Gly Thr Arg Leu Thr Val Thr) (‘572 SEQID NO: 4)
Cys Ala Ser Ser Ile Ala Gln Gly Ala Asp Thr Gln Tyr Phe (‘858 SEQ ID NO: 21)
Cys Ala Ser Ser Gly Gln Gly Ile Thr Leu Ala Gly Ala Asn (and more…Val Leu Thr Phe Gly Ala Gly Ser Arg Leu Thr Val Leu) (‘572 SEQ ID NO: 28).
For reasons recited above, unpredictability exists in comparing structures to identify function, given the variability in sequence.
Teachings in the Specification:
Examples (Pg 51) recite that target peptides derived from Bob1 protein were identified and five (SEQID NO: 1-5) that occurred frequently in HLA alleles were used in this work. “Successful isolation of relevant Bob1 targeting T cells” addressed whether TCRs recognized these peptides, followed by functionally assessment (e.g. cytokine production in culture). For two peptides, SEQID Nos: 1 and 3, TCRs were previously identified, and in this work isolation of other T cell clones was unsuccessful. Two HLAP-B*35:01 Bob1 specific T cell clones (1C5.6 and 4H5.6) were identified (with Bob1 derived peptides SEQ ID NOs: 3 and 5) as having specificity for Bob1 SEQ ID NO: 5, though high affinity was demonstrated by a only singular clone, 1C5.6.
Both TCR clone lines were cultured with Bob1 expressing leukemia/myeloma cell lines, cytokine production occurred upon stimulation with Bob1 expressing HLA-B*35:01 target cells. Clone 4H5.6 recognized 2 out of 5 of these Bob1 expressing cell lines but low affinity ended work with these cells. Potent recognition occurred for TCR from only 1C5.6 for the five Bob1 expressing HLA-B*35:01 positive B cell malignant cell lines. However, the differential responses of the two clonal lines indicates functional heterogeneity.
TCR identification of TCR Vα and β sequences was from mRNA via HiSeq genome scan then analysis with MiXCR and additional software to obtain V alpha and V beta family, and V(D)J segments of TCR α and β were codon optimized. TCR expression and tetramer binding was assessed.
Summarizing, five Bob1 peptides (from malignancies) were identified (some known), and a singular TCR clonal line responded sufficiently to the Bob1 peptides. The 37 sequences disclose the five BOB1 peptides, along with sequence for CDRs 1-3 V α and β domains of TCR (clone) 1C5.6 (nucleotide, amino acid, and codon optimized sequence), plus sequences for Valpha (VJ) domain and Vbeta (VDJ) domain (including murine sequences). Accordingly, although the specification describes the structure for CDRs 1-3 for each of the TCR V α and β domains, this single specific clone is not considered to be representative of the genus of antibodies that bind Bob 1 antigen having just the two CDR3 regions claimed without any recitation of CDRs 1 or 2, given the criticality of having all six CDR regions that determine antigen binding specificity. Given this criticality, one of ordinary skill in the art would conclude that Applicant was not in possession of the genus of TCR V α and β domains that do not specify the structure for all six CDRs.
Most importantly, there is no presentation or even an a priori discussion of how functionality of the TCR domains (response to Bob1 peptides) are impacted when the TCR domain sequences identified are mutated or differ in any way (e.g. more than one nucleotide or amino acid) from the actual sequence identified. Even the second TCR clonal line used in anticipation of results, did not respond sufficiently to these Bob1 peptides. There was no discussion regarding why this occurred, which is of particular interest since recognition was present but response was insufficient, though why function differed in this TCR clonal line was not articulated. No additional TCR clonal lines were tested for functionality.
Conclusion regarding possession:
Applicant does not have sufficient breadth of disclosure, namely a representative number of species with the appropriate structure: function relationship (nucleotide/amino acid sequence for TCR functional domains that respond to Bob1 antigen-specific binding protein) to effectively demonstrate possession of the invention, with respect to the the two large genus’ of sequences encoding TCR V alpha and V beta domains, comprising CDR3 that are 80% similar to SEQID NOs: 12 and 21, as disclosed in claim 1. Possession does not extend beyond the known sequences identified, since absent other evidence, unpredictability in the structure: function relationship of sequences is the null expectation, and the art recited above supports this unpredictability.
Claim 1, 26 and 27 are free of the art.
Related art US10189880B2 (discussed above) has claim limitations similar to instant claim 1 but the sequences recited in this patent are substantially different from the instant application.
At least an 80% match to SEQ ID NOs: 12 and 21 is found in Spindler (US20220213167 A1; efd 5/3/2019). SEQ ID NO; 13-790940 recite CD3 alpha and beta sequences for TCR clones 7-395464 [0089]. Many of these sequences are at least 80% complementary to SEQ ID NO: 12 and 21, however there is no obvious reason to combine this art with ‘167, particularly since this art focuses on melanoma and does not mention Bob1.
Another at least 80% match to SEQ ID NO: 12 is found in Davis (US10202640B2; published 2/12/2019), which addresses TCRs, and indicates that epitopic peptides derived from genes mutated in tumor cells, or from clonal rearrangements generating unique idiotypes in myeloma and B-cell lymphoma may be serve as antigens (Col 36, lines 45-55). Transcription factors specific for T cell function and particular T cell types, are briefly addressed (48, 5-10), but Bob1 is not, so it is not obvious why one would combine this sequence with ‘880.
Re: Claim 26 and 27, which disclose an isolated nucleic acid sequence comprising or consisting of the nucleotide sequence of any one of SEQ ID NOs: 13, 14, 22, 23, 25, 26, 28, 29, 32, 33, 36 or 37, no 100% match was found for these sequences.
Regarding 35 U.S.C. § 101: It is noted that elected the SEQ ID NO’s do not demonstrate perfect matches when evaluated in blast.ncbi.nlm.nih.gov. SEQ ID NO: 13 has one of the closest matches, and is 98% similar to a TCR-α chain (TCR-α) mRNA TCR V-α,J-α, C-α allele, but the subject fragment length is also much longer (234 nucleotides), than instant SEQ ID NO:13:
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The other sequences in blast also do not demonstrate perfect matches.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Lisa Horth whose telephone number is (703)756-4557. The examiner can normally be reached Monday-Friday 8-4 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Neil Hammell can be reached at (571) 270-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/LISA HORTH/Examiner, Art Unit 1636
/NEIL P HAMMELL/Supervisory Patent Examiner, Art Unit 1636
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