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 .
Status of Claims
Claims 1-35 are pending.
Claims 1-35 are currently under examination on the merits.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. The U.S. effective filing date of all claims under examination is set at 02/25/2021 based on the CN202110214637 application (filed on 02/25/2021).
Information Disclosure Statement
The information disclosure statements (IDS) submitted are being considered by the examiner.
Drawings
The drawings are objected to because:
Figures 2C and 2D have graphs that have illegible y-axis label.
Figure 5A construct has been labeled but some of the labeling are not fully legible. These include, from left to right, the words in box 1, 2, 3, 5, 6, 7, 9, and 11.
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.
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 –
Two amino acid sequences appear on Pg. 26 lines 27 and 28 of the specification that have not been identified by a sequence identifier in accordance with 37 CFR 1.821(d). The sequences are LSVMGLRIL and LLVIVLRIL.
The amino acid sequence of (G4S)3 on Pg. 27 line 22 of the specification has not been identified by a sequence identifier in accordance with 37 CFR 1.821(d). It is noted on Pg. 33 that the same sequence has been assigned with the identifier of SEQ ID NO:34.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the sequence identifier, 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
The disclosure is objected to because of the following informalities:
Pg.6 Figure 7D description has not been provided with a separate explanation to the two-part graph illustrations as compared to Figures 7A, 7B and 7C.
Appropriate correction is required.
The disclosure is also objected to because it contains an embedded hyperlink and/or other form of browser-executable code on Pg. 7:
https://www.ebi.ac.uklTools/psa/
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.
Claim Objections
Claim 2 is objected to because of the following informalities:
Claim 2 recites the word “or” in line 3. It is suggested that this word be moved to line 5 after the description of “ii)” and before the description of “iii)”
Appropriate correction is required.
Claim Objections
Claims 6-10, 12-31 and 33-35 are objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim 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 32 is objected to because of the following informality:
Claim 32 recites in lines 2-3 the limitation of “the STAR comprises an α chain set forth in SEQ ID NO:15 and a β chain set forth in SEQ ID NO:16. It has been noted that both SEQ ID NOs: 15 and 16 are identical (100% match). Therefore, it appears Applicant may have intended the claim to recite a different pair of SEQ ID NOs, other than SEQ ID NOs 15 and 16 because one would not expect this recited pairing of α chain and β chain to form a STAR with the recited functional property of binding GPC3. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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.
Claims 3 and 5 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AlA), 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-AlA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 3 and 5 recite the terms “e.g.” and “such as” in claim 3 and claim 5 respectively. The metes-and-bounds of the claims are unclear because it is unclear how, or if, possible limitations following “e.g.“ and “such as” limit the claims.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 1-5 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. (WO2020029774 Published Date 13.02.2020) in view of Fachin et al. (WO2017117112A1 Published Date 06.07.2017)
Please note that the citations from Liu et al. below reference positions in the translation attached as an office action appendix.
Liu et al. teaches a chimeric T-cell receptor, also known as a Synthetic T-Cell Receptor and Antigen Receptor (STAR), for treating tumors (Abstract). They teach that the STAR can specifically bind to a target antigen, wherein the STAR comprises: a) a first peptide chain obtained by fusing the variable region of the antibody heavy chain with the constant region of the first subunit of the T cell receptor (TCR); and, b) a second peptide chain obtained by fusing the variable region of the antibody light chain with the constant region of the second subunit of the T cell receptor; wherein, the antibody heavy chain variable region and the antibody light chain variable region specifically bind to an antigenic epitope of the target antigen (claim 1, paragraphs [0012] to [0015] and FIGs 1 and 2). They also teach that the target antigen is a tumor-specific antigen that can be GPC3 (claim 8 and paragraph [0018]). They further teach that STARs are expressed on the cell surface of effector T cells for use in treating or diagnosing a target antigen-related disease in a subject in need thereof (claims 18, 19 and 22 and paragraphs [0055], [0069], [0070] and [0074]).
Liu et al. also teaches that the first and second subunit constant regions of the STAR can be human or mouse in origin (paragraphs [0018] and [0040]). They teach that the amino acid at position 48 of the TCR α chain constant region is mutated to cysteine (paragraphs [0041], [0104] and [0137]). They also teach that one of the amino acid sequences comprising a cysteine mutation on the natural murine TCR α chain constant region is SEQ ID NO: 34. Alignment of SEQ ID NO: 34 (137 amino acids in length) taught by Liu et al. with instant modified TCR α chain constant region comprising instant SEQ ID NO: 28 (135 amino acids in length) showed that both amino acid sequences are identical from residue 1 to 135 (see alignment below, top sequence Qy is instant SEQ ID NO: 28, bottom sequence Db is SEQ ID NO: 34 taught by Liu et al.). Therefore, Liu et al. teaches a therapeutic T cell comprising a modified TCR α chain constant region that comprises instant SEQ ID NO: 28.
PNG
media_image1.png
409
929
media_image1.png
Greyscale
Liu et al. does not specifically teach an isolated therapeutic T cell that co-expresses CXCR2 and a STAR against GPC3. However, these deficiencies are made up in the teachings of Fachin et al.
Fachin et al. teaches methods of making immune effector T cells that can be engineered to express a chimeric antigen receptor (CAR) (Abstract). They teach that co-expression of CAR with a chemokine receptor such as CXCR2 in T cells enhances trafficking of said cells to chemokines such as CXCL1 that are secreted by solid tumors (Pg. 167 lines 23-27). They also teach that because the chemokine receptors expressed in CAR-expressing cells can recognize chemokines secreted by tumors, infiltration of the CAR-expressing T cell to the tumor is facilitated which can enhance the antitumor efficacy of the CAR-expressing cell (Pg. 167 lines 29-32).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform a combined method of producing a T cell that expresses a STAR against GPC3 as taught by Liu et al. and that also co-expresses a CXCR2 as taught by Fachin et al. because Liu et al. teaches that a STAR has improved α chain and β chain pairing, improved TCR binding to the tumor antigen, has minimal transformation of the original TCR relative to that of a CAR-T, and has reduced introduction of exogenous amino acids as such lowering the risk of side effects and improving safety of STAR-expressing T cells (paragraph [0086]), and Fachin et al. teaches that the CXCR2 chemokine receptor expressed in CAR-expressing cells can recognize the CXCL1 chemokine secreted by solid tumors, facilitating infiltration of CAR-expressing T cells to the tumor to enhance the antitumor efficacy of said cells (Pg. 167 lines 29-32). The advantage of having co-expression on a therapeutic T cell of both a STAR that recognizes the GPC3 on tumors and CXCR2 that recognizes CXCL1 secreted by solid tumors would be to provide two methods to enhance targeting of therapeutic T cells to the tumor environment thereby increasing infiltration of T cells for effective killing of tumors. This is an example of (A) Combining prior art elements according to known methods to yield predictable results; and (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. See MPEP 2143. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Allowable Subject Matter
The α chains set forth in SEQ ID NOs:13, 15, 17 and 19 and the β chains set forth in SEQ ID NOs:14; 16, 18 and 20 are free of prior art.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Yie-Chia Lee (Tonya) whose telephone number is (571)272-0123. The examiner can normally be reached Monday - Friday 7.30a - 3.30p Eastern Time Zone.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis can be reached on 571-270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/YIE-CHIA LEE (TONYA)/Examiner, Art Unit 1642
/SEAN E AEDER/Primary Examiner, Art Unit 1642