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 .
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, 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 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 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”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 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 statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - Sequences appearing in the specification are not identified by sequence identifiers (i.e., “SEQ ID NO:X” or the like) in accordance with 37 CFR 1.831(c). In particular, the 2A peptides pages 3 and 31 do not have sequence identifiers.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required sequence identifiers, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
Claim Objections
Claim 13 is objected to because of the following informalities: Claim 13 recites that the nucleic acid of claim 1 further comprises a peptide linker. A nucleic can encode –not comprise--the amino acid sequence of a peptide linker. Appropriate correction is required.
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.
Claims 1, 4-7, 26, 32, 34, 35, 41, 50, 53, and 55 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Tamada et al (CA3086658A1), hereinafter Tamada.
Tamada teaches an immunocompetent cell that expresses i) a chimeric antigen receptor (CAR) specific for human mesothelin, ii) interleukin 7 (IL-7), and iii) a chemokine (C-C motif) ligand 19 (CCL19), wherein the CAR comprises a single-chain antibody (scFv), a transmembrane domain, and a signaling domain (Abstract and Embodiment 6 of Para. 0009). The scFv specific for human mesothelin can comprise the VH chain of SEQ ID NO: 1 and the VL chain of SEQ ID NO: 2, which correspond and are identical in sequence to SEQ ID NOs: 7 and 8, respectively of the instant claims (Embodiment 9 of Para. 0009). The VH and VL regions are joined in the N-to-C-terminal direction via peptide linker of SEQ ID NO: 26 (G4S)3 (Para. 0026). The VH chain of SEQ ID NO: 1, the linker of SEQ ID NO: 26, and the VL chain of SEQ ID NO: 2 yield an amino acid sequence identical to SEQ ID NO: 9 of the instant claims. In particular, the amino acid sequence of SEQ ID NO: 9 has the VH chain of SEQ ID NO: 1 at positions 1-128, the (G4S)3 linker at positions 129 and 143, and the VL chain of SEQ ID NO: 2 at positions 144-259. The transmembrane domain may be derived from CD8 and further comprise a human CD8 hinge region (Para. 0032-0033 and Para. 0035). The signaling domain comprises at least one or more members selected from intracellular regions of polypeptides of CD28, 4-1BB (CD137), GITR, CD27, 0X40, HVEM, CD3, or Fc receptor-associated y chain, e.g. a polypeptide of a CD28 intracellular region, a polypeptide of a 4-1BB intracellular region, and a polypeptide of a CD3 intracellular region (Para. 0034). In particular embodiments, the CD3 intracellular region has the amino acid sequence of SEQ ID NO: 10 which fully comprises SEQ ID NO: 14 of the instant claims (Para. 0034). An exemplary third-generation CAR construct comprises from the N-to C-terminus an anti-human mesothelin scFv, human CD8 transmembrane region, and human CD28-4-1BB-CD3 intracellular signaling region (Para. 0094). Examples of the amino acid sequence of human IL-7 can include a sequence registered under GenBank accession No: NM 000880.3 (SEQ ID NO: 28) whereas the amino acid sequence of human CCL19 can include a sequence registered under GenBank accession No: NM 006274.2 (SEQ ID NO: 29) (Para. 0029). Further disclosed is an expression vector comprising a nucleic acid encoding the chimeric antigen receptor recognizing human mesothelin, a nucleic acid encoding IL-7, and a nucleic acid encoding CCL19 (Embodiment 20 of Para. 0009) as well as a method for producing said immunocompetent cell comprising introducing the nucleic acid encoding the CAR specifically recognizing human mesothelin, a nucleic acid encoding the IL-7, and a nucleic acid encoding the CCL19 to an immunocompetent cell (Embodiment 21 of Para. 0009). A kit comprising the expression vector encoding the chimeric antigen receptor and instructions for use is also disclosed (Para. 0088). The cell can be a lymphoid cell such as a T cell derived or separated from a mammal (e.g. a human) (Para. 0040). Lastly disclosed is a pharmaceutical composition for use in the treatment of cancer comprising the immunocompetent cell and a pharmaceutically acceptable additive (Para. 0080), wherein the cancer is a mesothelin-expressing cancer (Para. 0083). The pharmaceutical composition can be administered in combination with an additional anticancer agent (Para. 0084) and via different administration routes such as intratumorally (Para. 0081). With intratumoral administration, the tumor cell is contacted with the CAR-expressing immune cell, the minimal active step required to decrease tumor cell proliferation per instant claim 50. Thus, the disclosure of Tamada also encompasses methods of decreasing tumor cell proliferation.
Thus, Tamada meets the limitations of instant claims 1, 4-7, 26, 32, 34, 35, 41, 50, 53, and 55.
VH chain: SEQ ID NO: 7 (instant claims) vs SEQ ID NO: 1 (prior art)
PNG
media_image1.png
368
772
media_image1.png
Greyscale
VL chain: SEQ ID NO: 8 (instant claims) vs SEQ ID NO: 2 (prior art)
PNG
media_image2.png
316
770
media_image2.png
Greyscale
CD3 zeta: SEQ ID NO: 14 (instant claims) vs SEQ ID NO: 10 (prior art)
PNG
media_image3.png
286
772
media_image3.png
Greyscale
IL-7: SEQ ID NO: 18 (instant claims) vs SEQ ID NO: 28 (prior art)
PNG
media_image4.png
378
774
media_image4.png
Greyscale
CCL19: SEQ ID NO: 19 (instant claims) vs SEQ ID NO: 29 (prior art)
PNG
media_image5.png
295
770
media_image5.png
Greyscale
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Tamada, as applied to claims 1, 4-7, 26, 32, 34, 35, 41, 50, 53, and 55 above, and further in of June et al (US20130287748A1), hereinafter June.
The teachings of Tamada have been discussed above and differ from the instantly claimed invention in that -while a CD3 zeta chain having the amino acid sequence of SEQID NO: 14 is taught—a 4-1BB domain having the amino acid sequence of SEQ ID NO: 13 is not taught.
However, June teaches chimeric antigen receptors (CARs) comprising an antigen binding domain, a transmembrane domain, a costimulatory signaling region, and a CD3 zeta signaling domain, wherein the costimulatory signaling region is 4-1BB having the amino acid sequence of SEQ ID NO: 23 (Abstract and Para. 0151 and 0152). The inclusion of a 4-1BB costimulatory domain enhances anti-tumor activity as well as in vivo persistence of CAR T cells (Para. 0123). In addition, the 4-1BB signaling domain helps promote the development of memory in the context of TCR signaling (Para. 0297).
It would have been obvious to one of ordinary skill in the art to substitute the 4-1BB costimulatory signaling domain of Tamada with that disclosed by June. One of ordinary skill in the art would have been motivated to do so since the 4-1BB costimulatory signaling domains disclosed by Tamada and June have the same function and can be used for the same purpose. An express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213USPQ 532 (CCPA 1982). Therefore, one of ordinary skill in the art would reasonably expect that the 4-1BB signaling domain of June to enhance the anti-tumor activity as well as in vivo persistence of CAR-expressing immune cells.
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Tamada, as applied to claims 1, 4-7, 26, 32, 34, 35, 41, 50, 53, and 55 above, and further in of Bedoya et al (US20160185861A1), hereinafter Bedoya.
The teachings of Tamada have been discussed above but differ from the instantly claimed invention in that it is not specifically taught that the CD8 hinge or CD8 transmembrane domain comprises the amino acid sequences of SEQ ID NOs: 11 and 12, respectively.
However, Bedoya teaches that a CD8 hinge of SEQ ID NO: 2 (corresponding to SEQ ID NO: 11 of the instant claims) and a CD8 transmembrane domain of SEQ ID NO: 6 (corresponding to SEQ ID NO: 12 of the instant claims) can be used in a chimeric antigen receptor (Para. 00296).
It would have been obvious to one of ordinary skill in the art to substitute the CD8 hinge and CD8 transmembrane domain of Tamada with those disclosed by Bedoya. One of ordinary skill in the art would have been motivated to do so since the CD8 hinge and transmembrane domains disclosed by Tamada and Bedoya have the same function and can be used for the same purpose. An express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213USPQ 532 (CCPA 1982). Therefore, one of ordinary skill in the art would reasonably expect that the CD8 hinge and transmembrane domains of Bedoya can effectively be used in a chimeric antigen receptor.
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Tamada, as applied to claims 1, 4-7, 26, 32, 34, 35, 41, 50, 53, and 55 above, and further in of Sievers et al (US20190144515A1), hereinafter Sievers.
The teachings of Tamada have been discussed above and differ from the instantly claimed invention in that it is not specifically taught that the nucleic acid encoding the CAR further comprises a peptide linker 3 to 10 amino acid residue sin length linking the antibody and the CD8 hinge region.
However, Sievers teaches chimeric antigen receptor formats in which a short peptide or linker, preferably between 2 and 10 amino acids in length may form the linkage between the hinge/spacer domain (e.g. a CD8 hinge/spacer) and the antigen binding domain of the CAR., wherein a suitable linker is an alanine-alanine-alanine (AAA) triplet (Para. 0133 and 0135).
It would have been obvious to one of ordinary skill in the art to incorporate a short peptide linker (e.g. AAA) taught by Sievers in the chimeric antigen receptor disclosed by Tamada. One of ordinary skill in the art would have been motivated to do so since such linkers can be used to provide a connection between the antigen-binding domain and hinge region of a chimeric antigen receptor. Therefore, one of ordinary skill in the art would reasonably expect that the short peptide linkers of Sievers are suitable for operably connecting an antigen-binding domain and a hinge region of a chimeric antigen receptor.
Conclusion
No claims are allowable. Claims 24 and 25 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LIA TAYLOR whose telephone number is (571)272-6336. The examiner can normally be reached 8:30 - 5:00 M-F.
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, MISOOK YU can be reached at 571-272-0839. 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.
/LIA E TAYLOR/Examiner, Art Unit 1641
/MISOOK YU/Supervisory Patent Examiner, Art Unit 1641
Prosecution Insights