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 the Claims
Claims 75-90 are currently pending in the Application and are examined on the merits below.
Priority
Acknowledgment is made of applicant's claim for foreign priority based on an application filed in Australia on 11-27-2015. It is noted, however, that applicant has not filed a certified copy of the AU2015904933 application 15/778,836 as required by 37 CFR 1.55.
A certified copy of the priority document AU2016901328 however has been received in the parent Application 15,778,836 as required by 37 CFR 1.55.
Claim Objections
Claims 78, 79 are objected to because of the following informalities: The claims utilize the awkward claim language “the stem cell of any of claim 75”. Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 77 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 77 describes that the stem cell expresses “at least one homozygous HLA haplotype”. Regarding the claim it is not clear that the cell can express at least one homozygous HLA haplotype. The cell would express potentially a homozygous HLA haplotype with respect to the donor, but not with respect to other individuals. Does Applicant intend to limit the invention only to autologous or partially matched recipients? As a product claim this does not make sense. Appropriate clarification or correction is required.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 75-90 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 11400145 in view of Themeli et al. (US20160009813A1).
Claim 75 of the instant Application describes a genetically modified mammalian stem cell which may differentiate into a T cell expressing a TCR and which comprises a nucleic acid encoding a chimeric antigen receptor (CAR) which comprises an antigen recognition moiety as defined by the amino acid sequence of SEQ ID NO: 8 . Hinge, transmembrane and intracellular signalling domains are conventionally defined as derived from the molecules CD8, CD28 and 4-1BB, TCR-zeta signalling domain.
Regarding the instant claim 75, claim 1 of the reference patent describes nucleic acid encoding scFv antigen binding domain of a chimeric antigen receptor directed to TAG-72 which is defined as SEQ ID NO:7. The SEQ ID NO:7 translated (aligned provided) is identical to the SEQ ID NO: 8 amino acid sequence. Claim 7 of the reference application describes the nucleic acid of claim 1 which additionally comprises CD8 or CD28 hinge domain, CD8 transmembrane domain, a 4-1BB signalling domain and a TCR zeta signalling domain. Isolated T cells comprising the described nucleic acids are indicated (claim 8 and dependent claims). The claims of the reference patent do not describe that the nucleic acid is comprised in a genetically modified mammalian stem cell thereby resulting in a translated CAR molecule expressed on the cell surface which comprise the SEQ ID NO: 8.
PNG
media_image1.png
200
400
media_image1.png
Greyscale
The further disclosure of Themeli however relates to the production of CAR-modified T-iPSC derived T cells (0007-0009) in which the CAR moiety may target the TAG-72 tumor antigen. T-iPSC would inherently comprise a TCR derived from the original source T cell directed to an MHC-peptide “antigenic determinant”. Themeli describes that utilization of iPSC derived CAR-T cells is advantageous for the production of large numbers of phenotypically defined expanded CAR-T cells as opposed to those derived from leukapheresis products (0003-0006). It would therefore be obvious considering the reference patent claims and the disclosure of Themeli to provide a T-iPSC cell which comprises the instantly claimed CAR- molecule(s) for the purposes of providing a readily available defined source of CAR-T cells that are either autologous or allogeneic with respect to the subject of interest.
Regarding the instant claim 76 and the specific sequences that are instantly claimed, and for example SEQ ID NO: 14 as hinge domain the disclosure of Themeli provides a complete CAR (SEQ ID NO: 15) molecule which utilizes the exact sequence as aligned below as a hinge domain (align a). A CD28 transmembrane derived domain identical to SEQ ID NO:16 of the instant claim, (align b). A CD28 intracellular signalling domain (align c) identical to the instantly claimed SEQ ID NO:18.
PNG
media_image2.png
200
400
media_image2.png
Greyscale
It would therefore be obvious considering the reference claims and the further previously disclosed specific sequence disclosure of Themeli to provide CAR composition as instantly claimed in claim 76 for example.
Regarding the instant claim 77 the disclosure of Themeli indicates that “autologous” refers to genetically identical cells derived from the same donor (0073). Use of autologous cells is disclosed, and therefore it would be obvious to utilize a subject’s “autologous cells” as disclosed by Themeli which have identical HLA-haplotype “at least one homozygous HLA-haplotype” as the recipient.
Regarding the instant claim 78 the disclosure of Themeli indicates that the final product cells of the invention may be derived from a variety of precursor cells including “T-iPSC” cells as iPSC cells derived from T cells (0007). It would be obvious, considering the disclosure of Themeli and the reference claims, to provide CAR-T-iPSC cells for the purposes described above.
Regarding the instant claim 79 the reference claim 13 provides CAR molecules which comprise a cysteine which promotes dimerization of the CAR of the invention.
The instant claims 80-84 terminally describe a stem cell which specifically comprises a nucleic acid encoding a non-signalling CD47 directed receptor with hinge and transmembrane domains , the hinge has “cysteine residues either removed or substituted” . Regarding the claims 80-84 the reference claims 14-18 describe that non-signalling antigen binding receptors may be included in the CAR-T cell of the invention. The receptor may be directed to CD47 (claim 16) and describes that the non-signaling receptor does not form dimers (claim 18). It would be obvious considering the reference claim 6 and 14-18 to provide an additional non-signalling receptor which does not dimerize due to absence of cysteine residues within the hinge domain.
Regarding the instant claim 85 and T cells derived from the instantly claimed T-IPSC of claims 75-84, the disclosure of Themeli utilizes T-iPSC of the invention to produce mature CAR-T cells (0104, Figures 1A-1F). It would be obvious to provide CAR-T-iPSC cells and re-differentiate said cells into T cells for the beneficial purposes indicated above.
Regarding the instant claim 86, 87 and 88 the reference patent claims do not provide for a method of making the genetically modified mammalian stem cells. However the disclosure of Themeli and the reference claims together provide methods of making the instantly claimed genetically modified mammalian cells. As in instant claim 86, in preferred embodiments the disclosure of Themeli provides for introduction of CAR molecules into de-differentiated T-iPSC cells and subsequent re-differentiation into T cells (figure 1b). Additionally in embodiments the T-PSC are produced from peripheral blood T cells which are stably transduced with a vector encoding a CAR (0229). It would thus be obvious to provide CAR-T cells, de-differentiate said T cells and re-differentiate said CAR-T-iPSC for the beneficial purposes of providing increased numbers of CAR-T cells that may be customized for a particular recipient for example.
Regarding the claims 89 and 90 the disclosure of Themeli provides that final product T cells of the invention may be administered to a subject for the purposes of reducing tumor burden in a subject (0012). Considering the reference claims, and the disclosure of Themeli it would be obvious to utilize the cells of the instant invention in a subject for the purposes of treating a neoplastic condition such as a tumor.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
McGuinness et al. Anti-Tumor Activity of Human T Cells Expressing the CC49-z Chimeric Immune Receptor. HUMAN GENE THERAPY 10:165± 173 (January 20, 1999). (of record IDS 07-17-2025).
Themeli et al. (US20160009813A1). Disclosure described above.
The prior art of McGuinness teaches 1st generation CAR-T cells targeting a TAG72 antigen which comprises a CD3zeta intracellular signalling domain. Themeli discloses T-iPSC cells which may target TAG-72 antigen among a variety of other targets as indicated above. The disclosure McGuinness and/or Themeli do not disclose or make obvious CAR-T cells which comprises antigen recognition moiety with the exact sequence of the SEQ ID NO:8 for example.
Summary: No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRIAN HARTNETT whose telephone number is (571)272-3077. The examiner can normally be reached Monday-Friday 8:00 AM - 5:00 PM EST.
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, Daniel E Kolker can be reached at 571-272-3181. 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.
/BRIAN HARTNETT/Examiner, Art Unit 1644
/DANIEL E KOLKER/Supervisory Patent Examiner, Art Unit 1644