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 .
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 02/02/2026 has been entered.
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.
Claim 34 and 47-49 remain rejected and newly added claims 50-59 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of reducing T-cell mediated immune stimulation of a CAR-T cell or immune stimulation bystander cytotoxicity comprising administering a dimerizer to a CAR-T cell wherein the CAR-T cell expresses a) a CAR comprising an FRB domain and b) a polypeptide comprising and FKBP linked to SHP1, does not reasonably provide enablement for reducing CAR-T cell mediated immune stimulation without administering a dimerizer or where the CAR is expressed in non-T cells. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
Enablement is considered in view of the Wands factors (MPEP 2164.01(a)). The court in Wands states: "Enablement is not precluded by the necessity for some experimentation such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is 'undue,' not 'experimentation.' " (Wands, 8 USPQ2d 1404). Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. "Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations." (Wands, 8 USPQ2d 1404). The factors to be considered in determining whether undue experimentation is required include: (1) the quantity of experimentation necessary, (2) the amount or direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims. While all of these factors are considered, a sufficient amount for a prima facie case are discussed below.
MPEP §2164.01(a), 4th paragraph, provides that, “A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1157, 1562; 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).
The nature of the invention generally relates to systems for providing tighter regulation of T-cell response to antigen binding to a chimeric antigen receptor (CAR) expressed by a T-cell.
CARs are known in the art for use in treating diseases associated with elevated expression of an antigen, which is the ‘target antigen’. The claims have been amended to limit the functional effect of administering a cell comprising a CAR. The claims are drawn to reducing a T-cell mediated immune stimulation (claim 34) or bystander cytotoxicity (claim 51), comprising administering a cell (any cell type) comprising a vector encoding a CAR with an FRB and a nucleic acid encoding FKBP linked to SHP1. The claims only require administering the cell and do not require a dimerizer.
The Specification teaches the use of a system that comprises a CAR operably linked to an FRB and, separately, SHP1 linked to an FKBP where provision of a dimerizing molecule leads to dimerization of the CAR and SHP1 through binding of the dimerizer to FRB and FKBP. SHP1 tunes down the phosphorylation of CD3z on the CAR. Thus, administration of the dimerizer tunes down the CAR-induced activation of T-cells and subsequent immune response the activity of SHP1. Because the immune stimulation comes from T-cells, claims should be limited to administering T-cells, not any cell type. Likewise, with claim 51, the bystander cells are affected by the response of T-cells expressing a CAR.
Thus, the Specification does not provide the guidance necessary to reduce T-cell mediated immune stimulation when the cell administered is not a T-cell. As well, the T-cell response is not tuned down unless a dimerizer is added. The Specification teaches how to carry out general CAR T-cell treatment in a less toxic manner.
Given the unpredictable nature of developing CAR-T cell therapies for treatment of specific diseases, it would have required undue experimentation to determine how to tailor CAR-T cell therapy using non-T cells or to fine-tune the immune response in the absence of a dimerizer.
Newly added claim 56 is drawn to a method of treating a CD19-expressing cancer with a call expressing a CAR that binds CD19. Claims 56-59 have the issues set forth above with regard to treatment using non-T cells and not including a dimerizer, CD19-CAR T cells are known in the art to be effective in treatment of CD19-expressing cancers. Claim 56, as written, does not tune down the response with a dimerizer and thus, the system of the invention is not being used.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to VALARIE BERTOGLIO whose telephone number is (571)272-0725. The examiner can normally be reached M-F 6AM-2:30PM.
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, Peter Paras can be reached at 571-272-4517. 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.
VALARIE E. BERTOGLIO, Ph.D.
Examiner
Art Unit 1632
/VALARIE E BERTOGLIO/Primary Examiner, Art Unit 1632 Any inquiry concerning this communication or earlier communications from the examiner should be directed to VALARIE BERTOGLIO whose telephone number is (571)272-0725. The examiner can normally be reached M-F 6AM-2:30PM.
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, Peter Paras can be reached at 571-272-4517. 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.
VALARIE E. BERTOGLIO, Ph.D.
Examiner
Art Unit 1632