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 .
Claims 3, 7, 9, 10, 14, 16, 21, 32-45, 50-62 and 64-76 have been canceled. Claims 1, 4, 5, 8, 11-13, 15, 17-19, 22, 25, 31, 46-49 and 63 have been amended. Claims 1, 2, 4-6, 8, 11-13, 15, 17-20, 22-31, 46-49 and 63 are pending and examined 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. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) or 365(c) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed applications, Application No.s 63/342,031; 63/341,999; 63/636,972; 63/336,980; 63/311,042; 63/311,045; 63/311,043; 63/311,016; 63/226,712; 63/226,643; 63/226,736, and PCT/US2021/046014 fail to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application.
The prior applications fail to provide a written description of the chimeric Tim4 receptor comprising the extracellular domain of SEQ ID NO:6; a CD28 transmembrane domain of SEQ ID NO: 11; a primary CD28 intracellular signaling domain of SEQ ID NO: 12; a secondary CD3ζ signaling domain of SEQ ID NO: 14 and a tertiary TLR2 TIR signaing domain of SEQ ID NO: 17. Thus priority is extended to the first disclosure of the required sequences in PCT/US2021/046041 and PCT/US2021/046043, both filed on 08/13/2021.
Claim Objections
Claim 17 is objected to because of the following informalities: the double inclusion of the species “leukemia”. 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.
Claims 1, 2, 5, 6, 8, 11-13, 15, 17, 18-20, 22-31, 46-49 and 63 are 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.
Claims 1 is vague and indefinite in the recitation of TLR2 TIR. The specification states that this is a truncated version of TLR2 that in some embodiments is
a TLR2 signaling domain having the peptide sequence of HRFHGLWYMKMMWAWLQAKRKPRKAPSRN removed from the N-terminus of the TLR2 signaling domain.
This fails to provide a limiting definition for TLR2 TIR because it is qualified as an alternative for “some embodiments”. Thus, it is unclear what scope applicant intends to encompass with TLR2 TIR.
Regarding claim 17, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claims 17 and 22, the use of “e.g.” renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 17 is vague and indefinite in the recitation of “B-cell cancers, including B-cell lymphomas” because it is unclear how the inclusion affects the metes and bound of the claim with respect to B-cel cancers.
Claim 17 is vague and indefinite in the recitation of “immunoproliferative small” without naming the cell type and associated disease. The metes and bounds of the claim cannot be determined.
Claim 17 is vague and indefinite in the recitation of histiocytic disorders, giant cell tumors, neoplasms, B cell cancers, B-cell lymphomas, myelomas, and B-cell proliferations of uncertain malignant potential all recited in the plural. It is unclear if applicant is intending that the subject being treated must have more than one histiocytic disorder, giant cell tumor, neoplasm, B cell cancer, B-cell lymphoma, myeloma, and B-cell proliferation of uncertain malignant potential.
Claim 17 is vague and indefinite in the recitation of lymphomatoid granulomatosis and post-transplant lymphoproliferative disorder. It is unclear if applicant is intending that the subject being treated must have both of a lymphomatoid granulomatosis and post-transplant lymphoproliferative disorder. Amendment of the claim to read lymphomatoid granulomatosis or post-transplant lymphoproliferative disorder would overcome this part of the rejection.
Claim 25 is vague and indefinite in the recitation of Waldenstrom macroglobulinemia and marginal zone lymphoma. It is unclear if applicant is intending that the subject being treated must have both of Waldenstrom macroglobulinemia and marginal zone lymphoma. Amendment of the claim to read Waldenstrom macroglobulinemia or marginal zone lymphoma would overcome this part of the rejection. .
Claim 47 lacks specific antecedent basis in the recitation of “chimeric Tim 4 receptor”. Claim 15 requires the administration of the engineered T cell of claim 8, not the chimeric Tim4 receptor.
The recitation of “the additional therapeutic agent” in claims 46 and 47 lacks specific antecedent basis in claim 15.
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, 2 and 4 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 polynucleotides encoding the chimeric TIM4 receptor, wherein the chimeric receptor comprises an extracellular domain , does not reasonably provide enablement for the isolated polypeptides encoded therefrom. 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 use the invention commensurate in scope with these claims.
The factors considered when determining if the disclosure satisfies the enablement requirement and whether any necessary experimentation is undue include, but are not limited to: 1) nature of the invention, 2) state of the prior art, 3) relative skill of those in the art, 4) level of predictability in the art, 5) existence of working examples, 6) breadth of claims, 7) amount of direction or guidance by the inventor, and 8) quantity of experimentation needed to make or use the invention. In re wands, 858 F.2d 731, 737.8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
Claims 1, 2, 5, 9, 11 and 16 are drawn to a chimeric antigen receptor comprising a specific anti-CD147 scFv defined by CDR sequences, a hinge domain, a transmembrane domain and an intracellular domain comprising one or more co-stimulatory domains and an intracellular signaling region. When given the broadest reasonable interpretation, said claims read, in part, on an isolated fusion polypeptide comprising the required CAR.
Claim 1 requires that the single chain chimeric protein comprises a CD28 intracellular signaling domain, a CD3ζ intracellular signaling domain , and a TLR2 TIR intracellular signaling domain, and a CD28 transmembrane domain connecting the TIM4 binding domain and the CD28 intracellular signaling domain. Gilham et al (Trends in Molecular Medicine, 2012, Vol. 18, pp. 377-384) teach that surface expression of a CAR endows a T cell with redirected functional activity whereby CAR-T cells recognize the target cells through the antigen-specific binding of the antibody-defined targets on the cell surface (page 377, lines 3-7). Without a cell capable of integrating these various intracellular signals into a functionally activated T cell, there is no expectation that the fusion protein had any functional activity.
Claim 2 requires that the chimeric TIM4 receptor binding domain further comprises a signal peptide at the N-terminus. The art teaches that protein secretion is generally directed by an N-terminal signal peptide which is cleaved off during synthesis of the protein (Zhang et al, The Journal of Gene Medicine, 2005, Vol.7, pp. 354-365, see page 355, first column, lines 1-3 of the full paragraph). Although the art teaches that differing signal peptides can have an effect on secretion rates and levels of recombinant protein produced from a transfection (Zhang et al, page 360, first column, lines 15-17), the protein which is being produced is a mature protein without the signal peptide (Zhang et al, page 360, Figure 3). The art teaches that modification of the signal peptide which affect the cleavage from the N-terminus of the mature protein can be avoided by confining signal peptide modification to the C-terminal end of the signal peptide in order to ensure that the signal peptidase will digest at the correct site and preserve the biological function of the protein (Zhang et al, page 361, first paragraph under the heading “Modification of signal peptides on cleavage site…”). It is noted that the instant specification provides no objective evidence of the biological activity of the fusion protein carrying the intact signal peptide at the amino terminus of the fusion protein. Further, the instant specification provides no teachings or guidance as to the disabling of the signal peptidase, so that the cleavage of the signal peptide from the mature protein does not occur upon secretion. Thus, the specification is enabling for the polynucleotide encoding the chimeric Tim4 receptor of claim 1 including the Tim4 signal peptide, but not the protein encoded by the polynucleotide.
Allowable Subject Matter
Claim 4 is 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 KAREN A CANELLA whose telephone number is (571)272-0828. The examiner can normally be reached M-F 10-6:30.
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KAREN A. CANELLA
Examiner
Art Unit 1643
/Karen A. Canella/Primary Examiner, Art Unit 1643
Prosecution Insights