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 AI
Claims 1, 3-22, and 24 are pending and currently under consideration.
Specification
The specification is objected to on pages 77 and 131 for improper disclosure of polypeptide sequences, as it fails to comply with the requirements of 37 CFR 1.821 through 1.825. This definition sets forth limits, in terms of numbers of amino acids and/or numbers of nucleotides, at or above which compliance with the sequence rules is required. Nucleotide and/or amino acid sequences as used in 37 CFR 1.821 through 1.825 are interpreted to mean an unbranched sequence of four or more amino acids or an unbranched sequence of ten or more nucleotides. (see MPEP 2422). Reference must be made to sequences in the specification, claims, and drawings for which compliance with the sequence rules is required by use of the sequence identifier, preceded by “SEQ ID NO:” or the like (see MPEP 2412.04). Proper 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 4 and 10 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.
Claim 4 recites “…a ligand for the endogenous immunoreceptor.” There is insufficient antecedent basis for “the endogenous immunoreceptor” in the claim.
Claim 10 recites “…wherein the target antibody….” There is insufficient antecedent basis for “the target antibody” in the claim.
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.
Claim(s) 13-15, 17-22, and 24 and is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Urbanska et al (Journal of Translational Medicine, 2014, 12(347): 1-12; 1/31/23 IDS).
Urbanska et al teaches T cells expressing BsAb-28z IR and BsAb-z IR, which are chimeric receptors that each comprise an extracellular domain of an immunoreceptor Folate Receptor alpha (FR alpha) and an intracellular signaling domain of CD28 and/or CD3 zeta, wherein the immunoreceptor functions as a costimulatory molecule and delivers simultaneous T cell receptor CD3 activation and CD28 costimulating signals in a target dependent manner, resulting in activation, proliferation and anti-tumor activity (Figure 1 and right column on page 2, in particular). Urbanska et al further teaches the T cells express the chimeric receptors by transducing the T cells with viral vectors comprising nucleic acids encoding the chimeric receptors (right column on page 4, in particular).
While Urbanska et al does not explicitly state BsAb-28z IR or BsAb-z IR have attenuated binding to a ligand for an endogenous immunoreceptor (including an endogenous immunoreceptor that is not FR alpha), the constructs clearly would not predictably bind ligands for endogenous immunoreceptors that are not bound by FR alpha. Further, Urbanska et al teaches high levels of folic acid, which are known to bind FR alpha immunoreceptor, did not induce T-cell activation of T cells expressing BsAb-28z IR or BsAb-z IR (left column on page 6, in particular). Therefore, absent a showing otherwise, the BsAb-28z IR and BsAb-z IR constructs of Urbanska et al could be described as having attenuated binding to a ligand for an endogenous immunoreceptor.
Regarding instant claim 17, FR alpha of the BsAb-28z IR and BsAb-z constructs are “variants” of human CD137 extracellular domain lacking cysteine-rich domain 3 and cysteine-rich domain 4 of human CD137.
Urbanska et al further teaches previous bispecific antibodies (BsAbs) have been used to kill cancer cells by coupling cytotoxic T cells (though CD3 T-cell receptor) with target cancer cells (left column on page 2, in particular). Urbanska et al further teaches a challenge with BsAbs that couple cytotoxic T cells using the CD3 T-cell receptor is that CD3 is found on T-cells other than cytotoxic T cells (left column on page 2, in particular). Urbanska et al further teaches a challenge with BsAbs that couple cytotoxic T cells using the CD3 T-cell receptor is that sustained stimulation via T-cell receptor CD3 without parallel costimulatory signals, such as those provided by CD28 receptor, results in impaired T-cell activation with induction of anergy or apoptosis (left column on page 2, in particular). Urbanska et al further teaches a combination of (a) T cells expressing BsAb-28z IR and BsAb-z IR; and (b) frBsAb antibody has numerous benefits over conventional BsAbs (Figure 2, in particular). frBsAb is a bispecific construct that binds (i) the extracellular domain of FR alpha of T cells expressing BsAb-28z IR and BsAb-z IR and (ii) a cancer cell antigen (TAA). Urbanska et al teaches benefits of the combination include (i) the ability to redirect preselected T-cells to tumor and (ii) the ability to use parallel costimulatory signaling to overcome impaired T-cell activation with induction of anergy or apoptosis (Figure 2, in particular).
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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.
Claim(s) 1, 3-5, 7-9, 11-15, 17-22, and 24 is/are rejected under 35 U.S.C. 103 as being unpatentable over Urbanska et al (Journal of Translational Medicine, 2014, 12(347): 1-12; 1/31/23 IDS).
Teaching of claims 13-15, 17-22, and 24 by Urbanska et al is discussed above.
Urbanska et al does not specifically demonstrate treating a subject with cancer comprising administering (a) T cells expressing BsAb-28z IR or BsAb-z IR and (b) frBsAb antibody specific for a TAA of Urbanska et al. However, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to therapeutically treat a subject with cancer comprising administering to the subject a therapeutically effective amount of (a) T cells expressing BsAb-28z IR or BsAb-z IR and (b) frBsAb antibody specific for a TAA of the cancer because Urbanska et al teaches, as opposed to conventional BsAbs, a combination of (a) T cells expressing BsAb-28z IR and BsAb-z IR; and (b) frBsAb antibody has numerous benefits (Figure 2, in particular). Urbanska et al teaches benefits of the combination include: (i) the ability to redirect preselected T-cells to tumor and (ii) the ability to use parallel costimulatory signaling to impaired T-cell activation with induction of anergy or apoptosis (Figure 2, in particular). This is an example of some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference 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.
Claim Rejections - 35 USC § 103
Claim(s) 1, 3-6, 8, 9, 11-16, 18-22, and 24 is/are rejected under 35 U.S.C. 103 as being unpatentable over Urbanska et al (Journal of Translational Medicine, 2014, 12(347): 1-12; 1/31/23 IDS) as applied to claims 1, 3-5, 7-9, 11-15, 17-22, and 24 above, and further in view of Chang et al (Nature Protocols, 2020, 15: 1507-1524), and Houot et al (Lymphoid Neoplasia, 2009, 114(16): 3431-3438; 1/31/23 IDS).
Teachings of Urbanska et al are discussed above.
Urbanska et al does not specifically teach a chimeric receptor comprising the extracellular domain of human CD137. However, these deficiencies are made up in the teachings of Chang et al, and Houot et al.
Chang et al teaches extracellular ligand-binding domains of chimeric receptors, such as chimeric antigen receptors, can be swapped for any given ligand of interest with little to no tuning of signaling domains required (see Advantages and limitations on page 1508, in particular).
Houot et al teaches human primary lymphoma tumors are infiltrated with CD137+ T cells and that anti-CD137 agonistic antibodies induce an antitumor effect that is mediated by CD8 T cells and induced long-lasting immunity (Abstract, in particular).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to therapeutically treat a subject with lymphoma by performing a combined method comprising administering to the subject a therapeutically effective amount of (a) T cells that have been transduced with a vector harboring a nucleic acid encoding and expressing BsAb-28z IR or BsAb-z IR and (b) frBsAb antibody wherein (i) the extracellular domain of human CD137 is substituted in place of the FR alpha extracellular domain of the BsAb-28z IR and (ii) an anti-CD137 agonist binding domain is swapped in place of the portion of frBsAb antibody that binds FR alpha because Urbanska et al recognizes the BsAb-28z IR and BsAb-z IR immunoreceptors functions as costimulatory molecules to deliver simultaneous T cell receptor CD3 activation and CD28 costimulating signals in a target dependent manner, resulting in activation, proliferation and anti-tumor activity (Figure 1 and right column on page 2, in particular), Chang et al teaches extracellular ligand-binding domains of chimeric receptors can be swapped for any given ligand of interest with little to no tuning of signaling domains required (see Advantages and limitations on page 1508, in particular), and Houot et al teaches human primary lymphoma tumors are infiltrated with CD137+ T cells and that anti-CD137 agonistic antibodies induce an antitumor effect that is mediated by CD8 T cells and induced long-lasting immunity (Abstract, in particular). By both (i) swapping the CD137 extracellular domain in place of the FR alpha extracellular domain in the BsAb-28z IR and BsAb-z IR and (ii) swapping the anti-CD137 agonist binding domain in place of the portion of frBsAb antibody that binds FR alpha, one would be able to activate both the recombinant T cells and endogenous infiltrated CD137+ T CD8 T cells with the anti-CD137 agonist. This is an example of some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill 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.
Claim Rejections - 35 USC § 103
Claim(s) 1, 3-9, 11-22, and 24 is/are rejected under 35 U.S.C. 103 as being unpatentable over Urbanska et al (Journal of Translational Medicine, 2014, 12(347): 1-12; 1/31/23 IDS) in view of Chang et al (Nature Protocols, 2020, 15: 1507-1524), and Houot et al (Lymphoid Neoplasia, 2009, 114(16): 3431-3438; 1/31/23 IDS), as applied to claims 1, 3-6, 8, 9, 11-16, 18-22, and 24 above, and further in view of Yi et al (PLOS ONE, 2014, 9(1)(e86337): 1-10).
Teachings of Urbanska et al, Chang et al, and Houot et al are discussed above.
Urbanska et al, Chang et al, and Houot et al do not specifically teach a CD137 construct lacking all or part of a cysteine-rich domain 3 (CRDIII) and a cysteine-rich domain 4 (CRDIV) of a human CD137. However, these deficiencies are made up in the teachings of Yi et al.
Figure 2 of Yi et al teaches human CD137 extracellular domain constructs “hE2” and “hE3”, which lack CRDIII and CRDIV, cannot bind to the ligand of human CD137 (hCD137L).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method of Urbanska et al, Chang et al, and Houot et al wherein the extracellular domain of human CD137 of the recombinant T cells consists of hE2 or hE3 and wherein the bispecific antibody of the combined method binds epitopes within hE2 or hE3 in an effort to prevent offsite activation of the recombinant T cells by endogenous hCD137L, just as the construct of Urbanska et al was touted as having the benefit of lacking offsite activation by endogenous ligand of FA alpha. This is an example of some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill 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.
Conclusion
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/SEAN E AEDER/Primary Examiner, Art Unit 1642