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 .
Change in Examiner
The examiner for this application has changed. The new examiner is Alec Peters, AU 1641.
Applicant’s amendment, filed 9/18/2025, is acknowledged.
Claims 1-234, 236, 244-251, are cancelled.
Claims 235, 237-243, and 252 are pending and under examination.
Priority
Applicant’s claim for the benefit of a prior-filed U.S. Provisional Application 62/957,024 filed on January 3, 2020, and U.S. Provisional Application 63/070,596 filed on August 26, 2020, is acknowledged.
The amended claims are in compliance with 35 U.S.C.§ 112(a) with the priority documents, and the priority date of the instant claims are set to January 3, 2020. Support for the claims can be found in Application 62/957,024 on pg. 2, lines 30-31, Tables 1 and 2, and Example 33.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 9/18/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner in its entirety.
Drawings
In view of Applicant’s remarks, filed 9/18/2025, the Drawings submitted on 9/18/2025 are fully described and entered.
Specification
In view of Applicant’s remarks, filed 9/18/2025, the previous objection to the specification has been withdrawn.
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Claim Interpretation
Claim 235 recites a molecule with an antigen binding domain that specifically binds to TCRßV region with specific CDR sequences. The instant specification discloses (Table 13):
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The instant specification discloses that the anti-TCRßV2 (or 20-1) binding antibody clone MPB2D5 is a murine antibody and contains the CDR sequences in claim 235, as well as the VH of SEQ ID NO: 1112 and VL of SEQ ID NO: 1111.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim 235 and 237-241 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Schmetterer et al. (J Allergy Clin Immunol. 2011 Jan;127(1):238-45, 245.e1-3. doi: 10.1016/j.jaci.2010.10.023).
Schmetterer teaches the mouse antibody clone MBP2D5, binding to TCRßV2 (i.e., “TCRßV20-1”; Table E2):
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The CDR and VH/VL sequences of the MBP2D5 antibody clone are considered an inherent property of this antibody clone. Therefore, Schmetterer teaches the anti-TCRßV2 clone having the HCDR1-3 and LCDR1-3 of SEQ ID NO: 1102-1104 and 1107-1109, respectively; and the VH and VL of SEQ ID NO: 1112 and 1111, respectively.
Although the reference does not teach the sequences for the CDRs from the MBP2D5 monoclonal antibody, these are intrinsic properties of the MBP2D5 antibody. Also, it is an inherent property of the murine MBP2D5 immunoglobulin light and heavy chains to bind to the same antigen as the original antibody. Therefore, the light and heavy chain CDRs, and the murine VH and VL chains, that are instantly claimed are unpatentable over the prior art as the sequences are intrinsic properties of the antibody.
The Courts have held that there is no requirement that those of ordinary skill in the art know of the inherent property. See MPEP 2131.01(d) and MPEP 2112 - 2113.
The issues presented herein are akin to the holding in In re Crish, 73 USPQ2d 1364 (CAFC 2004) where the Federal Circuit held that the claimed promoter sequence obtained by sequencing a prior art plasmid that was not previously sequenced was anticipated by the prior art plasmid which necessarily possessed the same DNA sequence as the claimed oligonucleotides. The court stated that “just as the discovery of properties of a known material does not make it novel, the identification and characterization of a prior art material also does not make it novel.”
Like the references in Crish, the prior art of Schmetterer et al. reference discloses a material containing the same sequence recited in the claims. It is undisputed that Schmetterer et al. discloses an antibody that contains the amino acids recited in Applicant’s claims. That disclosure is anticipatory, even if it was not until the present application that Applicants characterized Mab MBP2D5 by its amino acid sequences.
Therefore, Schmetter et al. anticipates the limitations of instant claims 235 and 237-241.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
Claims 235 and 237-243 are rejected under 35 U.S.C. 103 as being unpatentable over Schmetterer et al. (J Allergy Clin Immunol. 2011 Jan;127(1):238-45, 245.e1-3. doi: 10.1016/j.jaci.2010.10.023, supra) in view of Rader (Curr Protoc Protein Sci. 2009 Feb;Chapter 6:Unit 6.9).
The teachings of Schmetterer et al. have been discussed in the 35 U.S.C. § 102 rejection supra. Schmetterer et al. does not teach a Fab version of the MBP2D5 antibody (i.e., the limitations of instant claims 242 and 243).
Rader, in the same field of endeavor, teaches that a Fab version of an antibody has advantages over a full-length antibody with an Fc region (Introduction): “[i]t was found that Fab are superior to IgG for certain in vivo applications due to their higher mobility and tissue penetration capability, their reduced circulatory halflife, their ability to bind antigen monovalently without mediating antibody effector functions, and their lower immunogenicity.” Rader et al. teaches multiple different methods of generating Fabs, including enzymatic digestion and expression in bacteria (Introduction): “…papain is still used to generate Fab for basic research and clinical applications. However, the ability to express Fab in Escherichia coli (Better et al., 1988) and their suitability for phage display (Huse et al., 1989) has facilitated the utilization of Fab in the generation and directed evolution of monoclonal antibodies (mAbs)…”
It would have been obvious to one with ordinary skill in the art, before the effective filing date of the instant application, to have modified the antibody of Schmetterer et al. in view of Rader to generate Fab versions of the MBP2D5 antibody (i.e., the limitations of instant claims 242 and 243) with a reasonable expectation of success, as Rader teaches methods of doing so such as enzymatic digestion of the antibody with papain. One would have been motivated to make this change to take advantage of the benefits a Fab version of MBP2D5 may offer, such as greater tissue penetration.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Claims 235, 237-241, and 252 are rejected under 35 U.S.C. 103 as being unpatentable over Schmetterer et al. (supra) in view of Tutt et al. (J Immunol. 1995 Sep 15;155(6):2960-71. PMID: 7673714, Abstract Only).
The teachings of Schmetterer et al. have been discussed in the 35 U.S.C. § 102 rejection supra. Schmetterer et al. does not teach methods of expanding T-cells comprising administration of the antibody (i.e., the limitations of instant claim 252).
Tutt et al., in the same field of endeavor, teaches a method of expanding T-cells comprising contacting the cells with an anti-CD2/anti-TCR bispeicifc antibody, which can be used to expand cells in vivo (Abstract): “…a bispecific F(ab')2 Ab (BsAb), which cross-links the TCR to CD2 ([anti-CD2 x anti-TCR])and is highly mitogenic in vitro, also induces marked T cell activation and proliferation when given as a small single dose (50 to 100 micrograms) to rats…[t]his resulted in a three- to fourfold increase in spleen weight, with histologic evidence of T-zone and red pulp expansion byCD8+ blast cells…a future two-stage targeting strategy for cancer immunotherapy in which a mitogenic BsAb would be given to patients to activate CTL nonspecifically, and then, at an appropriate time, a second BsAb [anti-TCR x antitumor] would be given to deliver activated cells to the tumor target cells.”
It would have been obvious to one with ordinary skill in the art, before the effective filing date of the instant application, to have modified the teachings of Schmetterer et al. to use the MBP2D5 anti-TCRßV antibody in the methods of expanding T-cells in vivo taught by Tutt et al. with a reasonable expectation of success, as Schmetter et al. teaches that MBP2D5 is a working anti-TCR antibody that could be incorporated into the bispecific antibody taught by Tutt et al. One would have been motivated to make this change to try a different anti-TCR antibody in the method of expanding T-cells, for example to determine if there is a greater expansion of T-cells with this setup.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
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.
The amendments to the reference applications and the instant application have obviated the previous non-statutory double patenting rejections for Copending Applications 17/402,322, 17/759,679, and 18/173,995. These applications and the instant application claim different antibody structures. Furthermore, Application 18/173,995 has been abandoned.
Claims 235 and 237-243 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 143-179 of copending Application No. 19/175,269 (App ‘269) in view of Schmetterer et al. (J Allergy Clin Immunol. 2011 Jan;127(1):238-45, 245.e1-3. doi: 10.1016/j.jaci.2010.10.023, supra). Although the claims at issue are not identical, they are not patentably distinct from each other.
App ‘269 claims molecule comprising anti-TCRßV binding moieties, including antibodies and Fabs (claims 143 and 146).
App ‘269 does not claim anti-TCRßV binding molecules comprising the CDRs recited in instant claim 235, or with the VH/VL sequences recited in instant claim 237-241.
Schmetterer teaches the mouse antibody clone MBP2D5, binding to TCRßV2 (i.e., “TCRßV20-1”; Table E2):
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The CDR and VH/VL sequences of the MBP2D5 antibody clone are considered an inherent property of this antibody clone. Therefore, Schmetterer teaches the anti-TCRßV2 clone having the HCDR1-3 and LCDR1-3 of SEQ ID NO: 1102-1104 and 1107-1109, respectively; and the VH and VL of SEQ ID NO: 1112 and 1111, respectively.
It would have been obvious to one with ordinary skill in the art to have modified the invention claimed by App ‘143 in view of Schmetterer et al. to make an anti-TCRßV antibody with the VH/VL of MBP2D5 with a reasonable expectation of success, as Schmetterer et al. teaches this specific embodiment of the anti-TCRßV binding molecules of App ‘143 that one with ordinary skill in the art would appreciate could act as a TCRßV binding molecule of App ‘143. One would have been motivated to make this change for the purposes of developing a functional anti-TCRßV molecule.
The combined reference of App ‘143 in view of Schmetterer et al. teach an anti-TCRßV antibody comprising the CDRs of HCDR1-3 and LCDR1-3 of SEQ ID NO: 1102-1104 and 1107-1109, respectively; and the VH and VL of SEQ ID NO: 1112 and 1111, meeting the limitations of instant claims 235 and 237-241.
Regarding instant claims 242 and 243, App ’143 claims anti-TCRßV binding agents comprising Fabs (claim 146), meeting the claim limitations.
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by App ‘143 in view of Schmetterer et al. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 252 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 143-179 of copending Application No. 19/175,269 (App ‘269) in view of Schmetterer et al. (supra), as applied to claims 235 and 237-243 above, and further in view of Tutt et al. (J Immunol. 1995 Sep 15;155(6):2960-71. PMID: 7673714, Abstract Only, supra).
The teachings of App ‘143 in view of Schmetterer et al. have been discussed supra. The combined references do not teach methods of expanding T-cells comprising administration of the antibody (i.e., the limitations of instant claim 252).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by App ‘143 in view of Schmetterer et al., and further in view of Tutt et al. for the same reasons discussed in the 35 U.S.C. § 103 rejection supra.
Claims 235, 237-243, and 252 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 139-158 of copending Application No. 18/654,860 (App ‘860) in view of Schmetterer et al. (supra). Although the claims at issue are not identical, they are not patentably distinct from each other.
App ‘860 claims methods of expanding immune cells comprising contacting the cells with a molecule comprising an anti-TCRßV binding moiety (claim 139), including in vitro (claim 141), wherein the cells are T-cells (claim 140) and TCRßV expressing T-cells (claim 146).
App ‘860 does not claim anti-TCRßV binding molecules comprising the CDRs recited in instant claim 235, or with the VH/VL sequences recited in instant claim 237-241.
Schmetterer et al. teaches the mouse antibody clone MBP2D5, binding to TCRßV2 (i.e., “TCRßV20-1”; Table E2, see supra). The CDR and VH/VL sequences of the MBP2D5 antibody clone are considered an inherent property of this antibody clone. Therefore, Schmetterer teaches the anti-TCRßV2 clone having the HCDR1-3 and LCDR1-3 of SEQ ID NO: 1102-1104 and 1107-1109, respectively; and the VH and VL of SEQ ID NO: 1112 and 1111, respectively.
It would have been obvious to one with ordinary skill in the art to have modified the invention claimed by App ‘860 in view of Schmetterer et al. to make and use a method of expanding TCRßV T-cells with the MBP2D5 antibody with a reasonable expectation of success, as Schmetterer et al. teaches this specific embodiment of the anti-TCRßV binding molecule that can be used in the methods claimed by App ‘860. One would have been motivated to make this change for the purposes of developing a methods of expanding TCRßV expressing T-cells with MBP2D5.
The combined reference of App ‘860 in view of Schmetterer et al. teach an anti-TCRßV antibody comprising the CDRs of HCDR1-3 and LCDR1-3 of SEQ ID NO: 1102-1104 and 1107-1109, respectively; and the VH and VL of SEQ ID NO: 1112 and 1111, meeting the limitations of instant claims 235 and 237-241. The combined references additionally teach a method of expanding TCRßV T-cells with MBP2D5, meeting the limitations of instant claim 252.
Regarding instant claims 242 and 243, App ’860 claims anti-TCRßV binding agents comprising Fabs (claim 151), meeting the claim limitations.
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by App ‘860 in view of Schmetterer et al. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALEC JON PETERS whose telephone number is (703)756-5794. The examiner can normally be reached Monday-Friday 8:30am - 6:00pm EST.
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/ALEC JON PETERS/Examiner, Art Unit 1641
/MISOOK YU/Supervisory Patent Examiner, Art Unit 1641
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