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 .
Status of Application/Amendments/Claims
Applicant’s response filed on 8/15/2025 has been considered. Claims 52 and 59 have been amended. Claim 60 has been newly added. Claims 1-5, 13-17, 33-35, 46-52 and 59-60 are pending. Claims 1-5, 13-17, 33-35 and 46-51 are currently withdrawn without traverse from further consideration pursuant to 37 CFR 1.142 (b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claims 52, 59 and 60 are the subject of the present Official action. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Priority
Applicant’s claim for the benefit of a prior-filed application EP17168805.4, PCT/EP2018/060887 and CON of 16/607,069 filed on 4/28/2017, 4/27/2018 and 10/21/2019, respectively, under 35 U.S.C 119(e) or under 35 U.S.C 120, 121 or 365(c) is acknowledged.
Accordingly, the effective priority date of the instant application is granted as 4/28/2017.
Withdrawn Objections
The objection of claim 52 is withdrawn in light of applicants claim amendments which remove references to withdrawn claims 46, 34 and 1.
The objection of claim 58 is withdrawn in light of applicants claim amendments which fully recite the acronym ROR1.
The objection of claim 58 is withdrawn in light of applicants claim amendments which correct a reference to “ROR1-possitive” leukemia.
Withdrawn Rejections
The 35 U.S.C. 112(b) rejection of claims 52 and 58-59 has been withdrawn in light of applicants claim amendments which specify that the method is for treating a patient that has a ROR1 positive cancer.
The 35 U.S.C. 112(b) rejection of claim 59 has been withdrawn in light of applicants claim amendments which specify that the cancer being treated is a ROR1 positive leukemia, mantel cell lymphoma, breast-cancer or lung cancer.
The 35 U.S.C. 102(a)(1) and 102(a)(2) rejection of claims 52, 58 and 59 has been withdrawn in light of applicants claim amendments which specify specific combinations of heavy chain and light chain variable domains by SEQ ID Nos.
Claim Rejections - 35 USC § 112d
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 60 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. This rejection is newly applied to address applicants claim amendments on 8/15/2025.
Claim 60 describes the method of claim 52 wherein the antibody binding domain comprises a heavy chain variable domain that is at least 90% identical to SEQ ID NO: 1 and a light variable domain that is at least identical to SEQ ID NO: 2. A similar description is recited for SEQ ID Nos 3-6. The variable domain is comprised of three CDR regions which are described in claim 52 (CDRs 1-3) in addition to the framework (FR) regions. Although “at least 90%” is inclusive of 100%, claim 60 recites that the variable domain is at least 90% identical to SEQ ID NO: 1, indicating that the heavy chain CDRs 1-3 may be 90% identical to the listed SEQ ID Nos if the FRs are identical to those of claim 58. Thus, claim 60 incorrectly expands the limitations set forth in claim 52, since the sequence limitations have moved from 100% sequence identity to <90% sequence identity for SEQ ID Nos 1, 3 and 5. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Interpretation
Given the 112d issue described above, it is assumed that if the prior art teaches a heavy chain variable domain and light chain variable domain sequence which is 100% identical to SEQ ID NO: 1 and 2, then both the limitations of claims 52 and 60 are meet since CDRs 1-3 make up (in part) the variable domain.
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 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.
Claims 52, 59 and 60 are rejected under 35 U.S.C. 103 as being unpatentable over Rader et al. US 2018/0340026, published 11/29/2018, priority date 1/20/2016 (hereinafter Rader, reference of record) in view of Hudecek et al. "Receptor affinity and extracellular domain modifications affect tumor recognition by ROR1-specific chimeric antigen receptor T cells." Clinical cancer research 19.12 (2013): 3153-3164 (hereinafter Hudecek, reference of record). This rejection is newly applied to address applicants claim amendments on 8/15/2025.
Claims 52 and 60: Rader describes recombinant T cell that expresses a chimeric antigen receptor (CAR) comprising a humanized monoclonal antibody (mAb) binding domain specific for receptor tyrosine kinase-like orphan receptor 1 (ROR1) and therapeutic applications thereof (Rader, abstract, para 8, 60 and Fig 26). Rader describes engineering ROR1 targeting mAbs from R11, R12 and 2A2 (Rader, para 60 and 63). Rader describes administering the recombinant T cells to a patient in need thereof (Rader, para 82, 125). Rader provides motivation for experimenting with different heavy and light chain CDRs in order to engineer desired mAb specificity (Rader, para 7, 72, 73, 82 and claims 1-4). Rader discloses SEQ ID NO: 152 which has a 100% sequence match to the heavy chain CDRs 1-3 of the heavy chain amino acid sequence of instant SEQ ID NO: 1 (sequence search results below).
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Sequence search results for SEQ ID NO: 1
Similarly, Rader also discloses SEQ ID NO: 153 which has a 100% sequence match to the light chain CDRs 1-3 of the light chain amino acid sequence of instant SEQ ID NO: 2 (sequence search results below).
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Sequence search results for SEQ ID NO: 2
Claim 59: Rader describes treating patients with ROR-1 positive cancers (Rader, para 57, 81, examples 12, 19, 125 and table 13). Rader provides specific embodiments towards treating ROR1-possitive breast cancer (Rader, para 60, 81, 125 and examples 12, 19).
Although Rader discloses the claimed heavy and light chain CDR sequences, Rader does not describe the specific combination of heavy and light chain CDRs 1-3 of SEQ ID Nos 1 and 2 together in a single humanized antibody binding domain as required by claim 52. However, Rader provides motivation for experimenting with different heavy and light chain CDRs in order to engineer desired mAb affinity (Rader, para 73, 82 and claims 1-4). Rader outlines the specific methodological steps in para 60 which are taken from Hudecek et al. which is described herein.
Claims 52 and 60: Hudecek investigates the therapeutic utility of ROR1-targeting mABs as an adoptive cellular therapy (Hudecek, abstract). Hudecek describes constructing ROR1-CARs from scFVs with different affinities and evaluates their antitumor reactivity (Hudecek, pg 3157 col 1 and Fig 2). Hudecek describes predictable methodological steps for generating the various T cells modified with ROR1-CARs (Hudecek, Methods – Vector construction and generation of T cel lines).
Thus, it would have been prima facie obvious to one of ordinary skill in the art to generate a humanized antibody biding domain comprising the heavy chain amino acid sequence of SEQ ID NO: 1 and the light chain amino acid sequence of SEQ ID NO: 2 in the ROR1-specific CAR T cell described by Rader. It would have been a matter of combining prior art elements according to known methods to yield predictable results since Rader discloses the heavy and light chain CDRs encoded by SEQ ID Nos 1 and 2. One would have been motivated to select this specific combination of heavy and light chain CDRs in order to optimize for antibody binding domain affinity against ROR-1 positive cancers. One would have a reasonable expectation of success since both Rader and Hudecek present methods for predictably generating T cells with different CDRs and experimental protocols for evaluating their antitumor reactivity (Hudecek, pg 3157 col 1 and Fig 2). Accordingly, in the absence of evidence to the contrary, one of ordinary skill in the art would have considered the claimed invention to have been prima facie obvious to at the time the invention was made.
Nonstatutory 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 Langi, 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 706.02(1)(1) - 706.02(1)(3) 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 52, 59 and 60 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of US Patent No. 11,149,073. Although the claims at issue are not identical, they are not patentably distinct from each other because the patented claims would anticipate the instant claims if they were available as prior art. This rejection is newly applied to address applicants claim amendments on 8/15/2025.
Claims 52 and 60: The patented claims describe a ROR1-specific CAR comprising a humanized targeting domain comprising an antibody heavy chain variable domain consisting of the amino acid sequence of SEQ ID NO: 1 and an antibody light chain variable domain consisting of the amino acid sequence of SEQ ID NO: 2 which are 100% identical to SEQ ID NO: 1 and 2 from the instant claims (Claims 1, 3). The patented claims also describe a method for treating a subject having a ROR-1 positive cancer comprising administering the recombinant mammalian cell to a patient (claim 14).
Claim 59: The patented claims also describe a method for treating a subject having a ROR-1 positive cancer comprising administering the recombinant mammalian cell to a patient (claim 14). The specification of the patented claims further describes treating patients with ROR-1 positive leukemia, breast and lung cancer (Claim 14 and spec col 8).
Thus, the claim sets are patentable indistinct.
Conclusion
No claims allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALEXANDER NICOL whose telephone number is (571)272-6383. The examiner can normally be reached on M-F 8-5 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maria Leavitt can be reached on (571)272-1085. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Alexander Nicol
Patent Examiner
Art Unit 1634
/ALEXANDER W NICOL/Examiner, Art Unit 1634