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 .
DETAILED ACTION
Response to Amendment and Arguments
The Amendment filed on 10/18/2025 in response to the previous Non-Final Office Action (8/1/2025) is acknowledged and has been entered.
Claims 1-34, 36 and 38 have been cancelled.
Claims 35, 37, and 39-55 are pending.
Claims 45-55 have been withdrawn from consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention/species.
Claims 35, 37, and 39-44, drawn to a chimeric antigen receptor (CAR) binding to human CD45RC comprising antibody to CD45RC comprising VH-CDR1-3 (elected SEQ ID NOs: 1, 4 and 3) and VL-CDR1-3 (elected 15, 16 and 17), a transmembrane domain, intracellular signaling domain, are under consideration.
Rejections/Objection Withdrawn
The objection of claims 35, 37, 39, and 41-44 because of improper Markush language is withdrawn in view of the claim amendment.
The rejection of Claim(s) 35 and 43 under 35 U.S.C. 102(a)(1) as being anticipated by or, in the alternative, under 35 U.S.C. 103 as being unpatentable over Brogdon et al (US2018/0334490, published on Nov 22, 2018) is withdrawn in view of the claim amendment.
The arguments are moot in view of withdrawals of the rejection(s).
Rejection Maintained and Response to Arguments:
Improper Markush Grouping
Claims 35 and 39-41 remain and are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 706.03(y).
The Markush groupings of the claims are improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons:
each of the antibodies has unique CDRs and VH/VL sequences which is not shared by the other antibodies listed in the claims. The elected antibody comprising VH-CDR1-3 of SEQ ID Nos: 1, 4, 3 paired to a VL-CDR1-3 of SEQ ID Nos: 15 (X12=N, S, G or absent), 16, and 17 and HCVR (VH) and LCVR (VL) of SEQ ID NOs: 61 and 81 do not share and have common structure in sequences and binding function with the other antibody in the list.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Response to applicant argument:
At page 13-15, applicant cites In re Narva and argues:
….the members of the Markush group belong to the same recognized chemical class. Not only are the claimed sequences all relatively short polypeptides, which are clearly all within the same chemical class, they also all are polypeptides that comprise heavy and light chain variable region's CDRs. Thus, they are polypeptide sequences that form the same portion of the same type of protein, namely an antibody. And they all are from antibodies that bind the same antigen. This alone should be sufficient to satisfy to the requirement for structural similarity under the relevant test as set forth in In re Narva.
Applicant also piles up the sequences of VH-CDR2 and VL-CDR1 (page 15) , then concludes that the sequences listed have structure and similarity that render the Markush grouping proper.
In response, the Office agrees on that all listed sequences belong to the same chemical class, they are relative short peptide as CDRs comprised within the heavy and light chain variable regions and they have the amino acids and sequence similarities. However, applicant should realize we are dealing with biological molecules antibodies that belong to one class of chemicals, but they are big molecules playing important role in live cells. Any small variations in the structure could result in huge functional differences in vivo and life. One skilled in the art would understand that the CDRs comprised in the VH and VL of an antibody are the most important binding regions for its antigen recognition. One skilled in the art would also know that even one amino acid substitution within one or more CDRs could change the antibody binding activities and affinity to its antigen, and even change the antigen recognition.
Therefore, one skilled in the art would agree that an antibody with the amino acid alternations in CDR region(s) from the parent antibody could consider as a new antibody because the characteristic of antigen binding and affinity has been altered. For this reason, the rejection is maintained currently. Applicant could pick up one sequence VH-CDR2 for VH and one VL-CDR1 for VL as a pair to form an antibody, but not Mixed and Matched CDRs. Applicant is also encouraged to discuss with the Examiner for clarification.
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 obviousness-type 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); and 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 a nonstatutory double patenting ground provided the conflicting application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement.
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 (MPEP 9th Ed, Feb 2023).
An obviousness-type double patenting rejection is appropriate where the conflicting claims are not identical, but an examined application claim not is patentably distinct from the reference claim(s) because the examined 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).
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.
Over Patent:
Claims 35, 37 and 39-44 remain and are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 12,168,694 (original application No 17/277511) in view of Brogdon et al (US2018/0334490, published on Nov 22, 2018) as sequence alignment in SCV.
The instant claims are drawn to
chimeric antigen receptor (CAR) specific for human CD45RC, wherein said CAR comprises:
(a) at least one extracellular binding domain, wherein said binding domain binds to said human CD45RC,
(b) optionally at least one extracellular hinge domain,
(c) at least one transmembrane domain, and(d) at least one intracellular signaling domain, wherein the intracellular domain comprises at least one T cell primary signaling domain and optionally at least one T cell costimulatory signaling domain.
the CAR according to claim 35, wherein the extracellular binding domain comprises at least one antigen-binding fragment that binds to human CD45RC comprising:
(a) a HCVR which comprises the following three CDRs:
(i) VH-CDR1 of sequence SEQ ID NO: 1;
(ii) VH-CDR2 with a sequence selected from the group comprising sequences SEQ ID NOs: 4 ,5, 6, 7, 8, 9, 10, 11, 100, 116, 117, 118 and 119; and
(iii) VH-CDR3 of sequence SEQ ID NO: 3; and
(b) a LCVR which comprises the following three CDRs:
(i) VL-CDR1 with a sequence selected from the group comprising sequences SEQ ID NO: 15 (SASSSVS-X12-YMH) and SEQ ID NO: 18 (RASSSVS-X12-YMH), wherein X12 is absent or is selected from Asn (N), Ser (S) and Gly (G);
(ii) VL-CDR2 with a sequence selected from the group comprising sequences SEQ ID NOs:16,19, 20,22, 111, and 120 and 127; and
(iii) VL-CDR3 with a sequence selected from the group comprising sequences SEQ ID NOs: 17 and 21. (see all examined claims).
The claims of ‘694 patent are drawn to
An isolated anti-human CD45RC antibody or binding fragment thereof, wherein said antibody or binding fragment thereof comprises:
(a) a heavy chain variable region (HCVR) which comprises the following three complementary-determining regions (CDRs):
(i) V.sub.H-CDR1 of sequence SEQ ID NO: 1;
(ii) V.sub.H-CDR2 with a sequence selected from the group consisting of sequences SEQ ID NOs: 4, 5, 6, 7, 8, 9, 10, 11, 100, 116, 117, 118 and 119; and
(iii) V.sub.H-CDR3 of sequence SEQ ID NO: 3; and
(b) a light chain variable region (LCVR) which comprises the following three CDRs:
(i) V.sub.L-CDR1 with a sequence selected from the group consisting of sequences SEQ ID NO: 15 (SASSSVS-X-YMH) and SEQ ID NO: 18 (RASSSVS-X-YMH), wherein X is absent or is selected from the group consisting of Asn (N), Ser(S) and Gly (G);
(ii) V.sub.L-CDR2 with a sequence selected from the group consisting of sequences SEQ ID NOs: 16, 19, 20, 22, 111, 120 and 127; and
(iii) V.sub.L-CDR3 with a sequence selected from the group consisting of sequences SEQ ID NOs: 17 and 21 (see all claims).
Both sets of the claims encompass the same antibodies with the same CDRs and VH/VL domains, which are all assigned to the same sequence identifiers (SEQ ID NOs, see SLIC, Sequence Listing Access).
The claims of the ‘694 patent do not recite CARs as the instant claims.
Brogdon et al teach chimeric antigen receptor (CAR) and general method of making a CAR comprising extracellular domain such as scFv binding and recognizing an antigen on surface of cells, transmembrane, stimulating, and intracellular signaling domains as set forth in the 103 rejection above.
It would have been obvious to one having ordinary skill in the art before the time the invention was made to form a CAR with the antibodies claimed in ‘694 patent and the domains taught in the publication of the Brogdon et al. One of ordinary skill would have been motivated with reasonably expect success to do based on the teaching of Brogdon et al, one of ordinary skill would arrive at the current invention without unexpected result.
Over application:
Claims 35, 7 and 39-44 remain and are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-12 of copending Application No. 18/934376 in view of Brogdon et al (US2018/0334490, published on Nov 22, 2018) as sequence alignment in SCV.
The instant claims are set forth above.
The claims of ‘376 application are drawn to
An isolated anti-human CD45RC antibody or binding fragment thereof, wherein said antibody or binding fragment thereof comprises:
(a) a heavy chain variable region (HCVR) which comprises the following three complementary-determining regions (CDRs):
(i) V.sub.H-CDR1 of sequence SEQ ID NO: 1;
(ii) V.sub.H-CDR2 with a sequence selected from the group consisting of sequences SEQ ID NOs: 4, 5, 6, 7, 8, 9, 10, 11, 100, 116, 117, 118 and 119; and
(iii) V.sub.H-CDR3 of sequence SEQ ID NO: 3; and
(b) a light chain variable region (LCVR) which comprises the following three CDRs:
(i) V.sub.L-CDR1 with a sequence selected from the group consisting of sequences SEQ ID NO: 15 (SASSSVS-X-YMH) and SEQ ID NO: 18 (RASSSVS-X-YMH), wherein X is absent or is selected from the group consisting of Asn (N), Ser(S) and Gly (G);
(ii) V.sub.L-CDR2 with a sequence selected from the group consisting of sequences SEQ ID NOs: 16, 19, 20, 22, 111, 120 and 127; and
(iii) V.sub.L-CDR3 with a sequence selected from the group consisting of sequences SEQ ID NOs: 17 and 21 (see all claims)… (see more in claims),
A nucleic acid encoding the isolated antibody or antigen binding fragment thereof according to claim 1.
Both sets of the claims encompass the same antibodies with the same CDRs and VH/VL domains, which are all assigned to the same sequence identifiers (SEQ ID NOs, see SLIC, Sequence Listing Access).
The ‘376 application is a continuation of the US Patent 12168,694 above.
The claims of the ‘376 application do not recite CARs as the instant claims.
Brogdon et al teach chimeric antigen receptor (CAR) and general method of making a CAR comprising extracellular domain such as scFv binding and recognizing an antigen on surface of cells, transmembrane, stimulating, and intracellular signaling domains as set forth in the 103 rejection above.
It would have been obvious to one having ordinary skill in the art before the time the invention was made to form a CAR with the antibodies claimed in ‘376 application and the domains taught in the publication of the Brogdon et al. One of ordinary skill would have been motivated with reasonably expect success to do based on the teaching of Brogdon et al, one of ordinary skill would arrive at the current invention without unexpected result.
This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
Response to applicant’s argument:
At page, 18, applicant argues:
….the present application is directed to a chimeric antigen receptor (CAR) specific for human CD45RC, while granted patent US 12,168,694 and co-pending application US 18/934,376 are directed to isolated anti-human CD45RC antibodies or binding fragments thereof…
The present application disclose CD45RC-CAR is functional since it induced a T-cell activation (as shown by CD69
expression) compared to Ctrl-CAR and untransduced Jurkat cells, " CD4+ Tregs could be transduced and that CD45RC-CAR CD4+ Tregs could be expanded, " in CD4+ Tregs transduced by CD45RC-CAR, but not by Ctrl-CAR, increased protein expression of CD69, CD25, CD71 and CTLA-4 upon incubation with CD45R-ABC protein for 24h, demonstrating that the CAR is signaling and directly activating the Tregs…
In response, the Office agrees on that antibody to CD45RC claimed in ‘694 patent and in copending application ‘376 and presently claimed Chimeric Antigen Receptor (CAR) are different molecule and having different functions. However, applicant should understand and agree the following:
First that the claimed CAR in this application comprises the identical anti-CD45RC antibody claimed in ‘694 patent and copending application ‘376. CD45RC antigen expressed in any of the cells would be bound by the antibody from ‘694 patent/copending application ‘376 as well as the CAR claimed in this application.
Second, one skilled in the art would understand the key component for the structure and function of the CAR is the antibody in the CAR, while making a CAR with a known antibody linked to few well-known domains have been practiced for decades, as disclosed in the reference by Brogdon et al set forth in the rejection.
Third, this rejection is 103 type of NSDP rejection with a cited reference by Brogdon et al, which provides detailed method comprising steps and material to make a CAR. Thus, one skilled in the art including the present investors would be motivated with reasonable expectation of success to use method and domain molecules required in CAR disclosed by Brogdon and anti-CD45RC antibody of the patent ‘694 and copending application ‘376 to arrive at current invention without unexpected result. For the reasons the rejection is maintained currently.
Conclusion
No claim is allowed.
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 Lei Yao, whose telephone number is (571) 272-3112. The examiner can normally be reached on 8:00am-6:00pm Monday-Friday.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis, can be reached on (571) 270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/LEI YAO/Primary Examiner, Art Unit 1642