DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s election without traverse SEQ ID NO: 186 as the species of motif, SEQ ID NO: 7048 as the species of MMP-2 protease cleavage site, and SEQ ID NO: 8007 as the species of extended recombinant polypeptide, in the reply filed on 6/5/26 is acknowledged. Claims 155-158 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
Claims 153-154 and 159-165 are being acted upon.
In view of Applicant’s claim amendments and terminal disclaimer filed 1/22/26, the previous grounds of rejection are withdrawn.
The following are new grounds of rejection necessitated by Applicant’s claim amendments.
Claim 164 is objected to for the following informalities: The claim recites that the polypeptide is at least “90% identical an amino acid sequence”. The claim should be amendment to recited at least 90% identical “to” an amino acid sequence.
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 153-154 and 159-165 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 153 is indefinite, since the scope of the limitation that an extended recombinant polypeptide is connected to each of the N-terminus and the C-terminus of the BsAb is unclear. There is a lack of antecedent basis for the terms “the N-terminus and the C-terminus of the BsAB”. Although a protein inherently has an N-terminus and a C-terminus, in the context of bispecific antibodies the limitation is unclear. For example, bispecific antibody constructs can be created as a single polypeptide chain having one N-terminus and one C-terminus. Alternately bispecific antibody constructs can be constructed such that they have two chains linked via disulfide bonds, wherein the bispecific antibody construct would have two N-termini and 2 C-termini (See Brinkmann, Fig. 2 in particular). Would the claims encompass such as construct, and if so, would the claim require an extended recombinant polypeptide connected to both N-termini and both C-termini, or would linking an extended recombinant polypeptide to one of the N-termini and one of the C-termini of the overall bsAb construct satisfy the limitations of the present claims? The specification does not provide any guidance to determine the scope since all of the examples and guidance in the instant specification involve a single fusion polypeptide having one N-terminus and one C-terminus.
Claim 153 is also indefinite in the recitation of CDR-H1-H3 and CDR-L1-L3 of SEQ ID NO: 783 and 883, respectively. There are numerous different methodologies for determining CDRs residues resulting in distinct CDR sequences with different lengths. The specification does not provide any guidance for what numbering schemes or methodologies are to be used when determining CDRs from SEQ ID NO: 783 and 883. The specification provides exemplary CDRs in Table 6, but does not provide a limiting definition for what specific residues would constitute the CDRs. Therefore, the scope of the claims is unclear and indefinite. Amendment to recite the particular CDR residues illustrated in Table 6, i.e. a VH-CDR1 comprising residues 26-33 of SEQ 783, for example, would be remedial.
Claim 163 is unclear and indefinite. The claims depends from claim 153, which recites that the polypeptide comprises an extended recombinant polypeptide connected to each of the N-terminus and the C-terminus through a protease cleavage site, wherein each extended recombinant polypeptide comprise a sequence motif selected from the group consisting of SEQ ID NO: 179-200 and 1715-1722. However, dependent claim 163 recites that each proteas cleavage site independently comprises an amino acid sequence selected form the group consisting of SEQ ID NO: 7001-7626. This overlaps with the sequence motifs in the extended recombinant polypeptide. For example, one could select SEQ ID NO: 1715 as the sequence motif in the extended polypeptide. Would this also satisfy the limitation of the protease cleave site (in which case, not every embodiment in the dependent claim would further limit claim 153). Or would the claim require a second occurrence of SEQ ID NO: 1715. The scope of the claim is unclear and indefinite.
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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 153-154 and 159-165 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
The specification and the claims as originally filed do not provide support for the invention as now claimed, specifically:
An extended recombinant polypeptide that comprises a sequence motif selected from the group consisting of SEQ ID NO: 179-200 and 1715-1722 (Claim 153 and dependent claims).
Applicant indicates that support for the new limitations can be found in paragraphs 115, 203, and Tables 1, 6b and 6f.
A review of the specification fails to reveal support for the new limitations.
In paragraph 115-116, the specification discloses extended recombinant polypeptides that are 100-1000 amino acids in length, wherein the extended recombinant polypeptides comprise a plurality of non-overlapping sequence motifs, wherein the non-overlapping sequence motifs comprise SEQ ID NO: 179-200 and 1715-1722 (Table1). Paragraph 203 discusses protease cleavage sequences. Tables 6b and 6f disclose HER2 and CD3 antibody sequences. The claims are broader than what is disclosed in the specification. For example, the claims would encompass extended recombinant polypeptides with a single motif of SEQ ID NO: 179. The specification, in contrast, only discloses extended polypeptides comprising a plurality of non-overlapping sequence motifs comprising the claimed SEQ ID Nos. Therefore, the specification does not provide support for an extended recombinant polypeptide comprise “a sequence motif selected from the group consisting of SEQ ID NO: 179-200 and 1715-1722” as now claimed.
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.
Claims 153-154, 159-163 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 17-18, 22, 24, 117, 123-125, 128-132 of copending Application No. 17/621,993, in view of WO2011/123813 (of record) and WO2019126576 (of record).
The ‘993 application claims a polypeptide comprising an anti-CD3 binding fragment having a VH and VL with CDRs of SEQ ID NO: 8-10 and 1, 4, and 6, which are identical to SEQ ID NO: 8-10 and 1,4,5 of the instant claims. The ‘993 application claims that the VH and Vl comprises SEQ ID NO: 27-28, which are identical to SEQ ID NO: 101 and 102 of the instant claims. The ‘993 application claims that the polypeptide can be used as a pharmaceutical composition to treat cancer.
The ‘993 application does not specifically claim said CD3 as part of a bispecific antibody construct further comprising a second antigen binding fragment that binds to HER2 and further comprising an extended recombinant polypeptide.
WO2011/123813 teaches polypeptides comprising bispecific antigen binding construct comprising an anti-CD3 binding fragment and further comprising a HER-2 binding fragment, which functions to target a tumor cell and activate T cells to specifically kill the tumor cells (see page 240-241, in particular). WO2011/123813 teaches using HER2 antibody pertuzumab, which inherently comprise the VH and VL of SEQ ID NO: 783 and 883 of the instant claims (see paragraph 189, in particular). WO2011/123813 teaches that the polypeptides can further comprise one or more extended recombinant polypeptides that increase half-life of the polypeptide (see page 2, in particular). WO2011/123813 teaches that said extended recombinant polypeptides can be 100-1000 amino acids in length and comprising a sequence motif identical to SEQ ID NO: 186 of the instant claims (see page 41, in particular). WO2011/123813 teaches that the recombinant extended polypeptide can be linked to each of the N-terminus and the C-terminus of the bispecific construct (see paragraphs 274-281 and Fig. 6, in particular). WO2011/123813 teaches that the extended recombinant polypeptides may comprise a protease cleavage sequence linking the extended recombinant polypeptide to the bispecific antibody construct, wherein the protease cleavage site is cleavable by a protease present in a tumor microenvironment, such as MMP-12 (see paragraphs 274-285, in particular).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to include a second binding arm targeting HER2 and extended recombinant polypeptides as taught by WO2011/123813, in the CD3 polypeptide claimed in the ‘993 application. The ordinary artisan at the time the invention was made would have been motivated to do so with a reasonable expectation of success, because WO2011/123813 teaches that including a HER2 binding arm targets the CD3 activity specifically to tumor cells, and that including the recombinant extended polypeptide increases half-life. Regarding claim 163, WO2019126576 teaches a protease cleavage site of SEQ ID NO: 47 that is identical to SEQ ID NO 8007 of the instant claims that can be used as a protease cleavage linker in extended recombinant polypeptides. It would be obvious to use said protease cleave site in the constructs made obvious above. Doing so would involve choosing among a finite number of predictable options which could be pursued with a reasonable expectation of success. A person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense (see KSR International Co. V. Telefex Inc 82 USPQ2d 1385).
This is a provisional nonstatutory double patenting rejection.
No claim is allowed. WO2020264200 (of record) teaches a CD3 binding arm having CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2, and CDR-H3 comprising, respectively, the amino acid sequences of SEQ ID NO: 1, 4, 6, 8, 9, and 10 of the instant claims. The reference has a publication date after the priority date of the instant application. Although the reference has an earlier filing date than the instant application, it is not prior art under 102 (a)(2) because it is a disclosure obtained from the inventor which is disqualified under the 102(b)(2) exception, since all of the inventors listed on the WO2020264200 are inventors of the instant application.
The claims are free of the prior art, since the prior art does not teach or suggest a CD3 antigen binding fragment having CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2, and CDR-H3 comprising, respectively, the amino acid sequences of SEQ ID NO: 1, 4, 6, 8, 9, and 10.
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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMY E JUEDES whose telephone number is (571)272-4471. The examiner can normally be reached on M-F from 7am to 3pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu can be reached on 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Amy E. Juedes
Patent Examiner
Technology Center 1600
/AMY E JUEDES/Primary Examiner, Art Unit 1644
Prosecution Insights