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 .
Claim Status
Claims 9, 12-20, and 29-30 are cancelled. Claims 1-8, 10-11, 21-28, and 31-36 as filed on 09 December 2025 are pending. Claim 28 is withdrawn. Claims 1-8, 10-11, 21-27, and 31-36 are under examination.
Rejections Withdrawn
Rejection of claims 1-8, 10-11, 21-28, and 31-36 under 35 U.S.C. 112(b) is withdrawn with applicant amendment of claims removing the parenthetical.
Rejection of claims 1-8, 10-11, 21-28, and 31-36 under 35 U.S.C. 112(a) is withdrawn with applicant amendment of claims limiting the position of the protease cleavage in the ligand binding fusion molecule.
Applicant made not arguments to the double patenting rejection so no response to arguments is made.
Rejection Maintained
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.
Claims 1-8, 11, and 21-27 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6, and 8-22 of copending Application No. 17/615,633 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding claims 1-7, reference application recites a polypeptide comprising a single-domain antibody that binds a ligand and a protease cleavage sequence wherein the binding of the single-domain antibody is attenuated when the cleavage site is cleaved (claims 1, 6, and 8-9). The reference application recites the cleavage sequences are in positions spanning fourth to fifteenth amino acids positions which would include the positions of the instant claims. The reference application recites the protease is matriptase or urokinase (claim 4) which cleaves a cleavage sequence of instant claim 7.
Regarding claim 8, reference application recites that the ligand is released from the ligand-binding molecule in a state where the cleave sire or protease cleavage sequence is cleaved (claims 6 and 9-10).
Regarding claims 13-14, reference application recites the molecule fused to the ligand (claim 11).
Regarding claim 15, reference application recites the fused molecule and ligand in a pharmaceutical composition (claims 12-13).
Regarding claims 16-18 and 21-27, the reference application recites a polynucleotide encoding the polypeptide, in a vector, and in a host cell (claims 14 and 16-121). Reference application recites a method of producing using a host cells comprising the molecule with and without the ligand (claims 18 and 22). The reference application recites a fusion of the ligand and the ligand-binding molecule (claim 11).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 4, 10 and 31-33 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 and 16-22 of copending Application No. 17/615,633 (reference application) in view of West (WO 2014/052462 A2) (IDS 04/14/2021 FP27).
The recitations of the application from the previous anticipatory style double patenting rejection are incorporated here in full.
Regarding claims 1 and 4, reference application recites a polypeptide comprising a single-domain antibody that binds a ligand and a protease cleavage sequence wherein the binding of the single-domain antibody is attenuated when the cleavage site is cleaved (claims 1, 6, and 8-9). The reference application recites the cleavage sequences are in positions spanning fourth to fifteenth amino acids positions which would include the positions of the instant claims. The reference application recites the protease is matriptase or urokinase (claim 4) which cleaves a cleavage sequence of instant claim 7.
The reference application recites the molecule fused to the ligand that it binds (claim 11).
The reference application does not recite the single-domain antibody has a neutralizing activity for the ligand or that the ligand is IL-6R.
These deficiencies are filled by West.
West teaches an activatable antibody that is part of a polypeptide that comprises an antibody that binds IL-6R, a protease cleavage sequence wherein the cleavage by a protease changes the activity of the antibody (abstract). West teaches the use of antibodies that neutralize activity for IL-6R ([000470]). West further teaches the use of single domain antibodies including ones that are VH or VL (claims 1 and 12).
It would have been obvious to one of ordinary skill in the art to substitute the single-domain antibody in the fusion of the reference application which comprises a generic single-domain antibody, a protease sequence, and the ligand that the single-domain antibody binds with the specific single-domain antibodies taught by West which bind IL-6R and the known ligand IL-6R. West teaches a protease cleavage activatable antibody that is a single-domain antibody that binds IL-6R. One of ordinary skill in the art would have been motivated to take the recited general single-domain antibody of the reference application with the specific types of single-domain antibodies that have inhibitory function of West as West teaches they are functional as antibodies under regulation by protease cleavage for use in treatment of human subjects. There would have been a reasonable expectation of success because the reference application and West are both working with the protease cleavage regulation of single-domain antibodies activity.
This is a provisional nonstatutory double patenting rejection.
Claims 1 and 34-36 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 and 16-22 of copending Application No. 17/615,633 (reference application) in view of Shen CN107814845A (Of Record)
The recitations of the application from the previous anticipatory style double patenting rejection are incorporated here in full.
Regarding claim 1, the reference application recites a polypeptide comprising a single-domain antibody that binds a ligand and a protease cleavage sequence wherein the binding of the single-domain antibody is attenuated when the cleavage site is cleaved (claims 1, 6, and 8-9). The reference application recites the cleavage sequences are in positions spanning fourth to fifteenth amino acids positions which would include the positions of the instant claims. The reference application recites the protease is matriptase or urokinase (claim 4) which cleaves a cleavage sequence of instant claim 7.
The reference application recites the molecule fused to the ligand that it binds (claim 11).
The reference application does not recite the single-domain antibody has a neutralizing activity for the ligand or that the ligand is PD-1.
These deficiencies are filled by Shen.
Shen teaches single domain antibodies, VHH, that bind PD-1 that block PD-1 binding to PD-L1 (abstract and claims 1-9). Shen teaches these VHH are for use in a method of treating tumors (claim 10).
Shen teaches the antibody fused to additional elements (page 8 in par 9). Shen teaches the framework and CDR sequences of the VHH that binds PD-1 (page 4 in pars 4-5).
Shen further teaches PD-1 including its size and the nature of the polypeptide (page 3 in par 5).
It would have been obvious at the time the application was filed to to substitute the single-domain antibody in the fusion of the reference application which comprises a generic single-domain antibody, a protease sequence, and the ligand that the single-domain antibody binds with the specific single-domain antibodies taught by Shen which bind PD-1 the known ligand PD-1. The reference claims are to a fusion polypeptide comprising a VHH that binds a target of interest, the ligand that VHH binds, and a cleavage sequence. One of skill in the art would have been motivated to substitute the generic ligand target of the reference claims with PD-1 to produce a ligand-binding molecule that can be used in treatment of cancer. There would have been a reasonable expectation of success as the reference claims recite the VHHs as generic and interchangeable.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claims allowable.
THIS ACTION IS MADE FINAL. 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 nonprovisional extension fee (37 CFR 1.17(a)) 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 FRANCESCA EDGINGTON-GIORDANO whose telephone number is (571)272-8232. The examiner can normally be reached Mon - Fri 8:00 - 5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Julie Wu can be reached at 571-272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/F.E./Examiner, Art Unit 1643
/JULIE WU/Supervisory Patent Examiner, Art Unit 1643
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