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 .
Claims 1-31 are canceled. Claim 32 is pending and examined on the merits.
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.
Claim 32 is rejected under 35 U.S.C. 103 as being unpatentable over Zwaagstra et al (Molecular Cancer Therapeutics, 2012, Vol. 7, pp. 1477-1488, reference of the IDS filed 12/18/2023) in view of Gotwals et al (WO98/48024, reference of the IDS filed 12/18/2023).
Zwaagstra et al teach a single chain trap for TNF-β comprising from N-terminus to C-terminus a first TGF-β receptor ectodomain and a second TGF-β receptor ectodomain wherein the C-terminus of one ECD is linked to the N terminus of the other ECD (page 1477, second column, lines 1-5 of the bottom paragraph) generating a (TβRII)2 trap and a (TβRIIb)2 trap which meets the limitation of claims 32, sections (i) and (ii). Zwaagstra et al teach that the (TβRII)2 trap reduces growth of 4T1 mammary tumors primarily by reversing TGF-βmediated immune suppression and angiogenesis (page 1483, heading in second column).
Zwaagstra et al do not teach the fusion of the single chain bivalent trap to a the third constant domain CH3.
Zwaagstra et al teach that although the (TβRII)2 trap was stable in serum, its size, including glycosylation, is slightly under the molecular cut-off for kidney filtration (page 1482, second column, lines 5-8).
Zwaagstra et al do not teach a (TβRII)2-fusion or a (TβRIIb)2-fusion wherein the second TβRII-ECD was fused to an antibody heavy chain fragment at the amino terminus of CH2 domain.
Gotwals et al teach soluble TGF-β receptor fusions and analogs as TGF-β (page 25, lines 24-25). Gotwals et al teach that the fusion protein comprises a second protein which is the second and third constant region of an immunoglobulin, CH2 or CH3(page 26, lines 17-20), and that the preferred fusions comprise the resulting homodimers linked by disulfide linkages (page 26, lines 20-21). Gotwals et al teach that that the soluble TGF- β receptor constructs are devoid of a transmembrane region and are secreted from the cell but retain the ability to bind TGF-β (page 26, lines 32-33). Gotwals et al teach an embodiment whein the entire extracellular portion of the type II receptor is used (page 27, lines 27-29).
Gotwals et al teach an isolated TGF-beta receptor fusion protein that competitively inhibits binding of TGF-beta to TGF-beta receptor wherein the fusion protein is a TGF-beta Type II receptor linked to a second protein that is a constant region of an immunoglobulin, such as the human TGFβII-Fc.
Gotwals et al teach an examples of the TGFβII-Fc as SEQ ID NO: 8 or 9 (claims 5 and 6 of ‘024). Examination of SEQ ID NO: 8 and 9 indicates that the two copies of CH3 are attached to the C-terminus of the TGFβII extracellular domain in an N to C orientation:
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It would have been prima facie obvious prior to the effective filing date to make a homodimer linked by disulfides from the bivalent (TβRII)2 of Zwaagstra et al attached to a second protein which is the third constant region of an immunoglobulin, CH3. One of skill in the art would have been motivated to do so by the teachings of Zwaagstra et al regarding the molecular weight of the bivalent (TβRII)2 being below the renal threshold. One of skill in the art would understand that the Fc fusion of the bivalent trap would bring the molecular weigh up to over the renal threshold and result in a longer circulating half-life of the TGF-β trap, and resulting in a longer window in which to trap circulating TGF beta resulting in greater therapeutic efficacy.
Regarding the requirement the polypeptide inhibits TGF-β1 and TGF- β3 activity with at least 100-fold greater potency than a non-Fc fused TβR-ECD doublet, Zwaagstra et al teach that both single chain bivalent traps bound to TGF-β1 and TGF-β3 (figure 2B and 2A). It would thus be an inherent feature of the dimerized monomeric fusion proteins that the inhibition of TGF-β1 and TGF-β3 would be at least 100-fold greater relative to the non-Fc fused doublet of Zwaagstra because of the greater circulating half-life of the fusion protein allowing for a longer therapeutic window in vivo. Further the instant specification teaches that the inhibition of TGF-β1 and TGF-β3 at least 100-fold greater relative to the non-Fc fused doublet is an inherent feature of the fused doublet.
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.
Claim 32 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-43 of U.S. Patent No.11,866,481. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the patent anticipate the instant claim. Claims 1-6 of the patent anticipate the structure of instant claim 32. The requirement that the polypeptide inhibits β1 and β3 with at least 100-fold greater potency is an inherent feature of the fusion polypeptide as taught by the ‘481 specification:
The polypeptide construct provided comprises a second, TGFβ receptor ectodomain ECD that is linked in tandem to the first ECD, wherein the polypeptide construct (i.e. an ECD doublet construct) linked to an antibody constant domain exhibits TGFβ neutralization (inhibits) that is at least 100, 200, 300, 400, 500, 600, 700, 800 or 900-fold greater than a counterpart construct in which the antibody constant domain is absent, (i.e. an ECD doublet construct, also referred to herein as a non-Fc fused doublet)
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Claim 32 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No.12,391,743. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the patent anticipate the instant claim. Claims 1-14 of the patent anticipate the structure of the polypeptide of claim 32. The requirement that the polypeptide inhibits β1 and β3 with at least 100-fold greater poettency is an inherent feature of the fusion polypeptide as taught by the ‘743 specification:
The polypeptide construct provided comprises a second, TGFβ receptor ectodomain ECD that is linked in tandem to the first ECD, wherein the polypeptide construct (i.e. an ECD doublet construct) linked to an antibody constant domain exhibits TGFβ neutralization (inhibits) that is at least 100, 200, 300, 400, 500, 600, 700, 800 or 900-fold greater than a counterpart construct in which the antibody constant domain is absent, (i.e. an ECD doublet construct, also referred to herein as a non-Fc fused doublet).
Claim 32 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 30, 42, 47, 50, 53, 56, 68, 69, 71, 74-76, 78, 83, 84, 106, 112, 115, 120, 127, 129-133 of copending Application No. 18/009,506(reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘506 claims either anticipate or render obvious the instant claim.
Claim 42 of the ‘506 application anticipate instant the structure of the polypeptide of instant claim 32.
The requirement that the polypeptide inhibits β1 and β3 with at least 100-fold greater potency is an inherent feature of the fusion polypeptide as taught by the ‘506 specification:
The potency enhancement is at least 100, 200, 300, 400, 500, 600, 700, 800, 900-fold and approximately 1000-fold greater for the Fc-fused doublet over the non-Fc doublet.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KAREN A CANELLA whose telephone number is (571)272-0828. The examiner can normally be reached M-F 10-6:30.
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KAREN A. CANELLA
Examiner
Art Unit 1643
/Karen A. Canella/ Primary Examiner, Art Unit 1643
Prosecution Insights