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 .
Information Disclosure Statement
The information disclosure statement (IDS) filed 08/07/2023 has been considered and the references therein are of record.
Claim Objections
Claim status identifiers are missing for many of the canceled claims in violation of rule 37 CFR 1.121. For the purposes of expedited prosecution, claims 25-46 and 48-51 are treated as canceled. Appropriate correction is required in response to this office action.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1, 3, 5-6, 8, 10, 12, 14-24, 47, and 52-58 are rejected under 35 U.S.C. 103 as being unpatentable over Timmer et al. 2019 (US10308720B2) in view of Alder et al. 2011 (WO2011012637A2) (see instant PTO-892).
Instant claims 1, 3, 5-6, 8, 10, 12, 14-24, 47, and 52-58 are drawn to a pharmaceutical formulation composition comprising 50 mg/ml DR5-binding polypeptide, 10 mM histidine HCl, 8% sucrose, and 0.2% poloxamer P188, and wherein the pH of the formulation is about 6. Some formulations also include 5 mM methionine, a lyophilized formulation formed by lyophilizing the pharmaceutical formulation, and a pharmaceutical formulation formed by reconstituting the lyophilized formulation in water. The instant claims also include a method of treating cancer with the composition, where the cancer is chondrosarcoma, mesothelioma, colorectal cancer, Ewing sarcoma, or pancreatic adenocarcinoma. The DR5-binding polypeptide has SEQ ID NO: 7, which as the structure of VHH-Linker1-VHH-Linker2-Hinge-Fc. The VHH domain is the DR5-binding region with SEQ ID NO: 4 and it contains CDRs 1-3, which are sequences SEQ ID NOs: 1-3, respectively. The linker1 has a sequence of PGGSGGS. The linker2 has a sequence of GG. The Hinge-Fc domain is SEQ ID NO: 6. The sequence of SEQ ID NO: 5 represents VHH-linker1-VHH.
Timmer teaches a DR5-binding polypeptide with a structure of VHH-Linker1-VHH-Linker2-Hinge-Fc that has identical sequence to instant SEQ ID NOs: 1-7. Timmer SEQ ID NO: 113 teaches a VHH-Linker1-VHH-Linker2-Hinge and Timmer SEQ ID NO: 2 teaches a Fc domain, which collectively have an identical sequence to instant SEQ ID NO: 7. Timmer explicitly teaches SEQ ID NOs: 113 and 2 being joined together to make the DR5-binding polypeptide that’s claimed in instant SEQ ID NO: 7 (claim 24). Timmer teaches a method of treating a subject with cancer by administering the DR5-binding polypeptide, where the cancer is sarcoma, mesothelioma, colorectal cancer, or pancreatic cancer (column 43, lines 21-30). The alignment data between Timmer SEQ ID NOs: 113 and 2 and instant SEQ ID NO: 7 is shown below. Timmer SEQ ID NO: 113 spans from position 1Db to 265Db. Timmer SEQ ID NO: 2 spans from position 266Db to 480Db. Instant SEQ ID NO: 7 spans from position 1Qy to 480Qy and contains instant SEQ ID NOs: 1-6.
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Timmer does not explicitly teach the pharmaceutical formulation beyond the DR5-binding polypeptide.
Alder teaches an anti-HER2 antibody composition comprising 50 to 350 mg/ml anti-HER2 antibody, about 1 to 100 mM histidine/HCl, about 1 to 500 mM sucrose, 5 to 25 mM methionine, 0.01 to 0.1% polyethylene-polypropylene copolymer (specifically Poloxamer 188), with a pH ranging from 5.5 +/- 2 9 that can be administered to patients as a cancer treatment (page 4). Some formulations also include a lyophilized formulation formed by lyophilizing the pharmaceutical formulation (claim 18), and a pharmaceutical formulation formed by reconstituting the lyophilized formulation in water (page 11, line 29-33 to page 12, line 1-6).
It would have been prima facie obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to arrive at the claimed invention from the disclosures of Timmer and Alder. One with ordinary skill in the art would have found it obvious to combine the DR5-binding polypeptide of Timmer with the antibody formulation of Alder to make the claimed composition because Alder teaches that the combination of ingredients creates a stable formulation for pharmaceutically active antibodies for therapeutic use and that this stable formulation can be both effectively lyophilized and reconstituted in water. As Timmer does not teach a formulation for DR5-binding polypeptide, an ordinary artisan would be motivated to use the antibody formulation of Alder to create a stable and pharmaceutically acceptable antibody formulation so that the DR5-binding polypeptide can be used to treat cancer patients. The person of ordinary skill in the art would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references.
The prior art only differs from the claimed invention with respect to the claimed concentration amounts and/or ranges of the ingredients in the formulation. The Court has stated that generally such differences amount to mere optimization and will not support patentability unless there is evidence indicating the claimed feature is critical. It would have been prima facie obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to arrive at the claimed invention because an ordinary artisan would have found it obvious to optimize the formulation through routine experimentation. An ordinary artisan would have been motivated to optimize the formulation to make the most stable and effective composition. MPEP 2144 sets forth Applicant’s burden for rebuttal of a prima facie case of obviousness based upon routine optimization. Applicant must provide either a showing that the particular amount or range recited within the claims is critical; and/or a showing that the prior art reference teaches away from the claimed amount. In the instant case, the specification as filed provides no evidence that the particular amount or range recited within the claims is critical because the specification teaches effective embodiments of the claimed invention with 20-70 mg/ml DR5-binding polypeptide, 5.3-6.7 pH, 5-20 mM histidine HCl, 7-10% sucrose, 0.1-0.8% poloxamer 188, and 1-10mM methionine (para[0095-0099]; embodiment 11), which is evidence of noncriticality to the claimed invention.
Therefore, claims 1, 3, 5-6, 8, 10, 12, 14-24, 47, and 52-58 are obvious in view of the disclosures of Timmer and Alder.
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, 3, 5-6, 8, 10, 12, 14-24, 47, and 52-58 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 24 of U.S. Patent No. 10308720B2. Although the claims at issue are not identical, they are not patentably distinct from each other.
Instant claims recite a composition of an DR5-binding polypeptide formulation and a method of using the composition to treat cancer, comprising SEQ ID NOs: 1-7.
Patented claim 24 recites an isolated polypeptide that binds DR5, comprising SEQ ID NO: 113 fused to SEQ ID NO: 2.
Instant SEQ ID NO: 7 has the identical sequence to the fusion protein of SEQ ID NOs: 113 and 2 in patented claim 24. Since instant SEQ ID NO: 7 encompasses instant SEQ ID NOs: 1-6, patented SEQ ID NOs: 113 and 2 anticipates instant SEQ ID NOs: 1-7. Therefore, the scope of the patented DR5-binding polypeptide in patent claim 24 encompasses the narrower scope of instant claims 1, 3, 5-6, 8, 10, 12, 14-24, 47, 52, and 55-58 drawn to the identical DR5-binding polypeptide in a pharmaceutical composition. While the additional formulation components of the instant claims limit the scope of the DR5-binding polypeptide composition, it is still encompassed by patented claim 24 since the patented claim encompasses any composition containing the DR5-binding polypeptide. Instant claims 53 and 54, which recite a method of using the composition, are dependent on claim 1 and therefore included in this rejection.
Claims 53 and 54 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 22-25 and 51-54 of co-pending application No. 18/853278. Although the claims at issue are not identical, they are not patentably distinct from each other.
Instant claims are recited above.
The co-pending claims recite a DR5 agonist administered with a PLK1 inhibitor or a CDK inhibitor to treat cancer, where the DR5 agonist has SEQ ID NO: 1-7, and specifies that the DR5 agonist can be administered separately from the PLK1 inhibitor or CDK inhibitor.
Instant SEQ ID NO: 1-7 has identical sequence to co-pending SEQ ID NO: 1-7. Since co-pending claims 22-25 recite that the DR5 agonist can be administered separately from the PLK1 inhibitor, instant claims 53 and 54 anticipate and/or encompass the co-pending claims because the instant claims also recite a method of administering the DR5 antagonist to treat cancer. Since co-pending claims 51-54 recite that the DR5 agonist can be administered separately from the CDK inhibitor, instant claims 53 and 54 anticipate and/or encompass the co-pending claims because the instant claims also recite a method of administering the DR5 antagonist to treat cancer. While the instant claims recite a more specific and limiting composition, the instant claims are encompassed by the co-pending claims because the co-pending claims encompasses any method of treating cancer by administering any composition containing the DR5-binding polypeptide. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 53 and 54 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 22-25 of co-pending application No. 18/865854. Although the claims at issue are not identical, they are not patentably distinct from each other.
Instant claims are recited above.
The co-pending claims recite a DR5 agonist administered with an IAP antagonist to treat cancer, where the DR5 agonist has SEQ ID NO: 1-7, and specifies that the DR5 agonist can be administered separately from the IAP antagonist.
Instant SEQ ID NO: 1-7 has identical sequence to co-pending SEQ ID NO: 1-7. Since co-pending claims 22-25 recite that the DR5 agonist can be administered separately from the IAP antagonist, instant claims 53 and 54 anticipate and/or encompass the co-pending claims because the instant claims also recite a method of administering the DR5 antagonist to treat cancer. While the instant claims recite a more specific and limiting composition, the instant claims are encompassed by the co-pending claims because the co-pending claims encompasses any method of treating cancer by administering any composition containing the DR5-binding polypeptide. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
Advisory Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPH CESARE whose telephone number is (571)272-6908. The examiner can normally be reached Monday - Friday 10am-4pm.
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/JOSEPH D. CESARE/ Examiner, Art Unit 1675
/JEFFREY STUCKER/Supervisory Patent Examiner, Art Unit 1675