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 .
Response to Amendment
1. The Amendment filed 4/15/2026 in response to the Office Action of 1/15/2026, is acknowledged and has been entered. Claims 1, 3, and 5-14 are pending. Claims 2 and 4 are canceled. Claim 1 is amended. Claims 1, 3, and 5-14 are currently being examined.
2. Claim objection noted in the Office Action of 1/15/2026 has been appropriately corrected and the objection is withdrawn.
3. Claim rejections to 35 U.S.C. 112(a), written description are withdrawn in light of the new written description rejection below.
4. Applicant amended claim 1 in response to the rejection under 35 U.S.C. 102. In light of the amendments, examiner withdraws the rejection of claims 1-3 and 5-14 under 35 U.S.C 102(a)(1) as being anticipated by Xie (Xie, J Cell Mol Med, 2021, 2021;25:7280-7293).
5. Applicant amended claim 1 in response to the double patenting rejection which did not include the limitations of claim 4 in the rejection. In response, examiner has withdrawn the original rejection.
New Rejections
(based on new considerations)
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph 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 the first paragraph of pre-AIA 35 U.S.C. 112:
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.
6. Claims 1, 3, and 5-14 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a WRITTEN DESCRIPTION rejection.
The claims are drawn to a method for improving wound healing by the administration of a chemokine C-C motif ligand 7 (CCL7) antagonist to a subject in need thereof to inhibit CCL7 activity, wherein the CCL7 antagonist is a CCL7 neutralizing antibody or a CCL7 RNA interference (RNAi) agent, and the subject suffers from diabetic foot ulcer.
Thus, the claims identify the antibody and RNAi agent only by the function of inhibiting CCL7 activity. Thus, the claims encompass a vast genus of antibody and RNAi variants that inhibit CCL7 activity.
The instant specification discloses treating cells in vitro with CCL7 siRNA purchased from Santa Cruz Biotechnology ([62]), but does not disclose the sequences used. The specification discloses:
[0062] Some cells were treated with siRNA Control (Santa Cruz Biotechnology, sc-37007, Dallas, TX, USA) and CCL7 siRNA (Santa Cruz Biotechnology, sc-72035, Dallas, TX, USA) to evaluate the direct endogenous role of CCL7. To mimic the hyperglycemia in DM, high glucose (HG; Sigma-Aldrich, St. Louis, MO, USA) in a concentration of 25 mM was administered to HDMECs.
[0077] As can be seen in the results of FIGS. 8-12, the inhibition of CCL7 by siRNA would recover functions of HG-impaired HDMECs with increased angiogenic protein expressions.
No sequence structure of the CCL7 siRNA that functions as an RNAi agent is disclosed.
The instant specification does not disclose any amino acid or nucleotide structure for an antibody or RNAi that function to inhibit CCL7 activity. Thus, the specification fails to identify any structurally distinct antibodies or RNAi sequences that possess the function of inhibiting CCL7 activity.
To provide adequate written description and evidence of possession of the claimed antibody and RNAi genus, the instant specification can structurally describe representative antibody or RNAi variants that function to inhibit CCL7 activity, or describe structural features common to the members of the genus, which features constitute a substantial portion of the genus. Alternatively, the specification can show that the claimed invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics (see University of California v. Eli Lilly and Co., 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997) and Enzo Biochem, Inc. V. Gen-Probe Inc.). A disclosure that does not adequately describe a product itself logically cannot adequately describe a method of using that product.
In this case, the only factor present In the claims is a recitation of “a chemokine C-C motif ligand 7 (CCL7) antagonist to a subject in need thereof to inhibit CCL7 activity,” and the limited structure of a CCL7 neutralizing antibody or a CCL7 RNAi agent. The instant specification fails to describe any structural features common to the members of the antibody genus or the RNAi genus, which features constitute a substantial portion of the genus because the instant specification fails to disclose representative antibody and RNAi variant sequences that function as claimed. A definition by function does not suffice to define the genus because it is only an indication of what the antibody and RNAi does, rather than what it is. The specification fails to provide any amino acid or nucleotide structural features coupled to the claimed functional characteristics. The instant specification fails to describe a representative number of antibody or RNAi sequence variants for the genus of antibodies or RNAi agents that function as claimed. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus required to make the claimed antibodies.
The claims broadly encompass any antibody or RNAi agent that function to inhibit CCL7 activity. Applicants have not established any reasonable structure-function correlation with regards to the required amino acid or nucleotide sequences in the antibody or RNAi agent that allow for the inhibition of CCL7 activity. Given the well-known high level of polymorphism of antibody and RNAi sequences and structure, the skilled artisan would not have been in possession of the vast repertoire of antibodies and RNAi agents encompassed by the claimed invention. One could not reasonably or predictably extrapolate the structure of a single antibody or RNAi agent to the structure of any variants required to inhibit CCL7 activity as broadly claimed. Therefore, one could not readily envision members of the broadly claimed genus.
Although Applicants may argue that it is possible to screen for antibodies and RNAi agents that bind CCL7 and function as claimed, the court found in (Rochester v. Searle, 358 F.3d 916, Fed Cir., 2004) that screening assays are not sufficient to provide adequate written description for an invention because they are merely a wish or plan for obtaining the claimed chemical invention. “As we held in Lilly, “[a]n adequate written description of a DNA … ‘requires a precise definition, such as by structure, formula, chemical name, or physical properties,’ not a mere wish or plan for obtaining the claimed chemical invention.” 119 F.3d at 1566 (quoting Fiers, 984 F.2d at 1171). For reasons stated above, that requirement applies just as well to non-DNA (or RNA) chemical inventions.” Knowledge of screening methods provides no information about the structure of any future antibodies or RNAi agents yet to be discovered that may function as claimed. The CCL7 antigen provides no information about the structure of an antibody or RNA agent that binds to it.
Given the lack of representative examples to support the full scope of the claimed variant antibodies and RNAi agents, and lack of reasonable structure-function correlation with regards to the unknown variable sequences in antibodies and RNAi agents that inhibit CCL7 activity, the present claims lack adequate written description. Thus, the specification does not provide an adequate written description of antibody and RNAi agent variants that inhibit CCL7 activity that is required to practice the claimed invention.
New Rejection- Double Patenting
7. 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.
8. Claims 1, 3, and 5-14 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 3-13 of copending Application No.18214178 in view of Bandyk (Seminars in Vascular Surgery, 2018 31:43-48) and Huang (Adv Sci, epub. Nov 2022, 10(2):e2203308).
The co-pending application claims a method for preventing or treating a peripheral arterial disease (PAD) in a subject in need thereof, comprising administering an effective amount of a chemokine C-C motif ligand 7 (CCL7) antagonist to the subject to inhibit CCL7 activity, wherein the CCL7 antagonist is a CCL7 neutralizing antibody. The method also claims the effective amount of the CCL7 antagonist can be about 0.01 µg/kg to about 100 mg/kg and 0.1 µg/kg to 1 mg/kg. The method also claims the CCL7 antagonist being administered to the subject orally, intraperitoneally, intravenously, intradermally, intramuscularly, subcutaneously, intrapleurally, and transdermally. The method also claims the administration enhances angiogenesis and protects endothelial cell functions in the subject.
The co-pending application does not claim the method for improving wound healing and in a subject that is suffering from a diabetic foot ulcer (DFU).
Bandyk teaches that Diabetic Foot Ulcer has a complex pathophysiology that includes peripheral arterial occlusive disease. (See Bandyk, abstract). Significant peripheral arterial disease is present in more than half of diabetic patients presenting with a foot ulcer and leads to endothelial injury and immunologic dysfunction. (See pgs. 43-44).
Bandyk does not teach the improvement of wound healing in DFU includes improvement of tube formation ability and migration ability of endothelial cells, the decrease of specific inflammatory factors, and the increase of specific angiogenic factors.
Huang teaches DFU as a chronic wound is characterized by an ongoing pro-inflammatory response typical of M1 macrophage polarization and an increase in inflammatory factors including Il-1, IL6, and TNF-α. (See Huang, section 3.2, also Table 1). Huang further teaches that DFU is characterized by poor remodeling and proliferation of the vasculature as compared to normal remodeling that includes the secretion of cytokines PDGF, TGFβ, and EGF for remodeling along with the extracellular matrix assembling to rebuild the tissue along with endothelial cells activated to induce angiogenesis. (See Huang, section 2, also Table 1).
Therefore it would have been prima facie obvious for a person of ordinary skill in the art prior to the effective filing date to use the method of the co-pending application with the teachings of Bandyk and Huang for the method of the present application. It would have been obvious because PAD is a part of the pathophysiology of DFU and is significantly present for more than half of patients experiencing DFU and treating PAD would help improve the treatment of DFU, Bandyk also teaches that immune dysfunction is a part of the pathophysiology, and Huang elaborates that this includes the ongoing pro-inflammatory response. Therefore, it would have been obvious to a person of ordinary skill in the art prior to the effective filing date to apply the method of treating PAD with an anti-inflammatory as claimed in the co-pending application to a DFU patient as taught in Bandyk with a reasonable expectation of success at improving wound healing by affecting the endothelial and immune reactions as taught in Huang.
This is a provisional nonstatutory double patenting rejection.
9. Claims 1, 3, and 5-14 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of copending Application No. 18649626 in view of Bonnet (Kidney International Reports, 2022, 7:381-388) and Huang (Adv Sci, epub. Nov 2022, 10(2):e2203308).
The co-pending application claims a method for preventing or treating a diabetic kidney disease in a subject by administering an effective amount of a CCL7 antagonist to inhibit activity of CCL7, where the CCL7 antagonist can be a neutralizing antibody or a CCL7 RNA interference agent. The co-pending application further claims administering the CCL7 antagonist orally, intraperitoneally, intravenously, intradermally, intramuscularly, subcutaneously, or transcutaneously. The co-pending application further claims the method is treating a disorder caused by diabetes and the disease includes an increased expression of inflammatory factors and the effective amount of the CCL7 antagonist is 0.01 µg/kg to 100 mg/kg.
The co-pending application does not claim the method for treatment of DFU and the administration affecting the endothelial function, inflammatory factors, and angiogenic factors.
Bonnet teaches that chronic kidney disease (CKD) and DFU are both significant complications resulting from Diabetes Mellitus and DFU patients that underwent dialysis had an effect on the inflammatory action on the vascular system. (See Bonnet, pg. 382, column 1 ‘PAD and CKD’).
Bonnet does not teach the administration of CCL7 antagonist as enhancing angiogenesis, protecting endothelial function, improving tube formation ability or migration ability of endothelial cells, the decreased expression of specific inflammatory factors, or increased expression of angiogenic factors.
Huang teaches DFU is a chronic wound and is characterized by an ongoing pro-inflammatory response typical of M1 macrophage polarization and an increase in inflammatory factors including Il-1, IL-6, and TNF-α. (See Huang, section 3.2, also Table 1). Huang further teaches that DFU is characterized by poor wound remodeling and proliferation of the vasculature as compared to normal remodeling that occurs after an acute wound that includes the secretion of cytokines PDGF, TGF-β, and EGF for remodeling along with the extracellular matrix assembling to rebuild the tissue along with endothelial cells activated to induce angiogenesis. (See Huang, section 2, also Table 1).
Therefore, it would have been prima facie obvious for a person of ordinary skill in the art prior to the effective filing date to use the method of the co-pending application for the treatment of DFU as taught by Bonnet with a reasonable expectation of success at achieving would healing improvement in the DFU microenvironment as taught by Huang. It would have been obvious because Bonnet teaches that both DFU and diabetic kidney disease are significant complications of diabetes that share similar pathophysiological aspects including an effect on the inflammatory response in the vascular system for patients experiencing DFU and Huang teaches that vascular remodeling and inflammatory response is impaired in DFU. Therefore, it would have been obvious for a person of ordinary skill in the art to use the method of the co-pending application of treating diabetic kidney disease with an anti-inflammatory with a DFU patient as taught in Bonnet to counteract the effects of wound impairment in DFU as taught in Huang.
This is a provisional nonstatutory double patenting rejection.
Conclusion
10. Claims 1, 3, and 5-14 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LINDSAY DUNN whose telephone number is (571)272-5825. The examiner can normally be reached Monday-Friday 8-4:30.
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/LINDSAY DUNN/Examiner, Art Unit 1644
/Laura B Goddard/Primary Examiner, Art Unit 1642
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