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 .
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.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission of RCE on 2/4/26 and the amendment of claims has been entered.
Status of the Claims
Applicant’s election without traverse of Group I, drawn to a method of treating or preventing a tissue differentiation factor associated disorder or disease, claimed in claims 1-5, 13, 25-28 and 34 in the reply filed on 11/29/23 was previously acknowledged. Election was made of an inhibitor of ACE, kidney or renal disease and anti-neoplastic agent.
In the reply filed 7/28/25, Applicants amended claim 1 and canceled claims 16 and 26.
In the RCE field 2/4/26, claim 1 was amended.
Claims 1, 3, 19-20, 25, 27-28, 34-35, 37, 39 and 41-43 are pending.
Claims 19-20, 27-28, 35, 37, 39 and 41-43 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected group, there being no allowable generic or linking claim.
Claims 1, 3, 25 and 34 read on the elected Group I and elected species and are under consideration.
Claim Rejection-Withdrawn
The rejection of claims 1, 3, 25 and 34 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treatment of kidney fibrosis with SEQ ID NO: 3 and Enalapril, does not reasonably provide enablement for prevention of renal fibrosis is withdrawn due to amendment of the claims.
Claim Objections-Withdrawn
The objection to claim 1 is withdrawn due to amendment of the claim.
Claim Rejections - 35 USC § 103-Maintained
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.
The rejection of claims 1, 3 and 34 under 35 U.S.C. 103 as being unpatentable over Bosukonda et al. (US2014/0057831, previously presented) in view of Karimian et al. (“Attenuation of hepatic fibrosis through captopril and enalapril in the livers of bile duct ligated rats” Biomedicine & Pharmacotherapy Vol 62, Issue 5, June 2008, 312-316) is maintained.
With respect to claim 1, Bosukonda et al. teach the invention contemplates pharmaceutical compositions and formulation for co-administering the peptides of the invention with one or more additive active agents, such as ACE inhibitors (e.g. perindopril, captopril, enalapril) can be tested and used to treat fibrosis in combination with the peptides [0213]. Bosukonda et al. claims a method of treating fibrosis with SEQ ID NO: 5 (claim 1). SEQ ID NO: 5 is identical to instantly claimed SEQ ID NO: 3 (Table 1 [0135]). Bosukonda et al. teach the fibrosis is renal fibrosis [0023] and teaches an example of treatment of renal fibrosis with THR-123 ([0054] and Fig. 40). Bosukonda et al. teach an example of treatment of mice with advanced fibrosis with a combination of THR-123 and captopril [Fig. 71A, [0085-0089]). Please note that “subject” is defined by the instant specification to include mammals and veterinary applications [PGPUB0038]. THR-123 of Bosukonda et al. is identical to SEQ ID NO: 1 of the instant application. Bosukonda et al. teach that the combination significantly reduced mesangial expansion and reversed it compared to untreated controls (Fig. 71 and [0403]). Bosukonda et al. teach the combination significantly inhibited progressive loss of renal function (Fig. 71M). Bosukonda et al. teach that THR-123 and captopril combination therapy exhibited additive anti-apoptotic effects (Fig. 74).
Bosukonda et al. does not teach an example of SEQ ID NO: 5 (identical to instant SEQ ID NO: 3) in combination with enalapril. However, the teachings of Karimian et al. cure this deficiency.
Karimian et al. teach treatment of hepatic fibrosis with two ACE inhibitors, captopril and enalapril (Abstract). Karimian et al. concludes that enalapril was significantly more effective than captopril for improvement of hepatic fibrosis. Enalapril was also show to have significant antioxidative effects in comparison to captopril (Abstract, Table 1, conclusions).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the invention use enalapril in the composition of SEQ ID NO: 5 for treatment of renal fibrosis. A person of ordinary skill in the art would be motivated to use one of the TDFRP peptide of Bosukonda et al. because the reference teaches the peptides for treatment of renal fibrosis. A person would have a clear motivation to substitute enalapril in place of captopril since Karimian et al. teach that enalapril was significantly better in reducing fibrosis and had significant antioxidative effects compared to captopril. There is a reasonable expectation of success given that both enalapril and captopril are both ACE inhibitors and have been shown to improve fibrosis.
Bosukonda et al. and Karimian et al. do not teach increased serum half-life of the TDFRP and inhibitor of ACE (claims 1 and 3). However, the composition of Bosukonda et al. and Karimian et al. would inherently have all of the activities and properties of the composition of claim 1 and 3. The MPEP § 2112 states: “Once a reference teaching product appearing to be substantially identical is made the basis of a rejection, and the Examiner presents evidence or reasoning tending to show inherency, the burden shifts to the Applicant to show an unobvious difference ‘[t]he PTO can require an Applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of his [or her] claimed product. Whether the rejection is based on inherency’ under 35 U.S.C. 102, on prima facie obviousness’ under 35 U.S.C. 103, jointly or alternatively, the burden of proof is the same…[footnote omitted].” The burden of proof is similar to that required with respect to product-by-process claims. In re Fitzqerald, 619 F.2d 67, 70, 205 USPQ 594, 596 (CCPA 1980) (quoting In re Best, 562 F.2d 1252, 1255, 195 USPQ 430,433- 34 (CCPA 1977)).” In other words, Bosukonda et al. and Karimian et al. make obvious the method of claim 1, therefore the serum half like would inherently be increased.
With respect to claim 34, Bosukonda et al. teach a peptide of the invention with one or more additional active agents [0230]. Bosukonda et al. teach that steroidal anti-inflammatory compounds, e.g. prednisone and ACE inhibitors can be tested and used to treat the fibrosis in combination with the peptides of the invention [0213]. Prednisone is immunosuppressive agent.
The rejection of Claims 1, 3, 25 and 34 are rejected under 35 U.S.C. 103 as being unpatentable over Bosukonda et al. (US2014/0057831) and Karimian et al. (“Attenuation of hepatic fibrosis through captopril and enalapril in the livers of bile duct ligated rats” Biomedicine & Pharmacotherapy Vol 62, Issue 5, June 2008, 312-316) in view of Carlson et al. (EP 2497780, 2012, previously cited) is maintained.
The teachings of Bosukonda et al. and Karimian et al. are presented above. However, the reference does not teach the TDFRP is a multiple domain TDFRP. The teachings of Carlson et al. cure this deficiency.
Carlson et al. teach and claim multiple domain TDFRPs for treatment of TDF associated disorders, such as renal disease ([0233, 0017], claims 48-49). SEQ ID NO: 333 of Carlson et al. is identical to instant SEQ ID NO: 3.
It would have been obvious to a person of ordinary skill in the art to use the multiple domain TDFRP of Carlson et al. because Carlson et al. teach the multiple domain TDFRPs for treatment of TDF associated disorders such as renal disease. A person of ordinary skill in the art would have a motivation to use the multiple domain TDFRP because it comprises the TDFRP of Bosukonda et al. that was successful in treating renal disease. There is a reasonable expectation of success given that the TDFRP was success for treatment of renal disease in Bosukonda et al.
Response to Arguments
Applicant's arguments filed 2/4/26 have been fully considered but they are not persuasive. Applicants argue that the Examiner did not establish a prima facie case of obviousness. Applicants further argue that the cited references do not teach the increased serum half-life and treatment of renal fibrosis. Applicants argue that the cited references doe not teach or suggest the would increase the serum half-life, let alone at 2-fold. Applicants argue that the serum half-life of the TDFRP is increased is dependent on the concentration of each component, enalapril and TDFRP. As shown in Fig. 2 and 3, not all combinations of ACE inhibitor and THR184 would result in an half-life increase of 2-fold or more, therefore it would not be inherent. Applicants argue that Applicants argue this is an unexpected property since captopril is an ACE inhibitor and functions to inhibit the production of angiotensin, which narrows blood vessels, thereby increasing the lumen of the blood vessels in the body. TDFRPs bind TGF-beta superfamily receptors acting as agonists. PHOSITA would not have contemplated that two compositions that function independently in the body would result in an increased half-life of TDFRPs of about 2 fold or more. Applicants argue that the property of increased half life depends on the amounts of both the TDRPs and enalapril
The arguments regarding unexpected results have been carefully considered, however such evidence as explained in MPEP 2145 does not necessarily control the ultimate conclusion of obviousness. The determination must be based on the preponderance of all evidence, including the teachings of the prior art. In the present case, the cited references clearly make obvious the claimed peptide and enalapril for treating renal fibrosis. A skilled artisan would have had a strong motivation to co-administer or combine the agents to achieve therapeutic treatment of renal fibrosis. While applicants data suggest that the peptide exhibits an increased half-life for the peptide when combined with enalapril, the result does not outweigh the strong evidence of obviousness. After weighing the totality of evidence, including the asserted unexpected results, the preponderance of evidence still supports a conclusion of obviousness. The art provides both a strong motivation to combine and a reasonable expectation of success. Furthermore, as indicated above, the combined references make obvious SEQ ID NO: 3 and enalapril. Importantly, the pending claims does not recited a specific dose or concentration. Therefore, the asserted results are not reasonable commensurate with the full scope of the claimed invention and do not outweigh the prima facie case of obviousness.
Applicants further argue that Carlson does not cure the deficiencies above.
This argument is not persuasive for the reasons presented above.
Double Patenting-Maintained
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.
The rejection of claims 1, 3, 25 and 34 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7, 10-11 16-19, 25, 32-34 of copending Application No. 18/369, 359 (reference application) is maintained.
Although the claims at issue are not identical, they are not patentably distinct from each other because the copending Application claims treatment of the same conditions with the same combination. The copending application claims a method for treating or preventing Tissue factor associated disorders or disease, in combination with an ACE inhibitor. The copending Application claims treatment of renal fibrosis, which meets the limitation of kidney or renal disease or disorder (copending claims 5, 7, 11). The copending application does not claim the serum half-life of the TDFRP is increased about 5 to 10-fold or more when the TDFRP is administered with the additional agent (claim 3). The specification of the copending Application teach the TDFRP has the general structure of SEQ ID NO: 1-208. SEQ ID NO:3 of the copending Application is identical to instantly claimed SEQ ID NO: 3. Claim 17 of the copending Application claims the ACE inhibitor is enalapril. Therefore, the copending Application anticipates the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant's arguments filed 2/4/26 have been fully considered but they are not persuasive. Applicants request the rejection be held in abeyance until allowable subject matter is indicated.
This is not persuasive as there is no allowable subject matter indicated. The rejection is maintained.
Conclusion
No claims are allowed.
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/TARA L MARTINEZ/Examiner, Art Unit 1654