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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 filed on 19 November 2025 has been entered.
Claim Status
Applicant’s remarks, amendments, and affidavit filed 19 November 2025, in response to the final rejection mailed 19 September 2025, are acknowledged and have been fully considered. Applicant’s amendments to the claims are acknowledged. The listing of claims filed 19 November 2025 replaces all prior versions and listings of the claims.
Claims 80, 83, and 87 are pending. Claims 1-79, 81, 82, 84-86, and 88-99 remain canceled by Applicant’s amendment. Claims 80, 83, and 87 are being examined on the merits.
Priority
Applicant’s claim for the benefit (as a continuation-in-part (CIP) application) of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 112(a) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed applications, Application Nos. 62/991,174; 62/992,825; 63/005,535; and 63/005,541, fail to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application.
Claim 80 is drawn to a method for treating cytokine storm in a viral disease due to SARS-CoV-2 in a patient in need, however none of the listed provisional patent applications disclose treatment of a cytokine storm. Application Nos. ‘174 and ‘825 disclose antiviral activity of OT-101 and antiviral treatments using antisense or TGF beta inhibitors, however cytokine storms are not disclosed. Application Nos. ‘535 and ‘541 disclose additional data regarding the antiviral activity of OT-101 and ‘535 proposes theories regarding the role of TGF-β2, however cytokine storms are not disclosed. These provisional applications disclose the antiviral activity of the TGF-β2 inhibitor OT-101, however, they provide no disclosure or evidence regarding the role of OT-101 in treating a cytokine storm induced by a viral disease due to SARS-CoV-2 or any other virus.
All other claims depend from claim 80. The earliest priority for the instant Claims 80, 83, and 87 is therefore 6 May 2020 because the provisional Application No. 63/020,889 discloses a TGF-beta storm treatment comprising the TGF-beta inhibitor OT-101 for treatment of COVID-19.
Terminal Disclaimer
The terminal disclaimer filed on 25 November 2025 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of Application No. 18/518,568 has been reviewed and is accepted. The terminal disclaimer has been recorded.
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 80, 83, and 87 are rejected under 35 U.S.C. 103 as obvious over Bogdahn et al. (Neuro-Oncology, 2011, 132-142) in view of Chen (Int J Biol Sci, 2020, pages 1954-1955).
The instant claims are as of record, drawn to a method for treating cytokine storm in a viral disease due to SARS-CoV-2 in a patient in need, the method comprising administering to the patient a composition comprising antisense oligonucleotide SEQ ID No:13 (OT-101; e.g., trabedersen).
Bogdahn et al. teach the antisense nucleotide trabedersen (OT-101; Bogdahn et al., page 133; as required for instant Claim 80) and its administration to patients via a subcutaneous port (intravenous; as required for instant Claim 83) with isotonic saline (sterile saline; Bogdahn et al., Treatment, page 133; as required for instant Claim 87). Trabedersen is known to be an inhibitor of TGF-β2 (Bogdahn et al., page 133; as required for instant Claim 80).
Bogdahn et al. do not teach treating cytokine storm in a viral disease due to SARS-CoV-2 in a patient in need.
Chen, however, teaches that the majority of patients with COVID-19 (e.g., the clinical disease caused by SARS-CoV-2), death has been caused by lung failure due to severe acute respiratory distress syndrome attributed to uncontrolled inflammatory responses characterized by a cytokine storm, particularly a massive increase of TGF- β (Chen, Rational and Hypothesis, page 1954; as required for instant Claim 80). Chen proposes that neutralizing and eliminating excess TGF-β with TGF-β inhibitors could treat this cytokine storm and that clinical trials comprising TGF-β1, 2, and 3 inhibitors should be completed (Chen, Proposed Therapy and Design of clinical trials, page 1955).
It would have been obvious to a person of ordinary skill of the art prior to the effective filing date of the instant application to utilize the method of Bogdahn et al. in patients with SARS-CoV-2 viral infections as taught by Chen in order to treat TGF-β-induced cytokine storms. A skilled artisan would know that trabedersen is a well-known TGF-β2 inhibitor that is safe and well tolerated by patients (Boghdan et al., Discussion, page 140) and would therefore be motivated to provide the drug to patients suffering from SARS-CoV-2 associated cytokine storm. Additionally, a skilled artisan could do so with a reasonable expectation of success because trabedersen is a TGF-β2 inhibitor and cytokine storms in SARS-CoV-2 are associated with increases in TGF-β (Chen, Rational and Hypothesis, page 1954).
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant's arguments filed 19 November 2025 have been fully considered but they are not persuasive.
Applicant’s arguments on pages 3-4 with respect to the Yang reference have been considered but are moot because the new ground of rejection does not rely on this reference as applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Applicant additionally argues that because the OT-101 technology and method for treating cytokine storms was licensed at a market value of over $50,000,000, this secondary consideration overcomes any suggestion of obviousness. Based upon the evidence presented in the 35 USC § 103 rejection presented above, the market value of the invention is not persuasive over the objective evidence of obviousness.
Conclusion
No claims are allowed.
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/J.L.C./Examiner, Art Unit 1655
/AARON J KOSAR/Primary Examiner, Art Unit 1655