FINAL 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 .
Applicant’s amendment and response filed October 9, 2025 is acknowledged.
Status of Claims
Claims 1-6 and 9-13 were previously represented. Claims 14-16 have been withdrawn. Claims 7-8 have been cancelled. Claims 1-6, 9-13 and 17 are under examination.
Rejections Maintained
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.
Brown et al. in view of Novik et al.:
Claim(s) 1-3, 6, 9-11, and 17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Brown et al. (US 2018/0271916 A1; published 27 September 2018) in view of Novik et al. (US 2017/0360836 A1; published 21 December 2017).
As a preliminary matter, please note that Brown et al. refer to their therapeutic composition as Amnion-derived Cellular Cytokine Solution (ACCS), and reference U.S. Patent Nos. 8,058,088 and 8,088,732 for details of making such at [0010]. These documents are incorporated by reference. Please also note that the instant specification indicates at paragraph [0004] that ST266 is described in detail in the same U.S. Patent documents, and incorporates them by reference. Accordingly, ACCS and ST266 are considered to be alternate names for the same therapeutic composition.
Brown et al. teach a method for treating a severe systemic inflammatory response such as cytokine storm caused by viral infections or SIRS in a patient in need thereof comprising the step of systemically administering to the patient a therapeutically effective dose of ACCS/ST266. See [0010]-[0012]. This is relevant to claims 1-3, 10, and 11.
Regarding claim 6, Brown et al. teach the method wherein patient suffers from trauma or burns. See [0017].
Brown et al. do not explicitly teach the reduction in a level of circulating inflammatory cytokine in the patient at least about 17% wherein the circulating cytokine is one or more of IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, KC/GRO, IL-10, IL-12p70, and/or TNF-α as now recited in the amended claims. However, it was recognized in the art that successful treatment of a cytokine storm would bring a dramatic decline in circulating levels of such inflammatory cytokines. For example, Novik et al. teach compositions comprising cell-based components (similar to ACCS/ST66) to treat cytokine storm (a severe systemic inflammatory response) caused by CAR-T cell therapy, wherein the cytokine storm involves pro-inflammatory cytokines including at least IL-10, IL-6, and TNF-α. See abstract, [0004]-[0009], [0016], [0081], [0110]-[0114]. For at least a 17% reduction in IL-10, IL-6, and TNF-α, please see Figures 4A, 4B, and 4E.
Brown et al. also do not explicitly teach the specific therapeutic dosage amounts and ranges recited in claims 9 and 17. However, Brown et al. discuss how one of skill can readily determine the appropriate dose, including for intranasal delivery, based on factors including severity of disease, patient age and weight, etc. See [0084]-[0085]. Intranasal delivery of 0.01 mL (10 µL) to 10,000 mL per dose is taught at [0084]-[0085]. The dosage ranges discussed by Brown et al. at [0085] include the values recited in the claims.
Furthermore, optimization of ranges such as dosages is considered well within the ordinary level of skill in the art, and is thus obvious absent evidence of unexpected results. See M.P.E.P. § 2144.05, section II, OPTIMIZATION OF RANGES:
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In the instant case, there is no evidence of record that the recited dosages are linked to a finding of unexpected results.
Therefore, it would have been obvious to a person of ordinary skill in the art at the time the application was filed to modify the method of Brown et al. by optimizing the dosages to arrive at the claimed dosages with a reasonable expectation of success in view of the teachings of Novik et al. that achieving the recited percentage decreases were possible and desirable. The motivation to do so is provided by Brown et al. who state that dosages can be routinely optimized by the ordinary skilled artisan for maximal effect, and the teachings of Novik et al. regarding the criticality of reducing cytokine storm.
Applicant argues (pp. 4-6, remarks received 10 March 2025) that the claims are not obvious over Brown since Brown does not address the dilution of intravenous drugs and since Brown does not teach the new claim limitations. This has been fully considered but is not found to be persuasive because the rejected claims do not recite intravenous administration, just systemic administration. Brown teaches several types of systemic administration routes. See, e.g., [0050], [0085]. Regarding the new claim limitations, such are addressed with the secondary reference, Novik et al.
Brown et al. in view of Novik et al. and Huang et al.:
Claim(s) 4, 5, 12, and 13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Brown et al. (US 2018/0271916 A1; published 27 September 2018) in view of Novik et al. (US 2017/0360836 A1; published 21 December 2017) as applied to claims 1-3, 6, 9-11, and 17 above, and further in view of Huang et al. (February 2020, Lancet 395:497-506; published on-line January 24, 2020, https://doi.org/10.1016/S0140-6736(20)30183-5).
As discussed above, Brown et al. in view of Novik et al. suggest a method for treating a severe systemic inflammatory response such as cytokine storm caused by viral infections or SIRS or CAR-T therapy in a patient in need thereof comprising the step of systemically administering to the patient a therapeutically effective dose of ACCS/ST266 such that levels of circulatory pro-inflammatory cytokines such as IL-10, IL-6, and TNF-α are drastically reduced. It is further noted that Brown et al. teach intravenous administration at [0050].
Brown et al. do not expressly teach treating a patient having a coronavirus infection such as COVID-19. However, Huang et al. teach that, compared to non-ICU admitted COVID-19 patients, ICU admitted COVID-19 patients had higher levels of several pro-inflammatory cytokines (including IL-10 and TNF-α), suggesting that cytokine storm was associated with disease severity. See abstract; p. 503, 2" paragraph.
Therefore, it would have been obvious to a person of ordinary skill in the art at the time the application was filed to modify the method of Brown et al. in view of Novik et al. by treating patients suffering from SARS-CoV2 (the coronavirus that causes COVID-19) infection and especially those patients experiencing the accompanying cytokine storm in view of Huang et al. A reasonable expectation of success can be found in the disclosure of Brown et al. who discuss how ACCS/ST266 is effective to treat cytokine storm associated with infection and the teachings of Novik et al. that reductions in pro-inflammatory cytokines as per the amended claims was possible and desirable. The motivation to treat COVID-19 patients can be found in Huang et al.’s discussion of how cytokine storm is linked to disease severity in COVID- 19 patients.
Applicant’s Arguments
Applicant’s arguments recap all of the 103(a) rejections that were set forth in the Office action mailed April 9, 2025. Applicant’s arguments with regard to all of the rejection under 103(a) are direct the intravenous administration, especially when the ST266 composition may be diluted by a factor of approximately 1:140(or far greater). Applicant argues that the reference does not teach the claimed dose.
Response to Applicant’s Arguments
Brown teaches intravenous administration and the reference specifically teaches that the dose is a result effective variable that can be determined by one of skill in the art. Therefore, it would be within the capabilities of one of skill in the art to optimize the dose to administer to achieve the reduction in circulating inflammatory cytokines. Further, given that the reference teaches the claimed patient population and the claimed agent, the prior art method would necessarily result in the results (i.e., percent reduction in cytokines) claimed by Applicant.
Although Applicant has submitted a declaration of unexpected results, the evidence is not commensurate in scope with the claims. The claims broadly encompass treating severe inflammatory response in any patient. However, the data in the declaration is directed to a patient population that has COVD-19. The claims are not limited to wherein the systemic inflammatory response is caused by coronavirus, but rather, encompasses SIR caused by infection or non-infectious stressor. This encompasses any viral, bacterial, or yeast infection. Further, the results are not unexpected. Novik teaches that compositions comprising cell-based components (similar to ACCS/ST66) cause a reduction in pro-inflammatory cytokines involved in cytokine storm.
No claims are allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Conclusion
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/VANESSA L. FORD/ Supervisory Patent Examiner, Art Unit 1674