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 .
1. Formal Matters
A. The amendment filed 5/1/26 has been entered.
B. Claims 1-18 are pending and are the subject of this Office Action.
2. Claim Rejections - 35 USC § 112(a) – scope of enablement
The rejection has been withdrawn in view of Applicants’ amendment to claim 7.
3. Claim Rejections - 35 USC § 102
The rejection has been withdrawn in view of Applicants’ amendment to claims 4 and 14.
4. Claim Rejections - 35 USC § 103
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.
A. Claims 1, 7 and 10-13 remain rejected, and new claims 17 and 18 are also rejected, over Zhang for the reasons of record on page 6 of the Office Action dated 2/4/26. Applicants have amended the claims to recite “reduce the risk..20%” and argue that Zhang describe the use of TNF and IFN stimulation to induce a macrophage phenotype, and do not suggest reducing the risk of infection by 20%.
These arguments have been considered, but are not deemed persuasive. While Zhang does discuss macrophage phenotype, the reference places a heavy emphasis on the role of both IFN-γ and TNF-α in severe COVID, making antagonizing them obvious.
The section on page 12 of 17 entitled “Identification of an IFN-γ and TNF-α synergistically driven inflammatory macrophage phenotype expanded in severe COVID-19 lungs and other inflamed disease tissues” initially states –
The blood derived macrophages in cluster 1 included macrophages stimulated by four different conditions all including IFN-γ, of which the most abundant population (37.5%) were macrophages stimulated by TNF-α with IFN-γ (Fig. 4c, d). Comparing our results to a previously reported macrophage spectrum with 28 unique stimulatory conditions [11], we observed the highest expression of cluster 1-associated genes in their macrophages exposed to conditions including both TNF and IFN-γ (Additional file 2: Figure S9a).
And concludes with -
Taken together, these results suggest we are able to recapitulate the gradient observed in vivo across multiple diseases by stimulating macrophages ex vivo with synergistic combinations of IFN-γ and TNF-α
Finally, the last paragraph of the conclusion states –
Our cross-tissue single-cell integrative strategy along with our disease association analysis provides a proof-of principle that identifying shared pathogenic features across human inflamed tissues and COVID-19 lungs has the potential to guide drug repurposing.
Regarding “20%”, this would have been an inherent property of the use of a combination of known IFN-γ and TNF-α inhibitors. Neither the instant claims, nor specification provide any teachings as to any specific inhibitors that would be expected to act in a manner other than what would be expected by the prior art. In addition, it would have been obvious to optimize the dosages in order to treat severe COVID-19 to the fullest extent safely possible. Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 454, 105 USPQ 223,235, (CCPA 1955). Furthermore, "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." In re Boesch, 617 F.2d 272, 276, 205 USPQ 215, 219 (CCPA 1980). See also Merck & Co. v. Biocraft Labs. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1847-48 (Fed. Cir. 1989) (determination of suitable dosage amounts in diuretic compositions considered a matter of routine experimentation and, therefore, obvious) and E.I. DuPont de Nemours & Co. v. Synvina C.V., 904 F.3d 996, 1006 (Fed. Cir. 2018) (“it is not inventive to discover the optimum or workable ranges by routine experimentation.”).
B. Claims 2, 3, 8 and 9 remain rejected and claims 4-6 and 14-16 are also rejected over Zhang et al. in view of Chugh et al. for the reasons already of record on page 6 of the Office Action dated 2/4/26.
Applicants’ arguments regarding Zhang, and the Examiner’s comments, are the same as in paragraph A of this section.
Regarding claims 4-6 and 14-16, given that TNFa and IFNg were singled out by Zhang as targets for inhibition using therapies known at the time, it would haven been obvious to have produced a kit consisting only of inhibitors for these two cytokines.
5. Prior Art of Interest Not Relied Upon
Arnaldez teaches both TNFa inhibitors (page 7, right column) and IFNg inhibitors (page 8, right column) for treatment of COVID-19, but is not currently being used in a rejection under 35 USC 103 in combination with Zhang, since it is believed that, though Arnaldez teaches the use of the claimed inhibitors for COVID-19, the teachings of Zhang, along with Chugh, who teach these well-known inhibitors, is sufficient to make the instant claims obvious even in the absence of a teaching of COVID-19 by Chugh.
5. Conclusion
No claim is allowable.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 extension fee 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 date of this final action.
Advisory information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ROBERT S LANDSMAN whose telephone number is (571)272-0888. The examiner can normally be reached M-F 8 AM – 6 PM (eastern).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Joanne Hama, can be reached at (571)272-2911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ROBERT S LANDSMAN/Primary Examiner, Art Unit 1647
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