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 Election/Restriction filed on June 30, 2026 is acknowledged.
Claims 1-18 are pending in this application.
Restriction
Applicant's election with traverse of the following:
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in the reply filed on June 30, 2026 is acknowledged. The traversal is on the ground(s) that there is no serious burden to the Office. This is not found persuasive because the burden has been established in the previous office action. The species are independent and distinct because tissue regeneration and tissue repair involve different mechanisms. Different species of caspase inhibitors are different due to different components (e.g., small molecules vs peptides), leading to different structures. Different species of TLR3 agonists are different due to different components involved (e.g., small molecules vs RNA), leading to different structures. Different species of route of administration involve different types of formulations (e.g., oral vs topical). Different patient population involve different organs and different end points. Search for each species would not necessarily lead to the other.
The requirement is still deemed proper and is therefore made FINAL. Applicant indicates claims 1, 3, 5, 7-10, 12, 14 and 16-18 read on the elected species. Claims 4 and 13 and are withdrawn from further consideration as being drawn to nonelected species. A search was conducted on the elected species and the species of polyinosinic:polycytidylic acid (Poly I:C) with Q-VD-OPh is free of prior art. A search was extended to ivermectin and prior art was found. Claims 9 and 18 are withdrawn from further consideration as being drawn to species not found in the prior art. Claims are examined on the merits in this office action. 1-3, 5-8, 10-12 and 14-17 are examined on the merits in this office action.
Objections
5. The abstract is objected to for the following minor informality:
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words. It is important that the abstract not exceed 150 words in length since the space provided for the abstract on the computer tape used by the printer is limited. The form and legal phraseology often used in patent claims, such as "means" and "said," should be avoided. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, "The disclosure concerns," "The disclosure defined by this invention," "The disclosure describes," etc.
In the instant case, the abstract recites, “The present invention relates to the field of caspase inhibition...” at line 1 of the abstract. Further, at line 2, the abstract recites, "More specifically, the present invention provides..." Applicant should correct these informalities. See MPEP 608.01(b). For example, the line 1 of the abstract is suggested to be amended to recite, “Caspase inhibition…is described.”
Please note, the specification has not been checked to the extent necessary to determine the presence of all possible error. Applicant's cooperation is required in correcting any errors of which applicant may become aware in the specification. MPEP § 608.01.
6. Claims 6, 8, 15 and 17 are objected to for the following: claims 6, 8, 15 and 17 contain the acronym “TLR3”; claims 8 and 17 also contain the acronym “P1”, and an acronym in the first instance of claims should be expanded upon/spelled out with the acronym indicated in parentheses, i.e., toll like receptor 3 (TLR3) and principal isoform a (P1). The abbreviations can be used thereafter.
7. Claim 6 is objected to for the following: Claim 6 recites, “The method of claim 1, further comprising administering the patient a therapeutically effective amount of a TLR3 agonist.” There appears to be a grammatical error in the claim. Applicant is recommended to amend the claim to recite, “The method of claim 1…administering to the patient a therapeutically effective…”
8. Claim 15 is objected to for the following: Claim 15 recites, “The method of claim 10, further comprising administering the patient a therapeutically effective amount of a TLR3 agonist.” There appears to be a grammatical error in the claim. Applicant is recommended to amend the claim to recite, “The method of claim 10…administering to the patient a therapeutically effective…”
Rejections
U.S.C. 112(b)
9. The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
10. Claims 8 and 17 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
11. Claims 8 and 17 recite, “…wherein the TLR3 agonist is…P1…” It is unclear what P1 is. Instant specification does not clearly define what a “P1” is referring to. Therefore, the metes and bounds of the claims are unclear.
12. Claim 17 recites the limitation "the TLR3 agonist" in the claim. There is insufficient antecedent basis for this limitation in the claim. Claim 17 is dependent from claim 14. Claim 14 recites, “The method of claim 10, wherein the skin or gut injury is a scar or a burn.” Claim 14 does not recite “TLR3 agonist”. Therefore, the is lack of antecedent basis.
U.S.C. 102
13. 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.
14. The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
15. Claim(s) 1-3 and 10-12 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Colak et al (Neurocirugia (Astur), Dec 2009, 20(6): 533-540).
16. Colak et al teach the study of examination of the neuroprotective effects of Q-VD-OPh, a pan-caspase inhibitor, in an in vivo studies (see “Background”). Colak et al teach spinal cord injury (SCI) rat model, treated with Q-VD-OPh (group 3), and Group 3 tissue samples showed five days after injury, the mean apoptotic cell counts was 1.25 +/- 0.34 in group 3, indicating that the number of TUNEL-positive cells in an injured spinal cord was greatly reduced by treatment with Q-VD-OPh. The neurologic function scores were significantly better in the Q-VD-OPh treated group than in the trauma-created control group (see “Results”).
U.S.C. 103
17. 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.
18. 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.
19. 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.
20. This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
21. Claim(s) 1-3, 5-8, 10-12 and 14-17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Colak et al (Neurocirugia (Astur), Dec 2009, 20(6): 533-540) in view of Singec et al (US 2021/0348119) and Cairns et al (ACS OMEGA, 2018, 3: 12392-12402).
22. Colak et al teach the study of examination of the neuroprotective effects of Q-VD-OPh, a pan-caspase inhibitor, in an in vivo studies (see “Background”). Colak et al teach spinal cord injury (SCI) rat model, treated with Q-VD-OPh (group 3), and Group 3 tissue samples showed five days after injury, the mean apoptotic cell counts was 1.25 +/- 0.34 in group 3, indicating that the number of TUNEL-positive cells in an injured spinal cord was greatly reduced by treatment with Q-VD-OPh. The neurologic function scores were significantly better in the Q-VD-OPh treated group than in the trauma-created control group (see “Results”).
The difference between Colak et al is that Colak et al do not teach ivermectin, and that the skin or gut injury is a scar or a burn.
23. Singec et al teach a medium composition comprising components configured to support at least one mammalian cell in vitro or ex vivo and Chronman 1 and/or a derivative thereof (see claim 8), the medium composition further comprising Emricasan and/or a derivative thereof (see claim 10). Singec et al teach “A “stem cell” is a cell characterized by the ability of self-renewal through mitotic cell division and the potential to differentiate into a tissue or an organ. Among stem cells, embryonic and somatic stem cells may be distinguished. For example, mammalian embryonic stem cells may reside in the blastocyst and give rise to embryonic tissues, whereas somatic stem cells may reside in adult tissues for the purpose of tissue regeneration and repair” (see paragraph [0056]). Singec et al teach “The term “caspase inhibitor” refers to small molecules that act by binding to the active site of caspases either in a reversible or irreversible manner. They are available as either pan-caspase or caspase-specific inhibitors. In some embodiments of the invention the caspase inhibitor is a caspase-3 inhibitor. Exemplary caspase-3 inhibitors are Emricasan, Z-VAD-FMK (benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone), Z-DQMD-FMK (Z-Asp(OMe)-Gln-Met-Asp(OMe) fluoromethyl ketone), Z-DEVD-FMK (benzyloxycarbonyl-Asp(OMe)-Glu(OMe)-Val-Asp(OMe)-fluoromethylketone) or Ac-DEVD-CHO (N-acetyl-Asp-Glu-Val-Asp aldehyde)” (see paragraph [0074]), and “The term “Emricasan” refers to 3-(2-(2-tert-butylphenylaminooxalyl) aminopropionylamino)-4-oxo-5-(2,3,5,6-tetrafluorophenoxy)pentanoic acid…Emricasan-related compounds or derivatives are structurally-related compounds” (such as Q-VD-OPh hydrate)” (see paragraph [0075]). Singec et al teach that cell survival improved with Chroman 1 and Emricasan (see for example, EXAMPLE 3).
24. Additionally, Cairns et al teach that ivermectin promotes peripheral nerve regeneration during wound healing (see, for example, Title). Cairns et al teach skin wound of the mouse model and mouse model of diabetic neuropathy (see for example, p. 12393, right column). Cairns et al teach dermal wound healing model, dorsal skin of adult male BALB/c mice (see p. 12399, left column, top) and in vivo model of full thickness skin repair (see p. 12399, right column, top).
25. Therefore, it would have been obvious to one of ordinary skill in the art to combine the teachings of Colak et al and Singec et al and Cairns et al because all of the references teach the promotion of tissue repair/regeneration. One of ordinary skill in the art would be motivated to combine with a reasonable expectation of success, since Singec et al teach that addition of Emricasan and Emricasan-related compounds or derivatives (e.g., Q-VD-OPh) enhanced the cell survival, and Cairns et al teach that ivermectin promotes peripheral nerve regeneration during wound healing, one would at least expect an additive effect. One of ordinary skill in the art would be motivated to administer for enhancing tissue regeneration and/or tissue repair on skin or gut injury wherein the skin or gut injury is a scar or a burn, with a reasonable expectation of success.
The MPEP states that “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); and Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious). But see In re Geiger, 815 F.2d 686, 2 USPQ2d 1276 (Fed. Cir. 1987) (“Based upon the prior art and the fact that each of the three components of the composition used in the claimed method is conventionally employed in the art for treating cooling water systems, the board held that it would have been prima facie obvious, within the meaning of 35 U.S.C. 103, to employ these components in combination for their known functions and to optimize the amount of each additive....Appellant argues... hindsight reconstruction or at best,... obvious to try’.... We agree with appellant.”). One of ordinary skill in the art would have a reasonable expectation of
Improper Markush
26. Claims 3, 8, 12 and 17 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush groupings of pan caspase inhibitor and TLR3 agonist are improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: The pan caspase inhibitors recited in claims 3 and 12 do not share a common core structure because Q-VD-OPh is a peptide and the others are small molecules; the TLR3 agonists recited in claims 8 and 17 do not share a common core structure because RNA is nucleic acids and the others are small molecules.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
CONCLUSION
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JULIE HA whose telephone number is (571)272-5982. The examiner can normally be reached Monday-Thursday 5:00 am- 6:30 pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, LIANKO GARYU can be reached at 571-270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JULIE HA/Primary Examiner, Art Unit 1654
7/16/2026
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