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 .
DETAILED ACTION
This application is in response to the papers filed on April 23, 2026. Claims 1-4, 7-11, 16-24, 31, and 33 are currently pending as per amendment to the claims filed on April 23, 2026. No claims have been amended, cancelled, or added in this amendment.
Applicant’s election without traverse of the invention of Group I, claims 1-4, 7-11, 16-24, drawn to a method of inducing biostasis in a tissue or organ, the method comprising contacting the tissue or organ in need of preservation with an agent that alters the function of at least one ion channel selected from the group consisting of EAAT1 ion channel and NCX1 ion channel, wherein the contacted tissue or organ exhibits biostasis, in the reply filed on April 23, 2026 in response to the restriction requirement filed on October 23, 2025 is acknowledged.
Claims 31 and 33 are withdrawn from further consideration by the Examiner, pursuant to 37 CFR 1.142(b), as being drawn to non-elected inventions, there being no allowable generic or linking claim. Reinstatement of claims drawn to non-elected inventions will be withdrawn during prosecution. The requirement for restriction between Groups I-II is maintained for reasons of record, and hereby made FINAL. Applicant timely responded to the restriction (election) requirement in the paper filed on April 23, 2026.
Therefore, claims 1-4, 7-11, 16-24 are currently under examination to which the following grounds of rejection are applicable.
Priority
The present application is a 35 U.S.C. 371 national stage filing of the International Application No PCT/US2021/012626, filed January 8, 2021. Applicant’s claim for the benefit of prior-filed parent provisional applications 63/020,475 filed on May 5, 2020 and 62/959,372 filed on January 10, 2020 under 35 U.S.C.119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged.
Thus, the earliest possible priority for the instant application is January 10, 2020.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on July 8, 2022 and December 29, 2023 were filed. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. There is an embedded hyperlink in paragraph 0393.
The disclosure is objected to because of the following informalities: SNC-80 is spelled incorrectly in paragraph 0398 line 6, as it is spelled “SNC-90.”
Appropriate correction is required.
Claim Objections
Claims 11 and 22 are objected to because of the following informalities:
Claim 11 appears to have improperly spaced lines 2 and 3 after the “or” in line 2.
Claim 22 has a typo as seen in the recitation “36 hours 48, hour,…”. Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
Claims 3, 4, 17, 18 and 20 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.
Claims 3 and 4 recites the limitation "the δ-opioid receptor". There is insufficient antecedent basis for this limitation in the claim. In particular, there is no introduction of such receptor prior to these claims, and therefore is unclear which δ-opioid receptor is being referenced.
Claims 17 and 20 recite the limitation "the agonist". There is insufficient antecedent basis for this limitation in the claim. In particular, there is no introduction of such agonist prior to these claims, and therefore is unclear which agonist is being referenced.
The term “substantially” in claim 17 is a relative term which renders the claim indefinite. The term “substantially” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Claim 18 is rejected by dependency to claim 17.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-4, 7-11, 16-24 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for using SNC-80 or Donepezil on a limb or cancer cells for the reduction in oxygen uptake and metabolic rate, and therefore biostasis, it does not reasonably provide enablement for any agent or agonist that alters the function of a EAAT1 ion channel and/or NCX1 ion channel in any organ or tissue, wherein the contacted tissue or organ exhibits biostasis. In particular, the scope encompasses chemical agents that have a particular effect, as opposed to claiming a chemical agent by structure and function.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
The factors to be considered in determining whether undue experimentation is required are summarized In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988). The Court in Wands states: "Enablement is not precluded by the necessity for some experimentation such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is 'undue,' not 'experimentation.' " (Wands, 8 USPQ2d 1404). Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. "Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations." (Wands, 8 USPQ2d 1404). The factors to be considered in determining whether undue experimentation is required include: (1) The breadth of the claims; (2) The nature of the invention; (3) The state of the prior art; (4) The level of one of ordinary skill; (5) The level of predictability in the art; (6) The amount of direction provided by the inventor; (7) The existence of working examples; and (8) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. While all of these factors are considered, a sufficient amount for a prima facie case is discussed below.
(1) The breadth of the claims and (2) The nature of the invention. The claims are directed to a method, particularly claims 1 is directed to a method of inducing biostasis in a tissue or organ, the method comprising contacting the tissue or organ in need of preservation with an agent that alters the function of at least one ion channel selected from the group consisting of EAAT1 ion channel and NCX1 ion channel, wherein the contacted tissue or organ exhibits biostasis. The scope encompasses any agent or agonist that impacts these receptors, and furthermore the tissue or organs to be treated is not limited. In reference to the limitation “biostasis” the Specification describes it as the following: “As used herein, "biostasis" refers to a state of a biological system in which metabolism is slowed and energy demands reduced such that a cell, tissue, organ or a whole organism remains viable but respiration, biochemical processes and metabolic demands are reduced such that the system maintains viability under conditions that, absent the induction of the biostatic state, would normally kill the cell, tissue, organ or organism. As the term is used herein, biostasis is reversible, such that the cell, tissue, organ or organism returns to substantially normal metabolic and physical activity upon withdrawal of an inducer or inducers of biostasis.” (par 0115).
(3) State of the prior art. The prior art is extensive in the knowledge of different agents that alter the function of either EAAT1 or NCX1. The Specifications describes each receptor (par 0200-0203), and states, “Inhibitors of EAAT1 are known in the art, and include, but are not limited to L-transPyrrolidine- 2,4-dicarboxylic acid, L-(-)-threo-3-Hydroxyaspartic acid, and UCPH 101.”; “Inhibitors of NCXl are known in the art, and include, but are not limited KB-R7943 Mesylate, Aprindine, and SN-6. While the mesylate salt of KB-R.7943 is noted here, it is specifically contemplated that other salts of KB-R 7943 would have similar activity.” However, the prior art does not teach the connection of these inhibitors in relation to biostasis of select organs and tissues.
Specification paragraph 0384 describes that the prior art has investigated δ-opioids function in torpor and hibernation, and that dosing with agonists have led to reduction in body temperatures, further stating that delta2 opioid receptors in the brain were responsible for the hypothermia response, and that the compound SNC-80 a δ-opioid receptor agonist have induced such response. The stating that “this molecule has never been explored or suggested to be useful to induce a hypometabolic state for tissue, organ, limb, or whole organism preservation.” However, the connection of these agonists to the aforementioned receptors is not clearly taught in the prior art, and therefore it is unclear that any agent that acts on these receptors would have an effect on biostasis. Furthermore, it is not clear if the outcomes observed by the Applicant would be similar across structurally similar chemical compounds, and would function similarly across different organs and tissues. There remains much unpredictability with the full scope presented in the claims.
(4) The level of one of ordinary skill. There is a high level of skill required as seen in determining the full extent of agents that would act on the claimed receptors while also having an impact on biostasis, and moreover conducting such studies on different types of organs and tissues to determine if these outcomes are shared.
(5) The level of predictability in the art. The art is unpredictable. As described above, the engineering of endonucleases, particularly I-CreI reveal that select nucleotides, and therefore the respective amino acids can be altered while some should be conserved to maintain catalytic activity. Moreover, there is no single approach for determining such modifications in addition to the specific methods of altering the I-CreI nuclease accordingly. Altogether, the 80% sequence similarity scope for SEQ ID NO: 1 is not enabled as it is not clear that the full range of sequence differences with the wild-type would allow for a functional nuclease.
(6) The amount of direction provided by the inventor; (7) The existence of working examples of working examples.. The Specification describes studies for the following as seen through the Examples: Example 1 describes how SNC-80 induce a torpor-like hypometabolic state in cell culture and whole animal (tadpole) models, stating “ It was shown herein that the compound results in a dose-dependent reduction in oxygen consumption and other metrics of metabolic rate in health tissues and whole organism (Xenopus tadpoles). Importantly, the compound at higher concentrations(> 100 uM) results in arrest of tadpole movement that can be subsequently reversed by removal of the drug. It was also shown that the dosing of SNC-80 on Xenopus embryos results in an approximately 50% similarity of the resulting gene regulatory network compared to Arctic ground squirrels during torpor, indicating that the drug indeed mimics torpor mechanistically to induce a similar physiological profile. Interestingly, while it was found that SNC-80 slows metabolism of cultured intestinal cancer cells (Caco-2 cells) as measured by a reduction in intracellular ATP levels, it did not inhibit oxygen utilization in these transformed cells.” (par 0385). The example teaches SNC-80 for tadpoles and cancer cells (Caco-2), and the findings are represented in Fig. 1-12. Example 2 explored similar outcomes with Donepezil for biostasis in Xenopus tadpoles. The compound had reduced tail-length over control and over SNC-80, furthermore oxygen consumption was markedly reduced compared to the other groups (Fig. 13A,B). The drug was seen to reduce movement at select dosages with the effect being reversible, and lastly did not have decreased cognitive or motor function performance (Fig. 14 and 15). Example 3 explored the effect of SNC-80 on a detached pig limb. The findings were SNC-80 had induced biostasis in the limb, and could reduce oxygen uptake greater than hypothermic conditions (Fig. 17-19).
The examples do not provide clarity to how the employed agents relate to EAAT1 and NCX1 receptors. The Specification does state “The therapeutic range of 5mg-23mg Donepezil for treatment of Alzheimer's disease is not sufficient to alter the function of the EAAT11 and/ or NCX 1 ion channels.” (par 0184), and further describes that despite such dosage for biostasis as being toxic to an individual, that it will not have a toxic effect on an isolated cell, tissue or organ when administered or contacted at 50μM for at least 30 minutes. Therefore, such dosage should be recited in the method of using since select dosages would not impart biostasis.
(8) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. There would be extensive experimentation required to determine which chemical compounds would alter the function of the claimed receptors, and furthermore provide biostasis effects. It would also require further experimentation to determine select dosages, and which tissues or cells can be contacted for such treatments.
Conclusion: The claims are enabled for SNC-80 and Donepezil at select dosages for limbs and/or cancer cells for biostasis wherein oxygen consumption is reduced and metabolism is reduced.
Conclusion
Claims 1-4, 7-11, 16-24 are rejected. No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHAEL A RIGA whose telephone number is (571)270-0984. The examiner can normally be reached Monday-Friday (8AM-6PM).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maria G Leavitt can be reached at (571) 272-1085. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MICHAEL ANGELO RIGA/Examiner, Art Unit 1634
/TERESA E KNIGHT/Primary Examiner, Art Unit 1634
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