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
Status of Claims
Claims 1-9 and 15-16 are pending and examined.
Election/Restrictions
Applicant's election with traverse CNS disease species, Huntington's Disease, in the reply filed on May 28, 2026 is acknowledged. The traversal is on the ground(s) that all CNS diseases are common to the central nervous system. This is not found persuasive because of the reasons spelled out in the species election requirement. Further, Applicant’s own specification contradicts the traversal where it notes that Huntington’s Disease is a unique CNS disease species associated with mutations in Htt gene, resulting in aggregate formation in nuclei of afflicted cells. See paragraphs 3-5 of the specification.
The requirement is still deemed proper and is therefore made FINAL.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on March 28, 2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Specification
Note to Applicant, References 1-16 in paragraph 7, while noted by the Examiner as part of the specification, does not substitute for Applicant’s obligation to cite to any possible relevant art under MPEP 609.04(a)I.2 via an Information Disclosure Statement.
Claim Objections
Claim(s) 5 and 9 is/are objected to because of the following informalities:
Claim 5, line 2 recites typo “Httgene” rather than “Htt gene.”
Claim 9, line 2 recites “are used as inhibitor. . . ” rather than “are used as an inhibitor. . . . “
Appropriate correction is required.
Claim Interpretation
The claims are directed to a broad class of treating humans subjects in need of any CNS disorders including cerebrovascular diseases, neurodegenerative diseases, multiple sclerosis and depression comprising administering to the subject a therapeutically effective amount of Antcin H and/or derivatives.
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See specification paragraph 39.
Note the claims are directed to derivatives of Antcin H also, the specification provides adequate description to define as such, see below:
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Note claim 9 and its recitation of Antcin H limitation of intended use as an NLPR3 inflammasome inhibitor is rejected as detailed below under 35 USC 112(d).
With regard to claim 15 directed to a package/kit comprising a pharmaceutical composition comprising Antcin H and instructions for use, MPEP 2111.05 I.B., provides guidance applicable here.
Additionally, where the printed matter and product do not depend upon each other, no functional relationship exists. For example, in a kit containing a set of chemicals and a printed set of instructions for using the chemicals, the instructions are not related to that particular set of chemicals. In re Ngai, 367 F.3d at 1339, 70 USPQ2d at 1864.
The above scenario is applicable to claim 15. MPEP 2111.05 states with regarded to printed instructions, "[O]nce it is determined that the limitation is directed to printed matter, [the examiner] must then determine if the matter is functionally or structurally related to the associated physical substrate, and only if the answer is ‘no’ is the printed matter owed no patentable weight." Because there is no functional relationship per the example of In re Ngai and MPEP 2111.05, the instructions of claim 15 are given no patentable weight.
While the instructions are not stated to be “printed” is unknown what form the instructions would take in claim 15, so they are interpreted to be printed matter per MPEP 2111.05. The specification does provide any guidance with regard to packages and instructions other than merely reciting them.
With regard to claim 16 and its composition’s intended use limitations of treating a subject afflicted with CNS diseases, this limitation is given no patentable weight, it does NOT result in a structural difference between the claimed invention and prior art. MPEP.02 2111(II). While MPEP 2111.02 is directed to the Effect of the Preamble, it is relevant here to discuss intended use of the pharmaceutical composition of claim 16. Prior art teaching a pharmaceutical composition comprising Antcin H per se will teach the structural elements of said pharmaceutical composition of claim 16, regardless of the stated intended use.
Claim Rejections - 35 USC § 112 (d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 9 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 9 depends from method/process claim 1.
Claim 9 recites “wherein said Antcin H and/or its derivatives are used as inhibitor of the NLRP3 inflammasome.” Both the specification and art recognize Antcin H is an inhibitor of NLRP3 inflammasome. See paragraph 6 citing to references Heneka et al., Song et al. and Shao et al.3
However, the recitation of intended use to inhibit NLRP3 inflammasome does not further limit the claimed method by a process step or further limit the composition comprising Antcin H per se, because it merely recites an intended use of inhibitory property necessarily present in Antcin H.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 112 (a)
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.
Claim(s) 1-4 and 6-9 is/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 treatment of Huntington’s disease with Antcin H per se (not derivatives), does not reasonably provide enablement for the full scope of treating CNS disorders with the full scope derivatives. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
Applicant’s attention is drawn to In re Wands, 8 USPQ2d 1400 (CAFC1988) at 1404 where the court set eight forth factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors: (1) the nature of the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary.
The predictability or unpredictability of the art:
The instant claimed invention is highly unpredictable since a person having ordinary skilled in the art (PHOSITA), recognizes the protective effects of Antcin H isolated from Antrodia cinnamomea in Huntington’s Disease models via NLRP3 inflammasome inhibition. See Chang et al.4
In contrast, to Chang and demonstrative that the full scope of the invention is not enabled as noted in the art.
For example, with regard to CNS disease, Parkinson’s disease (PD), while there is promising research that “NLRP3 inflammasome is currently a promising target for PD treatment, there is a considerable knowledge gap in the complex interaction between the NLRP3 inflammasome and other PD mechanisms and finding promising therapeutic candidates and demonstrating efficacy even in complex mechanisms.” See Nguyen et al.5
Therefore, the unpredictability of treating all CNS diseases as noted by the art is a Wands factor against the full scope of enablement of the claims.
The breadth of the claims
The instant claims are deemed very broad since these claims read on treatment of any CNS diseases with any Antcin H derivative. The broad scope is a Wands factors weighing against enablement of the full scope.
The amount of direction or guidance presented, and the presence or absence of working examples: It has been established that “the amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art.” In re Fisher, 427 F.2d 833, 839 166 USPQ 18, 24 (CCPA 1970).
It is pointed out that there are no working examples to support the full scope of CNS diseases, let alone the full scope of Antcin H derivatives.
At best, Examples 1-10, starting at paragraph 57, are all directed solely to Antcin H in various in vitro cell models of Huntington’s Disease, and in vivo mouse models of Huntington’s Disease.
The lack of working examples is a Wands factor against the full scope of enablement of the claims.
Therefore, in view of the Wands factors as discussed above, Applicant fails to provide information sufficient to practice the full scope of the claimed invention.
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.
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.
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.
Claim(s) 1-9 and 15-16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kumar and Ratan Oxidative Stress and Huntington’s Disease: The Good, The Bad, and The Ugly J. of Huntington's Disease Volume 5, Issue 3, 1 October 2016, Pages 217-237 in view of Huo et al. Antcin H Protects Against Acute Liver Injury Through Disruption of the Interaction of c-Jun-N-Terminal Kinase with Mitochondria Antioxidants & Redox Signaling Vol: 26 Iss: 5 Pp.: 207-220 DOI: 10.1089/ars.2016.6833
Kumar and Huo are cited on the PTO-892 form.
Regarding claims 1-5, Kumar teaches the claimed Huntington’s Disease human subject in need of treatment. See title and abstract. In particular, Kumar teaches that mitochondrial dysfunction is considered to be one of the key defects in HD pathogenesis human subjects. See page 225, column 1. Kumar notes that findings in recent studies are consistent with the notion that mitochondrial dysfunction and/or oxidative stress occurs at relatively late stages of the HD phenotype based on the timing in these HD models. See page 225, column 2.
Kumar notes that oxidative stress in Huntington’s Disease occurs when oxidants imbalance a cell’s antioxidants resulting in cell damage, dysfunction or death, where cells produce these oxidants in the form of reactive oxygen species (ROS). See page 218, column 1.
While Kumar teaches the claimed subject in need, it does not teach administration of Antcin H to a subject.
Huo teaches Antcin H was studied to be administered to subjects suffering from APAP induced injury. See abstract. Huo teaches “Antcin H blocks mitochondrial ROS generation induced by APAP, but is not a direct scavenger or antioxidant.” See page 210, column 2. Huo does not teach the claimed subject in need, suffering from Huntington’s Disease (HD).
Prior to the filing of the present patent application, it would have been prima facie obvious to a person having ordinary skill in the art (PHOSITA) following the prior art elements teachings of the Kumar to treat the HD subject in need modified by (i.e. according to the known methods of Huo) to administer Antcin H, based on its properties to lower mitochondrial ROS, to predictably arrive at the claimed invention. See MPEP 2143(a).6
The PHOSITA would have had a reasonable expectation of success because Kumar notes in subjects in need, HD is characterized by mitochondrial dysfunction and oxidative stress caused by reactive oxygen species (ROS), where Huo teaches Antcin H reduces ROS in the mitochondria of cells.
Regarding claim 6, Huo teaches Antcin H was isolated from Antrodia Camphorate (AC), i.e. sourced naturally. See page 217, column 1.
Regarding claim 7, Huo teaches were dosed at 25 and 50 mg/kg of Antcin H in a corn oil carrier within a 24 h period, falling within the claimed range of 0.001 mg/kg/day to about 500 mg/kg/day. See Fig. 1.
Regarding claim 8, Huo teaches i.e. aka intraperitoneal injection (parenteral) of Antcin H to its subjects. See page 208, column 2.
Regarding claim 9, while Huo does not teach the intended use of Antcin H as an inhibitor of NLRP3 inflammasome, such intended use was determined not to further limit the method/process of claim 1 from which claim 9 depends. See above. The intended use of inhibiting NLPR3 inflammasome is not a further limiting process step as it merely recites an intended use of property necessarily present to Antcin H. Further, as an intended use of a composition comprising Antcin H, it does not further limit said composition because the intended use merely describes a property that is necessarily present in a composition comprising Antcin H.
Regarding claim 15, noting a package comprising a composition comprising Antcin H, a unit dose comprising 0.001-500 mg Antcin H and instructions for use to treat a CNS disease. As detailed above per MPEP 2111.05 in the claim interpretation section of this action, the instructions are given no patentable weight.
With regard to the “package” limitation, while not expressly taught by Huo, the Examiner broadly and reasonably interprets that Huo must have placed the Antcin H in corn oil in some vessel or container, which reads upon a package of claim 15.
Further, while the claim recites 0.001-500 mg Antcin H in the package, a PHOSITA would routinely optimize in arriving at such an amount, where Huo teaches its doses 25 mg/kg and 50 mg/kg doses, formulated from purified Antcin H in a corn oil carrier. See Fig. 1. A package comprising a composition comprising Antcin H in the claimed amount range would be routine to arrive at by a PHOSITA because Huo teaches doses to be administered clinically to a subject.
Regarding claim 16, as detailed above, the intended use limitation of the claimed composition is given minimal to no patentable weight, the pharmaceutical composition comprising Antcin H in a unit dose of 0.001-500 mg Antcin H, stands on its own in terms of prior art analysis.
Further, while the claim recites 0.001-500 mg Antcin H in the composition, a PHOSITA would routinely optimize in arriving at such an amount, where Huo teaches its doses 25 mg/kg and 50 mg/kg doses, formulated from purified Antcin H in a corn oil carrier. See Fig. 1. A composition comprising Antcin H in the claimed amount range would be routine to arrive at by a PHOSITA because Huo teaches doses to be administered clinically to a subject.
Conclusion and Correspondence
In summary no claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to WILLIAM LEE whose telephone number is (571)270-3876. The examiner can normally be reached M-F.
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, Adam C. Milligan can be reached at (571) 270-7674. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/WILLIAM Y LEE/Examiner, Art Unit 1623
/GEORGE W KOSTURKO/Primary Examiner, Art Unit 1621
1 CONTINUING DATA
This application is a 371 of PCT/CN2021/121859 09/29/2021
PCT/CN2021/121859 has PRO 63/084,969 09/29/2020
2 The list of information complying with the format requirements of 37 CFR 1.98(a)(1) and the identification requirements of 37 CFR 1.98(b) may not be incorporated into the specification of the application in which it is being supplied, but must be submitted in a separate paper.
3 Heneka, M.T., McManus, R.M. & Latz, E. lnflammasome signaling in brain function and neurodegenerative disease. Nat Rev Neurosci 19, 610-621 (2018).
Song L, Pei L, Yao S, Wu Y and Shang Y (2017) NLRP3 lnflammasome in Neurological Diseases, from Functions to Therapies. Front. Cell. Neurosci. 11 :63.
Shao B-Z, Cao Q and Liu C (2018) Targeting NLRP3 lnflammasome in the Treatment of CNS Diseases. Front. Mal. Neurosci. 11 :320.
4 Chang et al. Protective Effects of Antcin H Isolated from Antrodia cinnamomea Against Neuroinflammation in Huntington’s Disease via NLRP3 Inflammasome Inhibition. J Neuroimmune Pharmacol 20, 1 (2025). https://doi.org/10.1007/s11481-024-10161-7 Published: 02 December 2024
5 Nguyen et al. Role of NLRP3 Inflammasome in Parkinson's Disease and Therapeutic Considerations. J Parkinsons Dis. 2022;12(7):2117-2133. doi: 10.3233/JPD-223290. PMID: 35988226; PMCID: PMC9661339.
6 (a) combining prior art elements according to known methods to yield predictable results
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