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 .
Status of the Application
The amendment and election of 1 June 2026 are entered.
Claims 1-15 are pending. Claims 14 and 15 are withdrawn without traverse. Claims 1-13 are being examined on the merits.
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-13) in the reply filed on 1 June 2026 is acknowledged.
Claims 14 and 15 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 1 June 2026.
Drawings
The drawings are objected to because the figures are of low resolution such that several panels are not readable. See at least Figures 1A 3A, 4I, 5K, 11A, and 12K. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
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 and 5-13 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 a method of treating diabetes or fatty liver disease by administering isthimin-1, does not reasonably provide enablement for a method for treatment of a glucose and lipid-associated disorder by administering an isthmin-1 agent. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
“[T]o be enabling, the specification of a patent must teach those skilled in the art how to make and use the full scope of the claimed invention without ‘undue experimentation.’” Genentech Inc. v. Novo Nordisk 108 F.3d 1361, 1365, 42 USPQ2d 1001, 1004 (Fed. Cir. 1997); In re Wright 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993); See also Amgen Inc. v. Chugai Pharm. Co., 927 F.2d 1200, 1212, 18 USPQ2d 1016, 1026 (Fed. Cir. 1991); In re Fisher 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). Further, in In re Wands 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988) the court stated:
Factors to be considered in determining whether a disclosure would require undue experimentation have been summarized by the board in Ex parte Forman [230 USPQ 546, 547 (BdPatAppInt 1986)]. They include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredict-ability of the art, and (8) the breadth of the claims.
A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557,1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).
Nature of the Invention
The invention is drawn to a method of treating a glucose and lipid-associated disorder in a subject. The method is achieved by administering an isthimin-1 agent in a dose sufficient to reduce symptoms.
Breadth of the Claims
The claims are somewhat broad. A glucose and lipid-associated disorder is broadly claimed. Given the claim language of “associated disorder” this does not limit to any particular disorder but any conditions where glucose and lipids are involved. For instance, high cholesterol in diabetic patients can be a glucose and lipid-associated disorder.
The isthmin-1 agent is somewhat broad as it encompasses both polypeptides as well as nucleic acid sequences per the definition as found in [0044].
State of the Prior Art
As noted below, the prior art in Svensson K (NIH 1R01DK125260-01) discloses isthmin-1 as a novel therapeutic to treat diabetes. This reasonably leads to treatment of type 1 and type 2 diabetes.
The prior art does not disclose any treatment of lipid-associated disorders such as NAFLD or NASH with isthmin-1.
Isthmin-1 is suggested as a treatment for lung disorders including inflammation (see e.g. WO 2020/0180256 A1).
Relative Skill of those in the Art
The relative skill of those in the art is high.
Predictability or Unpredictability of the Art
There is a general lack of predictability in the pharmaceutical art. In re Fisher, 427, F. 2d 833, 166, USPQ 18 (CCPA 1970).
Amount of Direction or Guidance Given
The specification does not offer specific guidance that limits a glucose and lipid-associated disorder to specific examples through a definition. The specification reasonably guides one of ordinary skill to understand that type 2 diabetes and fatty liver diseases fall under the purview of a glucose and lipid-associated disorder.
The specification guides that an isthmin-1 agent refers to both polypeptides and nucleic acids that encode them. The isthmin-1 terminology is further defined to encompass native sequences, variants, fragments, and chimeric ISM1 polypeptides (see e.g. [0044]). No particular guidance is present on critical regions or residues that might lead to production of variants, fragments, and chimeric ISM1 polypeptides or nucleic acids thereof.
Presence/Absence of Working Examples
The working examples demonstrate that ISM1 can serve to treat type 2 diabetes and fatty liver diseases. No Examples show administration of a nucleic acid treats a glucose and lipid-associated disorder. No Examples show that variants, fragments, or chimeras serve to treat a glucose and lipid-associated disorder.
Quantity of Experimentation Necessary
In this case, while the skilled artisan is provided with assays and means to determine if isthmin-1 can treat type 2 diabetes and fatty liver disease, the onus is left entirely on the skilled artisan to assess isthmin-1 variants, fragments, chimeras, and nucleic acids thereof for the ability to treat. Similarly, the onus is left on the skilled artisan to prepare assays and models to cover the range of glucose and lipid-associated disorders as claimed, and in turn determine not only if ISM1 treats the genus but if the claimed genus of ISM1 agents also treats across the genus. Since there is no apparent knowledge on critical portions of ISM1 to allow for biological activity, this combined with the need to test across a broad genus of disorders leads to a level of undue experimentation.
In view of the Wands factors as discussed above, it is the Examiner’s opinion that the claims are not fully enabled and one of skill in the art would have to engage in undue experimentation to practice the invention as claimed herein, without a reasonable assurance of success.
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.
Claim 5 is 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.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 5 recites the broad recitation “one or more disease indicia”, and the claim also recites “including reduction of liver weight or mass; reduction of blood glucose; reduced hepatic Fatty Acid Synthase (FAS) protein levels; and reduction of hepatic steatosis” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
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.
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.
Claims 1, 2, and 7-9 are rejected under 35 U.S.C. 103 as being unpatentable over Svensson K (NIH Project 1R01DK125260-01, published July 2020, hereafter referred toa s Svensson).
Please note that the NIH lists a Budget Start Date of 1 July 2020, and notes in the FAQs for RePORTER that materials are generally published within 7-10 days of the budget start date (see e.g. https://report.nih.gov/faqs).
The Svensson art discloses that isthmin-1 promotes glucose uptake in mouse and human adipocytes (see e.g. Abstract). Svensson also discloses that Ism1 improves glucose homeostasis in animals rendered diabetic through high fat feeding (see e.g. Abstract). Svensson suggests that Ism1 may be useful for overcoming insulin resistance and diabetes independent of insulin (see e.g. Abstract).
The Svensson art does not explicitly disclose a method of treating a glucose and lipid-associated disorder. However, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to utilize the disclosure of Svensson to derive a method of treating diabetes in a subject by administering isthmin-1. The rationale comes from Svensson disclosing the utility of Ism1 for improving glucose homeostasis and also suggesting it as an insulin-independent therapy for insulin resistance and diabetes. There would have been a reasonable expectation of success because the base utility of Ism1 was set forth by Svensson and the skilled artisan merely has to utilize subjects and monitor treatment in accordance with the suggestion of Svensson. The invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
With respect to claim 2, Svensson reasonably provides for treatment of type 2 diabetes.
With respect to claims 7 and 9, Svensson provides for administration of Ism1.
With respect to claim 8, treatment of a human would be an obvious choice for treatment of diabetes.
Allowable Subject Matter
Claims 3 and 4 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter: As noted above, the prior art does not recognize treatment of NASH, NAFLD, or concomitant treatment of hyperglycemia and hyperlipidemia with administration of isthmin-1. The closest art in Svensson leads to treatment of diabetes with isthmin-1, but provides no rationale or disclosure to lead to treatment of any lipid-associated condition such as NASH or NAFLD, nor reduction in hyperlipidemia. The claims are novel and unobvious pending consideration of any amendments Applicants may make in response to this Action.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ZACHARY J MIKNIS whose telephone number is (571)272-7008. The examiner can normally be reached M-F 9-5.
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, Melissa Fisher can be reached at (571) 270-7430. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ZACHARY J MIKNIS/Patent Examiner, Art Unit 1658
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