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 Claims
Claims 2, 4, 9, 12-14, 16, 21-23, and 25-34 are pending.
Priority
Applicant’s claim for benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged. This application is a national stage entry of and claims priority to Application Serial No. PCT/US2023/019686, filed 4/24/2023; and further claims priority to PRO application numbers 63/334,624, filed 04/25/2022, respectively.
Information Disclosure Statement
All references from IDS(s) received on 10/23/2024 have been considered unless marked with a strikethrough.
Claim Rejections - 35 USC § 102
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 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 2, 4, 9, 12-13, 16, 22, 25-26, 28, 30-31, and 33 are rejected under 35 U.S.C. 102(a)(1)/(2) as being anticipated by Lamming, W. et al. (US20190059433A1; “Lamming”).
Lamming teaches a method of improving metabolic health in a mammalian subject, for the ultimate goal of weight loss (field of disclosure) in need of improvement in metabolic health due to excess weight or poor control of blood glucose levels, comprising administering to the mammalian subject a compound (Claim 19), wherein the compound is a LAT1 inhibitor, including JPH203 (Claims 20-21 and para. 0154), as required by instant claims 2, 22, 28, and 33.
Lamming teaches that improving metabolic health includes reducing accumulation of white adipose tissue, including epididymal white adipose tissue (para. 0036), as required by instant claims 4 and 9.
Lamming teaches the compound may be administered orally (para. 0133), a form of systemic administration, as required by instant claims 12, 13, 25, 26, 30 and 31.
Lamming teaches the subject is a human (Claim 3), as required by instant claim 16.
Therefore, the limitations of claims 2, 4, 9, 12-13, 16, 22, 25-26, 28, 30-31, and 33 are anticipated by Lamming.
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 2, 4, 9, 12-13, 16, 21-23, 25-26, 28-31, and 33-34 are rejected under 35 U.S.C. 103 as being unpatentable over Lamming, W. et al. (US20190059433A1; “Lamming”) in further view of Zhou, J. et al. (Hepatol Commun. 2022 Jan 11;6(6):1301–1321; “Zhou”).
Lamming teaches a method of improving metabolic health in a mammalian subject, for the ultimate goal of weight loss (field of disclosure) in need of improvement in metabolic health due to excess weight or poor control of blood glucose levels, comprising administering to the mammalian subject a compound (Claim 19), wherein the compound is a LAT1 inhibitor, including JPH203 (Claims 20-21 and para. 0154), as required by instant claims 2, 22, 28, and 33.
Lamming teaches that improving metabolic health includes reducing accumulation of white adipose tissue, including epididymal white adipose tissue (para. 0036), as required by instant claims 4 and 9.
Lamming teaches the compound may be administered orally (para. 0133), a form of systemic administration, as required by instant claims 12, 13, 25, 26, 30 and 31.
Lamming teaches the subject is a human (Claim 3), as required by instant claim 16.
With respect to claim 21, Lamming does not explicitly teach an example where LAT1 inhibitors increase white adipose tissue browning. However, Lamming does teach that the increased energy expenditure mediated by FGF21 is associated with browning of white adipose tissue and increased activation of brown adipose tissue.
However, Zhao teaches the liver could regulate adipose tissue inflammation, lipid storage, and white adipose tissue (WAT) browning by secreting regulatory molecules. Thus, the molecular signals connecting the liver to adipose tissues may be viable targets for interventions to mitigate NAFLD and obesity (Introduction, para. 2). Zhao teaches that WAT browning is responsible for energy production and suggests that energy expenditure is a mechanism that contributes to the attenuation of obesity (Hepatocyte‐Specific Tgfbr2 Deletion Promotes the Expression of Thermogenic Genes in WAT).
Zhao fails to teach LAT1 or LAT1 inhibitors. However, Zhao generally teaches some underlying mechanisms of obesity and NAFLD. Therefore, it would be obvious to a person skilled in the art that by using a LAT1 inhibitor known to treat obesity or NAFLD, the LAT1 inhibitor would treat the underlying mechanisms of obesity, such as promoting WAT browning, as required by claim 21.
Knowing the underlying mechanisms, a person skilled in the art would be motivated to modify the LAT1 inhibitor to target the adipose tissue, as required by instant claims 23, 29, and 34.
The Supreme Court in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper "functional approach" to the determination of obviousness as laid down in Graham.
Examples of rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) "Obvious to try" – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Applying KSR example rationale (A), it would have been prima facie obvious to extract the method of improving metabolic health in a subject in need of a weight reduction using a LAT1 inhibitor, as taught by Lamming, and use the compound to improve white adipose tissue browning, as motivated by the teachings of Zhou. Further, this would motivate the POSITA to modify the inhibitor to promote adipose tissue targeting.
Therefore, claims 2, 4, 9, 12-13, 16, 21-23, 25-26, 28-31, and 33-34 would be obvious to a person skilled in the art at the time.
Claims 2, 4, 9, 12-14, 16, 21-23, and 25-34 are rejected under 35 U.S.C. 103 as being unpatentable over Han, S. et al. (Sci Rep 6, 37468 (2016); cited in IDS filed 10/23/2024; “Han”) in further view of Zhou, J. et al. (Hepatol Commun. 2022 Jan 11;6(6):1301–1321; “Zhou”) and Zhang, J. et al. (Front Chem. 2020 Oct 20;8:564809.) as evidenced by Tanaka, M. et al. (Diabetol Metab Syndr. 2020 Nov 25;12:103.; “Tanaka”)
Han teaches the use of a LAT1 inhibitor, such as BCH, for use in preventing metabolic alterations caused by high fat/high fructose diets, including improving liver metabolism and insulin resistance.
With respect to independent claim 2, Han teaches this mimics metabolic conditions in fasting and calorie restriction states and can be used as a new strategy to prevent western diet-induced NAFLD and T2D (Conclusion). Nonalcoholic fatty liver disease (NAFLD) and obesity are associated with the prevalence and incidence of type 2 diabetes, cardiovascular disease, carcinogenesis, and other metabolic diseases, as taught by Zhou.
With respect to claims 4 and 9, Han teaches BCHs activity in stimulating reductive amination reduces high calorie western diet-induced fatty liver and insulin resistance through activation of the SIRT/AMPK/PGC-1α axis (Introduction, para. 4).
Han fails to explicitly teach inguinal and epididymal white adipose tissue. However, it is known that white adipose tissue, such as inguinal and epididymal white adipose tissue, is a driver of mitochondrial biogenesis in the liver, as taught by Zhao (Hepatocyte‐Specific Tgfbr2 Deletion Promotes the Expression of Thermogenic Genes in WAT). Therefore, by treating fatty liver, the LAT1 inhibitor would reduce white adipose tissue.
With respect to claims 12-14, 25-27, and 30-32, Han teaches the administration of BCH intraperitoneally (Animal Treatment para.). Intraperitoneal administration includes administration to adipose tissue, as evidenced by Tanaka.
With respect to claim 21, 23, 27, 29, and 34, Zhao teaches the liver could regulate adipose tissue inflammation, lipid storage, and white adipose tissue (WAT) browning by secreting regulatory molecules. Thus, the molecular signals connecting the liver to adipose tissues may be viable targets for interventions to mitigate NAFLD and obesity (Introduction, para. 2). Zhao teaches that WAT browning is responsible for energy production and suggests that energy expenditure is a mechanism that contributes to the attenuation of obesity (Hepatocyte‐Specific Tgfbr2 Deletion Promotes the Expression of Thermogenic Genes in WAT).
Zhao fails to teach LAT1 or LAT1 inhibitors. However, Zhao generally teaches some underlying mechanisms of obesity and NAFLD. Therefore, it would be obvious to a person skilled in the art that by using a LAT1 inhibitor known to treat obesity or NAFLD, the LAT1 inhibitor would treat the underlying mechanisms of obesity, such as promoting WAT browning, as required by claim 21.
Knowing the underlying mechanisms, a person skilled in the art would be motivated to modify the LAT1 inhibitor to target the adipose tissue, as required by instant claims 23, 29, and 34.
The combined teachings of Han and Zhang fails to teach the LAT1 inhibitors JPH203 or OKY-034, as required by instant claims 22, 28, and 33.
However, it would be obvious to a person skilled in the art to substitute one LAT1 inhibitor for another. Furthermore, in a review of Han, Zhang suggests “the discovery of an LAT1 inhibitor with similar effects as BCH has become an urgent problem that must be solved” (Application of LAT1 in the Treatment, end of para. 2).
With respect to claim 16, Han teaches studies in rats and fails to teach studies in humans. However, Zhang teaches LAT1 is expressed in the lungs, hearts, and liver of both rats and humans. Moreover, NAFLD, obesity, insulin resistance, and fatty liver are prevalent human diseases. Therefore, it would be obvious to a person skilled in the art to extract the studies of Han in rats and translate them into human subjects.
Applying KSR example rationale (G), it would have been prima facie obvious to extract the method of treating/preventing metabolic alterations caused by high fat/high fructose diets, including improving liver metabolism and insulin resistance, which underlie obesity and NAFLD, and modify the LAT1 inhibitor to target adipose tissue. A person skilled in the art would have been motivated to do so because the liver regulates adipose tissue inflammation, lipid storage, and white adipose tissue (WAT) browning by secreting regulatory molecules, making adipose tissue a viable targets for interventions to mitigate NAFLD and obesity, as taught by Zhou.
Applying KSR example rationale (B), it would have been prima facie obvious to extract the method of treating NAFLD and obesity using a LAT1 inhibitor, as taught by the combined teachings Han and Zhou, and substitute the LAT1 inhibitor for another known LAT1 inhibitor, such as JPH203 or OKY-034. A person skilled in the art would have been motivated to do so because in a review of Han, Zhang suggests the discovery of an LAT1 inhibitor with similar effects as BCH has become an urgent problem that must be solved.
Applying KSR example rationale (G), it would have been prima facie obvious to extract the method of treating NAFLD and obesity using a LAT1 inhibitor, as taught by the combined teachings Han and Zhou, and translate the experiments from rat models to human models. A person skilled in the art would have been motivated to do so because LAT1 is expressed in the lungs, hearts, and liver of both rats and humans, as taught by Zhang. Moreover, NAFLD, obesity, insulin resistance, and fatty liver are prevalent human diseases.
Therefore, claims 2, 4, 9, 12-14, 16, 21-23, and 25-34 would be obvious to a person skilled in the art at the time.
Conclusion
Claims 2, 4, 9, 12-14, 16, 21-23, and 25-34 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NICOLA MARIA BAUER whose telephone number is (703)756-1269. The examiner can normally be reached Monday-Friday 7:30-5 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Clint Brooks can be reached at (571) 270-7682. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/N.M.B./Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621
