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 Claims
Claims 1-5, 9-13, and 17-26 are pending.
Priority
Instant application 19/045,439, filed 02/04/2025 claims priority as follows:
PNG
media_image1.png
70
661
media_image1.png
Greyscale
Information Disclosure Statement
All references from IDS(s) received 02/20/2025 and 06/18/2025 have been considered unless marked with a strikethrough.
Election/Restrictions
Applicant’s election of the compound species 3-(4-chlorophenyl)-N-(pyridine-4-ylmethyl)-1-adamantanecarboxamide and disease species obesity in the reply filed on 05/28/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 1-4, 9-13, and 17-26 read on the elected species. Claim 5 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 05/28/2026.
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 1, 3, 4, 9-13, and 17-25 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.
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 instant case, claims 1, 3, 4, and 25 recite the broad recitation “solvate”, and the claims also recite “e.g., hydrate” which is the narrower statement of the limitation. According to MPEP 2173.05(d), the phrase “for example” is an exemplary phrase that renders a claim indefinite because it is unclear whether the claim is limited to the example (hydrate) or encompasses the broader category (solvate).
Therefore, claims 1, 3, 4, and 25 are 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. Claims 9-13 and 17-24 depend from claim 1 and fail to resolve the issue identified above. Therefore claims 1, 3, 4, 9-13, and 17-25 are indefinite.
Please note: In the interest of compact prosecution, applicant is encouraged to amend the claims to remove every instance of the phrase “(e.g., hydrate)” in order to overcome the rejection.
Claims 22-24 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.
Claim 22 recites the limitation “obesity-related disease”. The phrase “obesity-related disease” fails to establish the nature or degree of the required connection between obesity and the “related” disease. The claims thus fail to provide a clear boundary between diseases that are and are not covered, rendering claim 21 indefinite.
Claims 23-24 recite the limitation “obesity-induced”. There is insufficient antecedent basis for this limitation in the claim. Claims 23-24 depend from claim 22, which recites the limitation “obesity-related”. Therefore claims 23-24 are indefinite.
Please note: In the interest of compact prosecution, applicant is encouraged to amend claim 21 to replace the phrase “obesity-related” with the phrase “obesity-induced” in order to overcome the rejection.
Claim Interpretation
The instant claims recite administering the aforementioned compound to “a subject”. The claims do not recite “a subject in need thereof”. Additionally, the claim preambles recite the intended use of the method as prevention or treatment of obesity or obesity-related diseases. Prevention encompasses the prophylactic administration of compounds to subjects who do not actually have the disease being prevented. Accordingly, in view of the foregoing analysis, prior art which discloses administering the claimed compounds to any subject (i.e., any human or animal patient receiving the administered compound) is being interpreted as reading on the claims. This interpretation applies to the rejection under 35 USC § 102 below.
Claim Rejections - 35 USC § 102
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 1-4, 9-13, 17-19, and 21-26 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by FRENCH et al (The Journal of Pharmacology and Experimental Therapeutics, vol. 333, no. 1, Apr. 2010, pp. 129–39; cited in IDS).
The claims are drawn to administering a compound to “a subject” in an amount effective to inhibit SphK2, DES1, and/or GCS. The elected species compound 3-(4-chlorophenyl)-N-(pyridine-4-ylmethyl)-1-adamantanecarboxamide, is also known as ABC294640 or opaganib, and has the structure:
PNG
media_image2.png
91
250
media_image2.png
Greyscale
.
French discloses administering ABC294640 (opaganib) to a subject in an amount effective to inhibit SphK2, DES1, and/or GCS. See page 134, “Solutions of ABC294640 HCl…were administered to fasted female Swiss-Webster mice at a dose of 100 mg/kg.” See also page 134, “It should be noted that these ABC294640 concentrations are sufficient to inhibit SK activity and proliferation of tumor cells.”
French therefore anticipates instant claims 1-4 and 25-26.
With respect to claims 9-13, administering opaganib to mice (who do not have obesity) in a 100 mg/kg dose is expected to necessarily prevent obesity, and by extension, any obesity-induced disease in that subject. A subject who does not develop obesity cannot develop any disease characterized as “obesity-induced”. Accordingly, claims 9-13 are anticipated by French.
With respect to claims 17-19, the 100 mg/kg dose administered to mice in French is the same dose administered to mice in the examples (e.g., Example 1) of the instant specification. Therefore, the dose disclosed by French is being interpreted as effective to inhibit SphK2, DES1, and GCS. Accordingly, claims 17-19 are anticipated by French.
With respect to claims 21-24, because claim 1 recites “a subject” rather than “a subject in need thereof”, the intended use recitation of “treating obesity” in claim 21 is not considered to limit the patient population to subjects having obesity; and similarly, for dependent claims 22-24 the intended use recitation of treating “an obesity-related disease” is not considered to distinguish the subject of the claims from the subject in French. Accordingly, claims 21-24 are anticipated by French.
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.
Claims 1-4, 9-13, and 17-26 are rejected under 35 U.S.C. 103 as being unpatentable over ROMERO (US 20190328720 A1; cited in IDS) in view of SMITH (The Journal of Pharmacology and Experimental Therapeutics, vol. 333, no. 1, Apr. 2010, pp. 129–39; cited in IDS).
The instant claims are drawn to a method of preventing or treating obesity comprising administering to a subject a compound (the elected species opaganib) in an amount effective to inhibit SphK2, DES1, and/or GCS. Should it be found that the claims require administering opaganib to a subject actually having obesity and/or an obesity-induced disease, the cited combination of references herein teaches administering opaganib to that patient population.
ROMERO teaches methods of treating a DES1-mediated disorder in a subject in need thereof, comprising administering to the subject a DES1 inhibitor (see e.g. abstract, [0070], [0116]). Romero specifically teaches the treatment of metabolic disorders (see e.g. [0251]) and expressly recites the metabolic disorder as one selected from a group that names metabolic syndrome, diabetes, dyslipidemia, fatty liver disease, nonalcoholic steatohepatitis, obesity, and insulin resistance (see e.g. [0252]). Romero further teaches administering to rodent high fat dietary models (see e.g. [0433]), which is are characterized as “models of human pathology including hyperlipidemia, type II diabetes, atherosclerosis, obesity, cardiovascular and liver disease.”
Romero further teaches that ceramide accumulates in obesity and gives rise to the hallmark events of metabolic disease, and that, in rodent models of obesity, genetic or pharmacological inhibition of ceramide or glucosylceramide biosynthesis is insulin sensitizing (see [0004]).
Romero therefore establishes that inhibition of DES1, including pharmacological inhibition, was an art-recognized strategy for treating obesity and obesity-induced diseases (e.g. metabolic syndrome and diabetes).
Romero does not teach and is not relied upon for the structure of the administered compound; and its teaching is not limited to the DES1 inhibitor species it happens to exemplify.
SMITH teaches that opaganib (ABC294640) is an orally active, isozyme-selective inhibitor that inhibits three key enzymes of sphingolipid metabolism, including DES1 (abstract and page 2200, “Development of Opaganib”). Smith further teaches that opaganib has been administered to patients in clinical trials (e.g., Table 1). Opaganib is therefore a known DES1 inhibitor, which Romero teaches to administer for the treatment of obesity and obesity-induced diseases such as metabolic syndrome, diabetes, etc.
Prima facie obviousness
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. See MPEP 2143.
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) and (G), it would have been obvious to one of ordinary skill in the art before the effective filing date to administer opaganib to a patient having metabolic syndrome. Romero teaches that administering a DES1 inhibitor treats obesity and obesity-induced diseases such as metabolic syndrome or diabetes; and Smith teaches that opaganib is a known DES1 inhibitor. The claimed method is no more than the use of a known DES1 inhibitor in a known method of treating obesity (or metabolic syndrome or diabetes) by DES1 inhibition to achieve the predictable result of treating that condition. Romero’s express teaching that pharmacologic inhibition of this pathway is insulin sensitizing and therapeutic for the claimed diseases supplies the requisite suggestion and motivation.
Accordingly, claims 1-4, 9-13, and 21-26 are obvious over Romero in view of Smith.
With respect to claims 17-19, Smith teaches that doses of opaganib as high as 500 mg twice daily or 750 mg twice daily were well tolerated by human patients (page 2200, “Development of Opaganib”). Absent evidence to the contrary, therapeutic amounts of opaganib (e.g. 500 mg or 750 mg twice daily taught by Smith) are being interpreted as effective to inhibit SpHK2, DES1, and GCS. Moreover, differences in result-effective variables will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating the value of the result-effective variable is critical. See MPEP 2144.05. In the instant case, the dose of opaganib administered is considered a result-effective variable that impacts, for example, the occurrence of adverse events. Absent a showing of criticality, optimizing result-effective variables is deemed routine optimization.
Accordingly, claims 17-19 are obvious over Romero in view of Smith.
With respect to claim 20, Romero teaches administering the DES1 inhibitor in combination with other pharmaceutically active compounds (e.g. [0285]), particularly GLP-1 analogs, phentermine, orlistat, or topiramate (e.g. [0288]). It would have therefore been obvious to administer opaganib in combination with one of these other therapeutic agents as taught by Romero in view of Smith.
Accordingly, claim 20 is obvious over Romero in view of Smith.
Conclusion
Claims 1-4, 9-13, and 17-26 are rejected. Claim 5 is withdrawn.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Kyle Nottingham whose telephone number is (571)270-0640. The examiner can normally be reached M-F from 10:00 am - 6:00 pm.
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, Clinton 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.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/K.N./Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621
Prosecution Insights