Detailed Action
The present office action is in response to the remarks filed on 04 May 2026.
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
Claims 1-2 and 4-6 of the pending application have been examined on the merits. Claims 3 and 7-12 are withdrawn (see “Response to Applicant Election” below). Acknowledgement is made of the amendments filed 04 May 2026. Acknowledgement is made of the cancellation of claims 13-19.
Priority
Applicants identify the instant application, Serial #: 18/478,684, filed 29 Sep 2023, as a Continuation of U.S. Patent Application #: 16/624,389, filed 19 Dec 2019, which is a National Stage Entry of International Patent Application #: PCT/US2018/038322, filed 19 Jun 2018, which claims priority from U.S. Provisional Application #: 62/521,872, filed 19 Jun 2017.
Information Disclosure Statement
The information disclosure statement(s) (IDS) submitted on 18 Jul 2024 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Response to Applicant Election
Applicant’s election of Invention I in the reply filed on 04 May 2026 is acknowledged. Applicant’s election of idodomethyl choline as the species of first or second agent and obesity as the species of disease or disorder in the reply filed on 04 Mar 2026 is acknowledged. Applicant did not provide the structure or location of the elected species in the remarks. Examiner is interpreting iodomethyl choline to have the following structure as found in the specification on pg. 17, Table 1:
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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)). A search for the elected species returned prior art.
Claims 2 and 7-12 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.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 04 May 2026.
Specification
The disclosure is objected to because of the following informalities: The chemical formulas in the specification are of low-resolution, verging on illegible. Examiner requests that the specification be amended by uploading high quality, black and white images in the following locations: pg. 3, line 22; pg. 4, line 1; pg. 4, line 11; pg. 6, line 14; pg. 8, line 6; pg. 14, line 25; pg. 15, lines 23-24; pg. 15, line 26; pg. 16, lines 3-4; pg. 16, line 6-8; pg. 16, lines 11-12; and pg. 17, Table 1.
Claim Rejections - 35 USC § 112(b)
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 6 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 6 recites the broad recitation
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, and the claim also recites
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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. Applicant may overcome this rejection by amending claim 6 to clarify the required features of the claim.
Further, claim 6 contains the limitation, “wherein n is an integer, or n is 0, indicating that CH2 is not present…” there is no further information in the specification which limits the definition of integer. There are an infinite number of integers and this results in a limitation where the person of ordinary skill in the art would not know what the end amount of “integer” means. Applicant may overcome this rejection by clarifying what is meant by “integer.”
Claims 1-2 and 4-5 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
Claim 1 states the limitation:
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This list of diseases would not be familiar to the person of ordinary skill in the art as being able to be treated with a single method. For instance, the artisan would not be sure based on the art or the specification how the treatment of sleep apnea and colorectal cancer are related. There are no examples in the specification that would show the artisan how treating these separate diseases would be in the class of treatment.
Claim 2 states the limitation:
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The above Markush group are not a recognized class and do not share a substantial structural feature or common use. For example, the fecal microbiota transplantation would not be recognized as sharing a class with acetylsalicylic acid. Claims 4-5 are rejected for not remedying the rejection of claim 1.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
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.
Claim(s) 1-2 and 4-6 is/are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al. (Front Physiol, 2017, 8:139), hereinafter Chen, further in view of US 2016/0089387 (provided in IDS 07/18/24), hereinafter ‘387, and Mistry et al. (J Med Chem, 1991, 34:2031-2036).
The instant claims are drawn towards a method of treating a disease or condition by administering an agent or procedure to a subject (claims 1-2 and 6). Applicant has elected obesity as the species of disease or condition and iodomethyl choline as the species of agent or procedure in the reply filed 04 May 2026. Claim 4 adds the step of determining levels of TMAO, TMA, FMO3 mRNA, and/or TMA-containing compound in a sample of the subject before and/or after the treatment. Claim 5 limits the subject to those who have elevated levels of TMA, TMAO, or FMO3 mRNA.
Chen teaches administering 3,3-dimethyl-1-butanol (DMB) in drinking water to western diet induced obese mice that mimic human obesity syndrome (Abstract; pg. 2, column 1). The obesity model mice had TMAO plasma levels taken after being fed DMB and the TMAO levels were increased after being fed the western diet (pg. 2, column 2; pg. 3, column 2). Chen teaches that for mice fed on a western diet, treating with DMB prevented cardiac dysfunction and interstitial fibrosis and inflammation in the heart compared to mice not treated with DMB (pg. 6, column 1). Chen did not find that body weight decreased in the obesity models (pg. 6, column 1). While Chen teaches administering DMB to obesity mouse models, Chen does not teach administering iodomethyl choline to obesity mouse models.
‘387 teaches treating cardiovascular disease by administering DMB or a DMB derivative represented by reference Formula I (paragraphs [0040]-[0041]):
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‘387 further teaches that Formula I may be a halomethyl choline, including iodomethyl choline (paragraph [0049]).
Mistry teaches iodomethyl choline as Compound 4 and provides data showing iodomethyl choline has inhibitory activity against acetylcholinesterase, choline acetyl transferase, and high-affinity choline transport (Table 1; and Fig. 1).
Based on the teachings of Chen, ‘387, and Mistry, the person of ordinary skill in the art would find it obvious that the DMB derivatives would have activity in preventing cardiac dysfunction and interstitial fibrosis and inflammation in the heart in obesity mouse models, as taught by Chen and ‘387. The artisan would further understand that of the DMB derivatives, iodomethyl choline would have relevant biological activity for testing, as taught by Mistry, and administer the compound to obesity model mice. By teaching the same steps as the instant claims of administering a DMB derivative to a subject having obesity, the references of Chen, ‘387, and Mistry necessarily teach the outcomes of the instant claims.
A reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976). In light of the foregoing discussion, the examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103. From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-2 and 4-6 are rejected on the ground of anticipatory-type nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,771,659. Although the claims at issue are not identical, they are not patentably distinct from each other.
The reference patent claims a method of treating a disease or condition or causing weight loss comprising treating a human subject who has elevated levels of TMA, TMAO, or FMO3 mRNA with a first agent or procedure that inhibits the TMA/FMO3/TMAO pathway to cause weight loss or treat a first or second disease or a second agent or second procedure that is a non-antibiotic that inhibits the TMA/FMO3/TMAO pathway to treat a second disease or condition where the reference diseases/conditions claimed are the same as those found in the instant claims and the reference agents or procedures to treat them are the same as those in the instant claims (reference claim 1). Thus the instant claims are anticipated by the reference.
Claims 1-2 and 5-6 are rejected on the ground of anticipatory-type nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. 11,331,280. Although the claims at issue are not identical, they are not patentably distinct from each other.
The reference patent claims a method of improving a disease or a condition associated with the conversion of choline to TMA by administering (2-hydroxyethyl) dimethylsulfoxonium to treat or prevent the disease or condition associated with choline-related TMA in the subject (reference claim 1). The reference further claims treatment of diseases which overlap with the instant claims (reference claims 2-3). The reference claims further limit the subject to an individual having elevated TMAO in the blood, plasma, serum, or urine.
Claims 1-2, 4, and 6 are rejected on the ground of anticipatory-type nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 9,694,020. Although the claims at issue are not identical, they are not patentably distinct from each other.
The reference claims are directed to treating a subject with symptoms of kidney and/or cardiovascular disease by treating a subject with a gut TMA lyase inhibitor selected from a halomethyl choline, a halomethyl betaine, a halomethyl betaine salt, a halomethyl betaine amide, and a halomethyl dimethyl amino alcohol (claim 1). The subject is also limited to having the levels of eGFR, eCrCl, Cystatin C, KIM1, elevated urine albumin/Creatinine ratio, TMAO, TMA, and/or a TMA-containing compound before or after treatment (claim 2). The artisan would use the specification to shed light on what is meant by “symptoms of kidney and/or cardiovascular disease” and would find that, at least for cardiovascular disease, the symptoms include cerebrovascular disease which overlaps with the instant claims (column 7, lines 35-51).
Claims 1-2, 4, and 6 are rejected on the ground of anticipatory-type nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 10,117,879. Although the claims at issue are not identical, they are not patentably distinct from each other.
The reference claims are directed to treating a subject with symptoms of kidney and/or cardiovascular disease by treating a subject with a gut TMA lyase inhibitor selected from the following structures (claim 1):
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The subject is also limited to having the levels of eGFR, eCrCl, Cystatin C, KIM1, elevated urine albumin/Creatinine ratio, TMAO, TMA, and/or a TMA-containing compound before or after treatment (claim 2). The artisan would use the specification to shed light on what is meant by “symptoms of kidney and/or cardiovascular disease” and would find that, at least for cardiovascular disease, the symptoms include cerebrovascular disease which overlaps with the instant claims (column 7, lines 40-57).
Claims 1-2, 4, and 6 are rejected on the ground of anticipatory-type nonstatutory double patenting as being unpatentable over claims 3-4 of U.S. Patent No. 10,933,072. Although the claims at issue are not identical, they are not patentably distinct from each other.
The reference patent claims a method of treating a subject with symptoms of kidney disease, progressive renal fibrosis, age related decline in kidney function, and/or cardiovascular disease by administering an agent that reduces the production of TMA or TMAO wherein the agent is a halomethyl choline (claim 3). The reference patent further claims assaying a sample from the subject to determine TMAO, TMA, or a TMA-containing compound prior to and/or after treatment (claim 4).
Claims 1-2 are provisionally rejected on the ground of anticipatory-type nonstatutory double patenting as being unpatentable over claims 1-15 of copending Application No. 18/992,085 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
The reference patent teaches a polyol compound, which is a DMB related compound, of formula (I):
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And further teaches the treatment of diabetes mellitus and obesity by administering a compound of formula (I) (claim 15).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-2 and 6 are provisionally rejected on the ground of anticipatory-type nonstatutory double patenting as being unpatentable over claims 1-16 of copending Application No. 18/992,082 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
The reference patent teaches a compound, which is a DMB related compound, of formula (I):
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And further teaches the treatment of diabetes mellitus and obesity by administering a compound of formula (I) (claim 16).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-2 and 6 are provisionally rejected on the ground of anticipatory-type nonstatutory double patenting as being unpatentable over claims 1-10, 12, 14-15, and 17-20 of copending Application No. 18/992,077 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
The reference patent teaches a compound, which is a DMB related compound, of formula (I):
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And further teaches the treatment of diabetes mellitus and obesity by administering a compound of formula (I) (claim 20).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. WO 2010/138899 is considered pertinent for teaching a method of treating diabetes mellitus, insulin resistance, metabolic syndrome, NAFLD, or NASH by administering a probiotic which reduces formation of TMA. WO 2016/049537 is considered pertinent for teaching the treatment of kidney disease by administering acetylsalicylic acid. WO 2016/049541 is considered pertinent for teaching the treatment of kidney and/or cardiovascular disease by administering to a subject DMB or a DMB derivative.
Conclusion
No claim is allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jonathan D. Mahlum whose telephone number is (703)756-4691. The examiner can normally be reached 8:30 AM - 5:00 PM ET, M-F.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Andrew Kosar can be reached at (571) 272-0913. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/J.D.M./Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625
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