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 .
DETAILED ACTION
Restriction and Status of the Claims
Applicant’s cancelation of claim 139 and addition of new claims 140-141 in the response filed on November 14th 2025 is acknowledged. As claim 139 was the only claim not encompassed by the elected invention, the restriction requirement filed on October 3rd 2025 is withdrawn. Claims 128-134, 136-138, and 140-141 are pending and are examined on their merits.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The Information Disclosure Statements filed on May 29th 2025 and August 23rd 2023 are in compliance with the provisions of 37 CFR 1.97 and have been considered in full. A signed copy of references cited from the IDS is included with this Office Action.
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.
Claims 131, 134, 138, and 140-141 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 131 is indefinite for the phrase, “wherein administration of the composition to the subject results in inhibition of absorption, assembly, and/or transport of lipids, cholesterol, and/or microbial metabolites,” because one of ordinary skill in the art could not reasonably determine how claim 131 further limits the method of claim 128. Specifically, claim 131 does not limit the compounds administered in the method, the method of administration, the amount administered, the patient population receiving administration, or any other aspect of the method other than its results. The specification recites these results (specification, pg. 8), but does not provide any guidance as to how the method must be further limited in order to achieve said results. As one of ordinary skill in the art could not reasonably determine how claim 131 further limits the method of claim 128, claim 131 is indefinite.
Claim 134 is indefinite for the phrase “wherein the additional therapeutic agent modulates the absorption, assembly, and/or transport of lipids, cholesterol, and/or microbial metabolites in the GI tract of the subject,” because one of ordinary skill in the art could not reasonably determine how claim 134 further limits the method of claim 133. Specifically, claim 134 does not limit the compounds administered in the method, the method of administration, the amount administered, the patient population receiving administration, the additional therapeutic agent administered or any other aspect of the method other than the results of administering the additional therapeutic. The specification recites these results (specification, pg. 8, 9), but does not provide any guidance as to how the method must be further limited in order to achieve said results. As one of ordinary skill in the art could not reasonably determine how claim 134 further limits the method of claim 133, claim 134 is indefinite.
Claim 138 is indefinite for the phrase “wherein treating comprises reducing serum triglycerides in the subject,” because one of ordinary skill in the art could not reasonably determine how claim 138 further limits the method of claim 128. Specifically, claim 138 does not limit the compounds administered in the method, the method of administration, the amount administered, the patient population receiving administration, or any other aspect of the method other than the results of administration. The specification recites these results (specification, pg. 17), but does not provide any guidance as to how the method must be further limited in order to achieve said results. As one of ordinary skill in the art could not reasonably determine how claim 138 further limits the method of claim 128, claim 138 is indefinite.
Claims 140 and 141 are indefinite for the limitation “further comprising administering the antipsychotic agent to the subject,” because one of ordinary skill in the art could not reasonably determine how the limitation further limits the method of claim 128. Claim 128 is directed towards a method of treating a disorder resulting from activation of pregnane X receptor (PXR) by an antipsychotic agent. Such a method necessitates that the subject has already received administration of the antipsychotic agent prior to administration of compound 2 in the described method. A limitation in the method of “administering the antipsychotic agent to the subject,” is redundant, as such administration is already required by the method. Thus, it is unclear how claim 140 further limits the method of claim 128.
Claim 141 is indefinite for the limitation “wherein the antipsychotic agent and compound 2 are administered to the subject at the same time,” because one of ordinary skill in the art could not reasonably determine how the limitation further limits the method of claim 140. As stated in the above 112(b) rejection for claim 140, the method of claim 128 (i.e. the treatment of a disorder caused by PXR activation by an antipsychotic agent) necessitates that the subject has already received administration of the antipsychotic agent. As such, the simultaneous administration of the antipsychotic agent and compound 2 is outside the metes and bounds of claim 128, upon which claim 141 depends, and claim 141 is thereby indefinite.
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.
Claims 128-134, 136-138, and 140-141 are rejected under 35 U.S.C. 103 as being unpatentable over Bartolozzi (WO 2006/113910 A2 published on October 26th 2006) in view of Meng (Meng et al., The atypical antipsychotic quetiapine induces hyperlipidemia by activating intestinal PXR signaling. JCI Insight. 2019 Feb 7) and Sfera (Sfera et al., The Other Obesity Epidemic—Of Drugs and Bugs, Frontiers in Endocrinology Volume 11 - 2020).
Claim 128 is directed towards a method of treating a disorder in a subject resulting from activation of pregnane X receptor (PXR) by an antipsychotic agent via administration of a composition comprising compound 2:
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.
By way of background, the class of atypical antipsychotics that act by blocking serotonin and dopamine receptors are well-known in the art to have associated metabolic side effects. Such drugs deplete helpful intestinal gut bacteria, resulting in the activation of PXR. Such PXR activation alters the expression of genes related to lipid homeostasis and often leads to metabolic disorders such as obesity or hyperlipidemia.
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(Sfera, pg. 2).
In particular, the atypical antipsychotic, quetiapine, has been demonstrated to act as a potent agonist of PXR (Meng, pg. 3), and can induce hyperlipidemia through PR up-regulation (Meng, pg. 19). Addressing such hyperlipidemia is therefore a major concern with these medications.
Regarding claim 128, Bartolozzi teaches the administration of applicant’s compound 2 (Bartolozzi, pg. 5, compound 11) for the treatment of hyperlipidemia (Bartolozzi, pg. 34, claim 14). One of ordinary skill in the art would therefore have a reasonable expectation of success in treating the aforementioned hyperlipidemia via administration of compound 2, and claim 128 is prima facie obvious.
Claim 129 requires that the antipsychotic of claim 1 is selected from clozapine, olanzapine, and quetiapine. As the treatment of quetiapine-induced hyperlipidemia with compound 2 was addressed above, claim 129 is prima facie obvious for the same reasons as claim 128.
Claim 130 requires that the antipsychotic of claim 128 is olanzapine. Sfera teaches that olanzapine (OLZ) administration carries substantially similar metabolic risks as quetiapine administration (Sfera, pg. 1, Introduction; pg. 2, col. 2). One of ordinary skill in the art would therefore reasonably use compound 2 to treat metabolic disorders induced by olanzapine administration and claim 130 is prima facie obvious.
Claim 131 is directed towards the method of claim 128, wherein administration results in inhibition of absorption of lipids in the subject. Bartolozzi teaches the reduction of serum lipids (Bartolozzi, Abstract), including serum triglycerides (Bartolozzi, pg. 35, claim 18). Claim 131 is therefore prima facie obvious.
Claim 132 requires that, in the method of claim 128, the composition is formulated for extended release. As extended-release compositions are well-known in the art, one of ordinary skill in the art would find optimizing the pharmokinetics of the drug’s release profile to be a matter of routine optimization. Claim 132 is thereby prima facie obvious.
Claim 133 requires that compound 2 is administered with an additional active agent. Bartolozzi teaches administration alongside additional lipid-lowering agents (Bartolozzi, pg. 34, claim 13), and claim 133 is therefore prima facie obvious.
Claim 134 requires that, in the method of claim 133, the administration of the additional agent results in the modulation of the absorption of lipids. Bartolozzi teaches administration alongside cholesterol-absorption inhibitors, including ezetimibe (Bartolozzi, pg. 23), and claim 134 is prima facie obvious.
Claim 136 is directed towards the method of claim 128 wherein the dosage of compound 2 is in the range of 0.1-5000 mg. Bartolozzi teaches dosage of 5-500 mg (Bartolozzi, pg. 23), and claim 126 is prima facie obvious.
Claim 137 is directed towards the method of claim 128 wherein the dosage of compound 2 is in the range of about 0.1-15 mg/kg body weight. Bartolozzi teaches a dosage range of 0.1-15 mg/kg body weight (Bartolozzi, pg. 23) and claim 138 is prima facie obvious.
Claim 138 is directed to the method of claim 128, wherein the treatment results in the reduction of serum triglycerides in the subject. Bartolozzi teaches the reduction of serum lipids (Bartolozzi, Abstract), including serum triglycerides (Bartolozzi, pg. 35, claim 18). Claim 138 is therefore prima facie obvious.
As one of ordinary skill in the art could not reasonably determine how claims 140 and 141 further limit the method of claim 128 (see the above 112(b) rejections for claims 140 and 141), they are prima facie obvious for the same reasons as claim 128.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Anthony Seitz whose telephone number is (703)756-4657. The examiner can normally be reached 7:30 AM ET - 5:00 PM ET M-F.
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/A.J.S./Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629