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 .
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.
Current Status of 18/548,798
This Office Action is responsive to the amended claims received 6 May 2026.
Claims 1-3, 7-9, 13-17, 19-20, 22-25, 27-30, and 32-33 are currently pending.
Priority
Applicant’s claim for the benefit of the prior-filed patent applications PCT/US2022/018672 (filed 3 March 2022), 63/165,457 (filed 24 March 2021), and 63/155,960 (filed 3 March 2021) under 35 U.S.C. 119(e), 120, 121, 365(c), or 386(c) is acknowledged.
Information Disclosure Statement
The information disclosure statement (IDS) received on 6 May 2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, this information disclosure statement is being considered by the examiner.
Response to Amendments
The objections to the claims, present in the previous office action, are hereby withdrawn due to Applicant’s amendments. New objections to the claims are presented herein, as necessitated by Applicant’s amendments.
The 35 U.S.C. 112 rejections to the claims, present in the previous office action, are partially maintained due to Applicant’s amendments.
The 35 U.S.C. 102(a)(1) and/or 35 U.S.C. 102(a)(2) rejections to the claims, present in the previous office action, are maintained herein, but they are altered as necessitated by Applicant’s amendments.
The 35 U.S.C. 103 rejections to the claims, present in the previous office action, are maintained herein, although they have been altered as necessitated by Applicant’s amendments.
Claim Objections
Claims 13, 15-17, 19-20, 22-25, and 27-30 are objected to because of the following informalities: Each use of the phrase “ALT or AST levels are” is grammatically incorrect. Because the two items are referred to in the alternative, and are each singular, each use of this phrase should be amended as follows “ALT or AST level is”. Each use of the phrase “ALT or AST levels” should be amended to recite “ALT or AST level”. Appropriate correction is required.
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, 7-9, 13-17, 19-20, 22-25, 27-30, and 32-33 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 1 recites section “c)”, which begins with the words “measuring the fasting triglyceride levels of the patient after the second dosing period”. It is unclear to the reader whether this measuring action of step “c)” is a required step within the method, because it appears that this measuring step is only applied to patients that received the optional second dosing period of lomitapide. The analogous measurement of step “d)” causes the same confusion. This renders claims 1-3, 7-9, 13-17, 19-20, 22-25, 27-30, and 32-33 indefinite. Applicant may choose to make it clear that the measuring actions of steps “c)” and “d)” are only required if the patient underwent the relevant additional dosing period. For example, Applicant may amend step “c)” to recite “measuring the fasting triglyceride levels of the patient after the second dosing period if the patient was administered lomitapide for the second dosing period…”.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 27-29 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claims 27-29 each depend directly or indirectly upon instant claim 1. Claim 1 provides a method of increasing the dose of lomitapide to a patient when the patient’s fasting triglyceride levels continue to be greater than 1000 mg/dL. For example, claim 1 step “b)” states that if a patient has measured fasting triglyceride levels of >1000 mg/dL after the first dosing period with fasting, the patient must be given an additional daily dose of about 10 mg of lomitapide for at least four weeks. Each of claims 27-29 attempt to expand the scope of the limitations of claim 1. Claim 27 allows for any dose adjustments at all to meet the ≤1000 mg/dL triglyceride levels. Claim 28 allows for increasing or decreasing the lomitapide dose every 2-4 weeks, and this change is not required to fall within the limitations of claim 1. Claim 29 allows for additional dosages that are outside of the required doses of claim 1.
Applicant may cancel the claim, amend the claim to place the claim in proper dependent form, rewrite the claim in independent form, or present a sufficient showing that the dependent claim complies with the statutory requirements.
Response to Arguments
Applicant's arguments received 6 May 2026 have been fully considered.
Applicant argues that CEFALU does not anticipate the instant claims “because it does not disclose a second dosing period lasting at least four weeks recited in step “b)” of instant claim 1. Applicant then argues that the rejections under 35 USC 103 should be withdrawn because the additional references provided by the Examiner do not remedy the deficiencies of CEFALU.
The Examiner clearly explained in the previous action, as below, that instant claim 1 did not and does not require the patient to undergo the second dosing period. Instant claim 1 requires a patient to undergo the second dosing period if the patient has: measured fasting triglyceride levels greater than 1000 mg/dL while they have been adhering to a low-fat diet after the first dosing period. If the patient had triglyceride levels below 1000 mg/dL after the first dosing period (taught by CEFALU at the top right of Pg. 346) and/or were not adhering to a low-fat diet after the first dosing period, instant claim 1 does not require the patient to undergo the second dosing period. Therefore, CEFALU teaches a method that falls within the scope of instant claim 1.
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 1-3, 7, 13-17, 19-20, 22-25, 30, and 32-33 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by:
CEFALU (Cited by Applicant in IDS of 28 March 2024; Cefalu, A.B.; Giammanco, A.; Noto, D.; et al. “Effectiveness and safety of lomitapide in a patient with familial chylomicronemia syndrome” Endocrine (2021) 71:344–350).
The Examiner is interpreting claim 1 to be interpreted as always requiring the following: the selection of a patient having FCS, the oral administration of lomitapide (as described in section “a)”), and the measurement of the patient’s fasting triglyceride levels after the first dosing period. As currently written, claim 1 does not require the patient to adhere to a low-fat diet, but does provide additional limitations if a patient is following a low-fat diet. All of the clauses that stem from the patient’s particular triglyceride levels in sections b-d of instant claim 1 are not interpreted to always be required limitations of the claim. Instant claim 7 does require the patient to follow a low-fat diet.
CEFALU generally teaches the results of treating a single patient having familial chylomicronemia syndrome (FCS) with lomitapide (abstract). CEFALU teaches lomitapide to be an inhibitor of the microsomal triglyceride transfer protein (MTP), which was previously known to treat homozygous familial hypercholesterolemia (Pg. 345, 3rd paragraph). CEFALU teaches the administration of lomitapide for the purpose of lowering a triglyceride (TG) concentration within the patient (title and abstract).
CEFALU teaches the titration of the lomitapide dose (Pg. 346, treatment with lomitapide section). CEFALU teaches that the patient was initially provided a lomitapide dose of 5 mg/day, in addition to omega-3 fatty acids and fenofibrate (Pg. 346, treatment with lomitapide section). After 4 weeks of this dosage, the patient’s triglycerides levels were measured and found to be 410 mg/dL, and the patient’s dosage of lomitapide was maintained at 5 mg/day for an additional 4 weeks. CEFALU satisfies the requirements of the first portion of instant claim 1 and sections “a)” and “b)”, and there is no requirement within claim 1 that sections “c)” or “d)” would then be performed.
CEFALU teaches that the patient was previously on a low-fat diet with a fat intake of “<20%” (case presentation section, Pg. 345), dietary restrictions were intensified before the lomitapide treatment (Pg. 346, 2nd paragraph). One of ordinary skill in the art would have understood that a fat intake of “<20 %” indicates a diet wherein less than 20 percent of the calories were provided by fat.
Regarding claim 2: CEFALU teaches that FCS can be caused by “homozygous, compound heterozygous, or double heterozygous loss-of-function mutations in genes involved in intravascular hydrolysis of TG rich lipoproteins” (introduction section).
Regarding claim 3: CEFALU teaches that FCS patients are defined by recurrent acute pancreatitis, in addition to other symptoms (abstract).
Regarding claim 7: CEFALU teaches that the patient therein was administered lomitapide, omega-3 fatty acid supplements, and fenofibrate for the treatment of FCS while adhering to a low-fat diet (Pg. 346, treatment with lomitapide section).
Regarding claims 13-17: Claim 13 states that “if the patient’s liver [enzymes] are ≥5 times the upper limit of normal… the patient is withdrawn from lomitapide treatment”. The “if” is very important within claim 13, because it causes the content of the claim to be optional. Claim 13 does not require the selection of a particular patient population. Therefore, claim 13 can be anticipated by any teachings that anticipate the parent claim, claim 1, unless the reference teachings are strictly related to a patient population with “liver [enzymes] are ≥5 times the upper limit of normal” and the teachings do not remove the lomitapide treatment under those conditions.
Regarding claims 19-20 and 22-25: Claim 19 recites “if the patient’s ALT/AST levels are from 3-5 times the ULN”. Claim 19 does not appear to require the selection of this type of patient or patient population. The “if” is very important within claim 19, because it causes the content of the claim to be optional. Therefore, claim 19 can be anticipated by any teachings that anticipate the parent claim, claim 1, unless the reference teachings are strictly related to a patient population with “ALT/AST levels are from 3-5 times the ULN” and the teachings do not require “confirming the patient’s ALT/AST levels” under those conditions.
Regarding claim 30: Claim 30 is understood to further narrow limitations of claim 1 that are not required.
Regarding claims 32-33: The outcomes within instant claims 32-33 are solely the result of administering lomitapide as described within instant claim 1. There are no positive steps recited therein that would alter these outcomes unrelated to administering the lomitapide as described within instant claim 1. Therefore, because the method of administering lomitapide as described in claim 1 has been found to be obvious, the direct outcomes of claims 32-33 are also rendered obvious.
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.
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 1-3, 7-8, 13-17, 19-20, 22-25, 30, and 32-33 are rejected under 35 U.S.C. 103 as being unpatentable over:
CEFALU (Cited by Applicant in IDS of 28 March 2024; Cefalu, A.B.; Giammanco, A.; Noto, D.; et al. “Effectiveness and safety of lomitapide in a patient with familial chylomicronemia syndrome” Endocrine (2021) 71:344–350).
Teachings of CEFALU are discussed within the rejections under 35 USC 102 above.
Regarding claim 8: CEFALU teaches that the patient was previously on a low-fat diet with a fat intake of “<20%” (case presentation section, Pg. 345), dietary restrictions were intensified before the lomitapide treatment (Pg. 346, 2nd paragraph). One of ordinary skill in the art would have understood that a fat intake of “<20 %” indicates a diet wherein less than 20 percent of the calories were provided by fat. CEFALU does not explicitly state that the patient followed a diet wherein less than 10 % of the patient’s calories came from fat.
CEFALU teaches that the low-fat diet followed by the patient was “intensified” from less than 20 % fat. It would have been obvious to one of ordinary skill in the art, before the instant effective filing date, to test a low-fat diet containing less than 10 % fat for the purpose of decreasing the triglyceride levels within a patient having FCS. The artisan would have expected success in this stricter low-fat diet, because CEFALU directly teaches a low-fat diet stricter than less than 20 % fat.
Claims 1-3, 7-20, 22-25, 30, and 32-33 are rejected under 35 U.S.C. 103 as being unpatentable over:
CEFALU (Cited by Applicant in IDS of 28 March 2024; Cefalu, A.B.; Giammanco, A.; Noto, D.; et al. “Effectiveness and safety of lomitapide in a patient with familial chylomicronemia syndrome” Endocrine (2021) 71:344–350)
in view of:
KOLOVOU (Kolovou, G.D.; Kolovou, V.; Papadopoulou, A.; Watts, G.F. “MTP Gene Variants and Response to Lomitapide in Patients with Homozygous Familial Hypercholesterolemia” Journal of Atherosclerosis and Thrombosis Vol. 23, No. 7, 878-883, 2016).
Teachings of CEFALU are discussed within the rejections under 35 USC 102 and 103 above. CEFALU does not provide teachings related to patients who express MTP gene variants that would improve the patient’s response to lomitapide treatment.
Regarding claim 9: KOLOVOU teaches six common variants of the MTP gene that were found to be shared by patients who were “hyper-responders” to lomitapide treatment (abstract).
It would have been obvious to one of ordinary skill in the art, before the instant effective filing date, to combine the lomitapide treatment for FCS (taught by CEFALU) with the “hyper-responder” population taught by KOLOVOU, for the purpose of providing the lomitapide treatment to the patient population who would benefit most from lomitapide. Without any teachings to the contrary, it is expected that some FCS patients would possess the MTP variants taught by KOLOVOU. The artisan would have expected success in this combination, because both references teach how to administer the same therapeutic compound, lomitapide.
Conclusion
No claims are currently allowable.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOHN D MCANANY whose telephone number is (571)270-0850. The examiner can normally be reached 8:30 AM - 5:30 PM.
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/JDMc/Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625
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