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.
Election/Restrictions
Applicant’s election of species in the reply filed on 11/24/2025 is acknowledged. Because applicant did not distinctly and specifically point election of species requirement with or without, therefore the election has been treated as an election without traverse (MPEP § 818.01(a)).
Applicants provided a compliant species of QT-prolonging drugs: Amantadine
Examiner found prior art. Therefore, Markush search was not extended to the full scope of independent claims 1, 18-19. Species reads on claims 1-2, 4, 9-10, 12, 14-15, 18-19, 21, 23, 40, 43 and 45.
Claim 22, 39, 41-42 and 44 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species there being no allowable generic or linking claim.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 11/24/2025.
Claims 1-2, 4, 9-10, 12, 14-15, 18-19, 21, 23, 40, 43 and 45 are examined in this office action.
Current Status of 17/926,978
This Office Action is in response to the amended claims of 11/24/2025.
Claims 4, 9-10, 12, 14-15, and 20-23 are currently amended; claims 1-2 and 18-19 are original; and claims 39-45 are new. are examined in this office action.
Claims 1-2, 4, 9-10, 12, 14-15, 18-19, 21, 23, 40, 43 and 45 are examined in this office action.
Priority
Effective filing date is 05/22/2020.
Information Disclosure Statement
The information disclosure statement (IDS) was submitted on 01/11/2023, and 11/24/2025. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
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 1-2, 4, 9-10, 12, 14-15, 18-19, 21, 23, 40, 43 and 45 are rejected under 35 U.S.C. 103 as being unpatentable over
Córdoba et. al (Therap Adv Gastroenterol. 2016 Nov;9(6):823-835).
In view of
Lee et.al. (Lee et.al;.Hepatology. 2018 Mar;67(3):1003-1013)
Anisel et.al. “PHARMACEUTICAL DOSAGE FORMS AND DRUG DELIVERY SYSTEMS” 7th edition, 1999.
The claims are drawn to method of treating or ameliorating hyperammonemia comprising of administrating ornithine phenylacetate(OP).
1. Determining the scope and contents of the prior art.
Cordoba et.al discloses methods of treating or ameliorating hyperammonemia comprising the administration of ornithine phenylacetate (OP) (abstract). The claim Cordoba further assessed or received baseline information of QTcF interval with electrocardiogram (page 824, section title patient selection) (claims 4, 9-10, 12, 45) and the patients taking (claim 18) or not taking QT prolonging drug (claim 19), such as haloperidol (QT prolonging drug) (page 824, section title patient selection) (this assessments are also interpreted as risk assessment for QT prolongation, claim 12) (partially teaching claim 1-2, 15, 18, 19, 45 ).
Lee et.al. teaches OP causes QT prolongation (page 20, table 2).
Anisel et.al. teaches dosages of pharmaceuticals and frequency of the dosage are routinely optimized based on body weight and body surface area (Anisel et.al. page 50)
2. Ascertaining the differences between the prior art and the claims at issue.
Cordoba et.al discloses methods of treating or ameliorating hyperammonemia comprising the administration of ornithine phenylacetate (OP) (abstract). Cordoba does not teach administering 2nd amount of OP.
Lee et.al. teaches OP causes QT prolongation. Lee et.al does not teach assessment of patient before administering OP.
Anisel et.al. teaches dosages of pharmaceuticals and frequency of the dosage are routinely optimized based on body weight and body surface area. Anisel et.al. does not teach assessment of patient with QT, the administering dosage of OP or ameliorating hyperammonemia.
3. Resolving the level of ordinary skill in the pertinent art.
The level of ordinary skill is an artisan who have sufficient background in developing treatment modality for ameliorating hyperammonemia without prolonging QT interval.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
A person skilled in the art would be expected to use the prior art of Lee et.al which teaches OP prolongs QT (Lee et.al. page 20 table 2) to assess the risk of taking OP in a patient with hyperammonenia. It would be expected a QT prolonging drug such as Amantadine (applicant’s elected species claims 21, 40 and 43) could result in fatality when administered together with OP since both OP and amantadine can prolong QT.
Therefore it would be obvious for a person skilled in the art to use the assessment conducted in the prior art of Cordoba and conduct baseline information of QTcF interval with electrocardiogram (page 824, section title patient selection) (claims 4, 9-10, 12) and to assess patients taking (claim 18) or not taking QT prolonging drug (claims 15 and 19), such as haloperidol (QT prolonging drug, stated in Cordoba) (Cordoba page 824, section title patient selection) (this assessments are also interpreted as risk assessment for QT prolongation, claim 12).
It would be obvious for a person skilled in the art to administer 2nd amount of OP to effectively reduce hyperammonemia if the 1st amount of OP was not effective in ameliorate hyperammonemia. It would be obvious for a person skill in the art to adjust the dosage of OP in the 2nd amount and expect the dosage to be lower than the 1st amount since the 1st amount administered would have already lowered the level of hyperammonemia, thus teaching claim 1.
It would be obvious for a person skilled in the art to assess whether a person is taking QT prolonging drug such as amantadine (claims 21, 40 and 43) to determine if OP can be administered safely without further prolonging QT thus teaching claim 18.
Claims 2 and 4 is regarded as routine assessments for measuring baseline QT interval, by taking average of two or more QT. A person skilled in the art is expected to conduct multiple QT measurement to assess the baseline QT and is considered as routine.
Regarding claim 19, it would be obvious for person skilled in the art not to use QT prolonging drug in combination with OP because the combination of OP with QT prolonging drug may result in fatality. Therefore, it would be expected for a person skilled in the art not to use QT prolonging drug with OP to prevent fatality thus teaching claim 19.
Regarding claim 14, Cordoba is silent about assessing hypokalemia, hypomagnesemia or congenital long QT syndrome. Examiner interpret this as routine risk assessment conducted before administering OP to not put the patient in risk of mortality, thus teaching claim 14
Claims 1,18 and 19 are directed to dosage OP. Examiner interprets these attributes as variables the artisan would normally be expected to routinely optimize. For example, Anisel et.al. teaches dosages pharmaceuticals are routinely optimized (Anisel et.al. page 50). Generally, concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such attributes are critical. The specification does not indicate the dosage and frequency of the dosage to be critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969). See MPEP 2144.05(II)(A).
Conclusion
No claims are allowable as written.
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/R.I./Examiner, Art Unit 1625
/JOHN S KENYON/Primary Patent Examiner, Art Unit 1625