DETAILED ACTION
Claims 1, 6, 8-9, 11, 14, 19, 22-25, 27-33, and 39-51 are pending.
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 .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1, 6, 8, 9, 11, 14, 19, 22-25, 27-28 and 41-51 in the Reply filed on 2/13/2026, 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 § 818.03(a)). The requirement is still deemed proper and is therefore made FINAL.
Claims 29-33 and 40 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the Reply.
Claims 1, 6, 8, 9, 11, 14, 19, 22-25, 27-28 and 41-51 are present for Examination and the subject of the Office Action below.
Priority
The instant application filed 6/8/2023 is a National Stage entry of PCT/GB2021/053382, with an International Filing Date of 12/21/2021, and claims foreign priority to 2020285.9, filed 12/21/2020 and to 2108231.8, filed 6/9/2021.
Information Disclosure Statement
The Information Disclosure Statements (IDS) submitted on 6/8/2023, 9/19/2024, and 9/19/2024, are in compliance with the provisions of 37 CFR 1.97. Accordingly, the Information Disclosure Statements are being considered by the Examiner.
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, 6, 8-9, 11, 14, 19, 22-25, 27-33, and 39-51 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.
Claims 1 and 6 recite the phrase, “a disorder associated with low BH4 bioavailability” and the Specification states:
PNG
media_image1.png
204
628
media_image1.png
Greyscale
Applicant defines the condition by a low level compared to “a healthy subject.” The problem being Applicant has not provided the metes and bounds of disorders included in this definition, and moreover Applicant has not defined the extent of how one determines what is “associated” with this condition. One is left with a ambiguous definition without clear metes and bounds. Applicant has not shown how to determine a “low BH4 bioavailability.” Applicant has not provided guidance in determining what disorders are included, therefore given the nebulous language. For Examination, disorders treated with BH4 or a reduced folate, that by chemical properties increase the BH4 level, and have efficacy will be considered to be “a disorder associated with low BH4 bioavailability.”
Regarding claims 11 and 43 the recitation of, “preferably wherein” renders the claims indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claims 14 and 44 “optionally wherein” renders the claims indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). For Examination the optional language will not be considered.
Regarding claims 27 and 50 the recitation of, “preferably wherein” renders the claims indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim Interpretation
“a disorder associated with low BH4 bioavailability” and “a pregnancy-related disorder” that is “caused by impaired activity of one or more enzymes within the pterin biosynthetic pathway” reads on phenylketonuria in a pregnant subject. The Specification states, “Numerous disorders are connected with dysfunction of these hydroxylase enzymes which can also be caused by a deficiency, or reduction in the bioavailability of, the required cofactor BH4. Such disorders include, for example, BH4 deficiency itself and phenylketonuria (PKU). In addition, due to its role in neurotransmitter production, BH4 is also implicated in neurological disorders such as autism, ADHD, depression, and Parkinson's. Low availability of BH4 in specific cells and tissues may not be related only to systemic BH4 levels, but may also be influenced by local BH4 oxidation or recycling, and the distribution of BH4, for example by cellular uptake or transport.”
Also, “a disorder associated with low BH4 bioavailability” and “a pregnancy-related disorder” includes any BH4 deficiency, in which the level required to meet deficient or low is unclear and
Claim Rejections - 35 USC § 102
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 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.
Claims 1, 6, 8-9, 11, 14, and 41-44 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Oppenheimer, US 20160367558 A1 published 12/22/2016.
Instant claim 1 a method of preventing or treating a disorder associated with low BH4 bioavailability in a subject, the method comprising administering to the subject a reduced folate; wherein the disorder associated with low BH4 bioavailability is a pregnancy-related disorder; and wherein the reduced folate is the sole active pharmaceutical agent.
Oppenheimer in claim 27, a method for the treating a pregnant female having hyperphenylalaninemia (HPA) comprising administering to said subject a protein-restricted diet in combination with a composition comprising tetrahydrobiopterin (BH4) or a precursor or derivative thereof, wherein the combined administration of the protein-restricted diet and BH4 is effective to lower the phenylalanine concentration in the plasma of said subject as compared to said concentration in the absence of said combined administration.
HPS is a tetrahydrobiopterin (BH4) deficiency causing the body to build up an abnormally high level of phenylalanine.
Oppenheimer in claim 32, the method of claim 31, wherein said folate comprises a tetrahydrofolate selected from the group consisting of tetrahydrofolate is 5-formyl-(6S)-tetrahydrofolic acid and salts thereof, 5-methyl-(6S)-tetrahydrofolic acid and salts thereof, 5,10-methylene-(6R)-tetrahydrofolic acid and salts thereof, 5,10-methenyl-(6R)-tetrahydrofolic acid and salts thereof, 10-formyl-(6R)-tetrahydrofolic acid, 5-formimino-(6S)-tetrahydrofolic acid salts thereof, (6S)-tetrahydrofolic acid and salts thereof, and combinations of the foregoing.
5-methyl-(6S)-tetrahydrofolic acid is 5-MTHF.
This teaching anticipates claims 1, 6, 8, 11.
Instant claim 9 recites, wherein the reduced folate increases or restores BH4 levels and/or wherein the reduced folate prevents oxidation of BH4. This is simply a recitation of the result of the method step, this flows naturally from the administration step and does not lend to patentability.
Instant 14 states, “method according to claim 1, wherein the disorder associated with low BH4 bioavailability is caused by impaired activity of one or more enzymes within the pterin biosynthetic pathway.” Hyperphenylalaninemia: is a condition is characterized by elevated levels of phenylalanine in the blood. In this condition, the enzyme phenylalanine hydroxylase (PAH) is either partially functional or not produced correctly, leading to some phenylalanine metabolism but not enough to prevent elevated levels. This meets the limitation required by instant claims 14 and 44.
Claims 1, 6, 8-9, 11, 14, and 41-44 are anticipated.
Claim Rejections - 35 USC § 102
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 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.
Claims 1, 6, 8, 9, 11, 19, 22-25, 27-28 and 41-51 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Bailey, WO 2008/137043 A1 published 11/13/2008
Instant claim 1 a method of preventing or treating a disorder associated with low BH4 bioavailability in a subject, the method comprising administering to the subject a reduced folate; wherein the disorder associated with low BH4 bioavailability is a pregnancy-related disorder; and wherein the reduced folate is the sole active pharmaceutical agent.
Bailey teaches in claim 1, a method for treating hypertension in a subject, said method comprising: administering to the subject an effective amount of at least one reduced folate.
Bailey teaches on Page 12, lines 25-34, “subjects who may benefit from such prophylactic treatment include individuals who suffer from diseases, disorders, syndromes, or other conditions which are known to cause a blood pressure increase; women who have previously suffered from pre-eclampsia; women who have previously suffered from pre-eclampsia and who are not presently pregnant; women who have previously suffered from pre-eclampsia and who are pregnant again; women who have previously suffered from pregnancy-induced hypertension…”
Bailey teaches in claim 3, wherein the reduced folate is 5-methyl-(6S)-tetrahydrofolic acid (5-MTHF).
Bailey teaches, “The reduced folates can be administered on a regular basis, for example, once per day,” see page 15 line 10.
Bailey teaches, “[s]uitable daily dosage ranges of reduced folates include: from about 0.45 micromoles to about 15 micromoles.” 5-MTHF has a mass of 459.463 g·mol−1, therefore this equates to 206 to 6892 micrograms (.2 to 6.9 mg), see Page 32, line 15. In Example 1 Bailey teaches a 5 mg dose of 5-MTHF. This meets instant claims 27-28 and 50-51.
Instant claims 22 and 46 wherein the reduced folate is for administration to a subject after having been diagnosed with a pregnancy-related vascular disorder. This is at once envisaged as doctor’s treat patients based on diagnosis.
Instant claims 23 and 47 wherein the reduced folate, combination or composition is effective in the prevention of a disorder associated with insufficient BH4 levels in subsequent generations. This is simply a recitation of the result of the method step positively recited, this flows naturally from the administration step and does not lend to patentability.
Instant claims 24 and 48 wherein the prevention or treatment is in a subject who has previously suffered with a disorder associated with insufficient BH4 levels. This is covered by the patient discussed above.
Instant claim 25 and 49, wherein the prevention or treatment is in a subject who has previously suffered with hypertension in pregnancy or is in a subject who has previously suffered with pre-eclampsia. This is covered by the patient discussed above.
Claims 1, 6, 8-9, 11, 14, and 41-44 are anticipated.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHAEL J SCHMITT whose telephone number is (571)270-7047. The examiner can normally be reached M-F 8-6 MidDay Flex.
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, Jeffrey Lundgren can be reached at 571-272-5541. 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.
/MICHAEL J SCHMITT/ Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/ Supervisory Patent Examiner, Art Unit 1629