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 .
Priority
This application, filed on September 23, 2024, is a National Stage entry from International Application No. PCT/EP2023/056759, filed on March 16, 2023, which claims priority under 35 U.S.C. 119 or 365 to the benefit of the United Kingdom Application No. GB2204185, filed on March 24, 2022. The certified copy of the foreign application has been received.
Information Disclosure Statement
The information disclosure statement (IDS) filed on May 30, 2025, has been acknowledged and considered.
Status of Claims
Pursuant to the Preliminary Amendment, filed on May 30, 2025, claims 1-24 are currently amended. Claims 1-24 are amended to correct typographical errors and to perfect antecedent basis. Claim 1 is further amended to recite that the MT-containing compound has the depicted formula. Claim 2 is further amended to recite "about" in place of "around any of." Claims 3, 9, 10, 12-16, 18, 21, 23, and 24 are further amended to remove multiple dependencies.
Claims 20, 22, and 24 are amended to perfect Markush language.
Claims 1-24 are pending in the present application. Claims 25 and 26 are canceled.
Specification
Applicant is reminded of the proper content of an abstract of the disclosure.
A patent abstract is a concise statement of the technical disclosure of the patent and should include that which is new in the art to which the invention pertains. The abstract should not refer to purported merits or speculative applications of the invention and should not compare the invention with the prior art.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means,” “said,” and “comprise,” should be avoided.
The instant abstract recites “novel,” which purports the merits of the invention, and “comprise,” in the first sentence. Appropriate correction is required.
See MPEP § 608.01(b) for guidelines for the preparation of patent abstracts.
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 10-11 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.
The description and the claims are separate statutory requirements. Under modern claim practice, claims must stand alone to define an invention. Ex parte Fressola, 27 USPQ2d 1608 (BPAI 1993). Claims 10 and 11 refer to “Table 7” and “Table 6,” respectively, to convey the signs/symptoms as well as the genes for genetic testing. As a result, one of ordinary skill in the art must refer back to the specification to understand what the claimed invention is. MPEP 2173.05.
Appropriate correction is required.
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 1-9 and 14-24 are rejected under 35 U.S.C. 103 as being unpatentable over US 9,283,230 (“Clunas”).
Clunas teaches a method of treating Alzheimer’s disease with phenothiazine compounds such as methylene blue that are “leuco” or reduced forms of N,N,N',N'-tetramethyl-10H-phenothiazine-3,7-diamine (MTC) (col. 4, ll. 25-50; col. 7, ll. 46-65). The reduced forms of MTC have improved properties, such as improved physical, pharmacokinetic, biochemical, etc., and example compounds are LMT⸳2HCl, LMT⸳2HBr, LMT⸳2HI, LMT⸳2MsOH, LMT⸳2EsOH, LMT⸳2TsOH, LMT⸳PDSA, etc. (col. 5, ll. 19-49; col. 6, ll. 8-11; cols. 16-17). Dosage units of the compounds range from 20 to 300 mg and can be administered 2-3 times daily to human subjects (col. 47, ll. 5-43; col. 57, ll. 7-19). Clunas teaches that dosages can vary from patient to patient and determining the optimal dosage will involve balancing the level of therapeutic benefit against any risk or deleterious side effects (col. 56, ll. 45-63). Clunas also teaches that MTC is currently used to treat methemoglobinemia (col. 3, ll. 44-47) and that after 28-days of dosing of LMT⸳2MsOH in minipigs, there was no indication of methemoglobinemia at 3mg/kg/day.
Clunas does not explicitly teach administering reduced forms of MTC to treat methemoglobinemia.
Clunas is considered analogous art to the claimed invention because it is in the same field of preparing reduced forms of MTC for potential treatment of methemoglobinemia. Therefore, it would have been prima facie obvious to a person having ordinary skill in the art (PHOSITA) following the teachings of Clunas to administer reduced forms of MTC, such as LMT⸳2HCl, at a dose ranging from 20 to 300 mg to a subject having methemoglobinemia. The instant claims encompass LMT⸳2HCl, where HnA is HCl, p=2, q=0, and n=1. Clunas teaches that MTC is already used to treat methemoglobinemia, but MTC itself has issues with absorption and can lead to diarrhea. However, Clunas teaches the reduced form increases bioavailability and limits undesired side-effects. (col. 4, ll. 62-67; col. 5, ll. 1-9). Accordingly, claims 1, 15, 17-20 are prima facie obvious.
Regarding claims 2-7, Clunas teaches reduced forms of MTC can be administered in a range from 20 to 300 mg, which overlap with the ranges instantly claimed (MPEP §2144.05(I)).
Regarding claim 8, Clunas teaches dosages can vary from patient to patient and determining the optimal dosage will involve balancing the level of therapeutic benefit against any risk or deleterious side effects (vide supra). Clunas establishes dosages as a result effective variable, therefore the dosage instantly claimed would have been obtained with a reasonable expectation of success by a PHOSITA and would have been achieved through routine optimization (MPEP §2144.05(II)).
Regarding claim 9, teaches reduced forms of MTC can be administered 2-3 times daily to human subjects (vide supra).
Regarding claim 14, Clunas reduced form of MTC can be the following formula:
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198
489
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, where X1 and X2 are independently HX1 and HX2 sulfonic acids or hydrohalides (col. 50, ll. 4-24); R3NA and R3NB are the same and are methyl groups; and R7NA and R7NB are the same and are methyl groups (col. 14, ll. 17-39).
Regarding claims 16, 21-22, and 24, Clunas teaches one of the reduced forms of MTC can be LMT⸳EDSA (col. 17, compound 5), which is a diprotic organic acid.
Regarding claim 23, Clunas teaches one of the reduced forms of MTC can be LMT⸳2MsOH.
Claims 10-13 are rejected under 35 U.S.C. 103 as being unpatentable over Clunas in view of David (J Pharmacol Pharmacother 2018;9:1-5).
The teachings of Clunas are discussed above and are incorporated by reference herein.
Clunas does not teach treating patient populations with signs or symptoms and a gene associated with methemoglobinemia. Nor does it teach treating patients that have acquired or inherited methemoglobinemia.
David teaches methemoglobinemia can be inherited congenitally or acquired through the consumption or exposure to certain foods and drugs. Inherited methemoglobinemia exists as two types through mutations of the CYB5R3 gene: type I is deficient CYB5R in the erythrocyte only and type II is deficient in CYB5R but generally occurs in all cell types of the patient which can cause severe neurological deficiency (p. 2, 1st col.). David states: “When the MetHb level exceeds 45%, the person may develop dyspnea, acidosis, cardiac dysrhythmias, heart failure, seizures, and coma. Severe methemoglobinemia may lead to death if not treated immediately.” (Id.). David also teaches the reduced form of methylene blue, or MTC, leucomethylene blue, reduces methemoglobin (MetHb) making it suitable to treat acute methemoglobinemia. (Id.).
Clunas and David are analogous art to the claimed invention because they are in the same field of treating methemoglobinemia with reduced forms of MTC. Therefore, it would have been prima facie obvious to a PHOSITA, before the effective filing date of the claimed invention, to combine the teachings of the prior art elements to arrive at the method instantly claimed. It would have been prima facie obvious to administer reduced forms of MTC, such as LMT⸳2HCl at a dose ranging from 20 to 300 mg, where HnA is HCl, p=2, q=0, and n=1, to a subject having methemoglobinemia, based on the teachings of Clunas, and include patients with symptoms, such as seizure, and gene mutations of genes, such as CYB5R3, based on the teachings of David. David teaches that CYB5R reduces MetHb back to hemoglobin. Therefore, a PHOSITA would have been motivated to identify mutations of this gene when treating patients with methemoglobinemia. Accordingly, claims 10-11 are prima facie obvious.
Regarding claims 12-13, David teaches administration of methylene blue to patients with inherited methemoglobinemia ranges from 50-250 mg per day orally for a lifetime, and for acquired methemoglobinemia, 1-2 mg/kg of 1% methylene blue solution is intravenously administered for >20 min (p. 2, 1st col.). David also teaches that MTC has adverse side effects (p. 2, 2nd col.) and that when MetHb levels are >45%, the patient can face mortality if not treated immediately. Therefore, it would have been prima facie obvious to administer reduced forms of MTC, such as LMT⸳2HCl, based on the teachings of Clunas, to patients with inherited or acquired methemoglobinemia, based on the teachings of David, because both Clunas and David teach MTC has adverse side effects if administered as is. Additionally, David implicitly teaches that patients with >45% MetHb need to be treated immediately to avoid mortality.
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 1-24 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 11,065,256 (“ ‘256 ”) in view of Mohorovic et al., Advances in Bioscience and Biotechnology, 2014, 5, 12-18 (“Mohorovic”). Although the claims at issue are not identical, they are not patentably distinct from each other because Claims 1-24 are obvious over claims 1-18 of ‘256 in view of Mohorovic.
Claim 1 ‘256 teaches the administration of a methylthioninium (MT)-containing compound at a dose between 0.5 and 20 mg wherein the compound is LMTX with protic acids HnA to treat Alzheimer’s disease, Pick’s disease, etc. Claim 2 teaches the dosage is 2 to 15 mg or 3 to 10 mg. Claim 3 teaches the protic acids are diprotic acids. Claim 4 teaches the protic acid is a bis-monoprotic acid. Claims 5 and 6 teach the protic acids are inorganic and organic acids, respectively. Claim 7 teaches the organic acid is methanesulfonic acid, 1,2-ethanedisulfonic acid, etc. Claim 8 teaches LMTM, which is LMTX with bis-methanesulfonic acids.
‘256 does not recite administering the MT compounds to treat methemoglobinemia.
Mohorovic teaches incidences of neonatal jaundice, heart murmur, and disorders such as dyslalia and learning/memory impairments were significantly higher in those children born from mothers with methemoglobinemia. Mohorovic also teaches prenatal iron abnormalities could lead to greater neuronal death, the disease ageing process, and neurodegenerative disorders such as Alzheimer’s disease (AD) and other neurodegenerative diseases (p. 12, Abstract). Mohorovic states: “The substantial difference of intracellular ferric iron originates from the physiological Fenton reaction, and ferric iron originates from pathological methemoglobin catabolism occurring as the level of methemoglobin cellular uptake increases, and the resulting methemoglobinemia causes ferric iron induced oxidative stress injury.” (p. 13, 1st col.)
It would have been prima facie obvious to a PHOSITA following the teachings of the ‘256 patent to administer LMTM, or an MT compound with inorganic protic acids, at a dose between 0.5 to 20mg, to patients having methemoglobinemia because Mohorovic states that the pathological methemoglobin catabolism increases as the level of methemoglobin cellular uptake increases, and the resulting methemoglobinemia causes ferric iron induced oxidative stress injury which has been linked to neurodegenerative disorders such as AD. Based on the teachings of Mohorovic that the presence of methemoglobinemia in a subject lead to AD, it would have been prima facie obvious to a PHOSITA to administer a compound such as LMTM to subjects having methemoglobinemia because methemoglobinemia and AD are pathologically linked through the accumulation of ferric iron (MPEP §2144.06(I)). Accordingly, claims 1-8 and 14-24 are prima facie obvious.
Claims 1-24 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 12,280,061 (“ ‘061 ”) in view of Mohorovic. Although the claims at issue are not identical, they are not patentably distinct from each other because Claims 1-24 are obvious over claims 1-20 of ‘061 in view of Mohorovic.
Claim 1 of ‘061 teaches administration of LMTM at a dose between 20.5 to 60 mg optionally split into 2 or more doses to a subject having AD.
The teachings of Mohorovic are discussed above and incorporated by reference herein.
It would have been prima facie obvious to administer a compound such as LMTM, at a dose between 20.5 to 60 mg, based on the teachings of ‘061, to patients having methemoglobinemia because Mohorovic states that the pathological methemoglobin catabolism occurring as the level of methemoglobin cellular uptake increases, and the resulting methemoglobinemia causes ferric iron induced oxidative stress injury, which has been linked to neurodegenerative disorders such as AD and other neurodegenerative diseases. Based on the teachings of Mohorovic and the presence of methemoglobinemia in a subject lead to AD, it would have been prima facie obvious to a PHOSITA to administer a compound such as LMTM to subjects having methemoglobinemia because methemoglobinemia and AD are pathologically linked through the accumulation of ferric iron (MPEP §2144.06(I)). Accordingly, claims 1-7, 9, 14-15, 17, 21-23 are prima facie obvious.
Claims 1-24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 10-11, 19, 22, 26, 32, 36-39, 45-46, 48-50, 53, and 55-56 of copending Application No. 18/869,709 (“ ‘709 “) in view of Mohorovic. Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1-24 are obvious over claims 1-2, 6-12, and 14-29 of ‘837 in view of Mohorovic.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 1 of ‘709 teaches administration of an MT containing compound at an average dose between 0.05 mg to 30 mg of MT per day to a subject having a neurodegenerative disease. Claim 19 recites the compound can be LMT. Claims 22 and 26 teach the MT compound has protic acids, and those protic acids are bis-monoprotic acids. Claim 32 recites the LMT compound is LMTM. Claim 55 recites the neurodegenerative disease of claim 1 is AD.
The teachings of Mohorovic are discussed above and incorporated by reference herein.
It would have been prima facie obvious to administer a compound such as LMTM, at a dose between 0.05 to 30 mg, based on the teachings of ‘709, to patients having methemoglobinemia because Mohorovic states that the pathological methemoglobin catabolism occurring as the level of methemoglobin cellular uptake increases and the resulting methemoglobinemia causes ferric iron induced oxidative stress injury, which has been linked to neurodegenerative disorders such as AD. Based on the teachings of Mohorovic, the presence of methemoglobinemia in a subject leads to AD, therefore it would have been prima facie obvious to a PHOSITA to administer a compound such as LMTM to subjects having methemoglobinemia because methemoglobinemia and AD are pathologically linked through the accumulation of ferric iron (MPEP §2144.06(I)). Accordingly, claims 1-8, 14-15, 17, 21-23 are prima facie obvious.
Claims 1-24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 6, 10-14, 18, 43, 49, 52-53, 60-62, and 68-69 of copending Application No. 19/113,777 (“ ‘777 “) in view of Mohorovic. Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1-24 are obvious over claims 1-4, 6, 10-14, 18, 43, 49, 52-53, 60-62, and 68-69 of ‘777 in view of Mohorovic.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 1of ‘777 recites a composition containing a LMT compound and excipients are recited in claims 2, 6, 10 and 14. Claim 60, dependent on claim 14, and claim 61-62, dependent on claim 60, of ‘777, recite methods of administrating an MT compound to a subject in a dosage range between 0.05 mg to 30 mg per day wherein the disease being treated is a neurodegenerative disease of protein aggregation. Claim 68 recites the disorder of claim 61 is AD.
The teachings of Mohorovic are discussed above and incorporated by reference herein.
It would have been prima facie obvious to administer a LMT compound, at a dose between 0.05 to 30 mg, based on the teachings of ‘777, to patients having methemoglobinemia because Mohorovic states that pathological methemoglobin catabolism occurs as the level of methemoglobin cellular uptake increases, and the resulting methemoglobinemia causes ferric iron induced oxidative stress injury, which has been linked to neurodegenerative disorders such as AD and other neurodegenerative diseases. Based on the teachings of Mohorovic and the presence of methemoglobinemia in a subject lead to AD, it would have been prima facie obvious to a PHOSITA to administer a compound such as LMTM to subjects having methemoglobinemia because methemoglobinemia and AD are pathologically linked through the accumulation of ferric iron (MPEP §2144.06(I)). Accordingly, claims 1-8 are prima facie obvious.
Claims 1-24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of copending Application No. 17/922,886 (“ ‘886 “) in view of Iolascon et al., Am J Hematol. 2021;96:1666–1678 (“Ialascon”). Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1-24 are obvious over claims 1-30 of ‘886 in view of Ialascon.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 1 of ‘886 teaches a method of alleviating hypoxemia in a subject by administering an MT containing compound at a dosage range between 0.5 mg to 250 mg, to a subject per day, optionally split into 2 doses. The compound is a reduced form of MTC and has protic acids HnA. Claim 9 recites the doses are split to twice or three times a day. Claims 20-21 recite the protic acids are mono-protic acids. Claim 22 recites the protic acid is a diprotic acid. Claim 23 recites the protic acid is a bis-monoprotic acid. Claims 24-26 recite the acid is inorganic and can be a hydrohalide, such as HCl, HBr, etc. Claims 27-29 recite the protic acid is an organic acid, and can be methanesulfonic acid, 1,2-ethanedisulfonic acid, etc.
‘886 does not teach administering the reduced MTC compounds to treat methemoglobinemia.
Ialascon teaches methemoglobinemia is a rare disorder associated with oxidization of ferro-iron of hemoglobin (Hb) to ferri-iron of methemoglobin (MetHb). Ialascon teaches methemoglobinemia is acquired or inherited and the diagnosis of methemoglobinemia should be suspected in case of unexplained cyanosis and hypoxemia. Table 1 shows the signs, symptoms, and causes of methemoglobinemia and different MetHb levels, where severe hypoxemia is associated with MetHb levels >70% (p. 1667, 1st col.).
It would have been prima facie obvious to administer the reduced MTC compounds in ‘886 at a dose range between 0.5 to 250 mg, twice a day, to treat methemoglobinemia because Ialascon teaches the diagnosis of methemoglobinemia is suspected and would be present if MetHb levels >70% (vide supra). Accordingly, claims 1-9 and 12-24 are prima facie obvious.
Claims 1-24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 6-12, and 14-29 of copending Application No. 17/922,837 (“ ‘837 “) in view of Alamdari et al., European Journal of Pharmacology 885 (2020) 173494 (“Alamdari”). Although the claims at issue are not identical, they are not patentably distinct because claims 1-24 are obvious over claims 1-2, 6-12, and 14-29 of ‘837 in view of Alamdari.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 1 of ‘837 teaches a method of treating COVID-19 in a subject by administering an MT containing compound at a dosage range between 10 mg to 30 mg, to a subject per day, optionally split into 2 doses. The compound is a reduced form of MTC and has protic acids HnA. Claim 9 recites the doses are split to twice or three times a day. Claims 17-18 recite the protic acids are mono-protic acids. Claim 19 recites the protic acid is a diprotic acid. Claim 20 recites the protic acid is a bis-monoprotic acid. Claims 21-23 recite the acid is inorganic and can be a hydrohalide, such as HCl, HBr, etc. Claims 24-26 and 29 recite the protic acid is an organic acid, and can be methanesulfonic acid, 1,2-ethanedisulfonic acid, etc.
‘837 does not teach administering the MT containing compounds to treat methemoglobinemia.
Alamdari teaches a probable reason for hypoxia in COVID-19 patients is methemoglobinemia, which results from oxidation of the iron contained in hemoglobin from the ferrous to the ferric form (p. 2, 1st col.). Alamdari teaches the reduced form of methylene blue, leucomethylene blue (LMB) can decrease methemoglobinemia in COVID-19 patients by reducing met-HB, decreasing oxidative stress, and decreasing inflammation (p.2, 2nd col.).
It would have been prima facie obvious to administer the reduced MTC compounds in ‘837 at a dose range between 10 to 30 mg, twice a day, to treat methemoglobinemia because Alamdari states a probable reason for hypoxia in COVID-19 patients is methemoglobinemia, and that reduced forms of LMB can decrease methemoglobinemia in COVID-19 patients through specific mechanisms. (vide supra). Accordingly, claims 1-9 and 14-24 are prima facie obvious.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAHIL CHANDER AGGARWAL whose telephone number is (571)272-7755. The examiner can normally be reached 7am-5pm.
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/SAHIL CHANDER AGGARWAL/Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623
