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
The office acknowledges Applicants’ filing of the claims on 8/29/2024. Claims 1-33 are pending and are examined based on the merits herein.
Application Priority
This application filed 08/29/2024 is a Continuation of 18491319, filed 10/20/2023, now U.S. 12102609, 18491319 is a Continuation in Part of 18176855, filed 03/01/2023, now U.S. 11793776, 18176855 is a Continuation of 18148682, filed 12/30/2022, now U.S. 11771666.
Information Disclosure Statement
The information disclosure statement(s) (IDS) filed on 8/29/2024, 12/11/2024, 7/2/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDS is being considered by the Examiner (all references considered except where lined through).
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.
Claim(s) 1-33 are rejected under 35 U.S.C. 103 as being unpatentable Sunosi (IDS: SUNOSI, Medication Guide, FDA, 03/2019) in view of Wright et al. (IDS: J of Perinatal & Neonatal Nursing, September 1997, 112(2), p 71-84) and Julie, (IDS: 2018 https://julieflygare.com/new-research-for-breastfeeding-mothers-with-narcolepsy/) and further in view of Abad (Nature and Science of Sleep, 2021, 75-91) and/or Cook et al. (US 8,952,062).
Sunosi document teach SUNOSI (solriamfetol) tablet is a dopamine and norepinephrine reuptake inhibitor (DNRI), indicated to improve wakefulness in adult patients with excessive daytime sleepiness (EDS) associated with narcolepsy or obstructive sleep apnea (OSA). It is taught that solriamfetol tablet is administered once daily upon awakening. The reference teaches starting dose for patients with narcolepsy is 75 mg once daily and starting dose for patients with OSA is 37.5 mg daily; the recommended dosage in OSA is 37.5 mg to 150 mg once daily (Dosage and Administration, Dosage in OSA, 2.4). The document wakefulness and sleepiness were assessed using the Epworth sleepiness scale (ESS). The reference teach 239 patients with narcolepsy were randomized to receive Sunosi 75 mg, 150 mg or 300 mg. Table 7 teach efficacy results for Epworth Sleepiness Scale in patients with narcolepsy (study 1), the baseline score mean is about 17.3 and 17.0 and the change from baseline at week 12, is -3.8, and -5.4 for subjects administered with 75 mg and 150 mg of solriamfetol. Patients randomized to the 150 mg dose received 75 mg for the first 3 days before increasing to 150 mg (see p 16, 14.1 Narcolepsy).
Sunosi reference teaches that adverse reactions in either the narcolepsy or OSA population include headache, nausea, decreased appetite, anxiety and insomnia (6.1, Clinical Trials experience, para 3). It is taught that there are no data available on the presence of solriamfetol or its metabolites in human milk, the effects on the breastfed infant, or the effect of this drug on milk production. Solriamfetol is present in rat milk. When a drug is present in animal milk, it is likely that the drug will be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for SUNOSI and any potential adverse effects on the breastfed child from SUNOSI or from the underlying maternal condition (See 8.2, Lactation, p 10).
In summary, Sunosi document teach (a) solriamfetol tablet improves wakefulness in adult patients with excessive daytime sleepiness associated with narcolepsy or obstructive sleep apnea (37.5 mg -150 mg); solriamfetol drug may likely be present in human milk; (b) developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for solriamfetol and any potential adverse effects on the breastfed child from solriamfetol.
Sunosi is not explicit in teaching feeding the infant breast milk obtained from the mother at least about 5 h after administration of the solriamfetol to the mother, thereby avoiding exposing the infant to the maximum concentrations of solriamfetol in the breast milk and wherein the daily infant dose of solriamfetol is reduced to about 2% or lower (claims 1, 18) or the milk obtained from the mother is at least 7 hours or 10 hours (claims 3-4, 19-20).
Wright teaches minimizing infant exposure to and risks from medications while breastfeeding. The reference teach that it is well established that all drugs are excreted into breast milk (Abstract). The reference teach that the drug’s characteristics determine the amount of the drug that will be transferred into the breast milk. The characteristics include half-life of the drug among other factors (p 7, col.1, line 18). Wright teach that the breast milk is manufactured while the infant is suckling; the timing of a drug dose in relation to breastfeeding influences how much of the drug will appear in the breast milk; if the infant is breastfeeding when the maternal serum drug level is peaking, the amount of a drug that transfers to the breast milk is higher than if her serum level is at a trough. In addition, the blood flow to the breast increases when the breasts begin to lactate. A peaking drug serum level combined with an increase in mammary blood flow will deliver a higher amount of the drug to the milk (See p 8, col. 2, Timing of Medication). Also taught is that the goal is to minimize the infant’s exposure to drugs in the breast milk; the strategies should be used with available information on the specific drug being considered for the lactating mother (see p 10, col. 2, strategies to minimize infant exposure and risk to drugs while breastfeeding).
Julie teach lactating women who take Xyrem (sodium oxybate) to treat narcolepsy with cataplexy can time their breastfeeding to avoid exposing nursing infants to elevated levels of the drug in milk (p 1, para 1). Further taught is that women medicated with sodium oxybate who desire to breastfeed might consider delaying feeding infants their own milk until at least 6 hour after their most recent dose (p 1, last 2 lines. p2, line 1). Another research group has published similar findings in an additional patient with narcolepsy and cataplexy, demonstrating that sodium oxybate was cleared from the patient’s milk 5 hours following administration (p 2, para 2).
The above references are not explicit in teaching additional therapeutic agent in the method.
Abad teach solriamfetol in the management of excessive daytime sleepiness associated with narcolepsy or obstructive sleep apnea. Abad teach for patients with residual symptoms after first-line treatment, combination therapy improved daytime sleepiness in 55% of these patients. Combination therapy, such as with sodium oxybate and modafinil, may result in synergistic effects to further improve ES (See p 84, col. 1, lines 33-38). Abad teach regarding a combination therapy of solriamfetol (75 mg, 150 mg) with stimulants in a study. It is taught that in a small (n=18) retrospective study of patients taking stimulants (drugs were not specified), the addition of solriamfetol (75 mg,150 mg) did not lead to significant increase in systolic or diastolic blood pressure, mean arterial pressure, or heart rate. Because of the small number of participants and retrospective nature of this study, it would be prudent to monitor BP and HR in patients where combination therapy of solriamfetol with a stimulant is prescribed (See p 87, col. 2, para 4).
Cook discloses the use of gamma-hydroxybutyrate salt (GHB) for the treatment of narcolepsy (See abstract and claims). Further taught is that a second pharmaceutical may be administered with the composition of GHB and within 24 hour period of the first dose of GHB (See p 9, lines 39-42).
From the combined teachings of the prior art a person of ordinary skill in the art before the effective filing date of the invention would have found it obvious to arrive at the clamed method to reduce the exposure of solriamfetol in an infant fed with the breast milk of the subject taking solriamfetol because (i) Wright and Julie teach risks are associated from medications taken by the lactating mother while breastfeeding and strategies must be determined on the specific drug to minimize the drug exposure to infants (ii) lactating women who take medication sodium oxybate to treat narcolepsy with cataplexy can time their breastfeeding to avoid exposing nursing infants to elevated levels of the drug in milk and consider delaying feeding infants their own milk until at least 5-10 hours after their most recent dose; (iii) Wright teach breast milk is manufactured while the infant is suckling; the timing of a drug dose in relation to breastfeeding influences how much of the drug will appear in the breast milk; (iv) Sunosi document teach (a) solriamfetol tablet improves wakefulness in adult patients with excessive daytime sleepiness associated with narcolepsy or obstructive sleep apnea (37.5 mg -150 mg); solriamfetol drug may likely be present in human milk; (b) developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for solriamfetol and any potential adverse effects on the breastfed child from solriamfetol. From the teachings of the prior art a person of ordinary skill in the art would have found it obvious to administer an oral daily dose of about 150 mg or 75 mg of solriamfetol once daily to the breastfeeding subject and feeding the infant breast milk at least about 5 hours or 7 hours or 10 hours after solriamfetol administration to the subject. It is within the skill of an artisan to adjust the dosage regimen (dose, time of administration, frequency etc.) based on the medical conditions, nature of the drug, pharmacokinetics of the drug etc. especially when the subject is breastfeeding. One of ordinary skill in the art would have been motivated to do so is to reduce or minimize the exposure of drug, herein solriamfetol and its adverse effects in the infant with a reasonable amount of success. As to the limitation of ‘wherein the cumulative amount of solriamfetol excreted in breast milk over 8 hours is reduced to about 2% or lower (claims 1, 18), administration of the same drug, herein 150 mg or 75 mg of solriamfetol to nursing mother (from Sunosi) and feeding the infant at least about 5 or 7 or 10 hours would result in substantially the same effects. A person skilled in the art would have found it obvious to add a stimulant or GHB in the method along with solriamfetol as combination therapy to treat narcolepsy from Abad and/or Cook. A person skilled in the art would have been motivated to add another agent for treatment of narcolepsy in combination with solriamfetol to obtain additive or synergistic therapeutic effects. As to the limitation ‘wherein the exposure to solriamfetol in the infant is reduced by at least about 50% compared to the exposure that would result with feeding the infant breast milk obtained from the mother less than 5 hours after administration of the solriamfetol’, it is noted that administration of the same agent, herein solriamfetol to the same set of subjects, nursing mothers will result in the same pharmacological effects as claimed. Thus claims 1, 3-4, 17, 19-20 would have been obvious over the combined prior art teachings.
As to claims 2, 18, in regards to the infant dose of solriamfetol, administration of the same agent, solriamfetol (150 mg or 75 mg) to the mother would result in about 2% or lower of the daily dose of solriamfetol.
As to claims 5-7, 21-23 in regards to the adverse effects, or to the infant would not experience some of the effects such as agitation, insomnia or reduced weight’, the adverse effects associated with solriamfetol is reduced in the infant if the breast milk is fed to the infant after about 5 or 7 or 10 hours of administration of solriamfetol (150 mg or 75 mg) to the nursing mother subject is addressed by the combined teachings of the prior art. In other words a person of ordinary skill in the art would have found it obvious that providing the breast milk to the infant after specific period (after 5 or 7 or 10 hours) of administration of solriamfetol (150 mg or 75 mg) to the mother would result in decrease or avoidance of adverse effects associated with the drug solriamfetol.
As to claims 8-11, 24-27 Sunosi teach that solriamfetol is administered to subjects with excessive daytime sleepiness
As to claims 12-14, 28-31, it is well known that postpartum is defined as a period after childbirth and can range from 1 day to 2 years for example. It is within the skill of an artisan that the subjects in the method include having a postpartum period of 1 day to 24 months, for e.g. 10 days. As to claims 19, 26, it is obvious to a person of ordinary skill in the art that the childbearing years of the woman subject can range from the years of 18-45.
As to claims 15-16, 32-33, from Abad and/or Cook a skilled artisan would have found it obvious to deliver concurrently GHB (an agent for neurological disorder, narcolepsy) an additional therapeutic agent along with solriamfetol to treat narcolepsy.
Note: The prior art made of record and not relied upon is considered pertinent to
applicant's disclosure: US 10,940,133 teach the use of daily administration of (R)-2-amino-3-phenylpropyl carbamate (APC) a.k.a. "solriamfetol" (75 mg, 150 mg) for treating excessive sleepiness in subjects with narcolepsy or obstructive sleep apnea (OSA). Insomnia is recognized as a side effect that should be minimized. Johnson teach that solriamfetol is used in excessive daytime sleepiness in narcolepsy (Comprehensive Pharmacology, chapter 3, p 180-199, June 2022). ClinicalTrials (2021, 2022) disclose that the purpose of study JZP110-401 is to evaluate solriamfetol pharmacokinetics (PK) in the breast milk and plasma of healthy postpartum women following the administration of the drug. The study also aims to estimate the potential daily solriamfetol dose received by the infant from the breast milk of the nursing mother.
Claim Objections
Claim 31 is objected to under 37 CFR 1.75 as being a substantial duplicate of claim 30.
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When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-33 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed by him. The courts have stated:
"To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir.1997); In re Gostelli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) ("[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966." Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents" of the University of California v. Eli Lilly & Co. the court stated:
"A written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as by structure, formula, [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials." Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) ("In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus ...") Regents of the University of Califorrnia v. Eli Lilly & Co., 43 USPQ2d 1398.
The MPEP states that for a generic claim the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. MPEP § 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP § 2163. Although the MPEP does not define what constitute a sufficient number of representative species, the courts have indicated what do not constitute a representative number of species to adequately describe a broad genus. In Gostelli, the courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gostelli, 872, F.2d at 1012, 10 USPQ2d at 1618.
The Guidelines for Examination of Patent Applications Under 35 USC 112, "Written Description" Requirement (Federal Register, Vol. 66, No. 4, pg. ll05, column 3), in accordance with MPEP § 2163, specifically state that for each claim drawn to a genus the written description requirement may be satisfied through sufficient description of a representative number of species by a) actual reduction to practice; b) reduction to drawings or structural chemical formulas; c) disclosure of relevant, identifying characteristics (i.e. structure) by functional characteristics coupled with a known or disclosed correlation between function and structure. The analysis of whether the specification complies with the written description requirement calls for the examiner to compare the scope of the claim with the scope of the description to determine whether applicant has demonstrated possession of the claimed invention (Federal Register, Vol. 66, No. 4, p. ll05, 3rd column, 3rd paragraph). Below is such comparison.
Scope of claims: The scope is very broad in regards to the ‘additional therapeutic agents’ in claims 1 and 17.
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According to the specification, ‘The additional therapeutic agent can be any agent that provides a benefit to the subject’ [0076].
The scope of the additional therapeutic agents is still broad in claims 16 and 33, even if they are limited to specific classes of agents, stimulants, anti-psychotics, anti-depressants, agents for neurological disorders, and chemotherapeutic agents. There are hundreds of agents in the limited category (claims 16 and 33) and since there is no data available in the specification or in the prior art, it is not predictable that solriamfetol can be combined with all the agents as claimed.
Scope of disclosure and reduction to practice:
As per the specification,
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There is no evidence or data in the specification that any additional therapeutic agent was administered in combination with solriamfetol. A limited prior art is available in regards to the combination therapy with solriamfetol (See Abad reference above).
Both Abad and Sunosi teach the contraindications associated with administration of solriamfetol with specific drugs. For example, Sunosi teach in page 1,
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Abad teach in page 84:
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Representative number of Examples:
There are no examples provided in the specification for a combination therapy. There is one example provided in the prior art Abad.
There is a substantial variation within the genus of the additional therapeutic agent to be combined with solriamfetol. From the data provided in the specification or from the prior art one of ordinary skill in the art cannot predict that any therapeutic agent available and known can be added in combination with solriamfetol in the method as it can affect the efficacy, can influence the exposure of other drugs to infant (who is provided the breast milk), can introduce additional adverse effects to the extent that they may overweigh the benefits. A skilled artisan would not be able to extrapolate from the data provided for the combination therapy.
Applicants have failed to provide guidance or data or evidence as to how the skilled artisan would be able to extrapolate from the disclosure to make and possibly use of the claimed invention for all therapeutic agents. “A description of what a material does, rather than of what it is, usually does not suffice." Rochester, 358 F 3d at 923; Eli Lilly, 119 at 1568. Instead, the “disclosure must allow one skilled in the art to visualize or recognize the identity of the subject matter purportedly described.”
The specification provides insufficient written description to support the genus encompassed by the claim, Vas-Cath Inc. Mahurkar, 19 USPQ2d 1111, makes clear the "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116).
The description requirement of the patent statue requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736, F.2d 1516, 1521,222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does "little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.").
Thus, the specification fails to provide adequate written description for the combination therapy of solriamfetol with all therapeutic agents and even with select list of agents as claimed and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention.
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 1-33 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-26 of US 12102609 (‘609) or claims 1-26 of U.S. 11,771,667 (‘667) or claims 1-21 of US 11771666 (‘666) or claims 1-18 of US 11779554 (‘554) or claims 1-24 of US 11793776 (‘776) or claims 1-18 of US 11872203 (‘203) or claims 1-28 of US 12036194 (‘194) or 1-18 of US 12064411 (‘411) or claims 1-26 of US 12263145 (‘145) or claims 1-52 of co-pending application, 18/758658 (‘658) or claims 53-68 of co-pending application, 19/494743 (‘743) in view of Abad (Nature and Science of Sleep, 2021, 75-91) and/or Cook et al. (US 8,952,062).
The instantly claimed method(s) are directed to a method of reducing the exposure to solriamfetol from breast milk in an infant receiving breast milk from a nursing human mother being treated concurrently with a once-daily dose of about 150 mg or 75 mg solriamfetol and an additional therapeutic agent, the method comprising feeding the infant breast milk obtained from the mother being treated concurrently with solriamfetol and an additional therapeutic agent at least about 5 hours after administering the solriamfetol to the mother, wherein the exposure to solriamfetol in the infant is reduced by at least about 50% compared to the exposure that would result with feeding the infant breast milk obtained from the mother less than 5 hours after administration of the solriamfetol; wherein the resulting relative infant dose of solriamfetol is about 2% or lower of the once-daily dose of about 150 mg solriamfetol; wherein the breast milk is obtained from the mother at least about 7 hours after administering the solriamfetol to the mother; wherein the infant does not experience agitation or insomnia or anorexia and/or reduced weight gaindue to exposure to the solriamfetol; wherein the mother is being treated with solriamfetol for excessive daytime sleepiness, narcolepsy, obstructive sleep apnea, shift work disorder, attention deficit hyperactivity disorder, Parkinson's disease, binge eating disorder, or cognitive impairment or improve wakefulness; wherein the lactating mother is from about 1 day to about 24 months postpartum; wherein the lactating mother is between the ages of 18 and 45 years; wherein the additional therapeutic agent is delivered concurrently to the nursing human mother in a composition separate from the solriamfetol.
‘609 reference claims are directed to a method for decreasing the potential for adverse events from solriamfetol in an infant fed breast milk obtained from a human subject treated with solriamfetol or to a method for treating a disorder treatable with solriamfetol in a human subject producing breast milk for feeding an infant comprising: administering solriamfetol orally at a once-daily dose of about 150 mg to the subject; and feeding the infant breast milk from the subject at least about 5 hours after administering the solriamfetol to the subject, wherein the cumulative amount of solriamfetol excreted in breast milk over 8 hours is about 0.26 or about 0.35 mg or lower. The dependent claims are limited to the subject is being treated with solriamfetol for narcolepsy, excessive daytime sleepiness, obstructive sleep apnea, attention deficit/hyperactivity disorder, cognitive impairment, or binge eating disorder; the adverse effects are agitation, insomnia or reduced weight gain, the infant not experiencing agitation, insomnia, anorexia or reduced weight gain due to the exposure to the solriamfetol, subject is 1-24 m or 10 weeks to 52 weeks postpartum and the age of the mother is 18-45 years.
‘667 reference claims are to a method of treating excessive daytime sleepiness, attention deficit hyperactivity disorder, binge eating disorder, depression, or cognitive impairment in a lactating human mother feeding an infant with her breast milk, comprising: orally administering solriamfetol to the mother at a once-daily dose of about 150 mg or 75 mg; and feeding the infant the breast milk obtained from the mother at least about 5 hours after administration of the solriamfetol to the mother; daily infant dose of solriamfetol is to about 0.3 mg or lower; and the potential for adverse events in the infant due to the solriamfetol is decreased or the exposure of the infant to the solriamfetol from the breast milk is decreased. The dependent claims are limited to the cause of excessive daytime sleepiness, the adverse effects are agitation, insomnia or reduced weight gain, characteristics of lactating mother (1-24 m postpartum, age 18-45 years) and the infant does not experience agitation, insomnia, anorexia or reduced weight gain due to solriamfetol exposure.
‘666 reference claims are directed to a method of reducing exposure or for decreasing the potential for adverse events or to solriamfetol in an infant fed breast milk obtained from a human subject treated with solriamfetol comprising: orally administering the solriamfetol to the subject at a once-daily dose of about 150 mg; and feeding the infant breast milk from the subject at least about 5 hours after administering the solriamfetol to the subject being treated for example, excessive daytime sleepiness, the daily infant dose of solriamfetol is about 0.3 mg or lower. Claims 12-21 are to a method of treating a disorder treatable with solriamfetol in a human subject producing breast milk for feeding an infant, comprising: administering solriamfetol orally at a once-daily dose of about 150 mg to the subject; and reducing exposure of the infant to solriamfetol and/or decreasing the potential for adverse events in the infant fed breast milk from the subject, comprising feeding the infant breast milk obtained from the subject at least about 5 hours after administering the solriamfetol to the subject, wherein the daily infant dose of solriamfetol is reduced to about 0.3 mg or lower. The dependent claims are limited to the subject being treated to specific disorders including excessive daytime sleepiness, to the characteristics of lactating mother (1-24 m postpartum, age 18-45 years) and the infant does not experience agitation, insomnia, anorexia or reduced weight gain due to solriamfetol exposure.
‘554 reference claims are directed to a method of reducing the risk of agitation in an infant that is fed breast milk obtained from a human subject treated with solriamfetol, comprising: orally administering the solriamfetol to the subject being treated for example, excessive daytime sleepiness, at a once-daily dose of about 150 mg or 75 mg; and feeding the infant breast milk obtained from the subject at least about 5 hours after administering the solriamfetol to the subject, daily infant dose of solriamfetol is about 0.3 mg or lower. The dependent claims are directed to wherein the infant does not experience agitation due to solriamfetol exposure, disorders being treated in the subject, the conditions associated with excessive daytime sleepiness or cognitive impairment, to the characteristics of lactating mother (1-24 m postpartum, age 18-45 years) and the infant does not experience agitation.
‘776 reference claims are directed to a method for treating a postpartum human subject, who is producing breast milk, for a disorder amenable to treatment with solriamfetol, comprising: orally administering solriamfetol to the subject at a once-daily dose of about 150 mg or 75 mg; and feeding an infant breast milk obtained from the subject at least about 5 hours after administering the solriamfetol to the subject; the daily infant dose of solriamfetol is 0.3 mg or lower; the potential for adverse events in the infant due to the solriamfetol is decreased, wherein the subject is being treated with solriamfetol for specific disorders including excessive daytime sleepiness. Claims 13 and 19 in addition to the above, have a limitation of, wherein the exposure of the infant to the solriamfetol from the breast milk is decreased. The dependent claims are limited to wherein the infant does not experience agitation, insomnia, anorexia, or reduced weight gain due to solriamfetol from the breast milk, to the characteristics of lactating mother (1-24 m postpartum, age 18-45 years), cause of excessive daytime sleepiness and the cause of such conditions.
‘203 reference clams are directed to a method of reducing the risk of anorexia and/or reduced weight gain in an infant fed breast milk obtained from a subject treated with solriamfetol, comprising: orally administering the solriamfetol to the subject at a daily dose of about 150 mg or 75 mg; and feeding the infant breast milk obtained from the subject at least about 5 hours after administering the solriamfetol to the subject, wherein the daily infant dose of solriamfetol is about 0.3 mg or lower. The dependent claims are limited to wherein the infant does not experience anorexia, reduced weight gain, or weight loss due to solriamfetol dose; characteristics of lactating mother (1-24 m postpartum, age 18-50 years), the subject is being treated with solriamfetol for excessive daytime sleepiness, narcolepsy, cognitive impairment etc., wherein the excessive daytime sleepiness is associated with narcolepsy, wherein the cognitive impairment is associated with narcolepsy etc., and wherein the subject is being treated with solriamfetol to improve wakefulness.
‘194 reference clams are directed to a method of reducing the exposure to solriamfetol from breast milk, in an infant receiving breast milk from a nursing human mother being treated with a once-daily dose of solriamfetol of about 150 mg for a disorder amenable to treatment with solriamfetol, the method comprising feeding the infant breast milk obtained from the mother at least about 5 hours after administering the solriamfetol to the mother, wherein the exposure to solriamfetol in the infant is reduced by at least about 50% compared to the exposure that would result with feeding the infant breast milk obtained from the mother less than 5 hours after administration of the solriamfetol, and wherein the daily infant dose of solriamfetol is reduced to about 0.3 mg or 0.15 mg or lower. The dependent claims include wherein the infant does not experience insomnia, agitation, anorexia and/or reduced weight gain due to exposure to the solriamfetol. The dependent claims are limited to the infant is not fed breast milk obtained within at least about 7 or 10 hours of the mother receiving an oral once-daily dose of solriamfetol, the infant does not experience agitation or insomnia, anorexia and/or reduced weight gain, plasmapause ratio, elimination half-life of solriamfetol excreted in the breast milk is approximately 5h, wherein breast milk produced by the nursing mother during the at least about 5 hours of the mother receiving an oral once-daily dose of solriamfetol is expressed and discarded, mother being treated with conditions including excessive daytime sleepiness, cognitive impairment, excessive daytime sleepiness is associated with narcolepsy etc., cognitive impairment is associated with narcolepsy etc., mother being treated for wakefulness, characteristics of lactating mother (1-24 m postpartum, age 18-45 years).
‘411 reference claims are directed to a method of reducing the risk of insomnia in an infant fed breast milk obtained from a subject treated with solriamfetol, comprising: orally administering the solriamfetol to the subject at a daily dose of about 150 mg or 75 mg; and feeding the infant breast milk obtained from the subject at least about 5 hours after administering the solriamfetol to the subject; wherein a daily infant dose of solriamfetol is reduced to about 0.3 mg or 0.15 mg or lower. The dependent claims are limited to herein the infant does not experience insomnia due to solriamfetol dose; characteristics of lactating mother (1-24 m postpartum, age 18-50 years), the subject is being treated with solriamfetol for excessive daytime sleepiness, narcolepsy, cognitive impairment etc., wherein the excessive daytime sleepiness is associated with narcolepsy, wherein the cognitive impairment is associated with narcolepsy etc., and wherein the subject is being treated with solriamfetol to improve wakefulness.
‘204 reference claims are directed to a method of preventing a reduction in number of feedings and/or a reduction in volume of milk ingested in an infant fed breast milk obtained from a subject treated with solriamfetol, comprising orally administering the solriamfetol to the subject at a daily dose of about 150 mg or 75 mg; and feeding the infant breast milk obtained from the subject at least about 5 hours after administering the solriamfetol to the subject, wherein the daily infant dose of solriamfetol is about 0.3 or 0.15 mg or lower. The dependent claims are limited to specific postpartum time, specific subject population (excessive daytime sleepiness, narcolepsy, obstructive sleep apnea, shift work disorder, attention deficit hyperactivity disorder, depression, binge eating disorder, Parkinson's disease, or cognitive impairment), and age of the woman.
‘145 reference claims are directed to (i) a method for decreasing the potential for adverse events from solriamfetol in an infant fed breast milk obtained from a human subject treated with solriamfetol comprising: administering solriamfetol orally at a once-daily dose of about 75 mg to the subject; and feeding the infant breast milk from the subject at least about 5 hours after administering the solriamfetol to the subject, and the cumulative amount of solriamfetol excreted in breast milk over 8 hours is about 0.26 mg or lower; or 0.35 mg or lower (ii) a method for treating a disorder treatable with solriamfetol in a human subject producing breast milk for feeding an infant, comprising: administering solriamfetol orally at a once-daily dose of about 75 mg to the subject; and reducing exposure of the infant to solriamfetol and/or decreasing the potential for adverse events in the infant fed breast milk from the subject, comprising feeding the infant breast milk obtained from the subject at least about 5 hours after administering the solriamfetol to the subject, and the cumulative median amount of solriamfetol excreted in breast milk over 8 hours is about 0.26 mg or lower ; or 0.35 mg or lower. The dependent claims are limited to disorder selected from narcolepsy, excessive daytime sleepiness, obstructive sleep apnea, cognitive impairment, attention deficit/hyperactivity disorder, or binge eating disorder; wherein the infant does not experience agitation, insomnia, or reduced weight gain due to solriamfetol exposure; wherein the subject is from 1 day to 24 months postpartum; wherein the subject is between the ages of 18 and 45 years.
‘658 co-pending reference claims are directed to a method for decreasing the potential for adverse events from solriamfetol in an infant fed breast milk obtained from a human subject treated with solriamfetol or treating a disorder treatable with solriamfetol in a human subject producing breast milk for feeding an infant, or a method of treating excessive daytime sleepiness, attention deficit hyperactivity disorder, binge eating disorder, or cognitive impairment in a lactating human mother feeding an infant with her breast milk, method for treating a postpartum human subject, who is producing breast milk, for a disorder amenable to treatment with solriamfetol comprising: administering solriamfetol orally at a once-daily dose of about 150 mg or 75 mg to the subject; and feeding the infant breast milk from the subject at least about 5 hours after administering the solriamfetol to the subject, wherein the daily infant dose of solriamfetol is reduced to about 0.1 mg/kg or lower. The dependent claims are limited to specific adverse events, agitation, insomnia, or reduced weight gain; subject is being treated with solriamfetol for narcolepsy, excessive daytime sleepiness, obstructive sleep apnea, attention deficit/hyperactivity disorder, cognitive impairment, or binge eating disorder; wherein the infant does not experience agitation, insomnia, or reduced weight gain due to solriamfetol exposure; the subject is from 1 day to 24 months postpartum; wherein the subject is a woman between the ages of 18 and 45 years.
‘743 co-pending reference claims are directed to (i) a method for decreasing the potential for adverse events from solriamfetol in an infant fed breast milk obtained from a human subject treated with solriamfetol comprising: administering solriamfetol orally at a once-daily dose of about 150 mg or 75 mg to the subject; and feeding the infant breast milk from the subject at least about 5 hours after administering the solriamfetol to the subject, wherein the daily infant dose of solriamfetol is reduced to about 0.1 mg/kg or 0.05 mg/kg or lower (ii) a method for treating a disorder treatable with solriamfetol in a human subject producing breast milk for feeding an infant, comprising: administering solriamfetol orally at a once-daily dose of about 150 mg or 75 mg to the subject; and reducing exposure of the infant to solriamfetol and/or decreasing the potential for adverse events in the infant fed breast milk from the subject, comprising feeding the infant breast milk obtained from the subject at least about 5 hours after administering the solriamfetol to the subject, wherein the daily infant dose of solriamfetol is reduced to about 0.1 mg/kg or 0.05 mg/kg or lower; wherein the disorder is narcolepsy, excessive daytime sleepiness, obstructive sleep apnea, cognitive impairment, attention deficit/hyperactivity disorder, or binge eating disorder; wherein the adverse events are one or more of agitation, insomnia, or reduced weight gain.
The above reference claims are not explicit in teaching the additional therapeutic agent in the method.
Abad and Cook as discussed above.
A person skilled in the art would have found it obvious to add a stimulant or GHB in the method along with solriamfetol as combination therapy to treat narcolepsy from Abad and/or Cook to obtain additive or synergistic therapeutic effects.
From the teachings of the reference claims and the prior art, a person of ordinary skill in the art would have found it obvious to arrive at the claimed method. As to reducing the exposure of solriamfetol from breast milk in an infant fed breast milk obtained from a human subject treated with solriamfetol (150 mg or 75 mg), when the milk is administered after about 5 hours or 7 h or 10 h, the reference claims teaches reduction of adverse effects associated with solriamfetol in an infant fed breast milk obtained from a human subject treated with solriamfetol is administered after about 5 hours. As to the limitation ‘wherein the exposure to solriamfetol in the infant is reduced by at least about 50% compared to the exposure that would result with feeding the infant breast milk obtained from the mother less than 5 hours after administration of the solriamfetol’, it is noted that administration of the same agent, herein solriamfetol to the same set of subjects, nursing mothers will result in the same pharmacological effects as claimed. Thus claims 1, 3-4, 17, 19-20 would have been obvious over the combined reference claims and prior art teachings.
As to claims 2, 18, in regards to the infant dose of solriamfetol, administration of the same agent, solriamfetol (150 mg or 75 mg) to the mother would result in about 2% or lower of the daily dose of solriamfetol.
As to claims 5-7, 21-23 in regards to the adverse effects, or to the infant would not experience some of the effects such as agitation, insomnia or reduced weight’, the adverse effects associated with solriamfetol is reduced in the infant if the breast milk is fed to the infant after about 5 or 7 or 10 hours of administration of solriamfetol (150 mg or 75 mg) to the nursing mother subject is addressed by the reference claims. A person of ordinary skill in the art would have found it obvious that providing the breast milk to the infant after specific period (after 5 or 7 or 10 hours) of administration of solriamfetol (150 mg or 75 mg) to the mother would result in decrease or avoidance of adverse effects associated with the drug solriamfetol.
As to claims 8-11, 24-27 the reference claims teach that solriamfetol is administered to subjects with excessive daytime sleepiness.
As to claims 12-14, 28-31, it is well known that postpartum is defined as a period after childbirth and can range from 1 day to 2 years for example. It is within the skill of an artisan that the subjects in the method include having a postpartum period of 1 day to 24 months, for e.g. 10 days. As to claims 19, 26, it is obvious to a person of ordinary skill in the art that the childbearing years of the woman subject can range from the years of 18-45. Further reference claims also teach the limitations in regards to postpartum period and subject’s age.
As to claims 15-16, 32-33, from Abad and/or Cook a skilled artisan would have found it obvious to deliver concurrently GHB (an agent for neurological disorder, narcolepsy) an additional therapeutic agent along with solriamfetol to treat narcolepsy.
Note: In regards to the co-pending applications, this is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-33 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of US 12090126 (‘126) or claims 1-30 of US 12005036 (‘036) in view of Abad (Nature and Science of Sleep, 2021, 75-91) and/or Cook et al. (US 8,952,062).
The instantly claimed method(s) as above.
‘126 reference claims are directed to a method of treating excessive daytime sleepiness in a lactating human mother, with an infant at risk of adverse events from the mother’s excessive daytime sleepiness, and who wishes to breastfeed the infant, said method comprising: a) determining the Epworth Sleepiness Scale (ESS) total score of the mother and if the mother experiences sleep attacks while caring for the infant, b) providing the mother having an ESS total score of 15 or greater and who experiences sleep attacks while caring for the infant a starting dose of solriamfetol of 37.5 mg once daily if the excessive daytime sleepiness is associated with obstructive sleep apnea, or 75 mg once daily if the excessive daytime sleepiness is associated with narcolepsy, and doubling the dose at intervals of at least 3 days up to 150 mg once daily; and c) feeding the infant breast milk obtained from the mother at least about 3.5 hours after administration of the solriamfetol to the mother, thereby avoiding exposing the infant to the maximum concentrations of solriamfetol in the breast milk, wherein the median Tmax of solriamfetol excreted in the breast milk is approximately 1.1 hours, and wherein the daily infant dose of solriamfetol is reduced to about 0.3 mg or lower after a 150 mg dose, about 0.15 mg or lower after a 75 mg dose, and about 0.08 mg or lower after a 37.5 mg dose. The dependent claims are limited to the mother experiencing a reduction in ESS total score or more, experiences a reduction in the frequency of sleep attacks, wherein the infant is not fed breast milk obtained within at least about 5 hours of the mother receiving an oral once-daily dose of solriamfetol, wherein the infant does not experience agitation or insomnia, anorexia and/or reduced weight gain due to exposure to the solriamfetol, plasma AUC ratio of approximately 2:1, the elimination half-life of the solriamfetol excreted in the breast milk is approximately 5 hours, wherein breast milk produced by the mother during the at least about 3.5 hours after administration of the solriamfetol to the mother is expressed and discarded and characteristics of lactating mother (1-24 m postpartum, age 18-45 years).
‘036 reference claims are directed to a method of avoiding exposing an infant of a nursing human mother being treated with solriamfetol to peak concentrations of solriamfetol excreted in breast milk, the method comprising not feeding the infant breast milk obtained within at least about 3.5 hours of the mother receiving an oral once-daily dose of about 150 mg or 75 mg of solriamfetol, wherein the median Tmax of solriamfetol excreted in the breast milk is approximately 1.1 hour, wherein the daily infant dose of solriamfetol is reduced to about 0.3 mg or lower. The dependent claims are limited to the infant is not fed breast milk obtained within at least about 5 hours of the mother receiving an oral once-daily dose of solriamfetol, the infant does not experience agitation or insomnia, anorexia and/or reduced weight gain, plasma : AUC ratio, elimination half-life of solriamfetol excreted in the breast milk is approximately 5h, wherein breast milk produced by the nursing mother during the at least about 3.5 hours of the mother receiving an oral once-daily dose of solriamfetol is expressed and discarded, mother being treated with conditions including excessive daytime sleepiness, cognitive impairment, excessive daytime sleepiness is associated with narcolepsy etc., cognitive impairment is associated with narcolepsy etc., mother being treated for wakefulness, characteristics of lactating mother (1-24 m postpartum, age 18-45 years).
The above reference claims are not explicit in teaching the additional therapeutic agent in the method.
Abad and Cook as discussed above.
A person skilled in the art would have found it obvious to add a stimulant or GHB in the method along with solriamfetol as combination therapy to treat narcolepsy from Abad and/or Cook to obtain additive or synergistic therapeutic effects.
From the teachings of the reference claims and the prior art, a person of ordinary skill in the art would have found it obvious to arrive at the claimed method. As to reducing the exposure of solriamfetol from breast milk in an infant fed breast milk obtained from a human subject treated with solriamfetol (150 mg or 75 mg), when the milk is administered after about 5 hours or 7 h or 10 h, the reference claims teaches reduction of adverse effects associated with solriamfetol in an infant fed breast milk obtained from a human subject treated with solriamfetol is administered after about 5 hours. As to the limitation ‘wherein the exposure to solriamfetol in the infant is reduced by at least about 50% compared to the exposure that would result with feeding the infant breast milk obtained from the mother less than 5 hours after administration of the solriamfetol’, it is noted that administration of the same agent, herein solriamfetol to the same set of subjects, nursing mothers will result in the same pharmacological effects as claimed. Thus claims 1, 3-4, 17, 19-20 would have been obvious over the combined reference claims and prior art teachings.
As to claims 2, 18, in regards to the infant dose of solriamfetol, administration of the same agent, solriamfetol (150 mg or 75 mg) to the mother would result in about 2% or lower of the daily dose of solriamfetol.
As to claims 5-7, 21-23 in regards to the adverse effects, or to the infant would not experience some of the effects such as agitation, insomnia or reduced weight’, the adverse effects associated with solriamfetol is reduced in the infant if the breast milk is fed to the infant after about 5 or 7 or 10 hours of administration of solriamfetol (150 mg or 75 mg) to the nursing mother subject is addressed by the reference claims. A person of ordinary skill in the art would have found it obvious that providing the breast milk to the infant after specific period (after 5 or 7 or 10 hours) of administration of solriamfetol (150 mg or 75 mg) to the mother would result in decrease or avoidance of adverse effects associated with the drug solriamfetol.
As to claims 8-11, 24-27 the reference claims teach that solriamfetol is administered to subjects with excessive daytime sleepiness.
As to claims 12-14, 28-31, it is well known that postpartum is defined as a period after childbirth and can range from 1 day to 2 years for example. It is within the skill of an artisan that the subjects in the method include having a postpartum period of 1 day to 24 months, for e.g. 10 days. As to claims 19, 26, it is obvious to a person of ordinary skill in the art that the childbearing years of the woman subject can range from the years of 18-45. Further reference claims also teach the limitations in regards to postpartum period and subject’s age.
As to claims 15-16, 32-33, from Abad and/or Cook a skilled artisan would have found it obvious to deliver concurrently GHB (an agent for neurological disorder, narcolepsy) an additional therapeutic agent along with solriamfetol to treat narcolepsy.
Conclusion
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/Umamaheswari Ramachandran/Primary Examiner, Art Unit 1627
