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 dated 06/25/2024. Claims 1-18 are pending and are being examined based on the merits herein.
Application Priority
This application filed 06/25/2024 is a Continuation of 17150428 , filed 01/15/2021, 17150428 is a Continuation of 16239947, filed 01/04/2019, now U.S 11090285, 16239947 is a Continuation of 15643664, filed 07/07/2017, 15643664 is a Continuation of 14510321, filed 10/09/2014, now U.S. 9730910, 14510321 is a Continuation of PCT/US13/76311, filed 12/18/2013, PCT/US13/76311 Claims Priority from Provisional Application 61903354, filed 11/12/2013. The claimed subject matter wherein the patient is being treated with a CYP3A4 inducer has support in PCT/US13/76311, 12/18/2013. It is noted that the effective filing date of the instant claims 1-12 is 12/18/2013.
Information Disclosure Statement
The information disclosure statement(s) (IDS) filed on 6/25/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDS is being considered by the Examiner.
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 1-12 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.
As the Federal Circuit has stated: 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. The MPEP does state 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 generic. In Gostelli, the courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gosteli, 872, F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989).
The factors considered in the Written Description requirement are:
(1) level of skill and knowledge in the art, (2) partial structure, (3) physical and/or chemical properties, (4) functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and (5) the method of making the claimed invention.
(1) Level of skill and knowledge in the art:
The level of skill to practice the art of the instantly claimed invention is high and requires a variety of skills usually found in institutions and companies that employ highly trained and skilled scientists to carry out these tasks.
(2) Partial structure: (3) Physical and/or chemical properties: and (4) Functional characteristics:
Claim 1 is directed to:
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The instant specification teaches the following: “Embodiments of the invention relate to the discovery that the daily dose of tasimelteon can be upwardly adjusted in patients also being treated with a CYP3A4 inducer”, e.g., rifampin (See p 5, para 1).
CYP1A2 and CYP3A4 are the major isoenzymes involved in the metabolism of tasimelteon. CYP3A4 inducers have been found to reduce tasimelteon exposure. For example, when a single 20 mg dose of tasimelteon was administered after 11 days of the administration of 600 mg of Rifampin, tasimelteon mean exposure was reduced by approximately 89%. Therefore, in cases where an individual is co-administered a CYP3A4 inducer, the dose of tasimelteon administered may be greater than if administered alone or in the absence of a CYP3A4 inducer (page 56, para 2).
Further it is taught that treating a patient with tasimelteon wherein the patient is also being treated with a CYP3A4 inducer, internally administering tasimelteon to the patient in an increased amount relative to an amount that would be administered to a patient suffering from a circadian rhythm or sleep disorder but not being treated with a CYP3A4 inducer, e.g., treating such patient with greater than 20 mg/d (page 60, para 2).
It is noted that the term 'CYP3A4 inducer’ is not limited to for example, rifampin.
(5) Method of making the claimed invention:
To provide adequate written description and evidence of possession of a claimed method with the recited compound(s), the specification must provide sufficient description or guidance to the method as claimed.
Applicants' provide support for rifampin and an example with the effects of co-administration of tasimelteon and fluvoxamine. From the description provided in the instant specification, one cannot extrapolate the data in the method with all the
'CYP3A4 inducer' in the claimed method.
CYP3A4 inducers in general include select anticonvulsants, antibiotics, antiretrovirals, dietary supplement(s), and other medications. It is taught that CYP3A4 inducers can be strong moderate or weak (See Wikipedia, 2026 and also UptoDate2026). Badolo teach the effect of the test compounds on mRNA expression vary and at least 100 inducers for CYP3A4 were identified (See p 182, col. 1, para 3, Table 5). Colchine was shown to downregulate CYP3A4 mRNA expression by 26 fold (See p 182, col. 2, para 1). Physico chemical analysis of CYP inducers were studied and it showed varying properties among the compounds tested (See p 183, col. 2, para 3-4, Table 7). A select list of potent CYP3A4 inducers is provided in Table 4. (Badolo, Xenobiotica, 2015; 45(2): 177–187).
Badolo teaches that “Owing to the role of CYP enzymes in drug metabolism and therefore, in drug pharmacokinetics, developing drugs with CYP induction potential may lead to significant drug–drug interactions in clinics. This risk is higher in combination therapies in disease for which chronic treatments are required. In these situations induction may lead to decrease of drug concentrations below the therapeutic
window while increasing the burden of metabolites to the liver and body as a result of the increase in drug metabolism” (See Conclusion, p 186 of Badolo, Xenobiotica, 2015; 45(2): 177–187).
In summary, the scope of the CYP3A4 inducers is large; properties of the CYP3A4 inducers vary; in combination therapy the adverse effects may be different for different CYP3A4 inducers; the risk is higher in combination therapy. One of ordinary skilled in the art would not be able to predict the effects or the results of the treatment or what amount of tasimelteon has to be administered for the treatment of Non-24 to be effective as the risk may be higher in combination therapy (see Badolo above).
One of ordinary skill in the art cannot extrapolate from the data provided to what extent each of CYPA3 inducer amount has to be added (reduced or increased) to treat the subjects with tasimelteon. 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 use the claimed invention.
It is noted that the pharmaceutical art is unpredictable, requiring each embodiment to be individually assessed for physiological activity. The fields of biology and chemistry are considered "unpredictable" because the complexity and unpredictability of chemical and biological interactions can make it difficult to understand the exact properties of an invention. The pharmaceutical industry is the prototypical example of a highly unpredictable field. Pfizer v. Teva Pharm., 482 F.Supp.2d 390, 413 (D.N.J. 2007); 2 Chisum on Patents § 5.04.
The level of detail required to satisfy the written description requirement varies depending on the nature and scope of the claims and on the complexity and predictability of the relevant technology. Ariad, 598 F.3d at 1351, USPQ2d at 1172; Capon v. Eshhar, 418 F.3d 1349, 1357-58, 76 USPQ2d 1078, 1083-84 (Fed. Cir. 2005).
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.").
The "written description" requirement may be satisfied by using such descriptive means as words, structures, figures, diagrams, formulas, etc., that fully set forth the claimed invention. See Noelle v. Lederman, 355 F.3d 1343, 1349, 69 USPQ2d 1508,
1514 (Fed. Cir. 2004) and Lockwood v. American Airlines, Inc., 107 F.3d at 1572, 41 USPQ2d at 1966. A definition by function alone "does not suffice" to sufficiently describe a coding sequence "because it is only an indication of what the gene does,
rather than what it is." Regents of the University of California v. Eli Lilly & Co., 119 F.3 at 1568, 43 USPQ2d at 1406 (Fed. Cir. 1997) (discussing Amgen Inc. v. Chugai
Pharmaceutical Co., 927 F.2d 1200, 18 USPQ2d 1016 (Fed. Cir. 1991). In Fiefs v.
Ravel, 984 F.2d at 1169-71, 25 USPQ2d at 1605-06 (1993), the CAFC found that "a mere wish or plan for obtaining the claimed chemical invention" is not sufficient to describe a chemical invention (discussed in Eli Lilly at 1404).
Applicant is reminded that Vas-Gath makes it clear that the written description provision of 35 U.S.C. § 112 is severable from its enablement provision (see Vas-Gath at page 1115). See also In re Barker, 559 F.2d 588, 591, 194 USPQ 470, 472 (CCPA 1977) (a specification may be sufficient to enable one skilled in the art to make and use the invention, but still fail to comply with the written description requirement).
It is deemed that the specification fails to provide adequate written description for the package 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.
This rejection can be overcome by amending the claims within the context and scope of the claims such as, incorporating specific CYP3A4 inducers (e.g. rifampin) actually contemplated in the specification.
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/ file/efs/guidance/eTD-info-I.jsp.
Claims 1-10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of US 11090285 (‘285) in view of Birznieks et al. (Applicants’ cited IDS: WO 2007/137244) and Sack et al. (Sleep Medicine Reviews, Vol. 5, No. 3, pp 189–206, 2001).
The instant claims 1-10 are to a method of treating Non-24 in a patient suffering therefrom, said method comprising internally administering to the patient an effective amount of tasimelteon, wherein the patient is being treated with a CYP3A4 inducer and wherein the effective amount is greater than 20 mg/d.
‘285 reference claim is directed to a method of administering tasimelteon to a patient who is being treated with rifampicin, the method comprising: maintaining the rifampicin treatment and administering to the patient a dose of tasimelteon that is greater than 20 mg/day, thereby avoiding reduced exposure to tasimelteon caused by induction of CYP3A4 by the rifampicin.
The reference claim is not explicit in teaching administering to the subject with Non-24.
Birznieks et al. teaches oral administration of tasimelteon (MA 1- (1 R-trans)-N [[2-(2,3-dihydro-4-benzofuranyl)cyclopropyl]methyl]propanamide, this compound is tasimelteon) as a melatonin agonist and in a method of treating a circadian rhythm disorder or a sleep disorder, for treating waking after sleep onset (See abstract, claims 1-6, 16). The dose administered according to the reference is 20-50 mg/day or about 100 mg/day (See claims 6, 11-13); wherein MA-1 is administered at or within about 2 h prior to bedtime (claims 7-8). The route of administration includes oral (p 3, line 4), tablets, pills, powders are some dosage forms (p 6, para 2). Birznieks explains that treatment with tasimelteon "is continued until the patient's circadian rhythm is restored to normal, i.e., until the patient's normal daily function is not inhibited by the underlying circadian rhythm disorder". Claim 8 specifies that the tasimelteon is "administered at about 0.5 hours prior to bedtime.
Sack teach circadian rhythm disorders subjects are blind and select population among the blind have no light perception (See Abstract, title, also, p 191, col. 1, para 2, 3). Further taught is that some blind people with free-running rhythms sleep in tune with their body clock on a non-24 hour sleep-wake schedule. (p 194, para 2, lines 1-4).
From Birznieks and Sack a skilled artisan would have found it obvious to administer tasimelteon and rifampicin in subjects with circadian rhythm disorder subjects, e.g. blind with Non-24 sleep wake cycle (blind and with no light perception) with a reasonable amount of success thus addressing claims 1-3. As to claims 4-8, Birznieks teach 20-50 mg, 100 mg/day of administration of tasimelteon for circadian rhythm disorders. Also it is noted that the dosage amount is routinely optimized and it is within the skill of an artisan. The dosage amount can be optimized based on the needs, combination therapy, age of the subject, condition(s) to be treated etc. As to claims 9-10, Birznieks specifies that the tasimelteon is "administered at about 0.5 hours prior to bedtime. It is within the skill of an artisan to routinely adjust the dosage regimen, e.g. administration time as it is an optimizable parameter. Thus the claimed method would have been obvious over the reference claims and the prior art.
Claims 13-18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of US 8785492 (‘492).
The instant claims 13 and 18 are directed to:
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The dependent claims 14-17 are limited to blind subjects, dosage/administration regimen.
‘492 reference claims are directed to:
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The dependent claims wherein the patient is limited to totally blind subjects and administration regimen.
Although the claims at issue are not identical, they are not patentably distinct from each other because both teach the entraining or treating a patient with Non-24 subjects with the target time following a sleep period of 7-9 hours with effective amount of tasimelteon. As to the dosage and administration regimen in the claims it is within the skill of an artisan to routinely adjust the optimizable parameter, dosage regimen. Thus the instantly claimed methods 13-18 would have been obvious over the reference claims.
Claims 13-18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim1 of US 9060995 (‘995) or claims 1-14 of US 9,549,913 (‘913) or claims 1-5 of US 9539234 (‘234) or claims 1-9 of US 9855241 (‘241) or claims 1-14 of US 10149829 (‘829) or claims 1-9 of US 10449176 (‘176) or Claims 1-13 of US 10945988 (‘988) or claims 1-12 of US 10980770 (‘770) or claims 1-11 of US 11633377 (‘377) or claims 1-3 of US 11285129 (‘129) or claims 1-4 of US 11826339 (‘339) or claims 1-3 of US 11850229 (‘229) or claims 1-3 of US 11918556 (‘556) or claims 1-9 of US 12201604 (‘604) or claims 1-15 of co-pending application, 19027122 (‘122) or claims 1-5 of US 9730910 (‘910) or claims 1-3 of US 11013713 (‘713) or claims 1-8 of co-pending application, 18/611987 (‘987) or claims 1-22 of US 11458116 (‘116) or claims 1-10 of US 12427132 (’132) or claims 1-13 of co-pending application, 19/318542 (‘542) or claims 1-10 of US 11918557 (‘557), Birznieks et al. (Applicants’ cited IDS: WO 2007/137244) and Botelho (https://www.washingtonpost.com/national/health-science/blind-people-often-find-it-hard-to-align-their-sleep-wake-cycle-with-24-hour-day/2012/08/06/5578f090-bb0d-11e1-abd4-aecc81b4466d_story.html, Aug 6, 2012).
The instant claims as discussed above.
The following are the reference claims from patents and co-pending applications.
‘995 reference claim is directed to:
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‘913 reference claims are directed to:
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The dependent claims are limited to specific dosage amount.
‘234 reference claims are directed to:
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‘241 reference claims are directed to:
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The dependent claims are limited to natural day/light cycle, administration regimen and dosage regimen.
‘829 reference claims are directed to:
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‘176 reference claims are directed to:
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The dependent claims are limited to natural day/light cycle, administration regimen and dosage regimen.
‘988 reference claims are directed to:
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The dependent claims are limited to administration regimen and dosage regimen.
‘770 reference claims are directed to:
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The dependent claims are limited to administration regimen and dosage regimen.
‘377 reference claims are directed to:
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129 reference claims are drawn to:
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‘339 reference claims are drawn to:
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‘229 reference claims are drawn to:
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‘556 reference claims are drawn to:
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‘604 reference claims are drawn to:
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‘122 reference claims are drawn to:
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The dependent claims are limited to specific dosage amounts.
‘910 reference claims are drawn to:
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‘713 reference claims are drawn to:
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‘987 reference claims are directed to:
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‘116 reference claims are directed to:
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‘132 reference claims are directed to:
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‘542 reference claims are directed to:
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Birznieks et al. teachings discussed as above.
Botelho teach that blind people find it hard to align their sleep-wake cycle with 24-h day (title). The reference describes a patient that has non-24-hour sleep-wake disorder, or "non-24; the chronic and little-known sleep condition is characterized by a body clock that is not aligned with a 24 hour day (see p 1, para 5-7). Botelho teach that tasimelteon is being tested to treat the condition (p 2, para 2). It is also taught that non-24 associated with blind people cannot sense light (para 6).
From the reference claims, Birznieks and Botelho a person skilled in the art would have found it obvious to arrive at the claimed methods of entraining and/or treating Non-24 subjects (blind) with an effective amount of tasimelteon. As to the dosage and administration regimen in the claims it is within the skill of an artisan to routinely adjust the optimizable parameters, dosage and administration regimen. Thus the instantly claimed methods would have been obvious over the reference claims and the prior art.
Note: As to the co-pending application(s), this is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to UMAMAHESWARI RAMACHANDRAN whose telephone number is (571)272-9926. The examiner can normally be reached M-F- 8:30-5:00 PM (PST).
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/Umamaheswari Ramachandran/ Primary Examiner, Art Unit 1627
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