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 .
Claims 1-60 are pending.
Claim Objections
Claims 5-21, 23, 25, 30-41, 45, 47-48, 50-58 are objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claims 5-21, 23, 25, 30-41, 45, 47-48, 50-58 are depending from another multiple dependent claims. See MPEP § 608.01(n).
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 1-23, 25-42, 46-59 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-25 of U.S. Patent No. 11,701,367 (‘367) in view of di Michele et al., J Neurol Neurosurg Psychiatry 2003;74:667–670. Although the claims at issue are not identical, they are not patentably distinct from each other because ‘367 teaches a method of treating tuberous sclerosis epilepsy using ganaxolone (see claim 1). ‘367 teaches the dosage of ganaxolone as up to 63mg/kg daily (see claims 6- 10). ‘367 teaches the dosage form of ganaxolone as capsule, suspension and tablet (see claims 2-4). ‘367 teaches the tuberous sclerosis complex-related epilepsy as an infantile spasm, a focal impaired awareness seizure, a focal seizure, or a generalized seizure (see claim 25).
‘367 does not expressly teach the reduction of seizure frequency. ‘367 does not expressly teach the dosing regimen. ‘367 does not expressly teach the endogenous neuroactive steroids level being decreased.
Di Michele et al. teaches in tuberous sclerosis epilepsy patients, the 3a,5a tetrahydroprogesterone level is decreased (see the abstract).
It would have been obvious to one of ordinary skill in the art to employ the herein claimed dosing regimen in a method of treating tuberous sclerosis related epilepsy.
One of ordinary skill in the art would have been motivated to employ the herein claimed dosing regimen in a method of treating tuberous sclerosis related epilepsy. The optimization of result effect parameters (dosage range, dosing regimens) is obvious as being within the skill of the artisan. The optimization of known effective amounts of known active agents to be administered, is considered well in the competence level of an ordinary skilled artisan in pharmaceutical science, involving merely routine skill in the art. It has been held that it is within the skill in the art to select optimal parameters, such as amounts of ingredients, in a composition in order to achieve a beneficial effect. See In re Boesch, 205 USPQ 215 (CCPA 1980). It is also noted that “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Adjusting the dosing regimen to maximize the therapeutic effects and minimize the side effect of the actives would be reasonably expected to be effective in treating tuberous sclerosis related epilepsy. Furthermore, the effects of reducing the frequency of seizure is considered as an inherent properties of the neuroactive steroids. The teachings of di Michele et al. provide an additional motivation to employ a neuroactive steroids in the method of treating tuberous sclerosis related epilepsy because patient with tuberous sclerosis related epilepsy have a reduced level of endogenous neuroactive steroids.
Claims 1-23, 25-42, 46-59 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-25 of U.S. Patent No. 11,980,625 (‘625) in view of di Michele et al., J Neurol Neurosurg Psychiatry 2003;74:667–670. Although the claims at issue are not identical, they are not patentably distinct from each other because ‘625 teaches a method of treating tuberous sclerosis epilepsy using ganaxolone (see claim 1). ‘625 teaches the dosage of ganaxolone as up to 63mg/kg daily (see claims 6- 10). ‘625 teaches the dosage form of ganaxolone as capsule, suspension and tablet (see claims 2-4). ‘625 teaches the tuberous sclerosis complex-related epilepsy as an infantile spasm, a focal impaired awareness seizure, a focal seizure, or a generalized seizure (see col. 12, lines 20-27).
‘625 does not expressly teach the reduction of seizure frequency. ‘625 does not expressly teach the dosing regimen. ‘625 does not expressly teach the endogenous neuroactive steroids level being decreased.
Di Michele et al. teaches in tuberous sclerosis epilepsy patients, the 3a,5a tetrahydroprogesterone level is decreased (see the abstract).
It would have been obvious to one of ordinary skill in the art to employ the herein claimed dosing regimen in a method of treating tuberous sclerosis related epilepsy.
One of ordinary skill in the art would have been motivated to employ the herein claimed dosing regimen in a method of treating tuberous sclerosis related epilepsy. The optimization of result effect parameters (dosage range, dosing regimens) is obvious as being within the skill of the artisan. The optimization of known effective amounts of known active agents to be administered, is considered well in the competence level of an ordinary skilled artisan in pharmaceutical science, involving merely routine skill in the art. It has been held that it is within the skill in the art to select optimal parameters, such as amounts of ingredients, in a composition in order to achieve a beneficial effect. See In re Boesch, 205 USPQ 215 (CCPA 1980). It is also noted that “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Adjusting the dosing regimen to maximize the therapeutic effects and minimize the side effect of the actives would be reasonably expected to be effective in treating tuberous sclerosis related epilepsy. Furthermore, the effects of reducing the frequency of seizure is seen to be an inherent properties of the neuroactive steroids. The teachings of di Michele et al. provide an additional motivation to employ a neuroactive steroid in the method of treating tuberous sclerosis related epilepsy because patient with tuberous sclerosis related epilepsy have a reduced level of endogenous neuroactive steroids.
Claims 1-23, 25-42, 46-59 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 of U.S. Patent No. 12,115,169 (‘169) in view of di Michele et al., J Neurol Neurosurg Psychiatry 2003;74:667–670. Although the claims at issue are not identical, they are not patentably distinct from each other because ‘169 teaches a method of treating tuberous sclerosis epilepsy using ganaxolone (see claim 1). ‘169 teaches the dosage of ganaxolone as about 50 mg are administered three times a day for about one week, followed by about 100 mg administered three times a day for about one week, followed by about 200 mg administered three times a day for about one week, followed by about 400 mg administered three times a day for about one week, followed by 600 mg administered three times a day for the remaining treatment period OR about 6 mg/kg/day for about one week, followed by about 12 mg/kg/day for about one week, followed by about 24 mg/kg/day for about one week, followed by about 42 mg/kg/day for about one week, followed by about up to 63 mg/kg/day for the remaining treatment period (see claims 3, 11-12). ‘169 teaches the dosage form of ganaxolone as capsule, suspension and tablet (see claims 4-5). ‘169 teaches the reduction of seizure frequency in the method of treating tuberous sclerosis epilepsy (see claim 10). ‘169 ‘625 teaches the tuberous sclerosis complex-related epilepsy as an infantile spasm, a focal impaired awareness seizure, a focal seizure, or a generalized seizure (see claim 17).
‘169 does not expressly teach the endogenous neuroactive steroids level being decreased.
Di Michele et al. teaches in tuberous sclerosis epilepsy patients, the 3a,5a tetrahydroprogesterone level is decreased (see the abstract). Di Michele et al. teaches the endogenous neurosteroids 3a-THP having about 1.5-2.5 nmol/L which is about 1.5-2.5 pmol/ml. which is less than 2500pg/ml (see Figure 1).
It would have been obvious to one of ordinary skill in the art at the time of filing to treat tuberous sclerosis epilepsy in patients with a decreased level of neuroactive steroid. The teachings of di Michele et al. provide an additional motivation to employ a neuroactive steroid in the method of treating tuberous sclerosis related epilepsy because patient with tuberous sclerosis related epilepsy have a reduced level of endogenous neuroactive steroids.
Claims 1-23, 25-42, 46-59 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 12, 390,477 (‘477) in view of di Michele et al., J Neurol Neurosurg Psychiatry 2003;74:667–670. Although the claims at issue are not identical, they are not patentably distinct from each other because ‘477 teaches a method of treating tuberous sclerosis epilepsy using ganaxolone (see claim 1). ‘477 teaches the dosage of ganaxolone as about 50 mg are administered three times a day for about one week, followed by about 100 mg administered three times a day for about one week, followed by about 200 mg administered three times a day for about one week, followed by about 400 mg administered three times a day for about one week, followed by 600 mg administered three times a day for the remaining treatment period OR about 6 mg/kg/day for about one week, followed by about 12 mg/kg/day for about one week, followed by about 24 mg/kg/day for about one week, followed by about 42 mg/kg/day for about one week, followed by about up to 63 mg/kg/day for the remaining treatment period (see claims 3, 12-13). ‘477 teaches the dosage form of ganaxolone as capsule, suspension and tablet (see claims 17-18). ‘477 teaches the reduction of seizure frequency in the method of treating tuberous sclerosis epilepsy (see claim 10).
‘477 does not expressly teach the endogenous neuroactive steroids level being decreased.
Di Michele et al. teaches in tuberous sclerosis epilepsy patients, the 3a,5a tetrahydroprogesterone level is decreased (see the abstract).
It would have been obvious to one of ordinary skill in the art at the time of filing to treat tuberous sclerosis epilepsy in patients with a decreased level of neuroactive steroid. The teachings of di Michele et al. provide an additional motivation to employ a neuroactive steroid in the method of treating tuberous sclerosis related epilepsy because patient with tuberous sclerosis related epilepsy have a reduced level of endogenous neuroactive steroids.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 46 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claims 46 recites the compound “ganaxolone”, which is not encompassed by the compounds of Formula IA recited in claim 45. Since claim 46 is depending from claim 45, claim 46 fails to further limit the subject matter from the claim it is depending from. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
Claim(s) 1, 3, 4, 9-21, 25, 42, 45-46, 47, 57-58 is/are rejected under 35 U.S.C. 103 as being unpatentable over CA 3017172 (‘172) in view of di Michele et al.
‘172 teaches the use of neuroactive steroids such as allopregnanolone for treating CNS disorders including tuberous sclerosis complex related epilepsy (see page 20, line 3 for example; page 22, line 16). ‘172 teaches the GABA related disorders treatment effectiveness may be assessed by EEG (see page 21, second-to-last paragraph). ‘172 teaches the dosage of the neuroactive steroids as about 10-80mg in multiple times daily for the duration at least 1-7 days (see page 21, last paragraph bridging page 22, fifth paragraph, page 59, third and fourth paragraphs). ‘172 teaches the GABA neuroactive steroids are administered orally or intravenously and in typical dosage forms such as tablets, capsules, , and suspension ((see for example, page 31, last paragraph; page 59, second paragraph). ‘172 teaches the seizure disorders to be treated include infantile spasm, partial seizures, generalized seizures, focal seizures (see page 40, 5th paragraph).
‘172 does not expressly teach the endogenous neuroactive steroids level being decreased.
Di Michele et al. teaches in tuberous sclerosis epilepsy patients, the 3a,5a tetrahydroprogesterone level is decreased (see the abstract).
It would have been obvious to one of ordinary skill in the art at the time of filing to treat tuberous sclerosis epilepsy in patients with a decreased level of neuroactive steroid.
One of ordinary skill in the art would have been motivated to treat tuberous sclerosis epilepsy in patients with a decreased level of neuroactive steroid. The teachings of di Michele et al. provide an additional motivation to employ a well-known neuroactive steroid, including allopregananolone, in the method of treating tuberous sclerosis related epilepsy because patient with tuberous sclerosis related epilepsy have a reduced level of endogenous neuroactive steroids.
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/SAN MING R HUI/Primary Examiner, Art Unit 1627
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