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 .
Election/Restrictions
Applicants’ election of Major Depressive Disorder as a species for examination is acknowledged. Applicants have identified claims 1-78 and 81 as claims readable of the elected species. Claims 1-78 are readable on the elected species of MDD, however claim 81 is directed to a method for treating lung diseases. Since MDD is not a lung disease, claim 81 is not readable on the elected species is not examined on the merits.
Claims 79-86 are withdrawn.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 18-21 and 51-53 rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance:
Claims 18 recites the broad recitation two weeks or less, and the claim also recites seven days or less, which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claims 19 and 51 recite the broad recitation “greater than or equal to 0.3”, and the claim also recites “greater than or equal to 0.7”, which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. Claims 20-21 depend from claim 19 and also comprise the indefinite limitation. Claims 52-53 depend from claim 51 and also comprise the indefinite limitation
Claim 37 and 68 recites the limitation "wherein instead of placebo or in addition to placebo is includes one of more of magnesium, zinc, or lithium". There is insufficient antecedent basis for this limitation in the claim. Claims 36 and 67, from which 37 and 68 depend, are limited to administration of placebo. Administration of zinc instead of placebo or together with placebo is outside of the scope of the term “placebo”, which implies a substance with no physiological activity. Zinc and other agents listed are known antidepressants (see current claim 23) and therefore are outside of the scope of “placebo”.
Claims 36, 37, 67 and 68 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. The claims comprise the limitation “wherein administration of composition is alternated with a placebo in the selected intermittent administration schedule”. It is unclear at what time periods the placebo is to be administered. For example, if the selected administration schedule once every week, does the claim require administration of a placebo in addition to weekly administration of the active compound, or does the claim require administration of active agent one week and placebo the next week? In the latter case, the claims lack antecedent basis. If weekly administration of active agent is selected as the limitation of claim 66, alternating the administration with placebo is not within the scope of the selected administration schedule because one a week administration of active agent is required.
Claims 66 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. The claim requires selection between “every other week” and “every two weeks” the difference between the two is unclear. The claim also comprises limitations “once every three days” and “every other three days”.
Claim 35 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. The claim requires administration of “one week per month”, “one week per year” and “one month per year”. It’s unclear how often the agent is administered when it’s administered for “one week per month”. Is it daily, or every other day, or just once in the given week.
Claim 69 rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Claims is directed to the method “further associated with digital application to monitor the course of the disorder”. It’s unclear what being associated with digital monitoring means. The claim does not require a step of digital monitoring. Since in order to digitally monitor MDD a subject must have MDD, a subject with MDD is interpreted is being associated with digital monitoring because if MDD can be monitored by digital monitoring, then it is associated with digital monitoring.
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.
Claim 77 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The claim is directed to a method of diagnosing a disorder that is caused, worsened or maintained by hyperactive NMDAR channels comprising administering to a subject dextromethadone. The claim stipulated that if upon administration of dextromethadone, an improvement in the condition of the patient is observed, then the disorder is caused or maintained by hyperactive NMDAR channels. In order for this to feasible, activity of dextromethadone must be limited to inhibition of NAMDR activity. However, US 9,468,611 describes dextromethadone as having NMDAR inhibition activity and also NE re-uptake inhibition activity (column 5, lines 32-35; column 3-4, lines 64-7)). Given that NMDAR antagonism is not the only physiological effect of d-methadone, an improvement in symptoms upon administration of d-methadone need not be due to antagonism of NMDAR but could be due to inhibition of re-uptake of NE. One therefore cannot conclude that the disorder is caused, worsened or maintained by hyperactive NMDAR channels, because the disorder could be caused by Norepinephrine receptor.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-78 is/are rejected under 35 U.S.C. 103 as being unpatentable over Manfredi et al. (US 9.468,611).
Claim interpretation
Claims 1, 40, 41, 42, 70 and 77 are independent claims.
Claim 1 is directed to a method of modifying the course and severity of a neuropsychiatric disorder (limited to MDD by applicants’ election). The claim requires administration of dextromethadone to a subject suffering from MDD.
Claim 40 is directed to a method of treating MDD comprising the steps of developing a course of treatment and administering dextromethadone.
Claim 41 is directed to a method of treating MDD comprising diagnosing the subject with MDD, developing a course of treatment and administering dextromethadone.
Claim 42 is directed to a method of treating a MDD comprising inducing transcription of NMDAR subunits, wherein the induction of transcription is accomplished by administration of dextromethadone.
Claim 70 is directed to a method of treating a disease or disorder characterized by a dysfunction of ion channels comprising diagnosing a subject with the disorder, developing a course of treatment and administering dextromethadone. In paragraph [00200] of the specification, applicants identify MDD as a disorder characterized by a dysfunction of ion channels. Claim 70 is therefore directed to treating MDD by administration of dextromethadone.
Claim 77 is directed to a method of diagnosing a disorder as caused worsened or maintained by pathologically hyperactive NMDAR channels. The method encompasses administration of dextromethadone to a subject with MDD.
All of the claims encompass administration of dextromethadone to a subject with MDD. Disclosure of administration of dextromethadone to a subject with MDD is interpreted as meeting limitations of all independent claims. Claim 77 further requires further diagnosing the subject as having a disorder caused maintained or maintained by pathologically hyperactive NMADR channels. This is a theoretical step that not require an active step. The step is not afforded patentable weight. If a subject with MDD is administered dextromethadone, the limitation directed to diagnosing the subject as having hyperactive NMDAR channels is considered to be met.
Scope of prior art
Manfredi et al teaches a method which comprises administration of dextromethadone to a subject with depression (column 3, lines 51-63; column 4, lines 11-17). Depression is defined to encompass MDD (column 1, lines 35-41). Dexromethadone can be isolated from its enantiomer or synthesized de novo (column 3, lines 62-63). Dextromethadone can be used alone or with other antidepressants (column 4, lines 10-17). Other antidepressants include lithium (column 4, line 43). Manfredi discloses a range of 1mg to 5000mg for the dose of dextromethadone. Manfredi teaches nasal, rectal, oral or topical administration (column 7, lines 64-67).
Ascertaining the difference
Claim 1 is directed to modifying the course and severity of MDD while Manfredi teaches treatment of depression and identifies MDD as being within the scope of depression
Manfredi teaches treating MDD, does not explicitly teach diagnosing a subject with MDD or developing a course of treatment.
Manfredi teaches d-methadone blocks the biological action of NMDA receptor (column 7, lines 37-49), but does not mention ion channel malfunction, specific subunits of NMDAR, induction of synthesis of NMDAR.
Manfredi does not teach effect size in phase 2 clinical trial, intermittent administration schedule, plasma levels, time it takes to achieve steady state, unbound levels of dextromethadone or 25mg/day dose.
Obviousness
A person of ordinary skill in the art would have found it obvious to treat MDD in a subject in need by administering to said subject an effective amount of dextromethadone. Suggestion, motivation and expectation of success are all provided by Manfredi when art teaches dextromethadone as NMDA antagonist and links NMDA antagonistic activity with treatment of depression including MDD. In order to treat MDD a skilled practitioner would have found it obvious and necessary to determine an optimal safe and effective dose of dextromethadone and would invariably arrive at the currently claimed 25mg/day dose. It also would have been obvious to administer dextromethadone in combination with lithium because combination treatment with lithium is described by Manfredi (column 4, lines 10-17 and 43). Limitations directed relief (claim 4) are met by Manfredi because reduction in severity is a part of treatment. Since Manfredi teaches treating the claimed subject population with the claimed agent, an amount that is effective to achieve treatment is an amount that is effective to achieve the currently claimed relief.
Claims 8-12 and 39 are directed to administration under conditions that achieve efficacy of dextromethadone at voltage dependent channel block of NMDAR. Since Manfredi teaches administration of effective amount of dextromethadone, the limitations directed to conditions that achieve efficacy at voltage dependent channel block of NMDAR are met. Efficacy of dextromethadone at specified ion channels is achieved by administering an amount sufficient to potentiate treatment, which is what Manfredi teaches.
Claims 18-21, 26, 42-55 are directed to the effects of administering an effective dose of dextromethadone and comprise no additional steps. These limitations are met by Manfredi because art teaches administration of an effective dose to the claimed subject population. Effects of said administration, such as duration therapeutic effect are inherently met because they are derived from physiological properties of dextromethadone which are inseparable from it’s chemical structure.
Claims 25 and 56 are directed to BMI of less than 35. BMI less than 35 corresponds to subjects who are not severely obese and encompasses vast majority of population. It would have been obvious to treat MDD by administering an effective amount of dextromethadone to any subject in need of treatment for MDD. While Manfredi does not make a recommendation with regards to BMI, it would have been obvious to treat subject with average healthy BMI.
Claims 29-34 and 60-66 are directed to pharmacokinetic properties of dextromethadone administration and a method of administration that includes a loading and maintenance dose. In order to practice the method of treating MDD as taught by Manfredi, a skilled artisan would have found it obvious to determine the proper administration schedule that would achieve the plasma levels of dextromethadone that are optimal for safe and effective treatment of MDD. Such determinations are within realm of routine experimentation and are obvious absent unexpected results.
Regarding claims 40, 41 directed to diagnosing MDD prior to treating MDD and devising a treatment protocol prior to administration dextromethadone: In practicing the method of treating MDD by administration of dextromethadone, as taught by Manfredi, it would have been obvious to select subjects who have been diagnosed with MDD prior to treatment. In administering dextromethadone it would have been obvious to devise a schedule according to which the agent is administered.
Regarding claim 70: Claim is directed to treating a disease characterized by a dysfunction of ion channels. According to current specification, MDD is such a disease and is therefore within the scope of the claim.
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 1-76 and 78 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 9,468,611. Although the claims at issue are not identical, they are not patentably distinct from each other. Claims of the ‘611 patent are directed to a method of treating psychological and psychiatric symptoms comprising administering to a subject suffering from depression NMDAR antagonist d-methadone. Depression is defined in the specification to include MDD (column 1, lines 35-41). It would therefore be obvious to administer d-methadone to a subject with MDD. A skilled artisan would have found it obvious to determine the optimal dose and frequency of administration within 1mg to 5000mg dose recited in claim 9 of ‘611.
Claims 8-12 and 39 are directed to administration under conditions that achieve efficacy of dextromethadone at voltage dependent channel block of NMDAR. Since Manfredi teaches administration of effective amount of dextromethadone, the limitations directed to conditions that achieve efficacy at voltage dependent channel block of NMDAR are met. Efficacy of dextromethadone at specified ion channels is achieved by administering an amount sufficient to potentiate treatment, which is what Manfredi teaches.
Claims 18-21, 26, 42-55 are directed to the effects of administering an effective dose of dextromethadone and comprise no additional steps. These limitations are met by Manfredi because art teaches administration of an effective dose to the claimed subject population. Effects of said administration, such as duration therapeutic effect are inherently met because they are derived from physiological properties of dextromethadone which are inseparable from it’s chemical structure.
Claims 25 and 56 are directed to BMI of less than 35. BMI less than 35 corresponds to subjects who are not severely obese and encompasses vast majority of population. It would have been obvious to treat MDD by administering an effective amount of dextromethadone to any subject in need of treatment for MDD. While Manfredi does not make a recommendation with regards to BMI, it would have been obvious to treat subject with average healthy BMI.
Claims 29-34 and 60-66 are directed to pharmacokinetic properties of dextromethadone administration and a method of administration that includes a loading and maintenance dose. In order to practice the method of treating MDD as taught by Manfredi, a skilled artisan would have found it obvious to determine the proper administration schedule that would achieve the plasma levels of dextromethadone that are optimal for safe and effective treatment of MDD. Such determinations are within realm of routine experimentation and are obvious absent unexpected results.
Regarding claims 40, 41 directed to diagnosing MDD prior to treating MDD and devising a treatment protocol prior to administration dextromethadone: In practicing the method of treating MDD by administration of dextromethadone, as taught by Manfredi, it would have been obvious to select subjects who have been diagnosed with MDD prior to treatment. In administering dextromethadone it would have been obvious to devise a schedule according to which the agent is administered.
Regarding claim 70: Claim is directed to treating a disease characterized by a dysfunction of ion channels. According to current specification, MDD is such a disease and is therefore within the scope of the claim.
Conclusion
Claims 1-86 are pending
Claims 1-78 are rejected
Claims 79-86 are withdrawn
Any inquiry concerning this communication or earlier communications from the examiner should be directed to YEVGENY VALENROD whose telephone number is (571)272-9049. The examiner can normally be reached Mon-Fri 9am-5pm.
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/YEVGENY VALENROD/Primary Examiner, Art Unit 1628
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