DETAILED ACTION
Claims 185-204 are pending.
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
The instant application filed 11/3/2023 is a National Stage entry of PCT/US2022/029192, International Filing Date: 5/13/2022. PCT/US2022/029192 Claims Priority from Provisional Application 63306616, filed 2/4/2022. PCT/US2022/029192 Claims Priority from Provisional Application 63188784, filed 5/14/2021.
Information Disclosure Statement
The Information Disclosure Statement (IDS) submitted on 6/24/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the Information Disclosure Statement is being considered by the Examiner.
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.
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.
Claims 185-204 are rejected under 35 U.S.C. 103 as being unpatentable over Murrough et al. (WO 2016/172672, PTO-1449), in view of Charney et al. (US 20140256821, PTO-1449 filed on 10/31/2023), and further in view of Singh et al. (WO 2020178653 A1, PTO-892 of record).
Instant claim 185 is directed towards a method of reducing the frequency and/or severity of suicidal ideation in a subject hospitalized for suicidality, the method comprising intranasally administering racemic ketamine hydrochloride to the subject, wherein: the administration occurs once on Days 1, 4, and 8 of hospitalization; and each administration comprises 2 sprays, 4 sprays, or 6 sprays from an intranasal delivery device, and each spray delivers 15 mg of ketamine.
Murrough teaches treating suicidal ideations (SI) or suicidality comprising administering to a patient that has attempted suicide as least once, racemic ketamine intranasally. See abstract; claims 1-7, 8, 11; Examples 1-3. The effectiveness of ketamine in reducing suicidal ideation is measured using for example MADRS-SI or the Columbia-Suicide Severe Rating Scale (C-SSRS). Claims 1-4. Murrough teaches administration of ketamine 0.5 mg/kg (35 mg based on average weight of 70 kg) intranasally to a group of patients between 18 and 80 years of age diagnosed with suicidal ideation as measured by a score of 3 or more on the C-SSRS. See Example 3, page 17. It is taught that prior to beginning ketamine therapy for suicidal ideation the patient is tested using one or more of standard suicidality rating scales. See page 9-page 10. It is taught that the typical dose of racemic ketamine for IN (intrasanal) administration is 1.0 mg/kg-1.5 mg/kg. See Examples 1, pages 15. It is taught that SI is sometimes referred as suicidality. See page 7, under Summary of Invention. It is taught that some patients may receive a course of treatment with ketamine that may involve administration of ketamine one or more times per week over a period of weeks or months before beginning treatment with lithium. See page 8, bottom para. If the patient does not respond to the initial ketamine dose, administration of ketamine is continued one, two or three times per week until the patient shows at least a fifty percent improvement in suicidal ideation severity compared to the initial (pre-ketamine administration) test score or otherwise attains a score consistent with amelioration of clinically significant SI (e.g., a score of less than 3 on the C-SSRS). See page 10; page 14, para 3.
Murrough does not explicitly teach administration of ketamine in amount of 30 mg, 60 mg, or 90 mg, of ketamine in 2, 4, or 6 sprays of 15 mg each.
Murrough does not explicitly teach the administration occurs once on Days 1, 4, and 8 of hospitalization.
Charney teaches a “method of treating the risk of suicide, comprising intranasally administering to a patient who suffers from said risk of suicide a composition comprising ketamine at a dosage sufficient to alleviate symptoms of said risk of suicide”. See claims 39, 40-43. It is taught that ketamine is in a pharmaceutically acceptable carrier and is administered at a dose of between about 0.1 mg/kg per day to about 3.0 mg/kg/day. Charney teaches a dosage range of about 1 mg to about 250 mg. See claim 40; paragraph [0076]. Charney teaches “In specific embodiments, the ketamine is administered at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine times in fourteen days. In other embodiments, the ketamine is administered at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine times in twenty-one days.” See paragraph [0023]. Charney teaches treating depression, comprising intranasally administering to a patient who suffers from said depression a composition comprising ketamine at a dosage sufficient to alleviate symptoms of said depression wherein the said symptoms of depression comprise at least one of recurrent thoughts of death, suicidal ideation or suicidal attempts. See claims 32, 39, 40; paragraphs [0069]; symptoms improved on ketamine for suicide see para [0140].
Singh teaches that a patient is classified as being suicidal when the patient has a mean baseline MADRS total score of about 38 or greater. See page 21 bottom para-page 22.
It would have been obvious to one of ordinary skill in the art to treat suicidality wherein ketamine is the sole therapeutic agent because 1) Murrough teaches administration of ketamine 0.5 mg/kg (35 mg based on average weight of 70 kg) intranasally to a group of patients between 18 and 80 years of age diagnosed with suicidal ideation as measured by a score of 3 or more on the C-SSRS and 2) Charney teaches that the administration of ketamine improves suicidal symptoms (see para [0140]), and can thus treat suicidality as the sole therapeutic agent. One of ordinary skill in the art would have been motivated to administer ketamine to a subject with reasonable expectation of success of reducing suicidality in the subject compared to suicidality in the subject prior to administration of ketamine; since Murrough teaches administration of ketamine 0.5 mg/kg (35 mg based on average weight of 70 kg) intranasally to a group of patients between 18 and 80 years of age diagnosed with suicidal ideation and Charney teaches that the administration of ketamine improves suicidal symptoms, and can thus treat suicidality as the sole therapeutic agent.
Further, it would have been obvious to a person of ordinary skill in the art to determine if the subject has MADRS total score of 35-60 units prior to intranasal administration of ketamine because 1) Murrough teaches that prior to beginning ketamine therapy for suicidal ideation the patient is tested using one or more of standard suicidality rating scales; and 2) it is well known that a patient is classified as suicidal when the patient has a mean baseline MADRS total score of about 38 or greater, and Singh teaches that a patient is classified as being suicidal when the patient has a mean baseline MADRS total score of about 38 or greater. Meeting instant claims 190, 194, 198, and 202.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to administer ketamine in amount of 30 mg, about 60 mg, or about 90 mg as in instant claims. One having ordinary skill in the art would have been motivated to determine the effective amounts of ketamine, since the optimization of effective amounts of known 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.
The amount of a specific dosage is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize.
Further, Murrough teaches administration of ketamine 0.5 mg/kg (35 mg based on average weight of 70 kg) intranasally to a group of patients between 18 and 80 years of age. Murrough teaches that the typical dose of ketamine for IN administration is 1.0 mg/kg-1.5 mg/kg i.e 70 mg to 105 mg based on average weight of 70 kg.
It would have been obvious to a person of ordinary skill in the art to administer ketamine in amount of 30 mg, about 60 mg or about 75 mg or about 90 mg on days 1, 4, and 8 as in instant claims because 1) Murrough teaches that if the patient does not respond to the initial ketamine dose, administration of ketamine is continued one, two or three times per week until the patient shows at least a fifty percent improvement in suicidal ideation severity compared to the initial (pre-ketamine administration) test score or otherwise attains a score consistent with amelioration of clinically significant SI (e.g., a score of less than 3 on the C-SSRS), and 2) Charney teaches “In specific embodiments, the ketamine is administered at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine times in fourteen days. In other embodiments, the ketamine is administered at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine times in twenty-one days.” See paragraph [0023].
Even though the range for dosages and treatment periods as taught by Murrough and Charney are not the same as the claimed dosages and treatment periods, Murrough and Charney do teach an overlapping range of dosages and periods of administration, and it has been held that in the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists.
It is pointed out that the optimization of result effect parameters e.g., dosage range, dosing regimens, dosing duration is obvious as being within the skill of the artisan, involving merely routine skill in the art.
Regarding the recitation, “wherein the sedation of the subject after the administration is less than the sedation exhibited by a subject administered an equivalent amount of intranasal (S)-ketamine.” This is obvious as a known property of racemic ketamine versus enantiomerically enriched (S)-ketamine. Racemic ketamine is comprised of the active and inactive form, as such the racemic administration is equivalent to given roughly half the dose of the more active (S) form. Therefore this is simply a recitation of the property of the racemic compound versus the single enantiomer. Looking to the MPEP 2111.04 discussing Claim Interpretation, we see this quote about interpreting Contingent Clauses (Wherein): the determination of whether each of these clauses is a limitation in a claim depends on the specific facts of the case. See, e.g., Griffin v. Bertina, 285 F.3d 1029, 1034, 62 USPQ2d 1431 (Fed. Cir. 2002) (finding that a "wherein" clause limited a process claim where the clause gave "meaning and purpose to the manipulative steps"). In In re Giannelli, 739 F.3d 1375, 1378, 109 USPQ2d 1333, 1336 (Fed. Cir. 2014), the court found that an "adapted to" clause limited a machine claim where "the written description makes clear that 'adapted to,' as used in the [patent] application, has a narrower meaning, viz., that the claimed machine is designed or constructed to be used as a rowing machine whereby a pulling force is exerted on the handles." In Hoffer v. Microsoft Corp., 405 F.3d 1326, 1329, 74 USPQ2d 1481, 1483 (Fed. Cir. 2005), the court held that when a "‘whereby’ clause states a condition that is material to patentability, it cannot be ignored in order to change the substance of the invention." Id. However, the court noted that a "‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’" Id. (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)). In this method, the wherein clause is simply expressing the intended result of a process step positively recited. When a patient is given racemic ketamine, the effect will be less than giving the equivalent amount of enantiomerically enriched ketamine. Therefore, the clause is not given weight, as it simply recites the effect of the drug’s chemical property. This is true for claims 191, 192, 195, 196, 199, 200, 203, and 204.
Regarding the recitations “wherein the subject exhibits a MADRS Total Score of less than 15 for at least three weeks after the second administration of racemic ketamine,” in claims 189, 193, 197, and 201. These claims simply express the intended result of a process step positively recited, when racemic ketamine is given to a subject hospitalized for suicidality, in a effective dose intranasally the result of treatment will flow naturally from the treatment based on the physical properties of the drug in the human body. Therefore this limitation is not given weight toward patentability. Moreover, the art recognized an improvement in the MADRS Total Score with treatment, and as such this outcome is predicted and expected.
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.
US 12440457
Claims 185-204 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-26 of U.S. Patent No. 12440457. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of ‘457 are directed to intranasally administering to the subject about 30 mg to about 90 mg of racemic ketamine, or a pharmaceutically acceptable salt thereof, once every 3 to 4 days for 15 days, wherein ketamine is the sole therapeutic agent administered during the 15 days (Claim 1) and once every 3 to 4 days for 15 days (Claims 2-5), and measuring and improving the MADRS score. These claims anticipate the instant claims directed to a method of reducing the frequency and/or severity of suicidal ideation in a subject hospitalized for suicidality, the method comprising intranasally administering racemic ketamine hydrochloride to the subject, wherein: the administration occurs once on Days 1, 4, and 8 of hospitalization; and each administration comprises 2 sprays, 4 sprays, or 6 sprays from an intranasal delivery device, and each spray delivers 15 mg of ketamine. These claims anticipate the instant claims directed to a method of reducing the frequency and/or severity of suicidal ideation in a subject hospitalized for suicidality, the method comprising intranasally administering racemic ketamine hydrochloride to the subject, wherein: the administration occurs once on Days 1, 4, and 8 of hospitalization; and each administration comprises 2 sprays, 4 sprays, or 6 sprays from an intranasal delivery device, and each spray delivers 15 mg of ketamine. The number of sprays in a design choice and is at once envisaged.
17792208
Claims 185-204 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 185-200 and 205 of copending Application No. 17792208 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘208 application is directed towards a method for treating suicidality in a subject in need thereof, comprising:(a) identifying the subject as having a Montgomery-Asberg Depression Rating Scale (MADRS) Total Score from 35-60 units; and(b) intranasally administering to the subject about 30 mg to about 90 mg of racemic ketamine, or a pharmaceutically acceptable salt thereof, (Claim 185) and occurs once every 3 to 4 days for 15 days, wherein ketamine is the sole therapeutic agent administered during the 15 days (Claim 206). The claims also require measuring and monitoring the MADRS score. The number of sprays in a design choice and is at once envisaged.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
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/MICHAEL J SCHMITT/Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629