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
1. Claims 59-75 are pending in the current application.
2. This application is a CON of 17/818,606 08/09/2022; 17/818,606 is a DIV of 16/438,163 06/11/2019 PAT 11453670; 16/438,163 has PRO 62/780,742 12/17/2018; 16/438,163 has PRO 62/683,411 06/11/2018.
Request for Continued Examination
3. A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on December 22, 2025 has been entered.
Claim Rejections Withdrawn
4. The rejections of canceled claims are withdrawn.
New Grounds of Rejection
5. Various new grounds of rejection are set forth below.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
6. Claim(s) 59-66 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Li “Discovery of a Tetracyclic Quinoxaline Derivative as a Potent and Orally Active Multifunctional Drug Candidate for the Treatment of Neuropsychiatric and Neurological Disorders” J. Med. Chem. 2014, 57, 2670−2682. Li discloses the compound of Formula 1J where Q is the claimed definition as compound 5 in Table 2. The compound 5 was isolated as the tosylate salt as a 97.7% pure compound on page 2678 column 2 step i) in the amount of 367 mg. According to line 12 on page 2676, “Properties of 5. Compound 5 is being developed as a tosylate salt, displaying a plate-like crystalline material.” Since no copper was used in the synthesis it is expected to be copper free, meeting limitations of claim 65. The compound was used as a composition in “ In Vivo Studies. The in vivo efficacy of compound 5 and selected analogues was evaluated in the rat quipazine headtwitch model. This model measures blockade of head twitches induced by quipazine which is a 5-HT 2A agonist. 36” [page 2676]. “Test compound suspended in 0.25% methylcellulose was dosed to animals orally by gavage. Assay protocol was described in the Experimental Section.” “Rat Quipazine Head Twitch. Different groups of male rats (N = 6rats/dose/test substance) were fasted overnight and then placed in individual cells of a clear Lucite box. Varying concentrations of a test substance were administered by oral gavage to each rat 30 min prior to behavioral testing and 25 min prior to intraperitoneal injection of a standard dose (2.5 mg/kg) of quipazine maleate.” The compound was made in entantiopure form “by forming a diastereomeric salt with (S)-mandelic acid with >99% enantiomeric excess… This route was easily scalable and used during the production of 5 and its analogues on large scales.”
7. Claim(s) 59-66 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Mittelman US 2022/0127268 A1. Mittelman on page 6 paragraph 91 describes chemically pure lumateperone ditosylate and monotosylate which is the compound of claim 28 where Q is the first selection, “[ 0091 ] The above described solid state forms of lumateperone ditosylate can be used to prepare chemically pure lumateperone ditosylate, Lumateperone tosylate and / or other salts of Lumateperone.” And at paragraph [0014] and [0015]. Compositions are disclosed on page 6 paragraph [0094] ff. According to paragraph 30, “[ 0030 ] As used herein, the term chemically pure refers to a material which is substantially free of chemical impurities , such as reaction by - products , un - reacted intermediates or degradation product . The term “ substantially free ” means that the chemically pure material of the present invention contains 3 % ( w / w ) or less of chemical impurities . According to some embodiments , the chemically pure material of the present invention contains 3 % ( w / w ) or less , 2 % ( w / w ) or less , 1 % ( w / w ) or less , 0.5 % ( w / w ) or less , or 0.2 % ( w / w ) or less of chemical impurities . In other embodiments, chemically pure material of the present invention contains from 0.01 % to 3 % ( w / w ) , of chemical impurities.” The ranges of the impurities are consistent with those in the claims 34-38. While no structure of the impurities are given, they are recognized. Having made a prima facie case of anticipation, the burden has shifted to the applicant. See In re Best, Bolton, and Shaw, 195 USPQ 430 (C.C.P.A. 1977): “Where, as here, the claimed and prior art products are identical or substantially identical, or are produced by identical or substantially identical processes, the PTO can require an applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of his claimed product.” The use of the compounds in various compositions is disclosed at “[ 0091 ] The above described solid state forms of lumate perone ditosylate can be used to prepare chemically pure lumateperone ditosylate , Lumateperone tosylate and / or other salts of Lumateperone . In certain embodiments , the present invention encompasses the above described solid state forms of lumateperone ditosylate for use in the chemi cal purification of lumateperone ditosylate , lumateperone tosylate , Lumateperone and / or other salts of Lumateperone . [ 0092 ] The above described solid state forms of lumateperone ditosylate can be used to prepare pharmaceutical compositions and / or formulations . In certain embodiments , the present invention encompasses the above described solid state forms of lumateperone ditosylate for use in the preparation of pharmaceutical compositions and / or formulations . [ 0093 ] Thus , any of the processes described herein may further comprise combining the Lumateperone ditosylate with at least one pharmaceutically acceptable excipient to prepare a pharmaceutical composition or formulation “.
8. Claim(s) 59-66 is/are rejected under 35 U.S.C. 102 (a)(1) as being unpatentable over Wennogle WO 2009114181 A2. Wennogle teaches the compound of claim 34 IJ as Example 5 on page 22 in paragraph [0050] where the compound was a 96.9% purity. Various compositions are disclosed including the one in claim 1. According to the title of Example 5 the compounds are in crystalline form, “EXAMPLE 5 - Preparation of the Solid Salt or Salt Crystals”. Additional crystalline forms are disclosed in additional examples and the description on page 10. According to Wennogle on page 10 “Preferably, the Salt Crystals of the Present Invention comprises greater than 99 wt.% a single crystal form. Similar to "substantially free" “The term "predominantly" or "substantially entirely in a single form" refers to less than about 10 wt. %, preferably less than about 5 wt. %, more preferably less than about 2 wt. %, still preferably less than about 1 wt. %, still preferably less than about about 0.1 %, most preferably less than about 0.01 wt.% of other crystal forms, e.g., amorphous or other crystal forms.”
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.
9. Claim(s) 59-75 is/are rejected under 35 U.S.C. 103 as being unpatentable over Li and Robichaud US 6,548,493 in view of Olsen “Impurity investigations by phases of drug and product development” TrAC Trends in Analytical Chemistry, 101, 2018, pages 17-23, Available online 11 November 2017 and Robert V. Hoffman “ORGANIC CHEMISTRY AN INTERMEDIATE TEXT” 2004, page 335. Li discloses the compounds above including the tosylate salt which were shown to be potent antagonists at 5-HT2A and 5-HT2C receptors, D2 receptors and inhibitors of SERT. Li discloses the compound of Formula 1J where Q is the claimed definition as compound 5 in Table 2. The compound 5 was isolated as the tosylate salt as a 97.7% pure compound on page 2678 column 2 step i) in the amount of 367 mg. According to line 12 on page 2676, “Properties of 5. Compound 5 is being developed as a tosylate salt, displaying a plate-like crystalline material.” Since no copper was used in the synthesis it is expected to be copper free, meeting limitations of claims 41-43, 56. The compound was used as a composition in “ In Vivo Studies. The in vivo efficacy of compound 5 and selected analogues was evaluated in the rat quipazine headtwitch model. This model measures blockade of head twitches induced by quipazine which is a 5-HT 2A agonist. 36” [page 2676]. “Test compound suspended in 0.25% methylcellulose was dosed to animals orally by gavage. Assay protocol was described in the Experimental Section.” “Rat Quipazine Head Twitch. Different groups of male rats (N = 6rats/dose/test substance) were fasted overnight and then placed in individual cells of a clear Lucite box. Varying concentrations of a test substance were administered by oral gavage to each rat 30 min prior to behavioral testing and 25 min prior to intraperitoneal injection of a standard dose (2.5 mg/kg) of quipazine maleate.” The compound was made in entantiopure form “by forming a diastereomeric salt with (S)-mandelic acid with >99% enantiomeric excess… This route was easily scalable and used during the production of 5 and its analogues on large scales.”.= The method of measuring the purity in claim 66 does not impart a structural difference to the claimed invention.
Robichaud teaches Compound 212 on column 144 which is compound 1K in claim 59 and also discloses the same activity for the compound, “The pharmacological analysis of each compound fro [sic] either antagonism [sic] or agonism of at 5-HT2A and 5-HT2C receptors consisted of in vitro and in Vivo Studies. In Vitro analyses included K determinations at 5-HT2A and 5HT2C receptors and an assessment of functional (i.e., agonism or antagonism) activity at each receptor class by IP3 hydrolysis assays.” Both the compound of Formula IJ and compound 1K are used for the same purpose. Combining two things known for the same purpose in a single composition is obvious. See In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (MPEP § 2144.06).
With regard to compound 1L, compound 261 on column 145 is the position isomer of compound 1L, differing only by the point of attachment of the phenyl ring F from the 4 position to the 2 position. Positional isomers, having the same radical on different positions of the molecule, are prima facie obvious, and require no secondary teaching. The medicinal chemist would be motivated to prepare these position isomers based on the expectation that such close analogues would have similar properties and upon the routine nature of such position isomer experimentation in the art of medicinal chemistry. The suggestion of the 2-F compound is made in the genus of column 4 where the phenyl ring is R2 described as “R1 is alkyl substituted with Z” where Z is C(=O)R2” R2 being “phenyl substituted with 0-5 R42”.R42 point of attachment is ambiguous. In a similar manner the compound 1M, bearing a 4-methyl group is explicitly suggested by such a description and is mentioned on column 39 line 21: “-(CH2)3C(=O)(4-methyl-phenyl)”. According to column 134 line 14: “The compounds of the present invention can be administered in such oral dosage forms as tablets, capsules (each of which includes Sustained release or timed release formulations), pills, powders, granules, elixirs, tinctures, suspensions, syrups, and emulsions.” This meets the limitations of claims 67-75. Capsules and tablets that disintegrate, are described further at column 134 lines 55-58. With regard to specific amounts of the compounds in claims 36 and 38, dosages are routinely optimized and is explicitly discussed by Robichaud on column 135 lines 24 ff:
The dosage administered will, of course, vary depending upon known factors, Such as the pharmacodynamic characteristics of the particular agent and its mode and route of administration; the age, health and weight of the recipient; the nature and extent of the Symptoms, the kind of concurrent treatment; the frequency of treatment; and the effect desired. By way of general guidance, a daily dosage of active ingredient can be expected to be about 0.001 to about1000 milligrams per kilogram of body weight, with the preferred dose being about 0.01 to about 100 mg/kg; with the more preferred dose being about 0.1 to about 30 mg/kg. Advantageously, compounds of the present invention may be administered in a Single daily dose, or the total daily dosage may be administered in divided doses of two, three, or four times daily. Dosage forms of compositions Suitable for administration contain from about 1 mg to about 100 mg of active ingredient per unit. In these pharmaceutical compositions the active ingredient will ordinarily be present in an amount of about 0.5-95% by weight based on the total weight of the composition.
The tablets of 1 to 60 mg overlaps with the prior art range of 1 to 100. For these reasons the instant claims are obvious over the prior art.
Olsen teaches that “Thorough knowledge and control of impurities is an expectation for the registration of pharmaceuticals. Actual and potential impurity investigations are phased during drug development to acquire the appropriate information necessary to ensure drug safety from the standpoint of patient exposure to impurities. Regulatory expectations and common practices for the timing of impurity investigations during development are discussed. Investigations for synthetic drug substances include process-related impurities such as intermediates, by-products, mutagenic impurities, residual solvents, and elemental impurities.” (abstract) “Impurity control is part of an overall control strategy developed for a drug product. Elements and development of a control strategy are described in ICH Q8, Pharmaceutical development, and related guidelines [5]. Impurities as they relate to safety are usually considered Critical Quality Attributes (CQA) of drug substances and products. It is also acknowledged in regulatory guidances that the control strategy develops over time as knowledge is gained [6]” (Page 1) A straightforward roadmap is given on page 18 section 2.1 “After the commercial synthetic route is chosen, impurity purging and fate studies are usually conducted to determine effective control points in the process. As development progresses, the structures of unknown impurities are identified and additional methods are developed, if necessary, to determine whether potential impurities are present or not.”
The difference between the instant claims and Li and Robichaud is the amount of various impurities in the compound lumateperone tosylate. Since the prior art recognized impurities a normal straightforward part of drug development would be to identify and remove the impurities. In this case there was a design need or market pressure to solve the problem of impurity removal and there were routine conventional purification techniques a person of ordinary skill had good reason to pursue. Such a strategy would lead to the anticipated success of removal of impurities whatever they might be.
According to Hoffman, “Today's chemist has a large number of tools available with which to probe the structure of molecules, but for determining the structures of organic molecules the ''big three” are nuclear magnetic resonance (NMR) spectroscopy, infrared (IR) spectroscopy and mass spectrometry (MS)…. By combining these three major methods, the functional groups, the molecular weight, and the connectivity of the atoms and groups can be established rapidly and efficiently. It is normally a trivial step then to write the structure of the molecule.”
10. Claim(s) 59-66 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wennogle WO 2009114181 A2 in view of Olsen “Impurity investigations by phases of drug and product development” TrAC Trends in Analytical Chemistry, 101, 2018, pages 17-23, Available online 11 November 2017 and Robert V. Hoffman “ORGANIC CHEMISTRY AN INTERMEDIATE TEXT” 2004, page 335. Wennogle teaches the compound of claim 28 IJ as Example 5 on page 22 in paragraph [0050] where the compound was a 96.9% purity. Various compositions are disclosed including the one in claim 15. According to the title of Example 5 the compounds are in crystalline form, “EXAMPLE 5 - Preparation of the Solid Salt or Salt Crystals”. Additional crystalline forms are disclosed in additional examples and the description on page 10. According to Wennogle on page 10 “Preferably, the Salt Crystals of the Present Invention comprises greater than 99 wt.% a single crystal form. Similar to "substantially free" “The term "predominantly" or "substantially entirely in a single form" refers to less than about 10 wt. %, preferably less than about 5 wt. %, more preferably less than about 2 wt. %, still preferably less than about 1 wt. %, still preferably less than about about 0.1 %, most preferably less than about 0.01 wt.% of other crystal forms, e.g., amorphous or other crystal forms.” This suggests that more pure forms of the product were desirable.
Various compositions are disclosed including the one in claim 25. Olsen teaches that “Thorough knowledge and control of impurities is an expectation for the registration of pharmaceuticals. Actual and potential impurity investigations are phased during drug development to acquire the appropriate information necessary to ensure drug safety from the standpoint of patient exposure to impurities. Regulatory expectations and common practices for the timing of impurity investigations during development are discussed. Investigations for synthetic drug substances include process-related impurities such as intermediates, by-products, mutagenic impurities, residual solvents, and elemental impurities.” (abstract) “Impurity control is part of an overall control strategy developed for a drug product. Elements and development of a control strategy are described in ICH Q8, Pharmaceutical development, and related guidelines [5]. Impurities as they relate to safety are usually considered Critical Quality Attributes (CQA) of drug substances and products. It is also acknowledged in regulatory guidances that the control strategy develops over time as knowledge is gained [6]” (Page 1) A straightforward roadmap is given on page 18 section 2.1 “After the commercial synthetic route is chosen, impurity purging and fate studies are usually conducted to determine effective control points in the process. As development progresses, the structures of unknown impurities are identified and additional methods are developed, if necessary, to determine whether potential impurities are present or not.”
The difference between the instant claims and Wennogle is the amount of various impurities in the compound lumateperone tosylate. Since the prior art recognized impurities of around 3.1% a normal straightforward part of drug development would be to identify and remove the impurities. In this case there was a design need or market pressure to solve the problem of impurity removal and there were routine conventional purification techniques a person of ordinary skill had good reason to pursue. Such a strategy would lead to the anticipated success of removal of impurities whatever they might be.
According to Hoffman, “Today's chemist has a large number of tools available with which to probe the structure of molecules, but for determining the structures of organic molecules the ''big three” are nuclear magnetic resonance (NMR) spectroscopy, infrared (IR) spectroscopy and mass spectrometry (MS)…. By combining these three major methods, the functional groups, the molecular weight, and the connectivity of the atoms and groups can be established rapidly and efficiently. It is normally a trivial step then to write the structure of the molecule.”
11. Claim(s) 67-75 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wennogle in view of Olsen and Hoffman as applied to claims 59-66 above and further in view of Robichaud. Wennogle has a a pharmaceutical composition but no specific details about capsules. According to column 134 line 14 of Robichaud: “The compounds of the present invention can be administered in such oral dosage forms as tablets, capsules (each of which includes Sustained release or timed release formulations), pills, powders, granules, elixirs, tinctures, suspensions, syrups, and emulsions.” This meets the limitations of claims 67-75. Capsules and tablets that disintegrate, are described further at column 134 lines 55-58. With regard to specific amounts of the compounds in claims 36 and 38, dosages are routinely optimized and is explicitly discussed by Robichaud on column 135 lines 24 ff:
The dosage administered will, of course, vary depending upon known factors, Such as the pharmacodynamic characteristics of the particular agent and its mode and route of administration; the age, health and weight of the recipient; the nature and extent of the Symptoms, the kind of concurrent treatment; the frequency of treatment; and the effect desired. By way of general guidance, a daily dosage of active ingredient can be expected to be about 0.001 to about1000 milligrams per kilogram of body weight, with the preferred dose being about 0.01 to about 100 mg/kg; with the more preferred dose being about 0.1 to about 30 mg/kg. Advantageously, compounds of the present invention may be administered in a Single daily dose, or the total daily dosage may be administered in divided doses of two, three, or four times daily. Dosage forms of compositions Suitable for administration contain from about 1 mg to about 100 mg of active ingredient per unit. In these pharmaceutical compositions the active ingredient will ordinarily be present in an amount of about 0.5-95% by weight based on the total weight of the composition.
The capsules of 1 to 60 mg overlaps with the prior art range of 1 to 100. For these reasons the instant claims are obvious over the prior art.
12. Claim(s) 67-75 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mittelman US 2022/0127268 A1 as applied to claim 59-66 above, and further in view of Mates US 2015/0072964. Mittleman describes the formulation of lumateperone tosylate as discussed above. Mittleman does not describe the dosage forms of the instant claims. Mates describes formulation of lumateperone tosylate which is the third compound on page 5 in paragraph [0093]. Paragraph [0120] discloses both capsules and tablets “Pharmaceutical compositions comprising the compounds of the invention may be prepared using conventional diluents or excipients and techniques known in the galenic art. For example the compounds can be administered in a wide variety of different dosage forms, i.e., they may be combined with various pharmaceutically-acceptable inert carriers in the form of tablets, capsules, lozenges, troches, hard candies, powders, sprays, aqueous Suspension, injectable solutions, elixirs, syrups, and the like.” Paragraph [0121] on page 8 describes tablets “For oral administration, …. disintegrants (e.g. potato starch or sodium starch glycolate);” which are those of claims 43 and 49. Page 2 describes a dose of 60 mg, [0013]. In an embodiment, the effective amount is about 1 mg to about 140 mg per dose per day, in another embodiment about 2.5 mg to about 100 mg, in another embodiment about 10 mg to about 100 mg per dose per day, in another embodiment about 10 mg to about 60 mg per dose per day, in another embodiment about 10 mg to about 40 mg per day, in another embodiment about 20 mg to about 40 mg per day, in another embodiment about 40-60 mg per day, in another embodiment, about 1 mg-10 mg per day.” Example 1 describes a study with a A single-site, prospective, open label pilot study is performed of Compound A (Formula I wherein X is —N(CH)—and Y is —C(O)—; tosylate salt) as adjunctive treatment to the selective serotonin-reuptake inhibitor (SSRI) in Veterans with non-remitting posttraumatic stress disorder.” It would be obvious to formulate the more pure lumateperone tosylate of Mittelman in the manner described by Mates since the material of Mittelman was more pure than the compounds of Mates, since Mates makes the compound by the method known to give impurities as discussed on paragraph [0008] and [0009].
13. Claim(s) 67-75 is/are rejected under 35 U.S.C. 103 as being unpatentable over as Li and Robichaud US 6,548,493 in view of Olsen “Impurity investigations by phases of drug and product development” TrAC Trends in Analytical Chemistry, 101, 2018, pages 17-23, Available online 11 November 2017 and Robert V. Hoffman “ORGANIC CHEMISTRY AN INTERMEDIATE TEXT” 2004, page 335 as applied to claims 59-66 above and further in view of Mates. Li while making a formulation for the in vitro and in vivo studies such as the Rat Quipazine Head Twitch and Conditioned Avoidance Response by oral gavage, this is not appropriate for a human. Mates describes formulation of lumateperone tosylate which is the third compound on page 5 in paragraph [0093]. Paragraph [0120] discloses both capsules and tablets “Pharmaceutical compositions comprising the compounds of the invention may be prepared using conventional diluents or excipients and techniques known in the galenic art. For example the compounds can be administered in a wide variety of different dosage forms, i.e., they may be combined with various pharmaceutically-acceptable inert carriers in the form of tablets, capsules, lozenges, troches, hard candies, powders, sprays, aqueous Suspension, injectable solutions, elixirs, syrups, and the like.” Paragraph [0121] on page 8 describes tablets “For oral administration, …. disintegrants (e.g. potato starch or sodium starch glycolate);” which are those of claims 43 and 49. Page 2 describes a dose of 60 mg, [0013]. In an embodiment, the effective amount is about 1 mg to about 140 mg per dose per day, in another embodiment about 2.5 mg to about 100 mg, in another embodiment about 10 mg to about 100 mg per dose per day, in another embodiment about 10 mg to about 60 mg per dose per day, in another embodiment about 10 mg to about 40 mg per day, in another embodiment about 20 mg to about 40 mg per day, in another embodiment about 40-60 mg per day, in another embodiment, about 1 mg-10 mg per day.” Example 1 describes a study with a single-site, prospective, open label pilot study is performed of Compound A (Formula I wherein X is —N(CH)—and Y is —C(O)—; tosylate salt) as adjunctive treatment to the selective serotonin-reuptake inhibitor (SSRI) in Veterans with non-remitting posttraumatic stress disorder.” Since the improved purity drug of Li would need to be formulated orally, the formulations of Mates would work well.
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 claims at issue 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); and 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 a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form 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 http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
14. Claims 59-75 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 11,053,245 in view of Olsen “Impurity investigations by phases of drug and product development” TrAC 101, 2018, pages 17-23, Available online 11 November 2017 and Robert V. Hoffman “ORGANIC CHEMISTRY AN INTERMEDIATE TEXT” 2004, page 335. Although the claims at issue are not identical, they are not patentably distinct from each other because the prior patent claims teaches the administration of the compound of claim 59 where the compound has impurities disclosed in column 13, lines 44 ff, “Further details for the preparation of these salts , e.g. , toluenesulfonic salt in amorphous or crystal form , may be found in PCT US08 / 03340 and / or U.S. Provisional Appl. No. 61/036,069 and WO 2009/114181” WO ‘181 is the disclosure of Wennogle as discussed above and has as Example 5 on page 22 in paragraph [0050] where the compound was a 96.9% purity. Olsen teaches that “Thorough knowledge and control of impurities is an expectation for the registration of pharmaceuticals. Actual and potential impurity investigations are phased during drug development to acquire the appropriate information necessary to ensure drug safety from the standpoint of patient exposure to impurities. Regulatory expectations and common practices for the timing of impurity investigations during development are discussed. Investigations for synthetic drug substances include process-related impurities such as intermediates, by-products, mutagenic impurities, residual solvents, and elemental impurities.” (abstract) “Impurity control is part of an overall control strategy developed for a drug product. Elements and development of a control strategy are described in ICH Q8, Pharmaceutical development, and related guidelines [5]. Impurities as they relate to safety are usually considered Critical Quality Attributes (CQA) of drug substances and products. It is also acknowledged in regulatory guidances that the control strategy develops over time as knowledge is gained [6]” (Page 1) A straightforward roadmap is given on page 18 section 2.1 “After the commercial synthetic route is chosen, impurity purging and fate studies are usually conducted to determine effective control points in the process. As development progresses, the structures of unknown impurities are identified and additional methods are developed, if necessary, to determine whether potential impurities are present or not.” The dosage amounts are the same in claim 14. Formulations for the delivery are described at column 13 lines 47 ff.
The difference between the instant claims and the claimed material is the amount of various impurities in the compound lumateperone tosylate. Since the prior art recognized impurities of around 3.1% a normal straightforward part of drug development would be to identify and remove the impurities. In this case there was a design need or market pressure to solve the problem of impurity removal and there were routine conventional purification techniques a person of ordinary skill had good reason to pursue. Such a strategy would lead to the anticipated success removal of impurities whatever they might be.
According to Hoffman, “Today's chemist has a large number of tools available with which to probe the structure of molecules, but for determining the structures of organic molecules the ''big three” are nuclear magnetic resonance (NMR) spectroscopy, infrared (IR) spectroscopy and mass spectrometry (MS)…. By combining these three major methods, the functional groups, the molecular weight, and the connectivity of the atoms and groups can be established rapidly and efficiently. It is normally a trivial step then to write the structure of the molecule.”
15. Claims 59-75 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 10,960,009 (cited on the IDS) in view of Olsen “Impurity investigations by phases of drug and product development” TrAC 101, 2018, pages 17-23, Available online 11 November 2017 and Robert V. Hoffman “ORGANIC CHEMISTRY AN INTERMEDIATE TEXT” 2004, page 335. Although the claims at issue are not identical, they are not patentably distinct from each other because the prior patent claims teaches the administration of the compound of claim 59 in dosage forms of the instant claims where the compound has impurities disclosed in column 31 lines 38-40 from WO 2009/114181. WO ‘181 is the disclosure of Wennogle as discussed above and has as Example 5 on page 22 in paragraph [0050] where the compound was a 96.9% purity. Olsen teaches that “Thorough knowledge and control of impurities is an expectation for the registration of pharmaceuticals. Actual and potential impurity investigations are phased during drug development to acquire the appropriate information necessary to ensure drug safety from the standpoint of patient exposure to impurities. Regulatory expectations and common practices for the timing of impurity investigations during development are discussed. Investigations for synthetic drug substances include process-related impurities such as intermediates, by-products, mutagenic impurities, residual solvents, and elemental impurities.” (abstract) “Impurity control is part of an overall control strategy developed for a drug product. Elements and development of a control strategy are described in ICH Q8, Pharmaceutical development, and related guidelines [5]. Impurities as they relate to safety are usually considered Critical Quality Attributes (CQA) of drug substances and products. It is also acknowledged in regulatory guidances that the control strategy develops over time as knowledge is gained [6]” (Page 1) A straightforward roadmap is given on page 18 section 2.1 “After the commercial synthetic route is chosen, impurity purging and fate studies are usually conducted to determine effective control points in the process. As development progresses, the structures of unknown impurities are identified and additional methods are developed, if necessary, to determine whether potential impurities are present or not.”
The difference between the instant claims and the claimed material is the amount of various impurities in the compound lumateperone tosylate. Since the prior art recognized impurities of around 3.1% a normal straightforward part of drug development would be to identify and remove the impurities. In this case there was a design need or market pressure to solve the problem of impurity removal and there were routine conventional purification techniques a person of ordinary skill had good reason to pursue. Such a strategy would lead to the anticipated success removal of impurities whatever they might be. According to Hoffman, “Today's chemist has a large number of tools available with which to probe the structure of molecules, but for determining the structures of organic molecules the ''big three” are nuclear magnetic resonance (NMR) spectroscopy, infrared (IR) spectroscopy and mass spectrometry (MS)…. By combining these three major methods, the functional groups, the molecular weight, and the connectivity of the atoms and groups can be established rapidly and efficiently. It is normally a trivial step then to write the structure of the molecule.”
16. Claims 59-75 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 of U.S. Patent No. 10,960,010 (cited on the IDS) in view of Olsen “Impurity investigations by phases of drug and product development” TrAC 101, 2018, pages 17-23, Available online 11 November 2017 and Robert V. Hoffman “ORGANIC CHEMISTRY AN INTERMEDIATE TEXT” 2004, page 335. Although the claims at issue are not identical, they are not patentably distinct from each other because the prior patent claims teaches the dosage forms for the compound of claim 59 where the compound has impurities disclosed in column 31 lines 59-62 from WO 2009/114181. WO ‘181 is the disclosure of Wennogle as discussed above and has as Example 5 on page 22 in paragraph [0050] where the compound was a 96.9% purity. Olsen teaches that “Thorough knowledge and control of impurities is an expectation for the registration of pharmaceuticals. Actual and potential impurity investigations are phased during drug development to acquire the appropriate information necessary to ensure drug safety from the standpoint of patient exposure to impurities. Regulatory expectations and common practices for the timing of impurity investigations during development are discussed. Investigations for synthetic drug substances include process-related impurities such as intermediates, by-products, mutagenic impurities, residual solvents, and elemental impurities.” (abstract) “Impurity control is part of an overall control strategy developed for a drug product. Elements and development of a control strategy are described in ICH Q8, Pharmaceutical development, and related guidelines [5]. Impurities as they relate to safety are usually considered Critical Quality Attributes (CQA) of drug substances and products. It is also acknowledged in regulatory guidances that the control strategy develops over time as knowledge is gained [6]” (Page 1) A straightforward roadmap is given on page 18 section 2.1 “After the commercial synthetic route is chosen, impurity purging and fate studies are usually conducted to determine effective control points in the process. As development progresses, the structures of unknown impurities are identified and additional methods are developed, if necessary, to determine whether potential impurities are present or not.”
The difference between the instant claims and the claimed material is the amount of various impurities in the compound lumateperone tosylate. Since the prior art recognized impurities of around 3.1% a normal straightforward part of drug development would be to identify and remove the impurities. In this case there was a design need or market pressure to solve the problem of impurity removal and there were routine conventional purification techniques a person of ordinary skill had good reason to pursue. Such a strategy would lead to the anticipated success removal of impurities whatever they might be. According to Hoffman, “Today's chemist has a large number of tools available with which to probe the structure of molecules, but for determining the structures of organic molecules the ''big three” are nuclear magnetic resonance (NMR) spectroscopy, infrared (IR) spectroscopy and mass spectrometry (MS)…. By combining these three major methods, the functional groups, the molecular weight, and the connectivity of the atoms and groups can be established rapidly and efficiently. It is normally a trivial step then to write the structure of the molecule.”
17. Claims 59-75 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 10,695,345 in view of Olsen “Impurity investigations by phases of drug and product development” TrAC 101, 2018, pages 17-23, Available online 11 November 2017 and Robert V. Hoffman “ORGANIC CHEMISTRY AN INTERMEDIATE TEXT” 2004, page 335. Although the claims at issue are not identical, they are not patentably distinct from each other because the prior patent claims teaches the dosage forms for the compound of claim 59 where the compound has impurities. Olsen teaches methods and motivation for removing such impurities as discussed above. In this case there was a design need or market pressure to solve the problem of impurity removal and there were routine conventional purification techniques a person of ordinary skill had good reason to pursue. Such a strategy would lead to the anticipated success removal of impurities whatever they might be and aid in increasing the purity of the claimed crystals. According to Hoffman, “Today's chemist has a large number of tools available with which to probe the structure of molecules, but for determining the structures of organic molecules the ''big three” are nuclear magnetic resonance (NMR) spectroscopy, infrared (IR) spectroscopy and mass spectrometry (MS)…. By combining these three major methods, the functional groups, the molecular weight, and the connectivity of the atoms and groups can be established rapidly and efficiently. It is normally a trivial step then to write the structure of the molecule.”
18. Claims 59-75 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7, 9-13, 15-18 of U.S. Patent No. 11,052,084 in view of Olsen “Impurity investigations by phases of drug and product development” TrAC Trends in Analytical Chemistry, 101, 2018, pages 17-23, Available online 11 November 2017 and Robert V. Hoffman “ORGANIC CHEMISTRY AN INTERMEDIATE TEXT” 2004, page 335. Although the claims at issue are not identical, they are not patentably distinct from each other because the prior patent claims teaches the dosage forms for the compound of claim 59 where the compound has impurities. Olsen teaches methods and motivation for removing such impurities as discussed above. In this case there was a design need or market pressure to solve the problem of impurity removal and there were routine conventional purification techniques a person of ordinary skill had good reason to pursue. Such a strategy would lead to the anticipated success removal of impurities whatever they might be and aid in increasing the purity of the claimed crystals. According to Hoffman, “Today's chemist has a large number of tools available with which to probe the structure of molecules, but for determining the structures of organic molecules the ''big three” are nuclear magnetic resonance (NMR) spectroscopy, infrared (IR) spectroscopy and mass spectrometry (MS)…. By combining these three major methods, the functional groups, the molecular weight, and the connectivity of the atoms and groups can be established rapidly and efficiently. It is normally a trivial step then to write the structure of the molecule.”
19. Claims 59-75 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 11,124,514 in view of Olsen and Robert V. Hoffman “ORGANIC CHEMISTRY AN INTERMEDIATE TEXT” 2004, page 335. Although the claims at issue are not identical, they are not patentably distinct from each other because the prior patent claims teaches the methods of using the compound of claim 59 where the compound has impurities, see column 13 lines 20ff for the sources of the material. Olsen teaches methods and motivation for removing such impurities as discussed above. In this case there was a design need or market pressure to solve the problem of impurity removal and there were routine conventional purification techniques a person of ordinary skill had good reason to pursue. Such a strategy would lead to the anticipated success removal of impurities whatever they might be and aid in increasing the purity of the claimed crystals. According to Hoffman, “Today's chemist has a large number of tools available with which to probe the structure of molecules, but for determining the structures of organic molecules the ''big three” are nuclear magnetic resonance (NMR) spectroscopy, infrared (IR) spectroscopy and mass spectrometry (MS)…. By combining these three major methods, the functional groups, the molecular weight, and the connectivity of the atoms and groups can be established rapidly and efficiently. It is normally a trivial step then to write the structure of the molecule.”
20. Claims 59-75 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 33-34, 38, 44, 50-62 of copending Application No. 17/818,606. Although the claims at issue are not identical, they are not patentably distinct from each other because the 17/818,606 is drawn to the same composition.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
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/DAVID K O'DELL/Primary Examiner, Art Unit 1621
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