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
Formal Matters
Claims 2, 7, 9-13, and 17-19 are cancelled. Claims 24-58 are new. Claims 1, 3-6, 8, 14-16, and 20-58 are pending and under examination.
Priority
The instant application is a continuation of 18/504345 filed on 11/8/2023, which is a continuation of 18/478,482 filed on 9/29/2023, which is a continuation of 17/582,516 filed on 1/24/2022, which is a continuation of 17/332,417 filed on 5/27/2021, which is a continuation of 16/903,133 filed on 6/16/2020, which is a continuation of 16/557,083 filed on 8/30/2019, which claims priority from US provisional applications 62/725,948 filed on 08/31/2018 and 62/779,923 filed on 12/14/2018.
Information Disclosure Statement
The information disclosure statements filed on 3/5/2024, 8/13/2024, 12/19/2024 and 2/23/2026 have been considered by the examiner.
Objection to Title
The title of “Novel Methods” is vague and non-descriptive of the invention. A more appropriate title needs to be provided.
Objection to Specification
The specification is objected to for the disagreement between the table on page 25 and the metabolites listed on page 24. There are Metabolites A, B, C, E and F on page 24 while the Metabolites in the table on page 25 are Metabolites A, B, C, D and E. There is no structure provided for a Metabolite D in the disclosure. Thus, it is likely the compounds or the table are mislabeled.
Claim Objections
Claim 1 is objected to for the recitation of “one or more…and (e) glidant” where the appropriate recitation is “one or more ….or (e) glidant…”.
Claim 30 is objected to for not having an “or” or “and/or” between (s) and (t) in the claim.
Claim 30 is objected to for the use of “o” rather than “0” when providing (AUC(o-inf)). The value should be 0 (zero) “(0->inf)”.
Claim 30 is objected to for use of Metabolite A, B, C, D, and E when the structures from the specification are reasonable enough to be imported into the claims for proper definition of what these metabolites are.
Claims 35, 47-48, and 52 are objected to as the “and” needs to be replaced with “or” or “or combination thereof” be added to the claim with the removal of “and”. The claim is not in the format of “selected from the group consisting of ….and….”.
Claims 34, 36, and 42 are objected to for not containing a conjunction (‘or”) between the last two items or not ending with “or combinations thereof” in order to denote the group of options via correct grammar.
Claim 49 is objected to for not having an “or” between the last two members of the group.
Appropriate corrections are required.
Claim Rejections - 35 USC § 112(a) – Written Description
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 51 and 58 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 written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. These claims provide for “derivatives” and “modified” but does not provide a definition for “derivatives” or “modified” or enough representative species that would encompass all the possible derivatives or modifications of polysaccharides or celluloses that can exist where derivatives and modifications include a number of various isomers and compounds with various addition groups that can provide varying properties to the compounds. Derivatives of such compounds would include those that yet to have been made, and thus, one would not have the methods to make them. The specification does provide a more limited number of species of such derivatives or modified forms, and thus, applicant may use those species in the claim as well as the subgenre like hydroxyalkyl celluloses.
Claim Rejections - 35 USC § 112(a) – Scope of Enablement
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 20 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treatment of schizophrenia, bipolar disorder or bipolar depression, does not reasonably provide enablement for prophylaxis/prevention. It is noted that the definition of treating in the specification also encompasses prophylaxis The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims. The claim provides for both treatment or prophylaxis.
Jacka et al (Schizophrenia Bulletin, 2014, volume 40, pages 237-239) questions whether there will be a way to prevent schizophrenia and whether it’s realistic (page 237). Jacka also provides “To design an optimal preventive paradigm for mental disorders, prevention and mental health promotion needs to be integrated not only within the mental health space, but in coordinated partnership with other health promotion agencies and stakeholders that influence key risk factors.” (page 238). Healthdirect (Bipolar disorder, https://www.healthdirect.gov.au/bipolar-disorder, downloaded March 2026) states “There's no guaranteed way to prevent someone from developing bipolar disorder. But many people manage it successfully with the right treatment and support.” (Can bipolar disorder be prevented?).
Applicant’s specification does not provide for preventing schizophrenia or bipolar disorder from occurring. However, lumateperone has been shown to affect signaling pathways that would be useful in treatment of such conditions.
One of skill in the art would be a pharmacologist or medical doctor. A pharmacologist or medical doctor would have undue experimentation to test the compound in various formulations and in different administrations to find which would prevent schizophrenia or bipolar disorder from occurring. Additionally, since the etiologies of these psychological conditions are not fully understood in order to clearly establish prophylaxis with lumateperone treatment of all patients with schizophrenia or bipolar disorder, it is difficult to target pathways in a manner that would prevent the conditions. Thus, although applicant has the ability to treat the listed conditions, applicant does not have the ability to prevent the conditions based on the state of the art and the lack of data in the specification to support prevention. Due to applicant’s specification, applicant may have to consider “treating”, “where treating does not include prevention”.
Claim Rejections - 35 USC § 112(b)
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 1, 3-6, 8, 14-16, and 20-58 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 pre-AIA the applicant regards as the invention.
Claim 1 is indefinite for “a single pharmaceutical capsule dissolves in 500 ml of 0.1N aqueous hydrochloric acid to the extent of at least 85% after 15 minutes.….” as although some conditions are provided, there is no indication of what method is being used to calculate the time of dissolving/dissolution or if applicant achieves this merely by placing the capsules in the 500ml of 0.1N aqueous HCl. The specification does not mention the type of method used (see paragraphs 115-116). There are multiple methods used in the art including USP Apparatus I (basket) or II (paddle) at 37 degrees C with stirring speed usually being included. Two other methods are the reciprocating cylinder and flow through cell (USP, (Dissolution and Drug Release Tests, downloaded March 2026, https://www.usp.org/small-molecules/dissolution)). Each of these can affect the rate of capsule dissolution in a somewhat different manner. For the purpose of compact prosecution, if prior art allows for such amounts of dissolution of capsules by its teachings, it will read on the limitation.
Claims 3-6, 8, 14-16, and 20-58 are rejected as being dependent on an indefinite claim.
Claim 4 is indefinite for the recitation of “lumateperone mono-tosylate in an amount equivalent to 10 to 20 mg of lumateperone free base from one or more of mono-tosylate salt form, di-tosylate salt form, and tri-tosylate form” as it is unclear what “lumateperone free base from one or more of mono-tosylate salt form, di-tosylate salt form, and tri-tosylate form” means when the mono-tosylate form is what is being used in amount that is equivalent to free base lumateperone. It is unclear what the ditosylate and tritosylate salt forms relate to the limitation. Applicant may consider deleting the portion that says “from one or more of mono-tosylate salt form, di-tosylate salt form, and tri-tosylate form”.
Claim 22 is indefinite as the claim is dependent on claim 21, which in turn is dependent on claim 16 with claim 16 presenting a first choice of sizes optionally another choice of sizes. If claim 22 is read with dependency to claim 21, then this presents a situation where both options are combined, which disagrees with the use of “optionally” in claim 16 as optionally suggests one chooses either the first or second option, but not a combination of both. Applicant may make claim 22 dependent on claim 16 to correct the issue.
Regarding claims 30, 47, 48, 50, 51, 52, 53, 54, 55, 56, and 58, the phrase (e.g., which is another way of saying "for example") renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
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 1 and 35 recites the broad recitation of “diluent” and the claim also recites “/filler”, 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. Diluent is seen as a broader recitation that includes fillers, applicant may present these as options of one another such as “diluent or filler”.
Claims 3-6, 8, 14-16, and 20-34 and 41-58 are rejected as being dependent on an indefinite claim without repairing the issue of indefiniteness.
In the present instance, claim 30 recites the broad recitation of a mean Cmax, a mean AUC(0-inf), and ratio, and the claim also recites (e.g. [narrower value of preceding range]) 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. Applicant should delete the recitations of (e.g…….) from the claim.
In the present instance, claim 50 recites the broad recitation of gums, and the claim also recites (e.g. acacia, guar, agar, xanthan, tragacanth, karaya, gellan), 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. Applicant should delete the recitations of (e.g…….) from the claim.
In the present instance, claim 51 recites the broad recitations of polysaccharide derivatives, cellulose derivatives and hydroxyalkyl celluloses, and the claim also recites (e.g. starches, dextrans, pectins, alginates, carrageenans, cellulose, cellulose derivatives…), (e.g. carboxymethyl cellulose, methylcellulose, hydroxyalkyl celluloses…) and (e.g. hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose), respectively, which are the narrower statements 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. Applicant should consider to delete the recitations of (e.g…….) from the claim.
In the present instance, claim 52 recites the broad recitations of gelatins including non-gelling and gelling types, and the claim also recites (e.g. mammalian gelatins….), which are the narrower statements 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. Applicant should consider to delete the recitations of (e.g…….) from the claim.
In the present instance, claim 53 recites the broad recitations of synthetic polymers, polyethylene oxide and/or polypropylene oxide polymers and copolymers, and polyacrylate polymers, and the claim also recites (e.g. polyvinyl pyrrolidones….), (e.g. poloxamers….) and (e.g. carbopols), respectively, which are the narrower statements 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. Applicant should consider to delete the recitations of (e.g…….) from the claim.
In the present instance, claim 54 recites the broad recitations of sugar alcohols, and the claim also recites (e.g. dextrose, lactose……), which are the narrower statements 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. Applicant should consider to delete the recitations of (e.g…….) from the claim.
In the present instance, claim 55 recites the broad recitations of anionic surfactants, cationic surfactants, zwitterionic surfactants, nonionic surfactants, fatty alcohol ethoxylates, sorbitan esters, and polyethoxylated sorbitan esters, and the claim also recites (e.g. sodium lauryl sulfate…..), (e.g. benzalkonium halides….), (e.g. cocamidoalkyl betaines….), (e.g. fatty alcohol ethoxylates), (e.g. polyethylene glycol polydodecyl ethers), (e.g. sorbitan monolaurate….), (e.g. polysorbate 20…), respectively, which are the narrower statements 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. Applicant should consider to delete the recitations of (e.g…….) from the claim.
In the present instance, claim 56 recites the broad recitations of antioxidants, and the claim also recites (e.g. ascorbic acid, ascorbyl palmitate……), which are the narrower statements 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. Applicant should consider to delete the recitations of (e.g…….) from the claim.
In the present instance, claim 58 recites the broad recitations of modified cellulose, and the claim also recites (e.g. hydroxypropyl methyl cellulose…), which are the narrower statements 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. Applicant should consider to delete the recitations of (e.g…….) from the claim.
Claim 20 recites the limitations of "the treatment" and “the 5-HT2A receptor” in the claim without prior recitations of “treatment” or “a 5-HT2A receptor”. There is insufficient antecedent basis for this limitation in the claim.
Claim 30 is indefinite as Metabolite D does not match to a structure in the specification (see page 24 of specification). Applicant only presents structures for metabolites A, B, C, E and F and lumateperone itself. If applicant made a mistake in lettering the metabolites or the table on page 25, applicant should correct the specification and/or claim accordingly.
Claims 31-34, and 50-56 recite the limitation "the pharmaceutically acceptable diluents or carriers" in dependence to claim 1 where it is introduced as “one or more pharmaceutically acceptable diluents or carriers”. There is insufficient antecedent basis for this limitation in the claim. The applicant may refer to these as “the one or more pharmaceutically acceptable diluents or carriers.
Regarding claims 52, 53 and 55, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim Rejections - 35 USC § 112(d)
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.
Claims 6, 23 and 30 are 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. Claim 1 provides for a range of 35 to 45 mg lumateperone free base form for the equivalent to lumateperone mono-tosylate. Claims 6, 23 and 26 provide for “about 42 mg” of the equivalent to free base form or about 60 mg of lumateperone mono-tosylate (60 mg of lumateperone monotosylate is similar to about 42 mg free base form). The use of “about” with these amounts may allow the claim to extend beyond the upper range of 45 mg as a 10% standard error would give about 42 an upper range of 46.2 mg, which is above 45 mg. 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. The applicant may remove “about” from before these amounts.
Claims 28 and 29 are 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 28 and 29 allow for equivalent to 1 to 40 mg or 1 to 10 mg of lumateperone free base while the claim has indirect dependency to claim 1 where the equivalent amounts are provided as either 10 to 20 mg, 20 to 30 mg, or 35 to 45 mg. Since these claims extend down to 1 mg, they do not limit the amounts set forth in claim 1, on which they have dependency due to claim 20. 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(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103(a) 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.
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
Claims 1-6, 14, 15, 20, 23-35, and 41-58 are rejected under 35 U.S.C. 103(a) as being obvious over Vanover US 20160310502, Andrade (J Clinical Psychiatry, 2015, volume 75, pages 995-999), and Biyani (Pharmaceutical Technology, Oct 2, 2017, volume 41, pages 36-41).
Vanover teaches the use of particular substituted heterocycle fused gamma-carboline compounds as pharmaceuticals for the treatment of residual symptoms of psychosis or schizophrenia (abstract). Vanover also provides for treatment of major depressive disorder as well as behavioral disturbances associated with dementia, autism and other CNS diseases (paragraph 7). Vanover teaches form of capsule (paragraph 79 and paragraph 206) and daily doses of 10-120 mg/day and about 60 mg of the p-toluene sulfonic acid addition salt of a compound of its formula (paragraph 80). The 60 mg translates to about 42 mg of the free base version if mono-tosylate (aka toluenesulfonate) is considered. Vanover teaches a capsule with 60 mg of a compound that translates to lumateperone in toluene sulfonic acid addition salt form (paragraph 208). The capsule also contains 20 %w/w compound/lumateperone formula, 73.7 %w/w mannitol, croscarmellose Na of 5 %w/w, glyceryl monostearate at 1%w/w and talc 0.3 %w/w (table 1, paragraph 208). Paragraph 206 provides for magnesium stearate as another lubricant option while also mentioning talc and silica (silicon dioxide). Vanover teaches glyceryl mono- and distearate as polymer matrix materials that are biodegradable and biocompatible (paragraph 164). Vanover teaches glycerol mono- and distearate as a wax in paragraph 99 formulations. Vanover teaches “ For immediate release formulation, the compound of Formula I, in free or pharmaceutically acceptable salt form as hereinbefore described may be formulated with a pharmaceutically acceptable diluents or carrier. For sustained or delayed release formulation, the compound of the compound of Formula I, in free or pharmaceutically acceptable salt form as hereinbefore described may be formulated as hereinbefore described in any of Compositions P.1-P.7” (paragraph 207, also see paragraph 98 with release types). Thus, immediate release is seen as an option for formulations of Vanover. Vanover teaches toluenesulfonic acid salts in amorphous or crystal form (paragraph 204). Vanover does teach a gelatin capsule and other layers associated with the capsule in instances (paragraphs 132-137). Vanover does teach general ingredients with conventional excipients for tablets or capsules including binding agents, fillers, lubricants, and disintegrants (paragraph 206). Vanover teaches “the gelatin capsule being surrounded by a composite wall comprising a bather layer contacting the external surface of the gelatin capsule,” (paragraph 133), which is construed to be a coating on the outer surface of the capsule. Since the capsule is a carrier and Vanover teaches gelatin capsule, it provides for gelatin as a carrier. Vanover teaches fillers including “lactose, microcrystalline cellulose or calcium phosphate” (paragraph 206). Vanover teaches polyvinylpyrrolidone as a binding agent (paragraph 206), where crospovidone is a form of polyvinylpyrrolidone. Vanover teaches sodium lauryl sulfate as a wetting agent ingredients (paragraph 206). Vanover teaches various polymers (paragraphs 162-163). Vanover teaches emulsifying agents including lecithin or acacia (paragraph 206). Vanover allows for antioxidants effective to inhibit or reduce oxidation of the active compound including ascorbic acid, lipoic acid, vitamin E, tocopherols, carotenes or phenolic antioxidants as well as BHT and BHA (paragraph 127-131). Binding agents are also taught to be hydroxypropyl methyl cellulose, polyvinylpyrrolidone and pregelatinized maize starch (paragraph 206). Vanover recognizes there are metabolites of the compound (paragraphs 235 and 237). Vanover notes considering pharmacokinetics (paragraph 102 and example 11), and thus, would test pharmacokinetics of all its dose forms.
Vanover teaches toluenesulfonic acid addition salt of lumateperone, and thus, encompasses use of the mono-tosylate form as well as Vanover teaching either crystal or amorphous forms, which allows one or ordinary skill in the art to use crystal forms. Crystals are a solid form.
The capsule in paragraph 208 in Vanover has a similar contained formulation to applicant’s claims, but does not indicate what the capsule portion is made up of in this example, what release profile or pharmacokinetics it is able to provide, or which toluenesulfonic acid addition salt is used (mono-, di- and/or tri-) or whether this form is either crystal or amorphous. The capsule in paragraph 208 of Vanover cannot be presumed to have an inherently immediate release rate, but it does carry the lumateperone in a toluene sulfonic acid addition salt form, excipients (mannitol, croscarmellose Na, glyceryl monostearate and talc) and general capsule.. Vanover teaches a formulation that treats psychiatric conditions.
Andrade teaches release formulations in neuropsychiatry (title). Andrade teaches that pills and capsules may release their contents within minutes of ingestion and are immediate release formulations (article abstract). Andrade teaches that time release formulation may be incompletely absorbed and that immediate release formulations are less expensive than time release (abstract). Andrade teaches most capsules are dissolved within minutes after swallowing (Introduction).
Biyani teaches choosing capsules and the hard gelatin and hard HPMC capsules for dry filled capsules (Selecting a capsule type). Biyani teaches that most filled capsules disintegrate in 5-10 minutes, but some may have lower disintegration time (Benefits of capsules as dosage form and Rapid dissolution section).
One of ordinary skill in the art before the time of filing would have utilized immediate release capsules as gelatin and HPMC capsules are known to be common and fast disintegrating within 10 minutes and immediate release forms like capsules are mostly used, beneficial for faster absorption and less expensive along with the ingredients in the capsule formulation of Vanover having similar contents (same amount/concentration of drug, same high amount of mannitol, same amounts of croscarmellose Na and talc) and amounts thereof including dosage of the lumateperone, and obtained a capsule formulation of applicant’s invention with a reasonable expectation of success. In doing so through the combination of the references, the dissolution profiles and pharmacokinetics (PK) (Cmax, Tmax, AUC values, PK pattern of metabolites) would be reasonably optimized and achieved when making and taking the oral capsule formulation motivated with faster dissolving capsule shell types by the teachings of Vanover, Andrade and Biyani with such fast dissolution/release and same amount of lumateperone in toluene sulfonic acid salt form. This use of immediate release hard gelatin or HPMC capsules of the prior art would be seen as beneficial for more complete absorption of drug and faster time to the lumateperone’s effect in patients with psychiatric conditions as well as being more cost effective to produce and likely less expensive for the patient.
Claims 16 and 21-22 are rejected under 35 U.S.C. 103(a) as being obvious over Vanover US 20160310502, Andrade, (J Clinical Psychiatry, 2015, volume 75, pages 995-999), Biyani (Pharmaceutical Technology, Oct 2, 2017, volume 41, pages 36-41) and Peddy WO 2018/189646 (filing April 9, 2018).
Vanover, Andrade and Biyani teach the claims as discussed above.
Vanover, Andrade and Biyani do not teach the solid crystal sizes of claims 21-22.
Peddy teaches solid state forms of lumeteperone p-tosylate in a dosage form (abstract). Peddy teaches particle size D90 of less than 500, less than 100, less than 50, or less than 10 microns (page 14). Peddy teaches “Milling or micronization can be performed to achieve the desired particle sizes or distributions”. Peddy teaches coating materials that are not limited and teaches hard or soft capsules (pages 11 and 12). Peddy teaches film coatings and enteric coatings. Peddy teaches release rate controlling agents like methyl methacrylates (page 12). Peddy teaches diluents. Peddy teaches polymers or carriers including celluloses, polysaccharides, and poloxamers (page 7). Peddy teaches suitable polymers or carriers including starches, lactose, guar gum, gelatin, crospovidone, croscarmellose sodium, antioxidants, colorants, silicon dioxide, sorbitol and mannitol (page 9).
One of ordinary skill in the art at the time of instant filing would have included forms of the active compound of Peddy as an acceptable size of lumateperone into capsule formulations with excipients taught by Mates and had a reasonable expectation of success in producing the instant claimed capsule formulation. Each of the references is to a form of lumateperone that is useful for treatment of central nervous disorders (MPEP 2144.06), which offers a motivation to combine for the same purpose.
Claim 8 is rejected under 35 U.S.C. 103(a) as being obvious over Vanover US 20160310502, Andrade, (J Clinical Psychiatry, 2015, volume 75, pages 995-999), Biyani (Pharmaceutical Technology, Oct 2, 2017, volume 41, pages 36-41) and Tomesch US 2011/0112105.
Vanover, Andrade and Biyani teach the claims as discussed above.
Vanover, Andrade and Biyani do not teach the x-ray diffraction pattern as in claim 16.
Tomesch teaches “The salt crystal according to claim 1, wherein said salt crystal exhibits an X-Ray Powder Diffraction pattern comprising at least two 2-theta values selected from:
Position D-spacing Relative (°2θ) (Å) Intensity (%) 5.68 15.543 100.0 12.11 7.303 26.0 16.04 5.520 22.3 17.03 5.202 66.8 18.16 4.882 21.6 19.00 4.668 20.8 21.67 4.097 15.7 22.55 3.940 23.9 23.48 3.786 18.9 24.30 3.660 23.5” (see claims 4 and 5 of Tomesch and paragraphs 101-104). Tomesch teaches the compound of the instant claims (paragraph 92). Tomesch teaches using a diluent (claims 15 and 16 of Tomesch). Tomesch provides the compounds are known to treat disorders of the central nervous system including sleep disorders, social phobias, anxiety and others (paragraph 3). Tomesch notes the stability of this form (paragraph 5).
One of ordinary skill in the art before the time of filing would have noted that crystals of this form of lumateperone having this x-ray powder diffraction pattern would be available to use in formulations and have desirable stability by teachings of Tomesch, and therefore, would utilize such drug crystal of Tomesch in capsule formulations motivated by Vanover, Andrade and Biyani. There would be a reasonable expectation of success in acquiring better formulation stability when using this crystal form of the compound.
Claims 36-40 are rejected under 35 U.S.C. 103(a) as being obvious over Vanover US 20160310502, Andrade, (J Clinical Psychiatry, 2015, volume 75, pages 995-999), Biyani (Pharmaceutical Technology, Oct 2, 2017, volume 41, pages 36-41) and Li US 20080131505.
Vanover, Andrade and Biyani teach the claims as discussed above.
Vanover, Andrade and Biyani do not teach other amounts of mannitol.
Li teaches a particulate co-processed composition comprising microcrystalline cellulose and a sugar alcohol such as mannitol that is used for preparations of solid dosage forms (abstract and claims 1-4 of Li, table 7A shows a ratio of 5% mannitol to 95% MCC and one of 15% mannitol to 85% MCC). Li teaches the ratio of microcrystalline cellulose to at least one sugar alcohol is 99:1 to 1:99 and the composition may also have about 1% magnesium stearate (claim 1 of Li). Li teaches “the ratio of microcrystalline cellulose to the at least one sugar alcohol is about 70:30 to 95:5” (claim 5 of Li). Paragraph 49 of Li teaches binders, antioxidants, and disintegrants. Paragraph 48 teaches diluents or fillers and paragraph 47 teaches lubricants and anti-adherents. Li teaches these co-processed compositions as ideal excipients for solid dosage forms (paragraph 53). Although Li provides for compression in tablets, Vanover recognizes the use of mannitol as an excipient and microcrystalline cellulose as a filler as well as the capsule form. Thus, the co-processed MCC/mannitol in different ratios is a suitable prior art excipient for Vanover’s formulations.
One of ordinary skill in the art before the time of filing would have considered using MCC as a portion with mannitol and adjusting different ratios of MCC and mannitol for excipients to use in a solid dosage form by teachings of Li, which recognize this co-processed excipient as ideal for solid dosage forms as in the solid oral capsules motivated by Vanover, Andrade and Biyani. Thus, there was a reasonable expectation of success in adjusting amounts of mannitol to lower amounts when used as a coprocessed excipient with MCC and using such an excipient in capsule formulations taught by Vanover, Andrade and Biyani (see MPEP 2144.05).
Obviousness-Type 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 §§ 706.02(l)(1) - 706.02(l)(3) for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1, 3-6, 8, 14-16, and 20-58 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4-12, and 14-18 of US 10695345. Although the claims at issue are not identical, they are not patentably distinct from each other because each claim set provides for capsules with the same pharmaceutical ingredient in free base form or a salt thereof as well as similar methods of using and making of capsules. The difference between claim 1 of the instant claims and claim 1 of ‘345 is that there is also offered a mass amount (in mg) of lumateperone mono-tosylate. The concentration range in claim 1 of ‘345 will allow for varying of mg amounts of the drug.
Claims 1, 3-6, 8, 14-15, 20, and 23-58 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of US Patent 11806348 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because each claim set provides for the lumateperone monotosylate capsule with the ingredients as claimed and the same use for treatment. As the formulations of the claims are similar to those of the examined specification, it will be expected to share the same properties. When the claims teach a method using a composition, the composition is made obvious over its use in the method claims.
Claims 1, 3-6, 8, 14-16, and 20-58 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-13, 15-18 of US 11052084. Although the claims at issue are not identical, they are not patentably distinct from each other because each claim set provides for the lumateperone monotosylate capsule with the ingredients as claimed and the same use for treatment. As the formulations of the claims are similar to those of the examined specification, it will be expected to share the same properties. ‘084 teaches a method of using by administering to a patient.
Claim 1, 3-6, 8, 14-16, and 20-58 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, 3-13 and 15-20 of US Patent 11690842. Although the claims at issue are not identical, they are not patentably distinct from each other because each claim set provides for the lumateperone monotosylate capsule with the ingredients as claimed and the same use for treatment. As the formulations of the claims are similar to those of the examined specification, it will be expected to share the same properties. ‘842 also teaches a method of using by administration of the capsule.
Claims 1, 3-6, 8, 14-15, 20, and 23-58 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of US Patent 12,533,355. Although the claims at issue are not identical, they are not patentably distinct from each other because each claim set provides for gelatin capsules with lumateperone mono-tosylate with the same ingredients and concentration ranges. The Patented claims also provide for methods of treatment that overlap in scope with the claimed invention. These would provide formulations having similar pharmacokinetic profiles of the drug (a property of the formulation) as covering similar formulations.
Claims 1, 3-6, 8, 14-16, and 20-58 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, and 3-28 of US Patent 12,070,459. Although the claims at issue are not identical, they are not patentably distinct from each other because each claim set provides for gelatin capsules with lumateperone mono-tosylate with the same ingredients and concentration ranges. The Patented claims also provide for methods of treatment that overlap in scope with the claimed invention. These would provide formulations having similar pharmacokinetic profiles of the drug (a property of the formulation) as covering similar formulations.
Claims 1, 3-6, 8, 14-16, and 20-58 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5-10, and 12-22 of US Patent 12,465,570. Although the claims at issue are not identical, they are not patentably distinct from each other because each claim set provides for gelatin capsules with lumateperone mono-tosylate with the same ingredients and concentration ranges. The Patented claims also provide for methods of treatment that overlap in scope with the claimed invention. These would provide formulations having similar pharmacokinetic profiles of the drug (a property of the formulation) as covering similar formulations.
Claims 1, 3-6, 8, 14-15, 20, and 23-58 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-29 of US Patent 12,128,043. Although the claims at issue are not identical, they are not patentably distinct from each other because each claim set provides for gelatin capsules with lumateperone mono-tosylate with the same ingredients and concentration ranges. The Patented claims also provide for methods of treatment that overlap in scope with the claimed invention. These would provide formulations having similar pharmacokinetic profiles of the drug (a property of the formulation).
Claim 1, 3-6, 8, 14-16, and 20-58 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of copending Application No. 19/317044 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because each claim set provides for gelatin capsules with lumateperone mono-tosylate with the same ingredients and concentration ranges. The copending claims also provide for methods of treatment that overlap in scope with the claimed invention. These would provide formulations having similar pharmacokinetic profiles of the drug (a property of the formulation) as covering similar formulations.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 1, 3-6, 8, 14-16, and 20-58 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 8, 9, 11-17, and 21-24 of copending Application No. 19/317053 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because each claim set provides for gelatin capsules with lumateperone mono-tosylate with the same ingredients and concentration ranges. The copending claims also provide for methods of treatment that overlap in scope with the claimed invention. These would provide formulations having similar pharmacokinetic profiles of the drug (a property of the formulation) as covering similar formulations.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
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/MARK V STEVENS/Primary Examiner, Art Unit 1613