DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the
first inventor to file provisions of the AIA .
Formal Matters
Claims 1-11 are original, pending, and under examination.
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in parent Application No. IN202121006827, filed on February 18, 2021. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement filed on 03/25/2024 has been considered by the examiner.
Claim Objections
Claims 2 and 3 are objected to for “selected from the group consisting of the following or a mixture thereof…..a)……and b)….” or “selected from the group consisting of the following or a mixture thereof….a)….b)….and c)”. Additionally, the use of “selected from….and…” in each of parts a) and b) or a), b) and c) is not the Markush phrase “selected from the group consisting of….and…” where “and” is normally used for the list of options, but applicant may use “selected from group consisting of…and…” or alternatively “selected from….or….”. The standard language for Markush language utilizing the phrase “selected from the group consisting of” would be “the vehicle is selected from the group of …..and ….”. If applicant desires the option of a mixture thereof, then applicant can end each group with “and a mixture thereof” or “or a mixture thereof” depending on the language used to introduce the group of options.
For claim 2, Applicant might consider the language “the vehicle is a) a non-aqueous solvent selected from the group consisting of ….and a mixture thereof or b) a lipophilic solvent selected from the group consisting of …..and a mixture thereof.” A similar strategy could be used for claim 3.
Claim 11 is objected to for “opioid addiction, acute pain and chronic pain” as these are options of conditions that would be treated. The appropriate language is “opioid addiction, acute pain or chronic pain”. Thus, delete the “and” in the phrase and replace with “or”.
Appropriate corrections are required.
Claim Rejections - 35 USC § 112(a)
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 1-11 are 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. Claim 1 recites the composition of “buprenorphine, its metabolite, a prodrug, or a salt thereof”. The specification, however, does not provide adequate written description to support the genus “a prodrug of buprenorphine”. The disclosure does not describe any specific buprenorphine prodrug species, structural features, attachment groups, representative members, or guidance defining the scope of the claimed prodrug genus. Per the specifications (page 1, Field of Invention), the term “prodrug” is stated, but not elaborated on with a definition or description of adequate species. It does not describe the specific mechanisms, specialized groups, or linkers by which the prodrugs release their active component when and where desired; these details are essential for defining the genus adequately.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-3, 5, 7-11 and are rejected under 35 U.S.C. 103 as being unpatentable over Li et al. (WO2019144079A1).
Li et al. teaches an injectable, low-viscosity liquid buprenorphine composition that forms a stable, in-situ depot for sustained drug delivery lasting from one week to three months, enhancing both stability and bioavailability (abstract). Li et al. teaches that this composition contains buprenorphine at concentrations ranging from 1% to 40% w/w (page 14, paragraph 50). Li et al. teaches that the composition may contain solvents/vehicles from the following group (alone or in combination): benzyl alcohol (which is also a stabilizer), benzyl benzoate, propylene glycol, and polyethylene glycol, at concentrations ranging from 5% to 90% w/w (page 7, paragraphs 15 & 16). Li et al. teaches that inherent release retardants including stearic acid and palmitic acid may be included in the composition at concentrations ranging from 0.1% to 40% w/w (page 15, paragraph 58). Li et al. teaches that additional antioxidants/stabilizers such as butylated hydroxyanisole and butylated hydroxytoluene can be incorporated into the composition (page 23, paragraph 80). Li et al. teaches that this composition can be delivered via intramuscular or subcutaneous administration, with the duration of sustained release able to be achieve 1-3 months or longer (page 25, paragraph 86). Li et al. teaches that this composition can be administered with a syringe that has a fill volume of 1 mL (page 18, paragraph 70), and further states that it may be may be pre-filled into one syringe for use (page 10, paragraph 34). Li et al. teaches that this composition can be used to treat pain opioid addiction (page 6 & 7, paragraph 0013).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed inventions, to formulate a sustained release injectable buprenorphine composition using solvents/vehicles, lipophilic release-retarding agents, and stabilizers disclosed in Li et al., because these excipient classes are routinely employed to control solubility, viscosity, depot formulations, oxidative stability, and duration of release in injectable drug delivery systems. Li et al. teaches buprenorphine concentrations overlapping the claimed range, solvents/vehicles including benzyl alcohol, benzyl benzoate, propylene glycol, and polyethylene glycol at overlapping concentration ranges with those claimed, inherent release retardants such as and palmitic acid within overlapping concentration ranges of those claimed, and stabilizers including BHA, BHT, and benzyl alcohol at concentration ranges overlapping with those claimed (MPEP 2144.05 regarding obviousness of ranges). Additionally, Li et al. further teaches intramuscular and subcutaneous administration of this composition, sustained release lasting weeks to months, prefilled syringe-based delivery, and treatment of opioid addiction and pain. Selecting particular members and concentrations from well-known excipient classes to achieve predictable sustained release depot would have required no more than routine optimization of result-effective variables or from overlapping ranges, and the overlapping ranges render the claimed ranges obvious absent any proof of criticality or unexpected results.
Claims 4 and 6 are rejected under 35 U.S.C. 103 as being unpatentable over Li et al. (WO2019144079A1) in view of Panzner et al. (US20070053918A1).
Li et al. teaches the claim limitations previously mentioned, which includes the use of an injectable and sustained release composition containing buprenorphine, select excipients for their respective purpose at concentration ranges overlapping with those claimed, and the delivery device being a 1 mL syringe that can be prefilled.
However, Li et al. fails to teach the sustained release injectable pharmaceutical composition of claim 3, wherein the phosphocholine is selected from the group consisting of: hydrogenated soya phosphatidyl choline (HSPC), 1,2-distearoyl-snglycero-3-phosphocholine (DSPC), dipalmitoyl phosphatidylcholine (DPPC), 1,2-dimyristoyl-sn-glycero-3-phospho-choline (DMPC), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (PO PC), Soya phosphatidyl choline (SPC) and soya-lecithin. Additionally, Li et al. fails to teach the use of cholesterol as an additive to the pharmaceutical composition.
Panzner et al. teaches methods for creating injectable, long-acting formulations using liposomes and polymers to deliver active substances (such as buprenorphine) that exhibit sustained release in mammals (abstract). Panzner et al. teaches that this composition can be administered subcutaneously or intramuscularly (page 4, column 1, paragraph 70). Panzner et al. teaches that such liposomal sustained release compositions (which are a form of release-retarding compositions) can be developed using the following phosphatidylcholines: Dimyristoylphosphatidylcholine (DMPC), Dipalmitoylphosphatidylcholine (DPPC), and/or Distearoylphosphatidylcholine (DSPC) (page 2, column 2, paragraph 29). Panzner et al. teaches the use of cholesterol as an additive in the composition to support its integrity (page 1, column 2, paragraph 10).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed inventions, to incorporate a phosphocholine selected from the claimed group into the sustain-release injectable buprenorphine composition of Li et al. because Panzner et al. teaches that liposomal and long-acting injectable formulations––which are release-retarding-systems––can be developed using phosphatidylcholines such as DMPC, DPPC, and DSPC, which are expressly included in the claimed phosphocholine group. Likewise, it would have been obvious to include cholesterol as an additive, as Panzner et al. teaches that it is routinely incorporated into such formulations to support its structural integrity, which would thus enhance stability of the sustained release composition. Since both references address injectable, sustained-release release drug delivery systems, a person of ordinary skill in the art would have been motivated to substitute or incorporate the known phosphatidylcholines and cholesterol from Panzner et al. into the composition of Li et al. to modulate depot stability, release rate, and formulation robustness, as these classes of vehicles were well-recognized structural lipids routinely employed in long-acting injectable and liposomal systems. Doing so would have constituted no more than the predictable use of known excipients for their established functions. Thus, selecting among the members of art-recognized phosphocholine class and cholesterol would have required only routine formulation optimization with a reasonable expectation of success.
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Li et al. (WO2019144079A1) in view of Shen et al. (CA2903020A1).
Li et al. teaches the claim limitations previously mentioned, which includes the use of an injectable and sustained release composition containing buprenorphine, select excipients for their respective use at concentration ranges overlapping with those claimed, and the delivery device being a 1 mL syringe that can be prefilled.
However, Li et al. fails to teach a sustained release injectable pharmaceutical composition of claim 6, wherein the additive is selected from the group consisting of cholesterol, Ethyl Hexyl Oleate, glyceryl esters like glyceryl monooleate, glyceryl monostearate, glyceryl palmitate, glyceryl palmitostearate, glyceryl dibehenate, glyceryl distearate, glyceryl isostearate, glyceryl laurate, glyceryl mono and dicaprylocaprate, glyceryl mono and dipalmitostearate, glyceryl monocaprylate, glyceryl monocaprylocaprate, glyceryl monocitrate, glyceryl oleate, glyceryl palmitate, glyceryl ricinoleate, glyceryl stearate, glyceryl stearate/peg-100 stearate, glyceryl tristearate polyoxyl glyceryl stearate, sucrose esters, glycol esters.
Shen et al. teaches an injectable semi-solid controlled release composition, formed as a solution within a biocompatible and bio-erodible semi-solid lipid matrix that incorporates local anesthetic agents (title and abstract). Shen et al. teaches that this composition can also be used for the controlled delivery of local or systemic active agents (page 3, paragraph 11), which can include buprenorphine. Shen et al. teaches that this composition can be used for both subcutaneous and intramuscular injection (page 5, paragraph 17). Shen et al. teaches that glycerides can be added to the composition as excipients to modify the release kinetics, viscosity, or dissolution kinetics (page 4, paragraph 14). Shen et al. teaches that specifically, any one of the of the following can be used as a modifying excipient: 1) triglycerides of mixed esters, 2) partial glycerides of fatty acids, and 3) low HLB polyglyceryl esters, (page 14, paragraph 47). Shen et al. teaches that examples of such excipients include the following: glyceryl laurate, glyceryl monostearate, and glyceryl palmitate (page 15, paragraph 47). Shen et al. teaches that additional examples of partial glycerides that may be included in the composition are the following unsaturated excipients: glyceryl oleate and glyceryl monooleate (page 12, paragraph 39).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to incorporate the claimed glyceride additives into the sustained-release injectable buprenorphine composition of Li et al., because Shen et al. teaches that teaches that triglycerides of mixed esters, partial glycerides of fatty acids, and low HLB polyglyceryl esters may be used in controlled-release injectable lipid matrices to modify release kinetics, viscosity, and dissolution behavior. It further provides explicit examples of the very glyceride species recited in the claim. Given that both references relate to injectable, sustained-release pharmaceutical composition of active ingredients––with one specifically including the delivery of buprenorphine––a person of ordinary skill in the art would have been motivated to incorporate these well-known glyceride excipients into the composition of Li et al. to adjust its depot stability, release rate, and rheological properties, with a reasonable expectation of success. Selecting particular glyceride additives from these recognized classes constitutes no more than routine formulation optimization of result-effective variables.
Conclusions
No claim is found allowable.
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Arya A. Bazargani, Ph.D.
Patent Examiner
Art Unit 1613
/MARK V STEVENS/ Primary Examiner, Art Unit 1613