DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicants’ election of Group I (claims 1-23) drawn to a composition comprising cabotegravir or dolutegravir; a monoglyceride; a triglyceride; and ethanol, benzyl alcohol or combination thereof, is acknowledged. The election was made without traverse.
As the requirement for restriction is deemed proper, it is maintained and hereby made FINAL.
Claims 24-34 are hereby withdrawn from further consideration by the Examiner, pursuant to 37 CFR 1.142(b), as being drawn to non-elected inventions, there being no allowable generic or linking claim. The instant claims have been examined commensurate with the scope of the elected invention. Applicants timely responded to the restriction requirement in the reply filed 3/24/26.
Accordingly, claims 1-23 are under current examination.
Status of Claims
No new claim set was filed in response to the Restriction/Election requirement.
Amended claims
Newly canceled claims
Newly added claims
Previously canceled claims
Instantly withdrawn claims
24-34
Claims under instant examination
1-23
Claim Objections
Claim 13 is objected to because of the following informalities: claim 13 recites “The composition of claim 2 wherein the polyoxyl castor oil…”. The Examiner suggests adding a comma after “claim 2” in order to keep the language consistent throughout the claims.
Appropriate correction is required.
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.
Claims 13-15 rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 13 recites “wherein the polyxoyl castor oil is present in an amount of 0.01 to 10%”. Claim 14 recites “wherein the ethanol, benzyl alcohol, or a combination thereof is present at 5 to 20%”. Claim 15 recites “wherein the ethanol, benzyl alcohol, or combination thereof is a combination of ethanol and benzyl alcohol present at 5 to 20%”. The claims do not recite the unit of measurement. Thus, the metes and bounds of the claims cannot be determined and the claims are indefinite.
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.
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 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, 3-4, 6-12 and 14-23 are rejected under 35 U.S.C. 103 as being unpatentable over Tiberg et al. (US 2014/0162944; published: 6/12/14), in view of Crauwels et al. (WO 2019/016732; published: 1/24/19).
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
Tiberg is directed to controlled release peptide formulations [Title].
With regards to instant claims 1, 4, 6-8, 10-11 and 14-15, Tiberg teaches compositions forming a low viscosity mixture of: a) 20-80 wt. % of at least one diacyl glycerol and/or a tocopherol; b) 20-80 wt. % of at least one phosphatidyl choline (PC); c) 5-20 wt. % of at least one biocompatible, organic mono-alcoholic solvent; d) up to 20 wt. % polar solvent e) at least one peptide active agent; f) optionally at least one antioxidant; wherein the ratio of components a:b is in the range 40:60 to 54:46; wherein the pre-formulation forms, or is capable of forming, at least one liquid crystalline phase structure upon contact with excess aqueous fluid [Abstract]. Tilberg teaches that the abovementioned pre-formulation (for i.m. or s.c. injection) shows a highly advantageous release profile, is easy to manufacture, may be sterile-filtered, has low viscosity (allowing easy and less painful administration typically through a narrow needle), allows a high level of bioactive agent to be incorporated (thus potentially allowing a smaller amount of composition and/or active agent to be used), requires shallow injection and/or forms a desired non-lamellar depot composition in vivo having a “non-burst” release profile [0017]. Tiberg teaches that the at least one peptide active agent can be an antimicrobial peptide (e.g., corticostatins, defensins, histatins) [0104] and furthermore, teaches that the composition can further contain an antimicrobial or microbial-static agent (e.g., benzyl alcohol) [0165]. With regards to the diacyl glycerol, Tiberg teaches wherein the non-polar groups are preferably palmitic, stearic, oleic and linoleic acids [0071]; e.g., GDO (glycerol dioleate) and as evidenced by instant claim 18, GDO contains 0.5% monoglycerides, 95.3% diglycerides and 4.0% triglycerides. It is noted that Tiberg also teaches that the non-polar groups of the diacyl glycerol that will comprises a mixture of monoglycerides, diglycerides and triglycerides, can also be caprylic and capric acids [0071]. With regards to the solvent, Tiberg teaches that most preferably it comprises ethanol [0084].
With regards to instant claim 3, Tiberg teaches wherein the phosphatidyl choline can be sourced from soybean (e.g., LIPOID S100 soybean phosphatidylcholine) [0075 and claim 18].
Ascertainment of the Difference Between the Scope of the Prior Art and Claims
(MPEP §2141.012)
Although Tiberg teaches that the at least one peptide active agent in the abovementioned injectable composition can be an antimicrobial peptide (e.g., corticostatins, defensins, histatins) [0104] and furthermore, teaches that the composition can further contain an antimicrobial or microbial-static agent (e.g., benzyl alcohol) [0165], Tiberg does not teach wherein the antimicrobial agent is cabotegravir or dolutegravir, as required by instant claim 1. However, this deficiency is cured by Crauwels.
Crauwels is directed to regimens for treating HIV infections and AIDS [Title]. Crauwels teaches an injectable formulation comprising cabotegravir, which is an antimicrobial that treats HIV and AIDS [Abstract].
Although Tiberg teaches a composition comprising monoglyceride and triglyceride, Tiberg does not teach the claimed amount (30-80% w/w triglyceride and 5-40% w/w monoglyceride), as required by instant claims 9 and 12.
Tiberg and Crauwels do not teach wherein the antimicrobial agent is present at 0.01 to 500 mg/mL, as required by instant claim 16.
Tiberg and Crauwels do not teach wherein at least 100, 500, 2,000, 3,000, 4,000 or 5,000 ng/mL of the antimicrobial (e.g., cabotegravir) is present in the blood stream of the subject for at least 48 hours or greater upon administration to a mammal, as required by instant claims 17-23. However, with regards to the “amount present in the blood stream for x amount of time upon administration to a mammal” limitations of instant claims 17-23, the prior art teaches the same compound (i.e., cabotegravir) in the same injectable composition as claimed and therefore, the compound's properties are necessarily present; the Examiner directs attention to MPEP 2112.01(II) which states: “A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present”.
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
Tiberg and Crauwels are both directed to injectable pharmaceutical compositions. Based on these teachings, it would have been prima facie obvious to one of ordinary skill in the art, before the invention was effectively filed, to modify the injectable composition of Tiberg by substituting the pharmaceutically active drug with cabotegravir taught by Crauwels to achieve the predictable result of obtaining a composition suitable for treating HIV and/or AIDS. One of ordinary skill in the art would have been motivated to do so because Tiberg teach that its injectable formulation advantageously shows a highly advantageous release profile, is easy to manufacture, may be sterile-filtered, has low viscosity (allowing easy and less painful administration typically through a narrow needle), allows a high level of bioactive agent to be incorporated (thus potentially allowing a smaller amount of composition and/or active agent to be used), requires shallow injection and/or forms a desired non-lamellar depot composition in vivo having a “non-burst” release profile [0017].
Regarding the concentration of monoglyceride and triglyceride as specified in claims 9 and 12, MPEP 2144.05 states:
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Furthermore, Tiberg teach the solvent is such that a relatively small addition to a mixture comprising a) and b) (i.e. preferably below 15%) gives large viscosity reductions, of one order of magnitude or more. The addition of 10% organic mono-alcohol solvent can give a reduction of two or more orders of magnitude in viscosity over the solvent-free composition, or over a depot containing only a polar solvent such as water, or glycerol, wherein a) is the glycerides [0085]. The Applicants' specification provides no evidence that the selected concentration range in claims 9 and 12 was not due to routine optimization and/or that the results should be considered unexpected compared to the prior art. Due to numerous physical/chemical/biological properties of various chemicals (e.g., overall viscosity of the composition), it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine these teachings and alter the concentration. One of ordinary skill in the art would have been motivated to change the concentration as this could be expected to be advantageous for altering the composition viscosity.
The amount of cabotegravir is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and would reasonably expect success. It would have been customary for an artisan of ordinary skill to determine the optimal amount of cabotegravir in order to best achieve the desired results as such would provide advantageous biological effect. It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to engage in routine experimentation to determine optimal or workable ranges that produce expected results. Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. In re Aller, 220 F. 2d 454, 105 USPQ 233 (CCPA 1955). In the instant case, Crauwels teaches that the amount of the compound actually administered will typically be determined by a physician, in the light of the relevant circumstances, including the condition to be treated, the chosen route of administration, the actual compound -administered, the age, weight, and response of the individual patient, the severity of the patient's symptoms, and the like. The Examiner considers it prima facie obvious to optimize the amounts of any biologically active agent to achieve their known biological effect, absent unexpectedly superior properties of the claimed invention. In the instant case, one of ordinary skill in the art would have recognized that the amount of cabotegravir would impact the efficacy in the treatment of HIV and/or AIDS and therefore be an optimizable variable.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the invention was effectively filed, as evidenced by the references, especially in the absence of evidence to the contrary.
Thus, the claimed invention was prima facie obvious before the effective filing date of the claimed invention.
Claims 2 and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Tiberg et al. (US 2014/0162944; published: 6/12/14), in view of Crauwels et al. (WO 2019/016732; published: 1/24/19) as applied to claims 1, 3-4, 6-12 and 14-23 above, and further in view of Reems et al. (US 2018/0250343; published: 9/6/18).
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
See the above rejection for the detailed teachings of instant claims 1, 3-4, 6-12 and 14-23.
Ascertainment of the Difference Between the Scope of the Prior Art and Claims
(MPEP §2141.012)
Tiberg and Crauwels do not teach wherein the composition further comprises polyoxyl castor oil in an amount of 0.01-10%, as required by instant claims 2 and 13. However, such deficiency is cured by Reems.
Reems is directed to therapeutic compositions [Title] comprising an active agent such as anti-infective agents (e.g., dolutegravir) [0062], wherein the composition is administered via injection [claims]. Reems teaches that the injectable therapeutic composition can include solubilizing or dispersing agents such as polyethoxylated castor oils [0078].
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
Tiberg, Crauwels and Remms are each directed to injectable pharmaceutical compositions. Reems teaches that polyethoxylated castor oils were known and routinely used in the prior art as solubilizer/dispersing agents (see [0078]). It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the composition of Tiberg by further incorporating a polyethoxylated castor oil to achieve the predictable result of obtaining enhanced solubilization and/or dispersant effect.
The amount of polyethoxylated castor oils is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and would reasonably expect success. It would have been customary for an artisan of ordinary skill to determine the optimal amount of polyethoxylated castor oils in order to best achieve the desired results as such would provide advantageous biological effect via the solubilization of active agent(s) contained in the composition. It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to engage in routine experimentation to determine optimal or workable ranges that produce expected results. Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. In re Aller, 220 F. 2d 454, 105 USPQ 233 (CCPA 1955). The Examiner considers it prima facie obvious to optimize the amounts of any biologically active agent to achieve their known biological effect, absent unexpectedly superior properties of the claimed invention. In the instant case, one of ordinary skill in the art would have recognized that the amounts of polyethoxylated castor oils in the treatment of HIV/AIDS and therefore be an optimizable variable.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the invention was effectively filed, as evidenced by the references, especially in the absence of evidence to the contrary.
Thus, the claimed invention was prima facie obvious before the effective filing date of the claimed invention.
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Tiberg et al. (US 2014/0162944; published: 6/12/14), in view of Crauwels et al. (WO 2019/016732; published: 1/24/19) as applied to claims 1, 3-4, 6-12 and 14-23 above, and further in view of Jacob et al. (WO 2018/111580; published: 6/21/18).
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
See the above rejection for the detailed teachings of instant claims 1, 3-4, 6-12 and 14-23.
Ascertainment of the Difference Between the Scope of the Prior Art and Claims
(MPEP §2141.012)
Tiberg and Crauwels do not teach wherein the composition further comprises cholesterol, as required by instant claim 5. However, such deficiency is cured by Jacob.
Jocob is directed to polypeptides for managing viral infections [Title] comprising a combination of active agents such as those comprising dolutegravir, wherein the composition is administered via injection. Jacob teaches that the injectable therapeutic composition can include solubilizing agents such as cholesterol [Description section]
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
Tiberg, Crauwels and Jacob are each directed to injectable pharmaceutical compositions. Jacob teaches that cholesterol was known and routinely used in the prior art as a solubilizing agent [see Description section]. It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the composition of Tiberg by further incorporating a cholesterol to achieve the predictable result of obtaining enhanced solubilization effect.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the invention was effectively filed, as evidenced by the references, especially in the absence of evidence to the contrary.
Thus, the claimed invention was prima facie obvious before the effective filing date of the claimed invention.
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 obviousness-type 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); 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 conflicting 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.
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
Claims 1-23 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 and 17 of U.S. Patent No. 12,350,281. Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets are drawn to the same composition comprising a pharmaceutically active agent, monoglyceride (e.g., glycerol monooleate) present at about 5-40$ w/w, a triglyceride (e.g., caprylic acid, capric acid) present at about 5-80% w/w, ethanol and benzyl alcohol present at about 1-25% w/w, wherein the composition forms a water-insoluble depot upon injection, wherein the composition can further comprise polyoxyl castor oil, soybean lecithin, anti-oxidant, cholesterol, wherein at least about 100-20,000 ng/mL of the pharmaceutically active agent is present in the blood stream of a subject for at least about 48 hours or greater upon administration to the mammal. It is noted that the ‘281 composition represents a species (with regards to amount of active, monoglyceride, triglyceride, ethanol/benzyl alcohol; additional ingredient: surfactant present in an amount of about 0.5-5.0% w/w, wherein at least 90% of the active is released by about 150 hours) within the scope of the instantly claimed genus. It has been held that a generic invention is “anticipated” by a “species” within the scope of the generic invention. See In re Goodman, 29 USPQ2d 2010 (Fed. Cor. 1993). The other difference is that the ‘281 composition comprises a fluroquinolone or florfenicol active agent, whereas the instant invention requires the active to be cabotegravir or dolutegravir. However, it is found prima facie obvious to substitute one known active for another known active agent in a formulation in order to treat various diseases. Thus, the instant claims and the application claims are obvious variants.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GENEVIEVE S ALLEY whose telephone number is (571)270-1111. The examiner can normally be reached Monday-Friday 8:00-5:00.
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/GENEVIEVE S ALLEY/Primary Examiner, Art Unit 1617
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