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 .
Priority
The instant application was filed 27 February 2023 and is the national stage entry of PCT/IN2021/050832 filed 27 August 2021. The Applicant claims priority to foreign application IN202041037143 filed 28 August 2020. An English translated copy of the foreign document has been provided. Therefore, the effective filing date of the instant application is 28 August 2020.
Examiner’s Note
The Applicant's amendments and arguments filed 03 June 2026 are acknowledged and have been fully considered. The Examiner has re-weighed all the evidence of record. Rejections
and/or objections not reiterated from previous office actions are hereby withdrawn. The
following rejections and/or objections are either reiterated or newly applied. They constitute the
complete set presently being applied to the instant application. In the Applicant’s response, filed
03 June 2026, it is noted that claims 1, 5, and 10 have been amended and no new claims have been added. Support for the amendments can be found in Table 4 of the specification. No new matter has been added.
Claim Rejections - 35 USC § 112
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.
Claim 1 is 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 has been amended to include spherical nanoparticles in addition to the calcium phosphate inorganic core and a trehalose layer, wherein the trehalose and calcium phosphate are interpreted as making up the aquasome formulation. It is unclear if the spherical nanoparticles are separate and in addition to the aquasome formulation or if the Applicant is describing the shape or structure of the aquasomes. The metes and bounds of the limitation cannot be determined.
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.
Claim(s) 1, 2, 5, 6, 10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Sharma (Aquasome: A Novel Drug Delivery Approach Using Nanocrystalline Biomaterial, Current Research in Pharmaceutical Sciences, 2012), Banerjee (Aquasomes: A novel nanoparticulate drug carrier, Journal of Drug Delivery Science and Technology, 2018), Malhotra (WO 2015/140569 A1), and McMillan et al. (Pharmacokinetics of a Long-Acting Nanoformulated Dolutegravir Prodrug in Rhesus Macaques, Antimicrob Agents Chemother., 2017).
Sharma teaches a composition and method for drug delivery using spherical aquasomes (abs; entire teaching; pg. 18), which are described as a type of nanoparticle or nanoparticulate system or the terms are used interchangeably (abs and pg. 5 of instant specification). The interchangeable use of aquasomes and nanoparticles is interpreted as addressing the spherical nanoparticle limitation of claim 1. The aquasomes may contain a calcium phosphate core (pg. 16) and trehalose as a coating for the core (pg. 19), partially addressing claim 1. Aquasomes have been used as a way of delivering therapeutics to treat Immune deficiency virus (pg. 20). Aquasomes have a particle size of 60-300 nm (pg. 18), addressing claim 2.
Applicant has amended claim 1 to include spherical nanoparticles, a uniform particle distribution, and a PDI of 0042 or less. This limitation in amended claim 1 is interpreted as providing structural context to the shape and size of the aquasome composition.
Sharma does not specifically teach the ratio or amounts of components in claims 1 and 6, zeta potential in claim 5, or dolutegravir or the PDI in claims 1 and 10.
Banerjee teaches that aquasomes may have a core to coating ratio of 1:4 or 1:5 (pg. 448). Drug loading also varies when loaded with different carbohydrates (pg. 448).
Malhotra teaches that Dolutegravir is used to treat HIV infections (pg. 3) and is particularly useful in a nanoparticulate system for improved surface area, solubility, and bioavailability (pg. 4). The amount of Dolutegravir may be 26.3 mg (Example 1) or 50-100 mg (pg. 9). The dolutegravir is described as adsorbed onto the nanoparticles (pg. 18, para. 3).
In regards to selecting the combination of calcium phosphate and trehalose, “[w]hen a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect from such an arrangement, the combination is obvious.” KSR v. Teleflex, 127 S.Ct. 1727, 1740 (2007) (quoting Sakraida v. A.G.Pro, 425 U.S. 273, 282 (1976)). “When the question is whether a patent claiming the combination of elements of prior art is obvious,” the relevant question is “whether the improvement is more than the predictable use of prior art elements according to their established functions.” (Id.). Addressing the issue of obviousness, the Supreme Court noted that the analysis under 35 USC 103 “need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ.” KSR at 1741. The Court emphasized that “[a] person of ordinary skill is… a person of ordinary creativity, not an automaton.” Id. at 1742.
Consistent with this reasoning, it would have been obvious to have selected various combinations of various disclosed ingredients from within a prior art disclosure, to arrive at compositions “yielding no more than one would expect from such an arrangement.”
Sharma teaches compositions and methods for making aquasomes with trehalose and calcium phosphate as components, whereas the claimed invention is directed towards a composition comprising calcium phosphate, trehalose, and Dolutegravir. Since Sharma teaches the individual components of the claimed composition, it is obvious for one of ordinary skill in the art to select the different combinations of ingredients to arrive at the claimed invention with a reasonable expectation of success.
Since Sharma does not specifically teach Dolutegravir in claim 1, one of ordinary skill in the art would have been motivated to use Malhotra’s teaching of using Dolutegravir with a reasonable expectation of success. Malhotra teaches Dolutegravir in a nanoparticulate system, which helps to improve solubility, bioavailability, and surface area. A skilled artisan would have recognized the added benefit of using Dolutegravir in aquasomes, which is also described as a nanoparticulate system (pg. 1, ln. 11 of instant specification), to improve the solubility, bioavailability, and surface area, especially if the intended purpose of the skilled artisan is to treat HIV.
In regards to claim 10, antiviral activity against HSV cells is interpreted as an inherent property of Dolutegravir. It is noted that “products of identical chemical composition cannot have mutually exclusive properties.” 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. In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990) (see MPEP 2112.01 (II)). The U.S. Patent Office is not equipped with analytical instruments to test prior art compositions for the infinite number of ways that a subsequent applicant may present previously unmeasured characteristics. When as here, the prior art appears to contain the exact same ingredients and applicant's own disclosure supports the suitability of the prior art composition as the inventive composition component, the burden is properly shifted to applicant to show otherwise.
In regards to the ratio and amounts of components in claims 1 and 6, as well as the zeta potential in claim 5, and the PDI in claim 1, Banerjee teaches that aquasomes may have a core to coating ratio of 1:4 or 1:5 (pg. 448) and that, in general, drug loading varies when loaded with different carbohydrates (pg. 448). McMillan teaches nanoparticles comprising dolutegravir with a zeta potential of -18.9 to -22.3 mV (pg. 2) and a narrow (also interpreted as uniform) PDI of 0.20 to 0.25 (pg. 2). Additionally, Malhotra teaches that the amount of Dolutegravir may be 26.3 mg (Example 1) or 50-100 mg (pg. 9) in their nanoparticulate drug delivery system. That being said and in lieu of objective evidence of unexpected results, the ratios, zeta potential, and amounts can be viewed as a variable that achieves the recognized result of successfully making the aquasome composition, which a skilled artisan would have been easily motivated to modify and adjust. The optimum or workable range of amounts, zeta potential, and ratios can be accordingly characterized as routine optimization and experimentation (see MPEP 2144.05 (II)B). “[Discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art.” In re Boesch, 617 F.2d 272, 276 (CCPA 1980). Applicants provide no evidence of any secondary consideration, such as unexpected results, that would render the optimized ratios, zeta potential, and amounts of components as nonobvious.
The adjustment of particular conventional working conditions (e.g., determining result effective amounts of the ingredients beneficially taught by the cited references, especially within the broad ranges instantly claimed), is deemed merely a matter of judicious selection and routine optimization which is well within the purview of the skilled artisan. “[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). Accordingly, this type of modification would have been well within the purview of the skilled artisan and no more than an effort to optimize results.
Response to Arguments
Applicant's arguments filed 03 June 2026 have been fully considered but they are not persuasive.
The Applicant argues that Sharma does not disclose the limitations recited in instant claim 1 (Remarks, pg. 7).
Applicant’s argument is not found persuasive. Sharma teaches a composition and method for drug delivery using spherical aquasomes (abs; entire teaching; pg. 18), which are described as a type of nanoparticle or nanoparticulate system or the terms are used interchangeably (abs and pg. 5 of instant specification). The interchangeable use of aquasomes and nanoparticles is interpreted as addressing the spherical nanoparticle limitation of claim 1. The aquasomes may contain a calcium phosphate core (pg. 16) and trehalose as a coating for the core (pg. 19).
The Applicant argues that Sharma does not disclose the ratio recited in the claims (Remarks, pg. 7).
Applicant’s argument is not found persuasive. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In regards to the ratio Banerjee teaches that aquasomes may have a core to coating ratio of 1:4 or 1:5 (pg. 448) and that in general, drug loading varies when loaded with different carbohydrates (pg. 448).
The Applicant argues that Sharma does not disclose the recited PDI (Remarks, pg. 7).
Applicant’s argument is not found persuasive. McMillan teaches nanoparticles comprising dolutegravir with a narrow (also interpreted as uniform) PDI of 0.20 to 0.25 (pg. 2). The adjustment of particular conventional working conditions (e.g., determining result effective amounts of the ingredients beneficially taught by the cited references, especially within the broad ranges instantly claimed), is deemed merely a matter of judicious selection and routine optimization which is well within the purview of the skilled artisan. “[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). Accordingly, this type of modification would have been well within the purview of the skilled artisan and no more than an effort to optimize results.
The Applicant argues that Banerjee, Malhotra, and McMillan do not individually address the limitations recited in claim 1 (Remarks, pgs. 7-8).
Applicant’s argument is not found persuasive. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Malhotra teaches Dolutegravir in a nanoparticulate system, which helps to improve solubility, bioavailability, and surface area. A skilled artisan would have recognized the added benefit of using Dolutegravir in aquasomes, which is also described as a nanoparticulate system (pg. 1, ln. 11 of instant specification), to improve the solubility, bioavailability, and surface area, especially if the intended purpose of the skilled artisan is to treat HIV. Furthermore, Banerjee teaches that aquasomes may have a core to coating ratio of 1:4 or 1:5 (pg. 448) and that in general, drug loading varies when loaded with different carbohydrates (pg. 448). McMillan teaches nanoparticles comprising dolutegravir with a zeta potential of -18.9 to -22.3 mV (pg. 2) and a narrow (also interpreted as uniform) PDI of 0.20 to 0.25 (pg. 2). Additionally, Malhotra teaches that the amount of Dolutegravir may be 26.3 mg (Example 1) or 50-100 mg (pg. 9) in their nanoparticulate drug delivery system. That being said and in lieu of objective evidence of unexpected results, the ratios, zeta potential, and amounts can be viewed as a variable that achieves the recognized result of successfully making the aquasome composition, which a skilled artisan would have been easily motivated to modify and adjust. The optimum or workable range of amounts, zeta potential, and ratios can be accordingly characterized as routine optimization and experimentation (see MPEP 2144.05 (II)B).
The Applicant argues that the cited references do not teach the claimed aquasome architecture recited in claim 1 (Remarks, pgs. 8-9).
Applicant’s argument is not found persuasive. Sharma teaches a composition and method for drug delivery using spherical aquasomes (abs; entire teaching; pg. 18), which are described as a type of nanoparticle or nanoparticulate system or the terms are used interchangeably (abs and pg. 5 of instant specification). The interchangeable use of aquasomes and nanoparticles is interpreted as addressing the spherical nanoparticle limitation of claim 1. The aquasomes may contain a calcium phosphate core (pg. 16) and trehalose as a coating for the core (pg. 19), partially addressing claim 1. Malhotra teaches that Dolutegravir is used to treat HIV infections (pg. 3) and is particularly useful in a nanoparticulate system for improved surface area, solubility, and bioavailability (pg. 4). The dolutegravir is described as adsorbed onto the nanoparticles (pg. 18, para. 3). Since Sharma does not specifically teach Dolutegravir in claim 1, one of ordinary skill in the art would have been motivated to use Malhotra’s teaching of using Dolutegravir with a reasonable expectation of success. Malhotra teaches Dolutegravir in a nanoparticulate system, which helps to improve solubility, bioavailability, and surface area. A skilled artisan would have recognized the added benefit of using Dolutegravir in aquasomes, which is also described as a nanoparticulate system (pg. 1, ln. 11 of instant specification), to improve the solubility, bioavailability, and surface area, especially if the intended purpose of the skilled artisan is to treat HIV.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/D.A.K./Examiner, Art Unit 1613
/ANDREW S ROSENTHAL/Primary Examiner, Art Unit 1613
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