+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 .
Claim Status
Applicants’ amendments and arguments filed 01/09/2026 have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.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.
Claims 5-16 remain withdrawn.
Claim 1 is amended.
Claims 1-4 are examined on the merits.
New Rejections Necessitated by Amendments
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 now recites “A method for enhancing the solubility of a pharmaceutical or nutraceutical active ingredient in water, the method comprising: adding a preparation comprising at least one polyunsaturated fatty acid salt comprising at least one omega-3 fatty acid selected from the group consisting of eicosatetraenoic acid (EPA) and docosahexaenoic acid (DHA) to the medium” which is unclear as to what defines “the medium” as claim makes no other mention of medium. For instance, is the medium the forementioned water or is it a different combination of components such as a combination of water and the pharmaceutical or nutraceutical active ingredient.
For the purpose of moving prosecution forward, the examiner broadly interprets medium to mean any solution of water and any additional ingredients to include a pharmaceutical and/or nutraceutical active ingredient.
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.
Claim 1 is rejected under 35 U.S.C. 103 as obvious over Mishra et al. (US6284268B1, published 09/04/2001, hereafter Mishra) as evidenced by Wikipedia (Aqueous solution. Wikipedia, the free encyclopedia. (2016, April 15). https://web.archive.org/web/20160415130924/https://en.wikipe dia.org/wiki/Aqueous_solution, via wayback machine, hereafter Wikipedia)
.
As evidenced by Wikipedia, an aqueous solution is a solution which the solvent is water (page 1, paragraph 1).
Regarding instant claim 1, Mishra claims a pharmaceutical composition containing an omega-3 fatty acid oil such as a fish oil and a poorly water soluble therapeutic agent (abstract and claim 1). Mishra teaches the solubility of a poorly water soluble drug was enhanced in oils containing a mixture of omega-3 fatty acid oils (column 4, lines 48-50). Mishra further claims the preferred omega-3 fatty acid oils as selected from a group to include eicosapentaenoic acid, docosahexaenoic acid, salts of eicosapentaenoic acid, salts of docosahexaenoic acid and mixtures thereof (claim 7). Mishra claims a self-emulsifying preconcentrate pharmaceutical composition capable of an emulsion in an aqueous solution that comprises a poorly water soluble therapeutic agent, wherein the agent is substantially soluble in the omega-3 fatty acid oil (claims 1 and 39). Lastly, Mishra provides multiple example formulations comprising the drug cyclosporin A (CyA) and various fish oil mixtures (see table 1, column 9) at concentrations of 100:37 mg to 100:550 mg CyA to fish oil (Columns 18-21, formulations 1-18).
Mishra does not teach with sufficient specificity to anticipate and so the claims are obvious. It would be obvious to one with ordinary skill in the art before the effective filing date to rearrange the teachings of Mishra with a reasonable expectation of success to obtain the method of the instant claims.
A reference is analyzed using its broadest teachings. MPEP 2123 [R-5]. “[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). “[W]hen 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 v. Teleflex, 127 S.Ct. 1727, 1741 (2007). The Court emphasized that “[a] person of ordinary skill is… a person of ordinary creativity, not an automaton.” Id. at 1742. A person of ordinary skill in the art who is not an automaton is capable of producing the method of the instant claims with predictable results.
Claims 2-3 are rejected under 35 U.S.C. 103 as obvious over Mishra et al. (US6284268B1, published 09/04/2001, hereafter Mishra) in view of Knaup et al. (WO2016102316A1, published 06/30/2016, hereafter Knaup) and evidenced by Wikipedia (Aqueous solution. Wikipedia, the free encyclopedia. (2016, April 15). https://web.archive.org/web/20160415130924/https://en.wikipe dia.org/wiki/Aqueous_solution, via wayback machine, hereafter Wikipedia).
As outlined above, Mishra teaches a method of enhancing solubility of a pharmaceutical in aqueous medium by combining a polyunsaturated fatty acid salt comprising omega-3 fatty acid selected from eicosapentaenoic acid and docosahexaenoic acid, with a pharmaceutical at a desired ratio.
Mishra fails to teach the addition of a counter ion as in instant claims 2 and 3.
Knaup claims a process for increasing the stability towards oxidation of a composition comprising polyunsaturated omega-6 fatty acids comprising the following steps: (i) providing a starting composition comprising at least one polyunsaturated omega-6 fatty acid component; (ii) providing a lysine composition; (iii) admixing aqueous, aqueous-alcoholic or alcoholic solutions of starting composition and lysine composition, and subjecting resulting admixture to spray drying conditions subsequently, thus forming a solid product composition comprising at least one salt of a cation derived from lysine with an anion derived from a polyunsaturated omega-6 fatty acid; the product composition exhibiting a solvent content SC selected from the following: SC < 5 wt%, SC < 3 wt%, SC < 1 wt%, SC < 0.5 wt%. Furthermore, Knaup teaches the use of such compositions for the manufacture of food, nutritional and pharmaceutical products are further comprised by the present invention (abstract). Knaup teaches that increased stability is achieved by the process of a salt formation between lysine and polyunsaturated fatty acid (PUFA) (page 3, lines 11-13). Furthermore, Knaup teaches omega-3, specifically eicosapentaenoic acid ("EPA") and docosahexaenoic acid ("DHA") to be PUFAs (page 2, lines 19-28). Lastly, Knaup claims the lysine composition in step (ii) is provided in such a manner that the ratio R = n(ca)/n(lys) of the amount of carboxylic acid functions n(ca) in the starting composition provided in step (i) and the amount of lysine n(lys) in the lysine composition provided in step (ii) is in a range selected from 0.9 < R < 1.1 , 0.95 < R < 1.05, 0.98 < R < 1.02 (claim 2).
It would be obvious to one skilled in the art before the effective filing date of the claimed invention to modify a method of enhancing solubility of a pharmaceutical in aqueous medium by combining a polyunsaturated fatty acid salt comprising omega-3 fatty acid selected from eicosapentaenoic acid and docosahexaenoic acid, with a pharmaceutical at a desired ratio as outlined by Mishra by addition of a counter ion, specifically lysine, at a desired ratio of omega-3 or 6 to counter ion as outlined by Knaup under TSM, see MPEP 2143(G). As outlined by Knaup, using a salt formation of a polyunsaturated fatty acid (PUFA) such as omega-3 in which the counter ion is lysine increasing the stability of a composition which would motivate someone skilled in the art to advantageously combine ammonium sulfate with the composition of Yu as it would have a reasonable expectation of success.
Claim 4 is rejected under 35 U.S.C. 103 as obvious over Mishra et al. (US6284268B1, published 09/04/2001, hereafter Mishra) in view of Dassinger et al (WO2017202942A1, published 11/30/2017, hereafter Dassinger), in view of Pharmaceutical Technology (Using Polymer Technology to Enhance Bioavailability. (2010). Pharmaceutical Technology, 2010(4), hereafter PT), as evidenced by Schwarz et al (Schwarz, W. (1990). Pvp: A Critical Review of the Kinetics and Toxicology of Polyvinylpyrrolidone (Povidone) (1st ed.). CRC Press. https://doi.org/10.1201/9780203741672, hereafter Schwarz), and as evidenced by Wikipedia (Aqueous solution. Wikipedia, the free encyclopedia. (2016, April 15). https://web.archive.org/web/20160415130924/https://en.wikipe dia.org/wiki/Aqueous_solution, via wayback machine, hereafter Wikipedia).
As outlined above, Mishra teaches a method of enhancing solubility of a pharmaceutical in aqueous medium by combining a polyunsaturated fatty acid salt comprising omega-3 fatty acid selected from eicosapentaenoic acid and docosahexaenoic acid, with a pharmaceutical at a desired ratio.
Mishra fails to teach the method further comprising an ionic polymer as in instant claim 4.
Dassinger claims a tablet comprising an omega-3 fatty acid amino acid salt that is characterized in that the omega-3 fatty is/are selected from eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and mixtures of the same (claims 1 and 2). Claim 5 of Dassinger further outlines the amino acid in the salt to be selected from lysine, arginine, ornithine and mixtures of the same. Dassinger teaches alkaline earth metal salts are practically water-insoluble which limits the bioavailability and mixtures or salts with amino acids are soluble and should therefore be readily bioavailable (page 4, lines 15-20). Dassinger further teaches that processing of omega-3 amino acid preparations to tablets is known and outlines the addition use of auxiliaries such at binders and structure-forming agents (page 2-3, lines 38-40 and 1-3 respectively). Furthermore, claim 1 of Dassinger claims the binder/structure-forming substance to be polyvinylpyrrolidone (PVP).
Both Mishra and Knaup fail to teach the addition of cationic (meth)acrylate.
PT teaches a list of several generally regarded as safe (GRAS) polymers that have been used in the pharmaceutical industry for decades (page 1, paragraph 1). Furthermore, PT teaches these polymers have been used to enhance solubility of active pharmaceutical ingredients (APIs) to increase bioavailability (page 1, paragraph 1). PT lists polymethacrylates as a type of enteric polymer stating that these polymers show faster disintegration properties than nonenteric polymers but the API dissolution of these solid-dispersions can be highly pH dependent, thereby affecting permeability and bioavailability (page 5, enteric polymers). Furthermore, PT teaches that polymethacrylates are commercially available for use as film forming agents, tablet binders, and tablet diluents (page 8, polymethacrylates). Lastly, PT teaches that povidone has been used for decades as a dissolution enhancer, suspending agent, and tablet binder (page 3, povidone).
One skilled in the art before the effective filing date of the claimed invention would claim a method of enhancing solubility of a pharmaceutical in aqueous medium by combining a polyunsaturated fatty acid salt comprising omega-3 fatty acid selected from eicosapentaenoic acid and docosahexaenoic acid, with a pharmaceutical at a desired ratio as outlined by Mishra with the ready for improvement with the known technique of adding a polymer binder to an omega-3 fatty acid salt composition as outlined by Dassinger and PT. Adding the forementioned components to the method of enhancing solubility as claimed by instant claim 4 would yield predictable results thus making them of obviousness as modification of a known product with a known technique is within the purview of the skilled artisan. Furthermore, one skilled in the art before the effective filing date of the claimed invention would claim a method of enhancing solubility of an active ingredient using omega-3 and a polymer binder as outlined by Mishra and Dassinger with the simple substitution of cationic methacrylate as the binder instead of povidone as outlined by PT. Simple substitution of one binder for another is within the purview of the skilled artisan and would yield predictable results. Therefore, claim 4 of the instant application would be of obviousness.
Response to Applicant’s Arguments
Applicant’s arguments filed in the response on 01/09/2026 have been fully considered.
In regards to the 35 USC § 103 rejections, Applicant first argues that Mishra never describes increasing the water solubility of the poorly water soluble drug. Applicant further argues the Mishra is directed towards the poorly water soluble drug is dissolved in the omega-3 fatty acid oil, and the oil mixture is emulsified in water in the presence of a surfactant system. Applicant then argues that Knaup never discloses or even suggests that the oxidation stabilized omega-6 PUFUs can increase the water solubility of pharmaceutical or nutraceutical active ingredient. Further, Applicant argues that Dassinger never discloses or suggests that the combination of an omega-3 PUFUs salt with a pharmaceutical or nutraceutical active ingredient. Applicant then argues that none of the references cited disclose or suggest that adding a preparation comprising at least one polyunsaturated fatty acid salt comprising at least one omega-3 fatty acid selected from the group consisting of eicosatetraenoic acid (EPA) and docosahexaenoic acid (DHA) to the medium comprising the pharmaceutical or nutraceutical active ingredient, enhances the solubility of the pharmaceutical or nutraceutical active ingredient in water by at least 100% in comparison to the pharmaceutical or nutraceutical active ingredient in water alone. In summary, Applicant argues that none of Mishra, Knaup, and Dassinger or any combination thereof make all the elements of Claim 1 known. Then Applicant argues that Pharmaceutical Technology does not cure this deficiency.
It is first noted that although the reference is silent “the solubility is enhanced by at least 100% in comparison to the pharmaceutical or nutraceutical active ingredient in the water” it does not appear that the claim language or limitations result in a manipulative difference in the method steps when compared to the prior art disclosure. See Bristol-Myers Squibb Company v. Ben Venue Laboratories, 58 USPQ2d 1508 (CAFC 2001). “It is a general rule that merely discovering and claiming a new benefit of an old process cannot render the process again patentable.” In re Woodruff, 16 USPQ2d 1934, 1936 (Fed. Cir. 1990). Granting a patent on the discovery of an unknown but inherent function would remove from the public that which is in the public domain by virtue of its inclusion in, or obviousness from, the prior art. /n re Baxter Travenol Labs, 21 USPQ2d 1281 (Fed. Cir. 1991). See M.P.E.P. 2145. On this record, it is reasonable to conclude that the same method of enhancing solubility of a pharmaceutical or nutraceutical active ingredient in water comprising a pharmaceutical or nutraceutical active ingredient, water, and a polyunsaturated fatty acid, in both the instant claims and the prior art reference. The fact that Applicant may have discovered yet another beneficial effect (i.e. enhancing by at least 100%) from the method set forth in the prior art does not mean that they are entitled to receive a patent on that method. Thus, the references teaches, either expressly or inherently, each and every limitation of the instant claims. Further, in regards to Applicant’s argument that Mishra is directed towards an emulsion, it is noted that Applicant’s instant claims are not directed towards a specific type of composition (i.e. emulsion), nor does Applicant claim the composition cannot be an emulsion. The MPEP 2111.03(III) states “applicant has the burden of showing that the introduction of additional steps or specific components which would materially change the characteristics of the claimed invention.” In summary, Applicants have failed to properly demonstrate how and which additional components, specifically the composition in the form of an emulsion, materially affect the basic and novel characteristics of the claimed method.
In regards to Applicants arguments against Knaup and Dassinger, specifically 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). Further, in regards to Mishra in view of Dassinger in view of Pharmaceutical Technology it is noted that Applicant has provided no reasoning as to why this combination does not teach the instant claim 4 other than the arguing against Mishra, Knaup, and Dassinger individually and then stating that Pharmaceutical Technology does not cure these deficiencies.
In summary, the examiner is not persuaded by Applicant’s arguments. Thus the rejections are maintained and updated for claim amendments.
Conclusion
No claims allowed.
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/Isis A Ghali/Primary Examiner, Art Unit 1611
/A.N.I./Examiner, Art Unit 1611