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
This Office Action is responsive to Applicant’s Amendment and Remarks, filed June 9, 2026. The amendment, filed June 9, 2026, is acknowledged, wherein claims 30 – 39 are new and claims 2 – 7, 9 – 12, and 14 – 22 are canceled.
Claims 1, 8, 13, and 23 – 39 are pending in this application and are currently examined.
Receipt is acknowledged of Declaration of Rosario Lizio filed on June 9, 2026.
Priority
This application is a national stage application of PCT/EP2021/057615, filed March 24, 2021, which claims benefit of foreign priority document EP20167493.4, filed April 1, 2020.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Withdrawn Rejections
Claims 1, 13, 23, and 25 – 28 are rejected in the previous Office Action, dated March 20, 2026, on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 2, 7 – 8, and 13 – 23 of copending Application No. 17/907,645 in view of Bell with evidence provided by EMA, and Engler. As terminal disclaimer is filed on June 9, 2026 and is approved on June 15, 2026, the rejection has been withdrawn.
Claims 8, 24, and 29 are rejected in the previous Office Action, dated March 20, 2026, on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 2, 7 – 8, and 13 – 23 of copending Application No. 17/907,645 in view of Thilavech et al. and Engler. As terminal disclaimer is filed on June 9, 2026 and is approved on June 15, 2026, the rejection has been withdrawn.
The following are maintained / new grounds of rejection necessitated by Applicant’s Amendment, filed June 9, 2026, wherein claims 30 – 39 are new and claims 2 – 7, 9 – 12, and 14 – 22 are canceled. Previously cited references have been used to establish the maintained / new grounds of rejection.
New Claim Objections
Claim 30 is objected to under 37 CFR 1.75 as being a substantial duplicate of claim 28. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim 34 is objected to because of the following informalities:
Claim 34, line 2, “,” should be inserted immediately before and after “optionally”.
Claim 34, line 2, “further” should be removed.
Appropriate correction is required.
New 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 23 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 23 recites the limitation "the (i)/(ii) weight ratio" in line 1. Claim 23 depends from claim 1 and claim 1 never recites “(i)/(ii) weight ratio”. Therefore, claim 23 lacks sufficient antecedence to an earlier claim.
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 36 – 37 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.
Regarding claims 36 – 37, claim 36 is drawn to the method of claim 1 and further recites that “the anthocyanin component and the omega-3 lysine complex are present, together, in a range of from 50 – 150 μg/L”. Claim 37 recites the corresponding limitation with respect to the method of claim 8.
The originally filed disclosure does not contemplate the anthocyanin component and the omega-3 lysine complex being present together at a concentration of 50 to 250 μg/L. Instead, Example 3 of the specification describes the vasorelaxant effect of AvailOm® in combination with the recited anthocyanins at 50, 100, and 150 μg/mL (page 12 – 13). The description of Figure 4 refers to increasing doses of AvailOm® in the μg/mL concentration range, including concentrations of 50 to 150 μg/mL.
The disclosed concentration of 50 to 150 μg/mL is not the same as the presently claimed concentration of 50 to 150 μg/mL. Specifically, 50 to 150 μg/mL corresponds to 50,000 to 150,000 μg/L, which is 1,000-fold greater than the concentration presently recited in claims 36 and 37. Thus, the disclosure of the μg/mL concentrations does not describe or encompass the presently claimed 50 to 150 μg/L range.
The originally filed disclosure therefore does not demonstrate or reasonably convey that the inventors were in possession of a composition in which the anthocyanin component and the omega-3 lysine complex are present together at 50 to 150 μg/L. Accordingly, the subject matter presently recited in claims 36 – 37 is not supported by the originally filed disclosure and does not satisfy the written description requirement of 35 U.S.C. 112(a).
Applicant identifies, inter alia, Figure 4 and the corresponding portions of the specification as support for the newly added claims. However, those portions disclose concentrations in μg/mL, rather than μg/L. Accordingly, the portions identified by Applicant do not provide written description support for the concentration range presently recited in claims 36 – 37.
New 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 factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
i. Determining the scope and contents of the prior art.
ii. Ascertaining the differences between the prior art and the claims at issue.
iii. Resolving the level of ordinary skill in the pertinent art.
iv. 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, 13, 23, 25 – 28, 30, and 32 are rejected under 35 U.S.C. 103 as being unpatentable over NBR (Nutraceutical Business Review, 2018, cited in the PTO-892 on March 20, 2026) in view of Bell (Journal of Applied Physiology, 2006, Vol. 100, Issue 4, page 1164 – 1170, cited in the PTO-892 on March 20, 2026), with evidence provided by EMA (ema.europa.eu, 2015, cited in the PTO-892 on March 20, 2026), Engler (Annals of Nursing and Practice, 2017, Vol. 4, Issue 1, page 1 – 9, cited in the PTO-892 on March 20, 2026), and De Lorgeril et al. (US2012/0202778A1).
NBR teaches that omega-3 fatty acids confer a protective effect by reducing plasma triglycerides, blood pressure and inflammation, all of which are risk factors for atherosclerosis (page 2, para. 2). NBR teaches AvailOm is a highly purified omega-3 product containing high levels of EPA and DHA presented as a complex between the omega-3 free fatty acids and the natural amino acid lysine. This product is in the form of a powder that has superior stability compared with the ethyl ester and the free fatty acid forms and has a higher bioavailability compared with other commercial forms of omega-3 (page 3, para. 3 – 4 and 6). NBR teaches that the minimum concentration of EPA and DHA in AvailOm is 45% (page 4, para. 5). Thus, NBR teaches a method of reducing atherosclerosis comprising administering a complex comprising lysine salt of EPA and DHA, wherein the minimum concentration of EPA and DHA is 45%, which reads on the limitations “omega-3 lysine complex”, “lysine salt of eicosapentaenoic acid and docosahexaenoic acid”, “40 to 65 wt.%”, and “atherosclerosis of claims 1 and 26 – 27. Moreover, atherosclerosis is a cardiovascular disease; therefore, the teaching reads on the limitation “cardiovascular disease” of claim 13.
However, NBR does not disclose administering the composition comprising cyanidin-3-galactoside with a weight ratio of polyunsaturated fatty acid component to the anthocyanin component in a range of from 1:1 to 1:6 and NBR does not explicitly teach the composition will induce vasorelaxation.
Bell teaches that chokeberry (Aronia melanocarpa) contains four different anthocyanins with ~90% of its Ta content due to cyanidin-3-galactoside and cyanidin-3-arabinoside (page 1165, Left Col., para. 1). Thus, Bell teaches chokeberry contains cyanidin-3-galactoside, which corresponds to “cyanidin-3-galactoside” of claim 1. Chokeberry and Bilberry extracts produce dose-dependent vasorelaxation in isolated rings with endothelium. Response to chokeberry extract product the greatest degree of relaxation (page 1167, Right Col., para. 3). Bell teaches that chokeberry produce % maximal relaxation at 5 mg total anthocyanins per liter (Abstract). According to EMA, bilberry contains 15.3% delphinidin-3-arabinoside, which is the highest among all anthocyanins (page 5 – 6, Table 1). Thus, EMA supports that bilberry contains delphinidin-3-arabinoside, which corresponds to the limitation of claim 25.
Engler teaches that both EPA and DHA exert vasorelaxant effects in isolated arteries (page 5, Left Col., para. 4).
De Lorgeril et al. teach compositions comprising at least one omega-3 fatty acid in combination with at least one polyphenol for administration to a human or animal as a food, health-diet, or pharmaceutical composition (Abstract; para. [0001]; para. [0008]). De Lorgeril et al. identify omega-3 fatty acids as including EPA and DHA (para. [0020]) and teach that the polyphenol may preferably be an anthocyanin, including cyanidin and delphinidin (para. [0010 – 0011]). De Lorgeril et al. further demonstrate the combined administration of EPA and DHA with anthocyanins and report that n-3 levels and the n-3:n-6 ratio increased in animals receiving the EPA+DHA+anthocyanin combination, with EPA and DHA levels increasing by 24% and 16%, respectively (para. [0038]; para. [0044]). De Lorgeril et al. teach compositions comprising from 1 to 99% by weight of an omega-3 fatty acid and from 99 to 1% by weight of at least one polyphenol (para. [0031]), and further teach embodiments wherein the omega-3 fatty acid and polyphenol components are each present in amounts between 10 and 90%, preferably between 20 and 80%, and more preferably between 30 and 70% by weight of the total composition (para. [0032 – 0033]). De Lorgeril et al. therefore teach formulation omega-3 fatty acid and polyphenol components, including anthocyanins, over broad relative weight proportions, including approximately equal amounts and amounts in which polyphenol component exceeds the omega-3 component.
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the AvailOm as taught by NBR with cyanidin-3-galactoside in view of Bell and Engler because both omega-3 fatty acids (EPA and DHA) and anthocyanins are known to induce vasorelaxation. It would have been obvious for one of ordinary skill in the art to do this because both AvailOm and chokeberry containing high amount of cyanidin-3-galactoside are known separately in the prior art for the purpose of vasorelaxation, and it would have been obvious to combine them for the same purpose. One would have been motivated to administer AvailOm rather than individual EPA and DHA because AvailOm offers superior bioavailability and stability. Moreover, Bell teaches that anthocyanin-rich berry extract exhibit vasorelaxation and further teaches that such vascular activity is associated with the anthocyanin content of the extract. EMA teaches that bilberry contains delphinidin-3-arabinoside as a known and major anthocyanin constituent. It would have been obvious to one of ordinary skill in the art to combine AvailOm and cyanidin-3-galactoside with delphinidin-3-arabinoside in the composition because delphinidin-3-arabinoside is a known anthocyanin from a berry source already taught in the art to provide vasorelaxation benefit. Therefore, one of ordinary skill in the art would have had a reasonable expectation of success to combine the AvailOm as taught by NBR with cyanidin-3-galactoside and delphinidin-3-arabinoside in view of Bell and Engler because it is well known to combine drugs for the same purpose to produce predictable effects.
Regarding the weight ratio of the polyunsaturated fatty acid component to the anthocyanin component recited in claims 1 and 23, NBR discloses the minimal concentration of EPA/DHA in AvailOm and Bell teaches the amount of total anthocyanins per liter for %maximal relaxation. De Lorgeril et al. further teach compositions comprising an omega-3 fatty acid in combination with at least one polyphenol, wherein the omega-3 fatty acid may be a mixture of EPA and DHA and polyphenol may be anthocyanin, and teach varying the relative amounts of the omega-3 fatty acid and polyphenol components over broad weigh ranges. Specifically, De Lorgeril et al. teach compositions comprising 1 – 99 wt.% omega-3 fatty acid and 99 – 1 wt.% polyphenol. Thus, De Lorgeril et al. establish that the relative amounts of an omega-3 fatty acid component and a polyphenol component, including an anthocyanin, are known formulation parameters and encompass relative amounts in which the components are present in equal amounts or the polyphenol component is present in excess of the omega-3 component. In view of NBR’s teaching of an EPA/DHA-containing composition and Bell’s teaching of the concentration-dependent vasorelaxant activity of anthocyanins, Bell would have provided one of ordinary skill in the art seeking a vasorelaxant composition with a reason to vary the amount of the anthocyanin component to obtain the desired vasorelaxant response. Having been motivated by NBR, Bell, and Engler to combine the EPA/DHA-containing AvailOm with an anthocyanin component for the known vascular or vasorelaxant activities, one of ordinary skill in the art would have had reason to look to De Lorgeril et al. for guidance regarding suitable relative amounts because De Lorgeril et al. teach formulating omega-3 fatty acids together with polyphenols, including anthocyanins, and disclose relative proportions for those components when combined. Accordingly, one of ordinary skill in the art would have had reason to select an anthocyanin amount sufficient to provide the concentration-dependent vasorelaxant activity taught by Bell while selecting the relative amounts of the omega-3 fatty acid and anthocyanin components from the formulation proportions taught by De Lorgeril et al., with a reasonable expectation that the resulting composition would retain the known vascular activities of the components. The claimed PUFA-to-anthocyanin weight ratio of 1:1 to 1:6, including the 1:1 ratio of claim 23, represents relative proportions encompassed by the known formulation ranges and would have been within the ordinary formulation choices available to one of ordinary skill in the art.
Regarding the amount of polyunsaturated fatty acid component recited in claims 1 and 26 – 27, NBR teaches that AvailOm contains a minimum concentration of EPA and DHA of 45 wt.%. Claim 26 requires that the polyunsaturated fatty acid component be present in a range of 40 to 60 wt.%, and claim 27 requires that the polyunsaturated fatty acid component be present in a range of 40 to 55 wt.%. The 45 wt.% EPA/DHA concentration taught by NBR falls within each of the recited ranges. Accordingly, the additional limitations of claims 26 – 27 are disclosed by NBR.
Regarding claims 28 and 30, NBR teaches that AvailOm contains a minimum concentration of EPA and DHA of 45 wt.%, thereby teaching an EPA/DHA concentration of at least 45 wt.%. The claimed range of 58 to 65 wt.% therefore falls within the broader concentration range taught by NBR. Accordingly, selection of an EPA/DHA concentration within the claimed 58 to 65 wt.% range would have been prima facie obvious in the absence of evidence establishing criticality or unexpected results associated with that particular range.
Regarding claim 32, NBR teaches that AvailOm contains a minimum concentration of 45 wt.% EPA and DHA. As discussed above with respect to claim 1, Bell teaches the use of an anthocyanin-containing component for providing vasorelaxation, and it would have been obvious to combine the AvailOm of NBR with the anthocyanin component of Bell in the claimed relative amounts, including a 1:1 weight ratio of the polyunsaturated fatty acid component to the anthocyanin component. When the 45 wt.% EPA/DHA component taught by NBR is combined with the anthocyanin component at a 1:1 weight ratio, the anthocyanin component is present at 45 wt.% of the total composition. Thus, the resulting composition necessarily contains greater than the at least 25 wt.% anthocyanin required by claim 32. Accordingly, the additional limitation of claim 32 would have been satisfied by the obvious combination of NBR and Bell for the reasons set forth above with respect to claim 1.
Claims 8, 24, 29, 31, 33, 35, and 39 are rejected under 35 U.S.C. 103 as being unpatentable over NBR (Nutraceutical Business Review, 2018, cited in the PTO-892 on March 20, 2026) in view of Thilavech et al. (Biomedicine & Pharmacotherapy, 2017, Vol. 95, Issue 2017, page 1251 – 1259, cited in the PTO-892 on March 20, 2026), Engler (Annals of Nursing and Practice, 2017, Vol. 4, Issue 1, page 1 – 9, cited in the PTO-892 on March 20, 2026) , and De Lorgeril et al. (US2012/0202778A1).
NBR teaches that omega-3 fatty acids confer a protective effect by reducing plasma triglycerides, blood pressure and inflammation, all of which are risk factors for atherosclerosis (page 2, para. 2). NBR teaches AvailOm is a highly purified omega-3 product containing high levels of EPA and DHA presented as a complex between the omega-3 free fatty acids and the natural amino acid lysine. This product is in the form of a powder that has superior stability compared with the ethyl ester and the free fatty acid forms and has a higher bioavailability compared with other commercial forms of omega-3 (page 3, para. 3 – 4 and 6). NBR teaches that the minimum concentration of EPA and DHA in AvailOm is 45% (page 4, para. 5). Thus, NBR teaches a method of reducing atherosclerosis comprising administering a complex comprising lysine salt of EPA and DHA, wherein the minimum concentration of EPA and DHA is 45%, which reads on the limitations “omega-3 lysine complex”, “lysine salt of eicosapentaenoic acid and docosahexaenoic acid”, and “atherosclerosis of claims 8 and 29. Moreover, atherosclerosis is a cardiovascular disease; therefore, the teaching reads on the limitation “cardiovascular disease” of claim 29.
However, NBR does not disclose administering the composition comprising cyanidin-3-rutinoside with a weight ratio of the lysine salt of the EPA and DHA to the cyanidin-3-rutinoside in a range of from 1:1 to 1:6 and NBR does not explicitly teach the composition will induce vasorelaxation.
Thilavech et al. teach that cyanidin-3-rutinoside induce vasorelaxation in aortic rings with the EC50 of 2.43±0.57 for 92% maximum relaxation (Abstract).
Engler teaches that both EPA and DHA exert vasorelaxant effects in isolated arteries (page 5, Left Col., para. 4).
De Lorgeril et al. teach compositions comprising at least one omega-3 fatty acid in combination with at least one polyphenol for administration to a human or animal as a food, health-diet, or pharmaceutical composition (Abstract; para. [0001]; para. [0008]). De Lorgeril et al. identify omega-3 fatty acids as including EPA and DHA (para. [0020]) and teach that the polyphenol may preferably be an anthocyanin, including cyanidin and delphinidin (para. [0010 – 0011]). De Lorgeril et al. further demonstrate the combined administration of EPA and DHA with anthocyanins and report that n-3 levels and the n-3:n-6 ratio increased in animals receiving the EPA+DHA+anthocyanin combination, with EPA and DHA levels increasing by 24% and 16%, respectively (para. [0038]; para. [0044]). De Lorgeril et al. teach compositions comprising from 1 to 99% by weight of an omega-3 fatty acid and from 99 to 1% by weight of at least one polyphenol (para. [0031]), and further teach embodiments wherein the omega-3 fatty acid and polyphenol components are each present in amounts between 10 and 90%, preferably between 20 and 80%, and more preferably between 30 and 70% by weight of the total composition (para. [0032 – 0033]). De Lorgeril et al. therefore teach formulation omega-3 fatty acid and polyphenol components, including anthocyanins, over broad relative weight proportions, including approximately equal amounts and amounts in which polyphenol component exceeds the omega-3 component.
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the AvailOm as taught by NBR with cyanidin-3-rutinoside in view of Thilavech et al. and Engler because both omega-3 fatty acids (EPA and DHA) and anthocyanins are known to induce vasorelaxation. It would have been obvious for one of ordinary skill in the art to do this because both AvailOm and cyanidin-3-rutinoside are known separately in the prior art for the purpose of vasorelaxation, and it would have been obvious to combine them for the same purpose. One would have been motivated to administer AvailOm rather than individual EPA and DHA because AvailOm offers superior bioavailability and stability. For the weight ratio of the lysine salt of the EPA and DHA to the cyanidin-3-rutinoside, NBR discloses the minimal concentration of EPA/DHA in AvailOm and Thilavech et al. teach the amount of EC50 for maximum relaxation. Based on this disclosure, one would have performed routine experimentation to discover the best weight ratio for optimal treatment characteristics. Therefore, one of ordinary skill in the art would have had a reasonable expectation of success to combine the AvailOm as taught by NBR with cyanidin-3-rutinoside in view of Thilavech et al. and Engler because it is well known to combine drugs for the same purpose to produce predictable effects.
Regarding the weight ratio of the polyunsaturated fatty acid component to the anthocyanin component recited in claims 8 and 24, NBR teaches AvailOm comprising lysine salt of EPA and DHA and teaches a minimum concentration of EPA and DHA of 45%. Thilavech et al. teach that cyanidin-3-rutinoside induces vasorelaxation in a concentration-dependent manner, including an EC50 of 2.43 ± 0.57 with 92% maximum relaxation, while Engler teaches that EPA and DHA exert vasorelaxant effects. De Lorgeril et al. further teach compositions comprising an omega-3 fatty acid in combination with at least one polyphenol, wherein the omega-3 fatty acid may be a mixture of EPA and DHA and polyphenol may be anthocyanin, and teach varying the relative amounts of the omega-3 fatty acid and polyphenol components over broad weigh ranges. Specifically, De Lorgeril et al. teach compositions comprising 1 – 99 wt.% omega-3 fatty acid and 99 – 1 wt.% polyphenol and further teach embodiments wherein the omega-3 fatty acid and polyphenol are each present at 10 – 90 wt.%, preferably 20 – 80 wt.%, and more preferably 30 – 70 wt.% of the total composition. Thus, De Lorgeril establish that the relative amounts of an omega-3 fatty acid component and a polyphenol component, including an anthocyanin, are known formulation parameters and encompass relative amounts in which the components are present in equal amounts or the polyphenol component is present in excess of the omega-3 component. In view of NBR’s teaching of an EPA/DHA-containing composition and Bell’s teaching of the concentration-dependent vasorelaxant activity of anthocyanins, it would have been obvious for one of ordinary skill in the art to formulate the known EPA/DHA and anthocyanin components in relative amounts within the ranges taught by De Lorgeril et al.. to provide an effective vasorelaxant composition. The claimed PUFA-to-anthocyanin weight ratio of 1:1 to 1:6, including the 1:1 ratio of claim 23, represents relative proportions encompassed by the known formulation ranges and would have been within the ordinary formulation choices available to one of ordinary skill in the art.
Regarding claims 31, NBR teaches that AvailOm contains a minimum concentration of EPA and DHA of 45 wt.%, thereby teaching an EPA/DHA concentration of at least 45 wt.%. The claimed range of 58 to 65 wt.% therefore falls within the broader concentration range taught by NBR. Accordingly, selection of an EPA/DHA concentration within the claimed 58 to 65 wt.% range would have been prima facie obvious in the absence of evidence establishing criticality or unexpected results associated with that particular range.
Regarding claims 33 and 39, NBR teaches that AvailOm contains a minimum concentration of 45 wt.% EPA and DHA. As discussed above with respect to claim 8, Thilavech et al. teach that cyanidin-3-rutinoside induces vasorelaxation, and Engler teaches that EPA and DHA exert vasorelaxant effects. Accordingly, one of ordinary skill in the art would have been motivated to combine the AvailOm composition of NBR with cyanidin-3-rutinoside for the known amounts within the 1:1 to 1:6 weight ratio range recited in claim 8. At the 1:1 endpoint of the recited range, the cyanidi-3-rutinoside component is present in an amount equal by weight to the EPA/DHA lysine salt component. Because NBR teaches an AvailOm composition containing at least 45 wt.% EPA and DHA, use of the components at the 1:1 relative proportion would result in the cyanidin-3-rutinoside component being present at an amount greater than the 25 wt.% minimum required by claim 33. Thus, the additional limitation of claims 33 and 39 would have been satisfied by an obvious embodiment of the combination of NBR, Thilavech et al., and Engler.
Claims 34 and 38 are rejected under 35 U.S.C. 103 as being unpatentable over NBR (Nutraceutical Business Review, 2018, cited in the PTO-892 on March 20, 2026) in view of Bell (Journal of Applied Physiology, 2006, Vol. 100, Issue 4, page 1164 – 1170, cited in the PTO-892 on March 20, 2026), with evidence provided by EMA (ema.europa.eu, 2015, cited in the PTO-892 on March 20, 2026), Engler (Annals of Nursing and Practice, 2017, Vol. 4, Issue 1, page 1 – 9, cited in the PTO-892 on March 20, 2026), and , and De Lorgeril et al. (US2012/0202778A1) as applied to claims 1, 13, 23, 25 – 28, 30, and 32 above, and further in view of Ostberg-Potthoff et al. (Nutrients, 2019, Vol. 11, Issue 5, PTO-892).
NBR, Bell, and Engler teaches the limitations discussed above.
However, NBR, Bell, and Engler do not explicitly teach that the anthocyanin component consists of cyanidin-3-galactoside, as additionally required by claims 34 and 38.
Ostberg-Potthoff et al. teach that cyanidin-3-galactoside is the main anthocyanin of Aronia melanocarpa. Ostberg-Potthoff et al. further teach fractionation of the Aronia anthocyanin fraction by high-performance countercurrent chromatography and report that cyanidin-3-galactoside is enriched in an anthocyanin-containing fraction and isolated from another fraction at about 95% purity (page 13, para. 1). Thus, Ostberg-Potthoff et al. teach that cyanidin-3-galactoside, rather than merely being on unidentified constituent of a heterogeneous berry extract, is a principal Aronia anthocyanin that may be separated and obtained in substantially purified form.
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to further modify the anthocyanin-containing chokeberry composition taught by Bell by selecting and isolating cyanidin-3-galactoside as the anthocyanin component in view of Ostberg-Potthoff et al. because Bell explicitly identifies the chokeberry used in its vasoactive studies as Aronia melanocarpa and teaches that approximately 90% of the total anthocyanin content of the chokeberry extract is attributable to cyanidin-3-galactoside and cyanidin-3-arabinoside. Thus, Bell identifies cyanidin-3-galactoside as one of the principal anthocyanins present in the vasoactive Aronia melanocarpa extract. Ostberg-Potthoff et al. concern the same botanical source, Aronia melanocarpa, and further teach that cyanidin-3-galactoside is the main anthocyanin of that source and may be separated from the Aronia anthocyanin fraction and isolated at about 95% purity by HPCCC. Accordingly, one of ordinary skill in the art would have had reason to isolate and use cyanidin-3-galactoside from the vasoactive Aronia melanocarpa anthocyanin mixture of Bell to provide a defined anthocyanin component consisting of cyanidin-3-galactoside, with a reasonable expectation of success because Ostberg-Potthoff et al. explicitly demonstrate successful isolation of cyanidin-3-galactoside from the same botanical source.
Regarding claim 38, the claim further requires that the anthocyanin component be at least 25 wt.% of the total composition weight. Claim 38 depends from claim 1, which requires the polyunsaturated fatty acid component to be present in an amount of from 40 to 65 wt.% based on the total composition weight and further requires a weight ratio of the polyunsaturated fatty acid component to the anthocyanin component of from 1:1 to 1:6. At the 1:1 endpoint, which represents the lowest relative amount of anthocyanin within the recited ratio range, the amount of anthocyanin is equal by weight to the polyunsaturated fatty acid component. Because the polyunsaturated fatty component is required to be present at no less than 40 wt.% of the total composition, the anthocyanin component is necessarily present at no less than 40 wt.% of the total composition. Accordingly, the requirement of claim 38 that the anthocyanin component be present at least 25 wt.% is necessarily satisfied by any composition meeting the quantitative limitations of claim 1.
Responses to Applicant’s Remarks:
Applicant’s Remarks and the Declaration, filed June 9, 2026, have been considered and are found to be not persuasive.
Applicant states that the reference cited by the Office are cumulative of the art already of record and argues that the Office Action merely presumes that an improvement would occur by combining the claimed components. Applicant contends that the rejection relies on hindsight from the present application rather than evidence existing in the prior art. Applicant further argues that the Office did not adequately consider the statements of the technical expert who conducted the research. However, the arguments are not persuasive. The references are not relied upon merely to repeat the same disclosure. Instead, the references provide distinct teachings that collectively support the rejection. NBR teaches the AvailOm® omega-3 lysine complex comprising EPA and DHA; Engler provides evidence that EPA and DHA exert vasorelaxant effects; Bell teaches that anthocyanin-rich chokeberry compositions exhibit vasorelaxation and identifies cyanidin-3-galactoside among the anthocyanin constituents; and the additional references are relied upon for particular anthocyanin identifies or other limitations, as set forth in the rejection. Thus, the combination is based on complementary teachings in the prior art, not on reconstruction of Applicant’s disclosure. The rejection does not require that the prior art predict an “improvement” or the degree of improvement ultimately reported by Applicant; instead, the issue is whether the prior art would have provided a reason to make the claimed combination with a reasonable expectation that the respective known vascular effects would be retained.
Applicant argues that the Declaration establishes that the claimed combination is unpredictable in effect and therefore nonobvious even if there may have been a motivated to combine. Applicant specifically disagrees with the Office’s position that the components would have been predictably combinable for the same purpose. However, the argument is not persuasive. The reasonable expectation inquiry does not require one of ordinary skill to have predicted the precise magnitude of vasorelaxation, nitric oxide production, or antioxidant effect observed. The cited art teaches that the individual components possess vascular or vasorelaxant activity. Thus, the relevant expectation is that combining known vascularly active components for the same or closely related vascular purpose would have provided a composition retaining useful vascular activity. Evidence that the resulting activity may have been greater than expected is properly considered as objective evidence of nonobviousness, but it does not by itself negate the underlying motivation to combine or reasonable expectation of obtaining a functional vascular composition.
Applicant relies heavily on Figure 4A and states that AvailOm® in combination with C3-gal provides an unexpected near-doubling of the effect. Applicant states that the combination shows significantly improved endothelial-dependent vasorelaxation at 50, 100, and 150 μg/mL relative AvailOm® alone and characterizes the result as “not just additive” but a clear synergy”. The Declaration further states the AvailOm® + C3-gal produces significantly stronger vasorelaxation than either component alone. The Figure 4A data have been considered and show enhanced vasorelaxation for the particular AvailOm®/C3-gal compositions and concentration tested. However, the data do not establish that the asserted synergistic effect extends throughout the full scope of the claims. The claims encompass broader quantitative ranges, including a polyunsaturated fatty acid to anthocyanin weight ratio of 1:1 to 1:6 and a polyunsaturated fatty acid content of 40 – 65 wt.% of the total composition. The evidence identified by Applicant evaluates only particular formulations and experimental conditions. Applicant has not demonstrated that comparable synergy occurs throughout the entire 1:1 to 1:6 ratio range, throughout the claimed polyunsaturated fatty acid weight percent range, or across all claimed treatment embodiments. Accordingly, while the data demonstrate enhanced activity for the particular embodiments tested, the evidence is insufficient to establish the asserted unexpected synergistic effect is commensurate in scope with the claimed subject matter.
Applicant states that Figure 4A shows that adding DP3-ara to the AvailOm®/C3-gal combination further increases vasorelaxation and characterizes this as additional evidence of true synergy. The Declaration also cites increased nitric oxide production for C3-gal and C3-gal + DP3-ara combinations. The evidence has been considered and is acknowledged to demonstrate an enhanced response for the tested AvailOm®/C3-gal and AvailOm®/C3-gal/DP3-ara compositions. Accordingly, the evidence is relevant to the claimed combinations and has been accorded appropriate weight. The cited prior art would have provided one of ordinary skill in the art with an expectation that combining EPA/DHA and an anthocyanin would produce vasorelaxant activity because Engler teaches vasorelaxant activity associated with EPA and DHA and Bell teaches dose-dependent vasorelaxant activity associated with anthocyanin-containing compositions. Thus, the vasorelaxant activity from the combination would have been expected. Figure 4A demonstrates that the tested combination provides a greater vasorelaxant response than either tested component individually. However, a response greater than either individual component does not, by itself, establish that the combination produces a synergistic, rather than additive, effect. To substantiate the asserted synergistic effect, the evidence would need to establish an appropriate expected response for the combination based on the effects of the individual components and demonstrate that the observed combination response exceeds that expected response. The Declaration does not establish such an expected combined response or demonstrate that the observed response exceeds it. Accordingly, Figure 4A provides probative evidence of an enhanced vasorelaxant response and has been accorded appropriate weight, but the evidence does not establish that the observed enhancement is greater than additive or otherwise unexpected relative to the response expected from the combination.
Applicant states that Figure 4B shows that C3-gal moderately increases nitric oxide production, AvailOm® moderately increases nitric oxide production, and the combination produces the highest nitric oxide level, significantly exceeding the individual agents. Applicant characterizes this as “mechanistic synergy at the NO-signaling level”. The Figure 4B data have been considered and are acknowledged to demonstrate a statistically significant enhanced nitric oxide response for the tested AvailOm®/C3-gal combination. Because nitric oxide signaling is associated with vasorelaxation, the evidence has a nexus to the asserted vasorelaxant effect and is therefore relevant evidence of nonobviousness. The cited prior art would have provided one of ordinary skill in the art with an expectation of vascular activity from combining EPA/DHA and an anthocyanin based on the known vascular activities of the individual components. However, Figure 4B’s demonstration that the combination produces a greater than nitric oxide response than either component individually does not, by itself, establish that the response is synergistic rather than additive. To substantiate the asserted synergistic effect, the evidence would need to establish an appropriate expected nitric oxide response for the combination based on the effects of individual components and demonstrate that the observed combination response exceeds that expected response. The Declaration does not establish such an expected combined response or demonstrate that the observed response exceeds it. Accordingly, Figure 4B provides probative evidence of an enhanced nitric oxide response and has been accorded appropriate weight, but the evidence does not establish that the observed enhancement is greater than additive or otherwise unexpected relative to the response expected from the combination.
Applicant states that C3-rut produces an unexpected recovery effect when combined with AvailOm® under oxLDL-induced oxidative stress. According to the Declaration, Figure 4C shows that AvailOm® + C3-rut dramatically reduces ROS compared with AvailOm® alone, and Figure 4D shows stronger restoration of vasorelaxation under oxLDL stress, particularly at intermediate concentrations. Applicant therefore characterizes the C3-rut combination as demonstrating antioxidant and vascular synergy. The evidence has been considered. However, the evidence is limited to particular concentrations and stress conditions. The ROS experiments concern oxidative-stress protection, while the claims are directed to methods of treatment requiring vasorelaxation. Applicant acknowledges in the Declaration that ROS suppression alone is not sufficient to predict vasodilatory synergy. Accordingly, the ROS data are relevant supporting evidence but do not by themselves establish unexpected vasorelaxation throughout the full scope of the C3-rut claims. Also, the vasorelaxation data of Figure 4D are limited to the tested experimental conditions and do not demonstrate the asserted effect throughout the entire claimed 1:1 to 1:6 range.
Applicant states that Figure 5 shows synergy with complex anthocyanin mixtures at a 1:6 AvailOm®:anthocyanin ratio. The Declaration states that six different anthocyanin mixtures were tested and the MIX6 produced the strongest ROS reduction and most complete restoration of vasorelaxation. Figure 5 has been considered and is acknowledged as probative evidence of an enhanced effect at the tested 1:6 ratio. The evidence is considered together with the Figure 4 evidence demonstrating enhanced effects for other tested AvailOm®/anthocyanin compositions and relative amounts. Accordingly the evidence is not discounted merely because Applicant did not separately test each intermediate ratio within the claimed 1:1 to 1:6 ratio. However, Figure 5 employs complex multi-anthocyanin mixtures that differ from the specifically recited anthocyanin components of the claims. Thus, while Figure 5 provides relevant evidence concerning combinations of AvailOm® and anthocyanins, the weight accorded to that evidence with respect to a particular claim depends upon the extent to which the tested anthocyanin composition corresponds to the anthocyanin composition required by that claim. The Figure 5 evidence has therefore been considered together with the remaining evidence of unexpected results and weighed against the evidence supporting the prima facie case of obviousness.
The Declaration states that the experiments of record are representative of the claim scope. Applicant therefore contends that the demonstrated synergistic effects are commensurate in scope with the claims. However, the argument is not persuasive because the Declaration does not provide a technical explanation showing why the limited number of tested formulations and ratios would reasonably predict the same unexpected effect across all claimed ratios, polyunsaturated fatty acid concentrations, anthocyanin concentrations, disease indications, and anthocyanin embodiments. The evidence must reasonably correspond to the breadth of the claimed subject matter. In particular, substantial portions of the claimed ranges and the combinations were not tested, and Applicant has not identified a demonstrated structure-function or dose-response relationship sufficient to extrapolate the observed synergy across the full claimed genus.
The Declaration contends that the cited prior art does not establish that combining the omega-3 fatty acids with the claimed anthocyanin component would have predictably produced the claimed result. Applicant further relies on the experimental evidence in Figures 4 and 5 as demonstrating enhanced or synergistic vascular effects that Applicant asserts would not have been expected from the activity of the individual components. Thus, Applicant’s argument is understood as challenging the Office’s conclusion that the proposed combination would have yielded predictable results. The experimental evidence has been considered as objective evidence of nonobviousness. As discussed above with respect to Figures 4 and 5, the evidence demonstrates enhanced effects for the tested combinations and has been accorded appropriate weight. However, the evidence does not sufficiently establish that the magnitude of the demonstrated enhancement would have been unexpected to one of ordinary skill in the art in view of the cited prior art. Accordingly, Applicant’s experimental evidence is weighed together with the evidence supporting the prima facie case in determining obviousness of the claimed subject matter as a whole.
The Declaration further addresses Engler and disputes the Office’s reasonable-expectation-of-success determination. Engler is relied upon as evidence of the known vascular activity associated with EPA and DHA, while the remaining cited references provide the relevant teachings concerning the anthocyanin components and the vascular activity. The Office does not rely on the known activity of the individual components as establishing that the particular magnitude of enhancement reported by Applicant necessarily would have been expected. Instead, those teachings establish the prior-art basis for combining components known to provide vascular benefits and the reasonable expectation of obtaining a vasorelaxant effect from the combination. Applicant’s experimental evidence is relevant to whether the result of that combination is nevertheless unexpected superior and has been considered for that purpose. For the reasons discussed above concerning Figures 4 and 5, however, the evidence does not sufficiently establish that the degree of enhancement is unexpected so as to outweigh the evidence supporting the prima facie case of obviousness.
Conclusion
No claim is found to be allowable.
THIS ACTION IS MADE NON-FINAL.
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/H.Y.L./Examiner, Art Unit 1693
/JONATHAN S LAU/Primary Examiner, Art Unit 1693
