DETAILED ACTION
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 10/08/2025 has been entered.
Previous Rejections
Applicant’s arguments, filed 02/26/2025, 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 Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.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.
Claim Rejections - 35 USC § 103 - Obviousness
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, 3, 5, 6, 7-11, 13-14, 15 and 16-20 are rejected under 35 U.S.C. 103 as being unpatentable over Seeram et al (US 2009/0326057 A1), in view of Rinsch et al (US 2022/0280475 A1), further in view of Yi et al (AAPS PharmSciTech, 2021, 22: 26, pages 1-12), further in view of Rao et al (US 2021/0267932 A1), further in view of Anderson et al (US 2010/0086573 A1) and further in view of Pitcher et al (US 2019/0240281 A1).
Seeram taught therapeutic uses [title] of urolithin compounds (e.g., urolithin A) [claims 10-12], formulated as liposomal compositions [0038]. The compositions found use in treating or preventing a neoplastic disease in a subject [abstract]. Oral administration was taught [0038-0039, 0041, 0044].
Seeram was not specific urolithin A (or amounts thereof) as a nutritional supplement, as recited in claim 1. Although Seeram taught liposomes, Seeram was not specific a liposomal blend comprising phosphatidylcholine derived from sunflower lecithin (nor amounts thereof), wherein the liposome encapsulated urolithin increased the absorption of the supplement and reduced the amount of ingested supplement lost through digestion, as recited in claim 1.
Rinsch taught urolithin compounds (e.g., urolithin A) presented in or as food products, nutritional or dietary supplements [abstract, claim 100, ¶0318], suitable for consumption or other administration, principally for its health-promoting properties [0184].
Since Seeram taught therapeutic uses of urolithin compounds, it would have been prima facie obvious to one of ordinary skill in the art to formulate Seeram’s compounds as nutritional supplements. The ordinarily skilled artisan would have been motivated to provide a formulation suitable for consumption, or other administration, principally for its health-promoting properties, as taught by Rinsch et al [Rinsch; abstract, claim 100 and at ¶s 0184 and 0318].
The combined teachings of Seeram and Rinsch did not teach a liposomal blend comprising phosphatidylcholine, wherein the liposome encapsulated urolithin increased the absorption of the supplement.
However, Yi taught [abstract] urolithin A-loaded liposomes (e.g., phosphatidylcholine, at page 2 and the section entitled Materials; further, at page 3 and the section entitled Preparation of Liposomes) to improve the bioavailability and anti-tumor efficacy of the compound. The liposomes displayed high-entrapment efficiency and stability. Furthermore, versus the free drug, the encapsulated liposomes substantially increased the uptake of urolithin A and exhibited a greater cytotoxicity, thereby enhancing the antitumor efficacy [Conclusion]. Finally, versus the free drug, the liposomes displayed a significantly prolonged half-life, indicating an improved bioavailability, increased absorption and a reduction of loss through the removal from the body [section entitled Pharmacokinetic Study].
Since Seeram taught urolithin A compounds formulated as liposomal compositions for the treatment of neoplastic diseases, it would have been prima facie obvious to one of ordinary skill in the art to encapsulate Seeram’s compounds within the liposome. The ordinarily skilled artisan would have been so motivated, because encapsulation improves the uptake, bioavailability and cytotoxicity of urolithin A, thereby improving the anti-tumor efficacy of the compound, as taught by Yi et al.
The ordinarily skilled artisan would have been motivated to improve bioavailability of the supplement, motivated by the desire to increase absorption and reduce the loss of supplement through the removal from the body, as taught by Yi at the section entitled Pharmacokinetic Study.
The ordinarily skilled artisan would have been motivated to include, within Seeram’s liposome, phosphatidylcholine, as taught by Yi. The ordinarily skilled artisan would have been motivated to form the liposome, as taught by Yi [Yi at page 3, section entitled Preparation of Liposomes].
The combined teachings of the prior art were not specific the amounts of urolithin A, as instantly recited.
Rao taught compositions, including pharmaceutical compositions, comprising urolithin derivatives in an amount of at least about 0.0001 % to at least about 99.99 % [0126, 0130]. In some embodiments, cancers were treated by compounds of the disclosure [0142]. As per Rao, “urolithin derivative” refers to a compound having a structure derived from the structure of a urolithin, and whose structure is sufficiently similar to a urolithin and based upon that similarity, would be expected by one skilled in the art to exhibit the same or similar activities and utilities as a urolithin, or to induce, as a precursor, the same or similar activities and utilities as a urolithin [0110].
It would have been prima facie obvious to one of ordinary skill in the art to include, within the combined teachings of Seeram, Rinsch and Yi, urolithin in amounts of at least about 0.0001 % to at least about 99.99 %, as taught by Rao. The ordinarily skilled artisan would have been motivated to form liposomes comprising urolithins. In the case of the amount of urolithin, the skilled artisan would have been motivated to include an amount effective for the treatment of cancers, as taught by Rao at ¶s 0126 and 0130.
Although Rao taught urolithin derivatives in an amount of at least about 0.0001 % to at least about 99.99 %, as previously discussed, the combined teachings of the prior art were not specific the amounts of phosphatidylcholine (claims 1, 7, 11, 16-17), as instantly recited.
However, Anderson taught liposomal preparations [abstract] formed from exemplary phospholipids (e.g., phosphatidylcholine) in an amount ranging from about 1 % to about 10 % by weight [0039, 0041].
It would have been prima facie obvious to one of ordinary skill in the art to include, within the combined teachings of Seeram, Rinsch, Yi and Rao, exemplary phospholipids (e.g., phosphatidylcholine) in an amount ranging from about 1 % to about 10 % by weight, as taught by Anderson. The ordinarily skilled artisan would have been motivated to form liposomes comprising urolithins. The skilled artisan would have been motivated to include an amount effective to form the vesicle, as taught by Anderson at ¶s 0031 and 0041.
The combined teachings of Seeram, Rinsch, Yi Rao and Anderson were not specific phosphatidylcholine extracted from sunflowers, as recited in claims 1, 6 and 15.
Pitcher taught phospholipid liposome structures for the encapsulation of active agents [abstract], where the liposome was constructed from sunflower-based lecithin (e.g., phosphatidylcholine). The sunflower lecithin was provided for encapsulating and protecting the active component within the aqueous space [0045-0047, 0082]. The sunflower lecithin was provided at from about 4 % to about 11 % by weight [0080], or from about 1 % to 20 % by weight [0150-0151].
It would have been prima facie obvious to one of ordinary skill in the art to include, within the combined teachings of Seeram, Rinsch, Yi, Rao and Anderson, phosphatidylcholine extracted from sunflowers, as taught by Pitcher. The ordinarily skilled artisan would have been motivated to form the liposomal vesicle, for encapsulating and protecting the active component within the aqueous space, as taught by Pitcher at ¶s 0045-0047 and 0082.
Seeram, in view of Rinsch, Yi, Rao, Anderson and Pitcher reads on claims 1, 3, 5-6, 10, 13-15 and 18.
The instant claim 1 recites about up to about 8 % liposomal blend comprising phosphatidylcholine derived from sunflower lecithin; 90-93 % urolithin A.
The instant claim 3 recites 85-99.9 % urolithin A.
The instant claim 7 recites about 0.01 to about 15 % liposomal blend.
The instant claim 8 recites about 2 to about 10 % liposomal blend and about 90 to about 98 % urolithin.
The instant claim 9 recites about 7.92 % liposomal blend and about 92.08 % urolithin.
The instant claim 11 recites about 99.99 to about 85 % liposomal blend and about 15 to about 0.01 % urolithin.
The instant claim 16 recites about 0.05 to about 5 % liposomal blend and about 95 to about 99.95 % urolithin.
The instant claim 17 recites about 0.99 % liposomal blend and about 85 to about 99.9 % urolithin.
Rao taught compositions, including pharmaceutical compositions, comprising urolithin derivatives in an amount of at least about 0.0001 % to at least about 99.99 % [0126, 0130].
Anderson taught liposomal preparations [abstract] formed from exemplary phospholipids (e.g., phosphatidylcholine) in an amount ranging from about 1 % to about 10 % by weight [0039, 0041].
Pitcher taught sunflower lecithin was provided at from about 4 % to about 11 % by weight [0080], or from about 1 % to 20 % by weight [0150-0151].
In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art", a prima facie case of obviousness exists. MPEP 2144.05 A.
Claims 19-20 are rendered prima facie obvious because Seeram taught powders, tablets, capsules [0039, 0041]; dissolvable formulations were taught [0042, 0049].
Response to Arguments
Applicant's arguments, filed 10/08/2025, have been fully considered but they are not persuasive. The 37 C.F.R. § 1.132 Declaration of Augustin Quancard, filed 10/08/2025, has been fully considered but it is are not persuasive.
Applicant and Declarant argued evidence of unexpected results. Applicant and Declarant argued that phosphatidylcholine levels below those conventionally regarded as sufficient for liposomal formation, the claimed liposomal blend nonetheless forms a dominant, stable, polydisperse liposomal population in the 300-350 nm range, contrary to expectations form Anderson’s teachings, regarding phase inversion at low phospholipid concentrations.
The Examiner disagrees. Anderson taught that phase inversion results with a phospholipid concentration above 15 %. In the rejection of the instant claims, Anderson was relied upon to teach a phospholipid concentration ranging from about 1 % to about 10 % by weight [0039, 0041], which overlaps the claimed up to about 8 % concentration. Nevertheless, Anderson’s phospholipid concentration does not promote phase inversion, as alleged by the Applicant and Declarant. Furthermore, stability, polydispersity and diameter are not claimed properties, and the combined teachings of the art were not relied upon to reject limitations that are not claimed.
Furthermore, Pitcher’s concentration of sunflower lecithin was from about 4 % to about 11 % by weight [0080], or as low as 1 %, 2 %, 3 % or 4 %, and up to 20 % [0150-0163], which are amounts that also overlap the claimed amounts. The Examiner’s position is that the claimed composition does not appear patentably distinct from the combined teachings of the art.
Applicant and Declarant argued that the claimed formulation exhibited an increase in theoretical bioavailability, compared with non-liposomal formulations, and corresponded to an improvement of the polydispersity index of the liposomal system, with good stability.
The Examiner responds that liposomal formulations increasing bioavailability over non-liposomal formulations is expected, rather than unexpected [see the teachings of Yi et al]. Additionally, and for the purposes of argument only, not as a basis of rejection, the Examiner cites Nantong Huashan Pharmacy Co (CN111588696A) and Danaei et al (Pharmaceutics, 2018, 10, 57, 1-17).
Nantong Huashan Pharmacy Co disclosed that liposomes protect encapsulated active agents from being damaged by gastric juice, bile, digestive enzymes and the like; improves the stability of the encapsulated active agent in the gastrointestinal tract; and, further increases the absorption and bioavailability of the active [abstract].
Danaei disclosed that lipid-based drug delivery systems enhance bioavailability, stability, efficacy and the polydispersity index [abstract].
It is the Examiner’s position that liposomal formulations increase absorption, stability and bioavailability, versus non-liposomal formulations.
Applicant and Declarant argued that stable, polydisperse vesicles are achieved at a sweet spot of approximately 2.5 % liposomal blend.
The Examiner responds that Anderson taught phosphatidylcholine in an amount ranging from about 1 % to about 10 % by weight [0039, 0041]; and, Pitcher taught sunflower lecithin provided as low as 1 %, 2 % or 3 % [0150-0153]. It does not appear that the claimed composition is patentably distinct from the combined teachings of the cited prior art.
Applicant argued that when the liposomal blend was below approximately 1 %, no encapsulation occurs and the system remains monodisperse; at approximately 3-4 %, particle agglomeration and phase inversion occur; samples containing sunflower lecithin above 4 % showed large and irregular agglomerates, with phase inversion and loss of vesicle integrity. Applicant argued that these findings demonstrate that the claimed range is critical for liposome formation and stability.
The Examiner disagrees. The instantly claimed range of the liposomal blend is up to about 8 % (claim 1); about 0.01 to 15 % (claim 7); about 2 to 10 % (claim 8); about 7.92 % (claim 9); about 15 % to about 0.01 % (claim 11); about 0.05 % to about 5 % (claim 16); about 0.99 % (claim 17).
According to the Applicant and Declarant’s remarks, the claimed liposomes have populations without encapsulation, with particle agglomeration and phase inversion, with large sizes and with loss of vesicle integrity. The Examiner disagrees that the instantly claimed ranges of liposomes are critical for liposome formation and stability.
Applicant and Declarant argued that the data establish that the claimed liposomal blend forms stable, bioavailable liposomes at unexpectedly low concentrations and that exceeding the claimed range results in failure of the system.
The Examiner disagrees that the liposomal formulation is claimed at unexpectedly low concentrations of the liposomal blend. See the (above) Examiner’s arguments disagreeing with evidence of unexpected results.
Applicant requested that the § 103 rejections of the instant claims be withdrawn, in view of the Inventor’s Declaration, and that the claims proceed to issue.
The Examiner disagrees that allowable subject matter has been identified in the present application. The Examiner finds the Inventor’s Declaration non-persuasive. The 35 USC § 103 rejection is maintained.
Conclusion
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/CELESTE A RONEY/Primary Examiner, Art Unit 1612