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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 submissions filed on 18 May 2026 have been entered.
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 .
Applicant’s arguments, filed 29 April 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 Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.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.
Election/Restrictions
Upon reconsideration in light of Applicant’s remarks and amendments dated 29 April 2026, the restriction/election requirement set forth in the Office action dated 21 March 2025 is hereby withdrawn.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-5, 7, 9, and 11-23 are rejected under 35 U.S.C. 103 as being unpatentable over Yu et al. (US 2015/0265535 A1, 09/24/2015, IDS reference of 07/08/2025) (hereinafter Yu) in view of Tabata et al. (US 2016/0067208 A1, 03/10/2016, IDS reference) (hereinafter Tabata).
Yu discloses a sustained release lipid pre-concentrate, comprising: (a) at least one liquid crystal former; and (b) at least one neutral phospholipid, that forms liquid crystal upon exposure to aqueous fluid (abs). The crystal former is responsible for the formation of non-lamellar liquid crystals and includes sorbitan unsaturated fatty acid esters and monoacyl glycerol ([0020]). The phospholipid includes phosphatidylcholine ([0032]). The ratio of (a) to (b) may be in the range of 10:1 to 1:10 ([0050]).
Yu differs from the instant claims insofar as not explicitly disclosing an instantly claimed structure as the unsaturated fatty acid chain.
However, Tabata discloses amphipathic compounds have a general formula (I),
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,
wherein X and Y together denote an oxygen atom; n denotes an integer from 0 to 2; m denotes the integer 1 or 2; AA (
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) denotes a single bond or double bond; and R denotes a hydrophilic group having two or more hydroxyl groups (abs). It was found that having an isoprenoid chain instead of a linear chain of fatty acid as a hydrophobic group results in high resistance to hydrolysis and relatively high oxidation stability ([0165}).
Accordingly, it would have been obvious to one of ordinary skill in the art to have included a hydrophobic group having an isoprenoid chain, including wherein X and Y together denote an oxygen; n denotes an integer from 0 to 2; m denotes the integer 1 or 2; and having 1 to 4 double bonds, in the sorbitan unsaturated fatty acid ester of Yu, since it is a known and effective chain resulting in improved hydrolysis and oxidation stability as taught by Tabata.
Regarding the claimed weight ratio ranges in claims 1, 4, and 5, the claimed ranges (i.e. 50:50 to 20:80; 50:50 to 30:70; or 45:55 to 30:70, respectively) would have been obvious to one of ordinary skill in the art since they overlap with the ranges of the prior art (i.e. 1:10 to 10:1). In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP § 2144.05(I).
Regarding claims 3 and 22, it would have been obvious to one of ordinary skill in the art to have selected 2 for n and 2 for m in the hydrophobic group since each is a known and effective integer suitable for the isoprenoid chain as taught by Tabata.
Regarding claim 7, Yu further discloses wherein the source of phospholipids includes soybeans ([0033]).
Regarding claim 9 and 23, it would have been obvious to one of ordinary skill in the art to have selected an isoprenoid chain wherein n = 2, m = 2, having 1 double bond and 3 single bonds, and arrived at a claimed compound through routine experimentation based on the general guidance given by Tabata.
Regarding claim 11, Yu further discloses wherein the pre-concentrate further comprises a liquid crystal hardener including tocopherol acetate ([0035]-[0036]). As noted by para. [0084] of the instant Specification, tocopherol acetate is an exemplary oil.
Regarding claim 12, Yu further discloses wherein the liquid crystals, having a non-lamellar phase structure in which oil and water are in an ordered mixture and arrangement without distinction between inner and outer phases ([0053]), are formed upon exposure to aqueous fluid (i.e. instantly claimed non-lamellar liquid crystal composition) ([0054]).
Regarding claim 13, Yu further discloses wherein the pre-concentrate further comprises anionic anchoring agents with polar head group and a hydrophobic tail (i.e. a surfactant) ([0040]). As such, the formation of a non-lamellar liquid crystal emulsion composition would have been obvious.
Regarding claim 16 reciting wherein the composition is for adhesion prevention of living tissue, this appears to be a recitation of the intended use of the composition. Since the composition of the prior art comprises substantially the same active ingredients as the claimed invention (i.e. an amphipathic compound and phospholipid), the composition of the prior art would be usable to prevent adhesion of living tissue, whether the prior art recognizes such use or not.
Regarding claims 17-19, Yu further discloses wherein the pre-concentrate further comprises pharmacologically active substances including leuprolide ([0048]).
Regarding claim 20, Yu further discloses wherein the pre-concentrate may be a pharmaceutical composition and be applied to the body via injection ([0056]).
Claims 1-5, 7, 9, 11-16, and 20-23 are rejected under 35 U.S.C. 103 as being unpatentable over Tabata et al. (US 2016/0067208 A1, 03/10/2016, IDS reference) (hereinafter Tabata) in view of Yu et al. (US 2015/0265535 A1, 09/24/2015, IDS reference of 07/08/2025) (hereinafter Yu).
Tabata discloses an amphipathic compound suitable as an adhesion preventing agent, having a general formula (I):
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,
wherein X and Y together denote an oxygen atom; n denotes an integer from 0 to 2; m denotes the integer 1 or 2;
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3
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denotes a single bond or double bond; and R denotes a hydrophilic group having two or more hydroxyl groups (abs), including, but not limited to, those generated by removal of one hydroxyl group from glycerol ([0020]). The amphipathic compound is a liquid crystal compound and capable of forming non-lamellar liquid crystal in an aqueous medium ([0160]). The amphipathic compound may be contained in the adhesion preventing agent in concentrations of 1-80% by weight ([0199]).
Tabata differs from the instant claims insofar as not explicitly disclosing wherein the composition comprises a phospholipid.
However, Yu discloses non-lamellar liquid-crystal forming compositions comprising a liquid crystal former, such as sorbitan unsaturated fatty acid esters and monoacyl glycerols ([0020]) and phospholipids. The phospholipids can participate in the liquid crystal former-driven formation of non-lamellar phase structures, serving to stabilize the resulting liquid crystals. Useful phospholipids include phosphatidylcholine ([0031]-[0032]). Suitable weight ratios of liquid crystal former : phospholipid may be in a range of 1:10 to 10:1 ([0050]).
Accordingly, it would have been obvious to one of ordinary skill in the art to have included a phospholipid with the amphipathic compound of Tabata, since it is a known and effective ingredient that can serve to stabilize resulting liquid crystals as taught by Yu.
Regarding the claimed weight ratios of claims 1, 4, and 5, it would have been obvious to one of ordinary skill in the art to have selected an amount of amphipathic compound from the disclosed range of 1-80% by weight, and an amount of phospholipid from the disclosed ratio of 1:10 to 10:1 to the liquid crystal compound. Such amounts selected appears to equate to a ratio that overlaps with the claimed ratio, thus making the claimed ratio obvious. Moreover, in any case, the selection of appropriate weight ratios would appear to require no more than routine testing on the part of the skilled artisan, and so alternatively it would have been obvious to determine workable ranges to arrive at the claimed weight ratios. "[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." See MPEP § 2144.05(II)(A).
Regarding claims 2, 3 and 9, Tabata further discloses wherein the amphipathic compound may include mono-O-(5,9,13,17-tetramethyloctadec-4-enoyl)glycerol ([0146]).
Regarding claim 7, Tabata differs from the instant claim insofar as not explicitly disclosing a source of phospholipid.
However, Yu further discloses wherein the source of phospholipids includes soybeans ([0033]).
Accordingly, it would have been obvious to one of ordinary skill in the art to have sourced the phospholipid from soybean (i.e. soybean phosphatidylcholine) since it is a known and effective source suitable for compositions comprising liquid crystal forming compounds as taught by Yu.
Regarding claim 11, Tabata further discloses wherein the adhesion preventing agent may further comprise a physiologically acceptable organic solvent ([0201]).
Regarding claim 12, Tabata further discloses wherein the adhesion preventing agent may further comprise an aqueous medium ([0201]).
Regarding claim 13, Tabata further discloses wherein the adhesion preventing agent may be in the form of emulsion ([0514]).
Regarding claim 20, Tabata further discloses wherein the adhesion preventing agent may be formulated as a spray agent ([0200]).
Regarding claims 21-23, as discussed above, Tabata discloses amphipathic compounds of the general formula (I), including an embodiment wherein X and Y together denote an oxygen atom; n denotes 2; m denotes 2; wherein the compound comprises a double bond and 3 single bonds; and R denotes a hydrophilic group having two or more hydroxyl groups.
Tabata differs from the instant claims insofar as not explicitly disclosing wherein the hydrophilic group having two or more hydroxyl groups includes sorbitan.
However, Yu further discloses wherein sorbitan unsaturated fatty acid ester are responsible for the formation of non-lamellar liquid crystals ([0020]) and preferably has two or more hydroxyl groups in the polar head ([0021]).
Accordingly, it would have been obvious to one of ordinary skill in the art to have included a sorbitan group as the hydrophilic group in the amphipathic compound of Tabata, since it is a known and effective hydrophilic group having two or more hydroxyl groups suitable as a liquid crystal former as taught by Yu.
Claims 1-5, 7, 9, and 11-23 are rejected under 35 U.S.C. 103 as being unpatentable over Ikeda (US 2012/0264923 A1, 10/18/2012, IDS reference) in view of Yu et al. (US 2015/0265535 A1, 09/24/2015, IDS reference of 07/08/2025) (hereinafter Yu).
Ikeda discloses an amphipathic compound having a general formula (I):
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including embodiments wherein X and Y together denote an oxygen atom; n denotes an integer from 0 to 2; m denotes the integer 1 or 2; and R denotes a hydrophilic group. The hydrophilic group R may be, but not limited to, a residue that is generated by removal of one hydroxyl group from glycerol ([0070]-[0072]). The amphipathic compound is more generally an ether or ester compound, wherein one molecule of long chain unsaturated hydrocarbon, e.g., long chain unsaturated fatty acid or long chain unsaturated alcohol, is bound via an ether or an ester bond to one molecule of polyhydric alcohol ([0241]). The amphipathic compounds can form non-lamellar liquid crystals in an aqueous medium, and may be at a concentration ranging from 0.1-90% by mass ([0269]).
Ikeda differs from the instant claim insofar as not explicitly disclosing wherein the formulation comprises a phospholipid.
However, Yu discloses non-lamellar liquid-crystal forming compositions comprising a liquid crystal former, such as sorbitan unsaturated fatty acid esters and monoacyl glycerols ([0020]) and phospholipids. The phospholipids can participate in the liquid crystal former-driven formation of non-lamellar phase structures, serving to stabilize the resulting liquid crystals. Useful phospholipids include phosphatidylcholine ([0031]-[0032]). Suitable weight ratios of liquid crystal former : phospholipid may be in a range of 1:10 to 10:1 ([0050]).
Accordingly, it would have been obvious to one of ordinary skill in the art to have included a phospholipid with the amphipathic compound of Ikeda, since it is a known and effective ingredient that can serve to stabilize resulting liquid crystals as taught by Yu.
Regarding the claimed weight ratios of claims 1, 4, and 5, it would have been obvious to one of ordinary skill in the art to have selected an amount of amphipathic compound from the disclosed range of 0.1-90% by weight, and an amount of phospholipid from the disclosed ratio of 1:10 to 10:1 to the liquid crystal compound. Such amounts selected appears to equate to a ratio that overlaps with the claimed ratio, thus making the claimed ratio obvious. Moreover, in any case, the selection of appropriate weight ratios would appear to require no more than routine testing on the part of the skilled artisan, and so alternatively it would have been obvious to determine workable ranges to arrive at the claimed weight ratios. "[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." See MPEP § 2144.05(II)(A).
Regarding claims 2, 3, and 9, Ikeda further discloses a specific embodiment wherein the hydrophilic group R is bound to a hydrophobic hydrocarbon chain being 5,9,13,17-tetramethyloctadec-4-enoyl ([0077]).
Regarding claim 7, Tabata differs from the instant claim insofar as not explicitly disclosing a source of phospholipid.
However, Yu further discloses wherein the source of phospholipids includes soybeans ([0033]).
Accordingly, it would have been obvious to one of ordinary skill in the art to have sourced the phospholipid from soybean (i.e. soybean phosphatidylcholine) since it is a known and effective source suitable for compositions comprising liquid crystal forming compounds as taught by Yu.
Regarding claims 11-12, Ikeda further discloses wherein the aqueous medium in which the amphipathic compound can form non-lamellar liquid crystal includes aqueous solutions containing water-soluble organic substances such as ethanol ([0267]).
As noted by para. [0087] of the instant Specification, ethanol is an alcohol that is an organic solvent.
Regarding claim 13, Ikeda further discloses wherein the amphipathic compounds may be formulated with a pharmaceutically applicable surfactant ([0284]). The formulation may be an emulsion ([0284]).
Regarding claim 16 reciting wherein the composition is for adhesion prevention of living tissue, this appears to be a recitation of the intended use of the composition. Since the composition of the prior art comprises substantially the same active ingredients as the claimed invention (i.e. an amphipathic compound and phospholipid), the composition of the prior art would be usable to prevent adhesion of living tissue, whether the prior art recognizes such use or not.
Regarding claim 17, Ikeda further discloses wherein other substances including a drug may be incorporated and stably retained within the liquid crystal in aqueous medium ([0282]) and used as a base for sustained release formulations ([0283]).
Regarding claims 18-19, Ikeda differs from the instant claims insofar as not explicitly disclosing wherein the drug includes a gonadotropin-release hormone agonist, or leuprolide, respectively.
However, Yu further discloses wherein non-lamellar liquid-crystal forming compositions may further comprise pharmaceutically active substances including leuprolide ([0048]).
Accordingly, it would have been obvious to one of ordinary skill in the art to have included leuprolide as the drug in the formulation of Ikeda since it is a known and effective drug suitable for inclusion with liquid crystal forming compositions as taught by Yu.
Regarding claim 20, Ikeda further discloses wherein the amphipathic compound may be used as a base for injection formulations (abs).
Regarding claims 21-23, as discussed above, Ikeda discloses the amphipathic compounds are able to form non-lamellar liquid crystals in aqueous medium (i.e. liquid crystal forming compound) and, more generally, are ether or ester compounds, wherein one molecule of long chain unsaturated hydrocarbon, e.g., long chain unsaturated fatty acid or long chain unsaturated alcohol, is bound via an ether or an ester bond to one molecule of polyhydric alcohol, as well as an embodiment wherein the hydrophilic group R is bound to a hydrophobic hydrocarbon chain being 5,9,13,17-tetramethyloctadec-4-enoyl.
Ikeda differs from the instant claims insofar as not explicitly disclosing wherein the hydrophilic group R includes sorbitan.
However, Yu further discloses wherein sorbitan unsaturated fatty acid ester are capable of forming non-lamellar liquid crystals ([0020]) and preferably has two or more hydroxyl groups in the polar head (i.e. polyhydric alcohol) ([0021]).
Accordingly, it would have been obvious to one of ordinary skill in the art to have included a sorbitan group as the hydrophilic group R in the amphipathic compound of Ikeda, since it is a known and effective hydrophilic group that is a polyhydric alcohol and is suitable as a liquid crystal forming compound as taught by Yu.
Response to Arguments
Applicant’s arguments have been considered but are moot because new rejections necessitated by Applicant’s amendment have been made.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-5, 7, 9, and 11-23 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 12,296,014 in view of Yu et al. (US 2015/0265535 A1, 09/24/2015, IDS reference of 07/08/2025) (hereinafter Yu), Tabata et al. (US 2016/0067208 A1, 03/10/2016, IDS reference) (hereinafter Tabata), and Ikeda (US 2012/0264923 A1, 10/18/2012, IDS reference).
Although the copending claims differ from the pending claims insofar as not explicitly teaching all the features of the claimed invention, such as an instantly claimed phospholipid or a hydrophilic group of claims 21-23.
However, these features are known in the art. As noted in the current rejections, the combined teachings of Yu and Tabata render obvious claims 1-5, 7, 9, and 11-23; the combined teachings of Tabata and Yu render obvious claims 1-5, 7, 9, 11-16 and 20-23; and the combined teachings of Ikeda and Yu render obvious claims 1-5, 7, 9, and 11-23.
Therefore, as claims 1-11 of U.S. Patent No. 12,296,014, Yu, Tabata, and Ikeda all disclose compositions comprising amphipathic compounds capable of forming liquid crystals in presence of aqueous media, it would have been prima facie obvious to one of ordinary skill in the art to have modified the copending application and to include the teachings of Yu, Tabata, and Ikeda as discussed in the rejections above, because all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as instantly claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." See MPEP 2144.06(I).
Response to Arguments
Applicant’s arguments have been considered but are moot because new rejections necessitated by Applicant’s amendment have been made.
Examiner’s Note
The Examiner acknowledges and appreciates Applicant’s explanation regarding the species included in Table 9 on page 14 of the Remarks dated 29 April 2026. Based on Table 9 (para. [0237]) and para. [0242]-[0248] of the instant Specification, it appears to the Examiner that a combination of: specific isoprenoid lipid species having a higher number of carbon atoms; certain amounts (%) or more of phospholipid and isoprenoid lipid with or without oil; and weight ratios of isoprenoid lipid to phospholipid, appear to contribute to the objective data presented by the Applicant. It is suggested for Applicant to review how the instant claims, reciting general formulas including wherein n may be 0 and m may be 1, wherein the compound may comprise 0 to 4 double bonds, and any amounts of amphipathic compound and phospholipid, are reasonably representative of the specific formulation species demonstrating no side effects versus the formulation species that resulted in side effects.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LUCY TIEN whose telephone number is (571)272-8267. The examiner can normally be reached Monday - Thursday 8:30 AM - 6:30 PM EST.
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/LUCY M TIEN/Examiner, Art Unit 1612
/SAHANA S KAUP/Supervisory Primary Examiner, Art Unit 1612
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