DETAILED ACTION
Notice of 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 .
Response to Arguments
Applicant’s arguments, filed 5/18/2026, have been fully considered.
Applicant traverses the rejection of claims under 35 U.S.C. 103(a). As argued by Applicant, it would not have been “obvious to convert Wei’s system into the claimed NLC” (Applicant Arguments, Page 3). In particular, Applicant argues that “[t]he rejection treats NLC formation as a generic and predictable substitution of one lipid nanoparticle format for another” whereas “NLC structure depends on the particular identity, phase behavior, crystallization behavior, miscibility, and processing compatibility of the selected lipids. Different lipid selections and processing conditions can lead to materially different nanoparticle structures, including homogenous dispersions, SLNs, imperfect-matrix NLCs, amorphous systems, or shell-core particles” (Applicant Arguments, Page 3).
The argument is not found persuasive. 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 (CCPA 1981); In re Merck & Co., 800 F.2d 1091 (Fed. Cir. 1986). In the instant case, the claims are rejected in further view of Seyfoddin et al (which teach that “SLNs can be successfully converted to physically superior NLCs” (Abstract), which “are structural modifications of SLNs developed to address their insufficiencies, such as… stability problems” (Page 513, Column 1)) and Viladot Petit et al (which teach “nanostructured lipid carriers (NLC)” (Abstract) wherein “[t]he solid lipid is selected, without restriction, from… sterols, cholesterol and cholesterol esters” and so on, (Paragraph 0041) and “[t]he liquid lipid is selected, without restriction, from the group formed by vegetable oils, such as… castor oil” (Paragraph 0040)). As discussed in the previous rejection at Paragraph 27 and reiterated below:
“in further view of Seyfoddin et al and Viladot Petit et al it would have been prima facie obvious to modify the method of Wei et al by utilizing an NLC for administration as opposed to an SLN. It would have been obvious to do so to provide a physically superior delivery device having enhanced stability, as taught by Seyfoddin et al, and with a reasonable expectation of success, based on Seyfoddin et al (which teach that “SLNs can be successfully converted to physically superior NLCs”) and based on Viladot Petit et al (which generically disclose the feasibility of NLCs comprising a solid outer shell comprising cholesterol and a liquid core comprising castor oil triglyceride)”
While it is recognized that “NLC structure depends on the particular identity, phase behavior, crystallization behavior, miscibility, and processing compatibility of the selected lipids. Different lipid selections and processing conditions can lead to materially different nanoparticle structures, including homogenous dispersions, SLNs, imperfect-matrix NLCs, amorphous systems, or shell-core particles”, as argued by Applicant (Applicant Arguments, Page 3), it is maintained that, at the time the invention was made, a person of ordinary skill in the art would have been motivated to modify the method of Wei et al by utilizing an NLC for administration as opposed to an SLN, and would have been able to carry out said modification with a reasonable expectation of success.
Applicant next argues that “[t]he presently claimed method requires administration of an NLC particle having a solid outer shell comprising cholesterol and a liquid core comprising castor oil triglyceride, with no therapeutic agent other than the liquid lipid” (Applicant Arguments, Page 3). And, as further argued by Applicant, “[t]he cited combination does not teach or suggest that Wei’s lipid nano-dispersion/SLN-type system should be modified to provide this specific cholesterol-shell/castor oil-core architecture, nor does it provide a reasonable expectation that such a modification would produce the claimed drug-free ocular treatment composition” (Applicant Arguments, Page 3).
The argument is not found persuasive. As noted by Applicant, “[a] proper obviousness rejection must be supported by an articulated reason with rational underpinning for modifying or combining the cited references, and there must be a reasonable expectation of success at arriving at the claimed invention as a whole” (Applicant Arguments, Page 2). Significantly, obviousness does not require a teaching or suggestion that the prior art “should be modified” as argued by Applicant (Applicant Arguments, Page 3), only that “a person of ordinary skill in the art would have been motivated to modify” the prior art (Applicant Arguments, Page 2). In the instant case, it is maintained that, at the time the invention was made, a person of ordinary skill in the art would have been motivated to modify the method of Wei et al by utilizing an NLC for administration as opposed to an SLN, and would have been able to carry out said modification with a reasonable expectation of success, for the reasons discussed above. Namely, it would have been prima facie obvious to modify the method of Wei et al by utilizing an NLC for administration as opposed to an SLN in an effort to provide a physically superior delivery device having enhanced stability, as taught by Seyfoddin et al (which teach that NLCs “are structural modifications of SLNs developed to address their insufficiencies, such as… stability problems”) and with a reasonable expectation of success, based on Seyfoddin et al (which teach that “SLNs can be successfully converted to physically superior NLCs”) and based on Viladot Petit et al (which generically disclose the feasibility of NLCs comprising a solid outer shell comprising cholesterol and a liquid core comprising castor oil triglyceride).
Applicant next argues that the ophthalmic lipid nano-dispersions of Wei et al rely “on materials such as petroleum jelly, wool fat/lanolin, and waxes. Those materials are soft or semi-solid excipients and are not the same as a defined cholesterol outer shell surrounding a castor oil triglyceride core. Although lanolin may contain cholesterol as one component, lanolin is a complex mixture of esters, fatty acids, alcohols, and other materials having properties materially different from purified cholesterol” (Applicant Arguments, Page 3).
Yet, the claims are not drawn to a nanostructure lipid carrier comprising a solid outer shell consisting of purified cholesterol. Rather, the claims are drawn to a nanostructure lipid carrier comprising a solid lipid, wherein the solid lipid comprises cholesterol.
Applicant, however, further argues that “Wei also relies on emulsifier-stabilized dispersions, including lecithins, poloxamers, and nonionic surfactants” which “are directed to forming and maintaining liquid dispersions, not to producing the presently claimed NLC particle having a defined solid cholesterol-containing outer shell and a liquid castor-oil-triglyceride core” (Applicant Arguments, Page 4).
It is not disputed that the lipid nano-dispersion/solid lipid nanoparticle taught by Wei et al is structurally different from the instantly claimed nanostructured lipid carrier. Nevertheless, it is maintained that, at the time the invention was made, a person of ordinary skill in the art would have been motivated to modify the method of Wei et al by utilizing an NLC for administration as opposed to an SLN, and would have been able to carry out said modification with a reasonable expectation of success, for the reasons discussed above.
Lastly, Applicant “submits additional experimental data showing that sterilization of the claimed NLCs at 121oC for 15 minutes reduced both particle size and polydispersity index (PDI) resulting in improved nanoparticle uniformity” (Applicant Arguments, Page 4). As argued by Applicant, “[t]hese results are contrary to what would have been expected for lipid nanoparticle systems subjected to thermal sterilization” (Applicant Arguments, Page 5).
Applicant is advised that the arguments of counsel cannot take the place of evidence in the record. As such, Applicant's assertion of unexpected results must be supported by an appropriate affidavit or declaration.
For all the foregoing reasons, Applicant’s arguments are not found persuasive. The rejection of claims is MAINTAINED.
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.
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 17-18, 20 and 25-26 are MAINTAINED rejected under 35 U.S.C. 103(a) as being unpatentable over Wei et al (US 2016/0074321; of record) in view of Seyfoddin et al (Drug Development and Industrial Pharmacy 39:508-519, 2013; of record) and Viladot Petit et al (US 2013/0017239; of record).
Claim 17 is drawn to a method of treating or preventing a dry eye disorder (more specifically, dry eye syndrome (aka keratoconjunctivitis sicca) (claim 20)) in a subject, the method comprising administering to an eye or eyelid of the subject (more specifically, topically to the surface of the eye or eyelid (claim 18)), a composition comprising a Nanostructured Lipid Carrier (NLC) particle comprising:
(i) a solid outer shell comprising a solid lipid, wherein the solid lipid comprises cholesterol; and
(ii) a liquid core comprising a liquid lipid, wherein the liquid lipid comprises castor oil triglyceride;
wherein the NLC does not comprise or encapsulate a therapeutic agent other than the liquid lipid.
Wei et al teach “an ophthalmic composition including a… lipid nano-dispersion” (Paragraph 0007), which “refers to a dispersion system of solid lipid nanoparticle (SLN)” (Paragraph 0065), wherein “the lipid nano-dispersion includes a first lipid, a second lipid, and emulsifier; in which the first lipid exists in form of solid lipid… and the second lipid exists in form of liquid lipid” (Paragraph 0007), wherein “[p]referably, the solid lipid includes yellow Vaseline and wool fat” (Paragraph 0008), which comprises cholesterol, and “the liquid lipid includes at least one of… castor oil”, listed among seven options (Paragraph 0011), wherein the composition “can be used for prevention or treatment of dry eye syndrome without containing any active pharmaceutical agent” (Paragraph 0058), said method comprising “the step of administering to the subject an effective amount of the ophthalmic composition” (Paragraph 0040), in particular topically to the surface of the eye of said subject (see, e.g., Paragraph 0170).
However, although Wei et al state that “[t]he lipid nano-dispersion is similar to the nanostructured lipid carrier that was developed from SLN” (Paragraph 0066) and disclose “preparation of the lipid nano-dispersion” in a way which would seemingly provide an NLC having the liquid lipids enclosed in the solid lipid shell (Paragraph 0031-0035), Wei et al nevertheless state that, “[c]ompared to NLC, lipid nano-dispersion has a higher concentration of liquid lipids. Therefore, the solid lipids maybe entrapped in the liquid lipids” (Paragraph 0067).
As such, the method of treating dry eye syndrome taught by Wei et al differs from the instantly claimed method in that Wei et al teach the administration of a lipid nano-dispersion (i.e., solid lipid nanoparticle) comprising a solid lipid comprising cholesterol and a liquid lipid comprising castor oil as opposed to a nanostructured lipid carrier comprising the solid lipid cholesterol as a solid outer shell and liquid lipid castor oil as a liquid core as claimed.
Yet, as taught by Seyfoddin et al, “SLNs can be successfully converted to physically superior NLCs” (Abstract), which “are structural modifications of SLNs developed to address their insufficiencies, such as… stability problems” (Page 513, Column 1).
And, Viladot Petit et al teach “nanostructured lipid carriers (NLC)” (Abstract) wherein “[t]he solid lipid is selected, without restriction, from… sterols, cholesterol and cholesterol esters” and so on, (Paragraph 0041) and “[t]he liquid lipid is selected, without restriction, from the group formed by vegetable oils, such as… castor oil” (Paragraph 0040).
Accordingly, in further view of Seyfoddin et al and Viladot Petit et al it would have been prima facie obvious to modify the method of Wei et al by utilizing an NLC for administration as opposed to an SLN. It would have been obvious to do so to provide a physically superior delivery device having enhanced stability, as taught by Seyfoddin et al, and with a reasonable expectation of success, based on Seyfoddin et al (which teach that “SLNs can be successfully converted to physically superior NLCs”) and based on Viladot Petit et al (which generically disclose the feasibility of NLCs comprising a solid outer shell comprising cholesterol and a liquid core comprising castor oil triglyceride).
Based on all of the foregoing, claims 17-18 and 20 are rejected as prima facie obvious.
Claims 25-26 are drawn to the method of claim 17 wherein the NLC particle comprises about 1:1 of solid outer shell relative to the liquid core (claim 25), more specifically about 1:1 of cholesterol relative to castor oil (claim 26).
As taught by Wei et al, “[p]referably, based on the total volume of the ophthalmic composition, the ophthalmic composition includes 0.1% ~ 6% (w/v) of the first lipid” (Paragraph 0071) and “0.1% ~ 10% (w/v) of the second lipid” (Paragraph 0074).
And, as taught by Viladot Petit et al, “in the mixtures of lipids of the NLC the liquid lipids and solid lipids are mixed in a proportion which… [is] preferably between 50:50 and 0.1:99.9%” (Paragraph 0042).
As such, claims 25-26 are also rejected as prima facie obvious. As discussed by MPEP 2144.05, “[i]n the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists” (citing In re Wertheim, 541 F.2d 257 (CCPA 1976); In re Woodruff, 919 F.2d 1575 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465 (Fed. Cir. 1997)).
Claims 21-23 are MAINTAINED rejected under 35 U.S.C. 103(a) as being unpatentable over Wei et al (US 2016/0074321; of record) in view of Seyfoddin et al (Drug Development and Industrial Pharmacy 39:508-519, 2013; of record) and Viladot Petit et al (US 2013/0017239; of record; of record) as applied to claims 17-18, 20 and 25-26 above, as evidenced by Mubofu (Sustain Chem Process 4:11, 2016; of record).
Claims 21-23 are drawn to the method of claim 17 wherein the triglyceride comprises ricinoleic acid, oleic acid and linoleic acid (claim 22), wherein ricinoleic acid is the majority fatty acid component of the NLC particle (claim 21), more specifically, wherein the triglyceride comprises at least 85% ricinoleic acid (claim 23).
As evidenced by Mubofu, castor oil “exists as a mixture of saturated and unsaturated fatty acids attached to a glycerol” wherein, “[i]n the mixture of castor oils fatty acids, ricinoleic acid accounts for about 90% of the mixture with all other components in small proportions of not more than 5%” (Page 3, Column 2), wherein the other components include oleic acid and linoleic acid (Page 4, Figure 4).
As such, claims 21-23 are also rejected as prima facie obvious.
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 §§ 706.02(l)(1) - 706.02(l)(3) 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 17-18, 20-23 and 25-26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of U.S. Patent No. 11,779,543.
Although the claims at issue are not identical, they are not patentably distinct from each other. The ‘543 claims are similarly drawn to a method of treating/preventing an eye disorder in a subject comprising administering to said subject’s eye an NLC comprising a solid outer shell comprising cholesterol, and a liquid core comprising a liquid lipid comprising a triglyceride and “the therapeutic agent” which is understood to either include said triglyceride (claim 21) wherein the triglyceride can be castor oil (claim 4), or further entail an agent separate from said triglyceride which is castor oil (claim 21).
Claims 17-18, 20-23 and 25-26 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 9-21 and 24-25 of copending Application No. 18/458,828.
Although the claims at issue are not identical, they are not patentably distinct from each other. The ‘828 claims are similarly drawn to a method of treating/preventing an eye disorder in a subject comprising administering to said subject’s eye an NLC (claims 24-25) comprising a solid outer shell comprising cholesterol (claims 1-3), and a liquid core comprising a liquid lipid comprising a triglyceride containing castor oil (claims 1 and 4).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No new ground(s) of rejection are presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CRAIG D RICCI whose telephone number is (571) 270-5864. The examiner can normally be reached on Monday through Thursday, and every other Friday, 7:30 am - 5:00 pm ET.
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/CRAIG D RICCI/Primary Examiner, Art Unit 1611
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