DETAILED ACTION
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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 1 July 2025 has been entered.
Status of Claims
The amendments and arguments filed 1 July 2025 are acknowledged and have been fully considered. Claims 1-17 currently pending. Claims 1 and 13-17 are amended; no claims are cancelled; claims 4-12 are withdrawn; no claims are new.
Claims 1-3 and 13-17 are examined on the merits herein.
Objections/Rejections Withdrawn
Rejections and/or objections not reiterated from previous Office Actions are hereby withdrawn.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, and constitute the complete set presently being applied to the instant application.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 14 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 14 recites the composition of claim 1, wherein the nanostructured lipid carriers (NLC) comprise greater than 50% solid lipid, requiring the NLCs to comprise more solid lipid than the remaining ingredients combined. However, claim 1 recites that the surfactant to lipid ratio is greater than 1:1 by weight, requiring the NLCs to comprise more surfactant than lipid. As it is impossible for the NLCs to comprise more surfactant than lipid, and more solid lipid than the remaining ingredients combined, claim 14 fails to include all of the limitations of the claim upon which it depends.
For examination purposes, claim 14 is interpreted as “wherein the nanostructured lipid carriers comprises greater than 50% solid lipid based on the total weight of lipid in the composition.”
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
Claims 1, 13-15, and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Garg et al. (Colloids and Surfaces B: Biointerfaces, 2016, Vol. 147, 17-24) in view of Tan et al. (Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2010, Vol. 372, 73-79).
Claim 1 is drawn to a lipid nanoparticle composition comprising one or more small molecule inhibitors of an inflammatory cytokine encapsulated within nanostructured lipid carriers, wherein the nanostructured lipid carriers have a surfactant to lipid ratio of greater than 1:1 by weight.
Garg et al. teach nanostructured lipid carriers for the delivery of methotrexate (Title, Abstract), further teaching methotrexate as an inflammatory cytokine inhibitor (pg. 18 left column first paragraph).
As such, Garg et al. a lipid nanoparticle composition comprising one or more small molecule inhibitors of an inflammatory cytokine encapsulated within nanostructured lipid carriers.
The composition of Garg et al. differs from the instantly claimed composition in the following ways:
the composition of Garg et al. does not comprise a surfactant.
Yet, as to 1: Tan et al. also teach nanostructured lipid carriers for the delivery of pharmaceutical agents (Abstract). Tan et al. further teach “reduction in particle size and increase in system stability of either SLN or NLC are often observed when surfactants are incorporated in the formulation and especially when used in combination” (Pg. 73-74 bridging paragraph), teaching a surfactant to lipid ratio of 2.8 (Table 1 on pg. 75), as calculated by examiner.
Therefore, it would have been prima facie obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have modified the composition of Garg et al. to comprise a surfactant having a surfactant to lipid ratio greater than 1:1 as taught by Tan et al. It would have been obvious to use the known technique of inclusion of a surfactant in NLCs to improve the composition of Garg et al. in the same way to have increased stability, with a reasonable expectation of success.
Based on all of the foregoing, claim 1 is rejected as prima facie obvious.
Claim 13 is drawn to the composition of claim 1, wherein the nanostructured lipid carriers have a surfactant to lipid ratio of 2:1 by weight.
Garg et al. and Tan et al. do not teach a surfactant to lipid ratio of 2:1 by weight.
However, Tan et al. teach that inclusion of surfactants in NLCs causes reduction in particle size and system stability (Pg. 73-74 bridging paragraph), indicating that the concentration of the emulsifier is a result effective variable.
And, as discussed by MPEP 2144.05, “[g]enerally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical” (see also In re Aller (220 F.2d 454)): “where 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…” Indeed, as further discussed by the court, “[s]uch experimentation is no more than the application of the expected skill of the [ordinarily skilled artisan] and failure to perform such experiments would, in our opinion, show a want of the expected skill”; see also In re Peterson, 315 F.3d at 1325 (Fed. Cir. 2005): “[t]he normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages” and “[o]nly if the ‘results of optimizing a variable’ are ‘unexpectedly good’ can a patent be obtained for the claimed critical range” (quoting In re Antonie (559 F.2d 618 (CCPA 1977))).
In the instant case, the concentration of the surfactant is clearly a result-effective variables, determining the size of particles and stability of the composition. Accordingly, it would have been customary for an artisan of ordinary skill in the art to determine the optimal concentration of surfactant in order to best achieve the desired results.
As such, claim 13 is rejected as prima facie obvious.
Claim 14 is drawn to the composition of claim 1, wherein the wherein the nanostructured lipid carriers comprise greater than 50% solid lipid based on the total weight of lipid in the composition.”
Claim 15 is drawn to the composition of claim 1, wherein the nanostructured lipid carriers comprise a solid to liquid lipid blend ratio of 50:50 to 90:10 by weight.
Garg et al. are silent as to the ratio of solid to liquid lipids. However, Tan et al. teach a solid to liquid lipid ratio of 80:20 (Table 1 on pg. 75), as calculated by examiner, overlapping with the instantly claimed range.
Therefore, it would have been prima facie obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have modified the composition of Garg et al. to comprise a solid to liquid lipid ratio of 80:20 as taught by Tan et al. It would have been obvious to combine the known NLC composition with the known ratio of solid to liquid lipid ration taught to be suitable for an NLC composition, with a reasonable expectation of success.
As such, claims 14-15 are rejected as prima facie obvious.
Claim 17 is drawn to the composition of claim 1, wherein the nanostructured lipid carriers have a latent heat of melting of less than 2 J/g.
Garg et al. and Tan et al. are silent as to the latent heat of melting of the nanoparticles.
However, as discussed in MPEP 2112.01, “Products of identical chemical composition can not have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 16 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable.
In the instant case, the latent heat of melting is a property inherent to nanostructured lipid carriers having the instantly claimed surfactant to lipid ratio as evidenced by the instant specification. As Garg et al. and Tan et al. teach the instantly claimed nanostructured lipid carriers having the instantly claimed surfactant to lipid ratio, the instantly claimed latent heat of melting is necessarily present.
As such, claim 17 is rejected as prima facie obvious.
Claims 2-3 are rejected under 35 U.S.C. 103 as being unpatentable over Garg et al. and Tan et al. as applied to claims 1, 14-15, and 17 above, and further in view of Bredehorst et al. (US 2018/0085452).
The teachings of Garg et al. and Tan et al. have been set forth above.
Claim 2 is drawn to the composition of claim 1, wherein the one or more small molecule inhibitors is Janus kinase inhibitor.
Claim 3 is drawn to the composition of claim 2, wherein the Janus kinase inhibitor is tofacitinib (Applicant’s elected species).
Garg et al. further teach the NLC composition for the treatment of rheumatoid arthritis (Abstract).
Bredehorst et al. also teach compositions for treatment of rheumatoid arthritis (Par. [0003]). Bredehorst et al. further teach “tofacitinib has been approved by FDA to treat adults with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response to, or who are intolerant of, methotrexate” (Par. 0487]). Bredehorst et al. further teach tofacitinib is suitable for delivery via liposomes (Par. [0347]), a lipid-based nanostructure.
Therefore, it would have been prima facie obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have modified the composition of Garg et al. and Tan et al. to comprise tofacitinib as taught by Bredehorst et al. It would have been obvious to substitute one active ingredient for treating rheumatoid arthritis for another to obtain the predictable result of a composition for treatment of rheumatoid arthritis in a person who has had an inadequate response to, or is intolerant of, methotrexate, with a reasonable expectation of success.
As such, claims 2-3 are rejected as prima facie obvious.
Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over Garg et al. and Tan et al. as applied to claims 1, 13-15, and 17 above, and further in view of Tan et al. (US 2018/0250228; of record) hereinafter Tan Patent and Gupta et al. (Pharm Res, 2015, Vol. 32, 2912-2927).
The teachings of Garg et al. and Tan et al. have been set forth above.
Claim 16 is drawn to the composition of claim 1, wherein the nanostructured lipid carriers are less than 30nm.
Garg et al. and Tan et al. do not teach the nanostructured lipid carriers being less than 30nm.
Tan Patent also teaches lipid nanoparticles for medical use (Abstract). Tan Patent further teaches nanoparticles having a size most preferably 5 to 15nm (Par. [0145]) overlapping with the instantly claimed range, and the size of the nanoparticles is small, thereby readily entering tissue (Par. [0194]).
Gupta et al. teach optimizing nanostructured lipid carriers for delivery of a pharmaceutical agent (Abstract). Gupta et al. further teach that variables including the amount of surfactant, amount of lecithin, oil-to-total lipid ratio, and drug-to-total lipid ratio have an effect on the particle size (Fig. 2C on pg. 2918).
Therefore, it would have been prima facie obvious to a person having ordinary skill in the art to have modified the composition of Garg et al. and Tan et al. to have a size less than 30nm as taught by Tan Patent utilizing the methods taught by Gupta et al. It would have been obvious to combine the known NLC composition, the known size for readily entering tissue, and known methods for controlling size of NLCs to yield the predictable result of a methotrexate NLC composition that readily enters tissue, with a reasonable expectation of success.
As such, claim 16 is rejected as prima facie obvious.
Response to Arguments
Applicant's arguments filed 1 July 2025 have been fully considered but they are moot in view of the new grounds of rejection set forth above.
Conclusion
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/PAUL HOERNER/Examiner, Art Unit 1611
/CRAIG D RICCI/Primary Examiner, Art Unit 1611