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 .
Response to Amendments
Applicant’s amendments to the claims of April 8, 2026, in response to the Office Action of January 8, 2026, are acknowledged.
Response to Arguments
Applicant argues that there is no motivation to combine references with a reasonable expectation of success. Paek provides many active agents according to Applicant and there is too much picking and choosing.
Applicant argues that there is excellent dissolution characteristics and content uniformity with 5 to 60 μm particle size. Applicant argues there is a difference in dissolution rate depending on particle size. Applicant argues that Figure 3 shows PK differences based on particle size.
Applicant requests the Double Patenting rejections be held in abeyance. As such, the examiner maintain those rejections.
The examiner notes that Paek is published by Assignee LG Life Sciences Ltd. Paek provides compounds that are sphingosine-1-phosphate receptor agonists and provides formulas that encompass thousands or more compounds. Thus, when Paek synthesizes 161 compounds, a POSA understands that those made and referred to in examples are preferred. The claimed compound is compound 153, as noted in the previous Office Action. While the examiner acknowledges some picking and choosing was used to arrive at that compound, the selection of a preferred compound that has been made and identified as an S1P receptor agonist is a proper teaching.
Liu provides a teaching for the claimed particle size. Liu teaches an S1P receptor agonist with a range of particle sizes. A most preferred particle size is a less than 20 microns and Liu notes that particle sizes should be less than 50 microns. See par. 44.
Similarly, Kulkarni teaches stable compositions comprising S1P receptor agonists. The particles having a specific size will achieve homogeneity (i.e., uniformity). See par. 10. A most preferred particle size is less than 25 microns. See par. 40.
The motivation to combine references is that the references are each directed to S1P receptor agonist compounds with similar and overlapping excipients and they are each taught to treat multiple sclerosis, e.g. The use of a particle size of 20 and 25 microns is taught to enhance homogeneity.
Unexpected Results are Alleged to be Content Uniformity and Dissolution Profile:
The examiner notes that unexpected results means unexpectedly superior as compared to the closest prior art. Figure 3 shows overlapping and substantially similar plasma concentrations over time. According to Khadka et al., “Pharmaceutical particle technologies: An approach to improve drug solubility, dissolution and bioavailability,” Asian Journal of Pharmaceutical Sciences 9 (2014) 304-316, size reduction is one of the oldest strategies to improve solubility of a drug because it increases the surface area to volume ratio and are routinely used for poorly soluble drugs. See p306. Even further, according to Alyami et al., “An investigation into the effects of excipient particle size, blending techniques and processing parameters on the homogeneity and content uniformity of a blend containing low-dose model drug,” PLOS One June 13, 2017, particle size has an impact on uniformity of content, with smaller particles allowing for more uniform blends to be achieved. See p2, 6th par. In one example, particles were optimized to ensure better uniformity by passing them through a 20 micron mess sieve. See p3. Additionally, Meda et al., “Impact of Particle Size on Content Uniformity,” International Journal of Innovative Research in Science, Engineering and Technology Vol. 3, Issue 2, February 2014, explains: “Results showed that smaller the particles better the content uniformity.” Abstract.
The examiner notes that a prima facie showing is established because the claimed compound is taught to be an S1P receptor agonist for treating conditions including MS. The secondary references teaches using S1P receptor agonists in a micronized form with a particle size of less the 60 microns as most preferred. As such, it would be obvious to arrive at the claimed composition in view of the prior art.
While Applicant alleges unexpected results, the Remarks and allegations are directed towards a uniformity of product at lower particle sizes and acceptable or “different” dissolution rates. The use of smaller particles sizes is well known to improve dissolution profile and content uniformity. The “difference” in PK does not appear to be an unexpected result. It is not clear what “difference” in particular Applicant is alleging to constitute the unexpected results. There is no data provided showing a statistical significance. There is also no comparison to show the claimed APIs dissolution provided in a non-micronized form at different pHs to show that the level of micronization claimed is responsible for the unexpected property. For example, Table 1 in the Remarks provide date on a composition that comprises five components at specific concentrations of each. Conversely, independent claim 1 merely requires an API and any carrier or excipient at any concentration. Even if unexpected, the showing is not commensurate in scope with the breadth of the claims.
Applicant should provide a showing that is commensurate in scope with the claims. The specific property should be alleged as unexpected and a reason that it is unexpected when smaller particle sizes are taught to be advantageous for dissolution and uniformity.
Figure 1 shows uniformity is higher with lower sizes. Similarly, Figure 3 shows initial dissolution to be higher at smaller particle sizes and lower with larger particle sizes. This is known in the art.
Drawings
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Foreign Priority Claim
The examiner acknowledges receipt of a translation of foreign priority documents.
Election by Original Presentation
According to M.P.E.P. 818.02(a):
Where claims to another invention are properly added and entered in the application before the earlier of the mailing of a first restriction requirement or the mailing of a first Office action on the merits, those claims, along with the ones presented upon filing the application, will be considered originally presented claims for purposes of restriction only.
The claims originally presented and acted upon by the Office on their merits determine the invention elected by an applicant in the application, and in any request for continued examination (RCE) filed for the application. Subsequently presented claims to an invention other than that acted upon should be treated as provided in MPEP § 821.03.
In this case, the claim set filed on October 12, 2023, included claims that were all directed to products starting with a preamble reciting: “A pharmaceutical composition” or “The pharmaceutical composition” and are interpreted as product claims. In the most recent claim set of April 8, 2026, Applicant amended claims 8-11 to method claims including a step for administration. As such, claims 8-11 are withdrawn as being directed to a non-elected group.
Status of the Claims
Claims 1 and 3-11 are pending. Claims 8-11 are withdrawn.
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 and 3-7 are rejected under 35 U.S.C. 103 as being unpatentable over Paek et al., (US2015/0376173) (cited in ISR), in view of Liu (US2016/0206557), and in view of Kulkarni et al., (US2014/0199382), and in view of Ruegger et al., (US2010/0267675).
Paek teaches sphingosine-1-phosphate (S1P) receptor agonists which can be used to treat autoimmune diseases, including multiple sclerosis and to treat and prevent immunoregulation. See Abstract. The compounds can including pharmaceutically acceptable salts including hydrochloric acid, sulfuric, nitric, and others salts. See par. 32. Pharmaceutical carriers including diluents can be used. See par. 284. Diluents including lactose can be used, lubricants including magnesium stearate can be use, disintegrants and binders are also contemplated. See par. 289. Compound 153 was synthesized as an example and is shown below.
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This is the claimed compound. Compounds can be obtained, separate, and purified by methods including recrystallization. See par. 276.
Paek does not teach particle size.
Liu teaches a sphingosine-1-phosphate (S1P) receptor agonist that can has a range of particle sizes to include one with a mean particle size of less than 50 microns and most preferably less than 20 microns. Particle size can be determined by any method employed in the art. The hydrochloride salt is contemplated. See par. 44. A preferred lubricant is sodium stearyl fumarate. See par. 132. Hydroxypropyl cellulose is used as a moisture facilitating excipient. See par. 40. Croscarmellose sodium is used as a disintegrant. See par. 61.
Kulkarni also teaches stable S1P receptor agonists with excipients for treating multiple sclerosis. See Abstract. Excipients that can be used include diluents, lubricants, binders, and others. See par. 20. Salts forms include a hydrochloride salt, among many others. See par. 27. Further, croscarmellose sodium is a suitable disintegrant, HPC is a suitable binder, sodium stearyl fumarate is an acceptable lubricant. See par.’s 31, 32, 33, and 34. The S1P receptor agonist is micronized and has a D90 that is less than 50 microns and a D50 that is less than 25 microns. See prior art claim 4.
Ruegger teaches compositions comprising S1P receptor modulators, including agonists. See par. 6. A final formulation typically includes binders, fillers, lubricants, and disintegrants. See par. 67. A filler includes lactose monohydrate as preferred. See par. 72. Magnesium stearate is a preferred lubricant. See par. 73. Croscarmellose sodium is also contemplated for use. See par. 75. Hydroxypropyl cellulose is also contemplated. See Example 6, Table 7. The examiner notes that prior art claim 1 includes: lactose monohydrate, sodium stearyl fumarate, hydroxypropyl cellulose, and croscarmellose sodium as one of a few optional fillers, binders, disintegrants, lubricants, and matrix formers.
It would have been prima facie obvious to a person of ordinary skill in the art prior to the filing of the instant application to combine the teachings of Paek, Liu, and Ruegger to arrive at the claimed products. One would be motivated to do so because Paek teaches the claimed API as a S1P receptor agonist for use with claimed excipients to treat a number of conditions including MS. Similarly, Liu teaches S1P receptor agonists with a preferable particle size of less than 20 microns for treating similar conditions with similar excipients. Kulkarni independently teaches an API with the same excipients claimed and a particle size that is Finally, Ruegger also teaches compositions comprising S1P receptor agonists including the claimed excipients each of which are taught for use in prior art claim 1. Thus, the claimed excipients are usable together and they appear to be commonly employed excipients for use in compositions comprising S1P receptor agonists. Thus, there is a reasonable and predictable expectation of success in arriving at the claimed products in view of the cited prior art as the use of the claimed excipients and particle sizes for S1P receptor agonists are known and employed in the art.
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 1-11 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 9,540,362, in view of Liu (US2016/0206557), in view of Kulkarni et al., (US2014/0199382), and in view of Ruegger et al., (US2010/0267675).
Although the claims at issue are not identical, they are not patentably distinct from each other because the claimed API is claimed in claim 3 of the ‘362 patent. See col. 186, line 47. Further, the patent application publication of the ‘362 patent corresponds to the teaches of Paek et al. as set forth above. It would have been prima facie obvious to a person of ordinary skill in the art prior to the filing of the instant application to combine the teachings of Liu, Kulkarni, and Ruegger to arrive at the claimed products. One would be motivated to do so because Paek teaches the claimed API as a S1P receptor agonist for use with claimed excipients to treat a number of conditions including MS. Similarly, Liu teaches S1P receptor agonists with a preferable particle size of less than 20 microns for treating similar conditions with similar excipients. Kulkarni independently teaches an API with the same excipients claimed and a particle size that is Finally, Ruegger also teaches compositions comprising S1P receptor agonists including the claimed excipients each of which are taught for use in prior art claim 1. Thus, the claimed excipients are usable together and they appear to be commonly employed excipients for use in compositions comprising S1P receptor agonists. Thus, there is a reasonable and predictable expectation of success in arriving at the claimed products in view of the cited prior art.
Claims 1-11 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 and 8-13 of U.S. Patent No. 12,479,836, in view of Liu (US2016/0206557), and in view of Kulkarni et al., (US2014/0199382), and in view of Ruegger et al., (US2010/0267675).
Although the claims at issue are not identical, they are not patentably distinct from each other because the claimed API is claimed within the scope of Formula (I) of the ‘836 patent. Further, claims 12 and 13 of the ‘836 patent are directed to treating conditions that fall within the “use” claims of the instant application and are taught by Paek et al. These conditions include MS, among others. It would have been prima facie obvious to a person of ordinary skill in the art prior to the filing of the instant application to combine the teachings of Liu, and Ruegger to arrive at the claimed products. One would be motivated to do so because Paek teaches the claimed API as a S1P receptor agonist for use with claimed excipients to treat a number of conditions including MS. Similarly, Liu teaches S1P receptor agonists with a preferable particle size of less than 20 microns for treating similar conditions with similar excipients. Kulkarni independently teaches an API with the same excipients claimed and a particle size that is Finally, Ruegger also teaches compositions comprising S1P receptor agonists including the claimed excipients each of which are taught for use in prior art claim 1. Thus, the claimed excipients are usable together and they appear to be commonly employed excipients for use in compositions comprising S1P receptor agonists. Thus, there is a reasonable and predictable expectation of success in arriving at the claimed products in view of the cited prior art.
As such, no claim is allowed.
Conclusion
THIS ACTION IS MADE FINAL. 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 mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JARED D. BARSKY whose telephone number is (571)-272-2795. The examiner can normally be reached on Monday through Friday from 8:30 to 5:30. If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Amy L. Clark can be reached on 571-272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JARED BARSKY/Primary Examiner, Art Unit 1628
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