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 .
DETAILED ACTION
The examiner for this application has changed. SPE Jean-Louis can be reached at 571-270-3503.
Response to Arguments
This Office Action is in response to the amendment submitted on 05/12/25. Claims 26, 30-39, 41-43, and 46-54 are currently pending in the application, with claims 1-25, 27-29, 40, and 44-45 having being cancelled. Accordingly, claims 26, 30-39, 41-43, and 46-54 are being examined on the merits herein.
Receipt of the aforementioned amended claims is acknowledged and has been entered.
IDS
The information disclosure statements (IDS) submitted on 05/27/25 and 07/01/25 acknowledged and have been entered. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements have been considered by the examiner.
In light of Applicant’s request to hold the Non-Statutory Double Patenting (NSDP) rejections in abeyance, applicant’s amendment of the claims, and given that Applicant failed to file terminal disclaimers disclaiming the terminal portion of any patent granted on applications 11,458,146; 10,238,664; 12,029,742; and co-pending application, the NSDP rejections remain proper and are maintained.
Given that applicant has amended the claims to now recite slowing the progression of specific inflammatory disorders and given that applicant has cancelled claims 27 and 40, the 112(a) enablement rejection is now moot. Consequently, the 112(a) enablement rejection of claims 26-27 and 31-44 is hereby withdrawn.
Given that applicant has amended the claims to now recite specific oxysterol compounds, and given that applicant has cancelled claims 27, 40, and 44, the 112(a) Written Description rejection is now moot. Consequently, the 112(a) lack of Written Description rejection of claims 26, 29-43, and 45 is hereby withdrawn.
Given that applicant has amended the claims to now recite specific diseases or inflammatory disorders, and given that applicant has cancelled claims 27, 40, and 44, the 112(b) indefiniteness rejection is now moot. Consequently, the 112(b) indefinite rejection of claims 26-27 and 30-44 is hereby withdrawn.
Given that applicant has amended the claims to now incorporate claim 29 and 45 into claim 26 and 43, and given that applicant has cancelled claims 27, 40, and 44, the 102 rejection is now moot. Consequently, the 102 rejection of claims 26-27, 37-38, and 40-44 over Parks et al. is hereby withdrawn.
Given that applicant has amended the claims to now incorporate claim 29 and 45 into claim 26 and 43, and given that applicant has cancelled claims 27, 40, and 44, the 102 rejection is now moot. Consequently, the 102 rejection of claims 26-27, 37-38, and 40-44 over Benner et al. is hereby withdrawn.
Given that applicant has amended the claims to now incorporate claim 29 and 45 into claim 26 and 43, and given that applicant has cancelled claims 27, 40, and 44, the 102 rejection is now moot. Consequently, the 102 rejection of claims 26-27, 37-38, and 40-44 over Benner et al. is hereby withdrawn.
Given that applicant has amended the claims to now incorporate claim specific diseases to be treated utilizing specific compounds, and given that applicant has cancelled claims 27, 40, and 44, the 103 rejection is now moot. Consequently, the 103 rejections of claims 31-36 and 38-39 over Parks in view of Chiu and Goldminz are hereby withdrawn.
For the foregoing reasons, the rejections of record are hereby withdrawn. However, in view of applicant’s amendment, the following NSDP and modified 103 (a) Final rejection are being 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 26, 30, 32, 37-39, 41-43, and 48-53 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 11,458,146. Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are directed to treating diseases or disorders related to inflammation such as necrotizing enterocolitis utilizing oxysterols. Unlike the instant claims which recites a broad genus of disorders utilizing particular compounds, the reference claims are also limited to the treatment of necrotizing enterocolitis (see instant claims 26 and 43). Therefore, the claimed invention is rendered obvious by the reference claims.
Claims 26, 27 and 31-44 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 10,238,664 in view of Shah et al. (J. of Peds. Vol. 153, Iss. 2; 2008, pgs. 170-175). Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are directed to “treating diseases or disorders related to inflammation” by administering at least one oxysterol. Unlike the instant claims which recites a broad genus of inflammatory disorders, the reference claims are limited to “myelin repair due to brain injury”. However, Shah et al. teach that necrotizing enterocolitis (recited in instant invention) is mediated by white matter injury (which itself is due to myelin injury). Consequently, treatment targeting necrotizing enterocolitis as recited in instant claim 26 would also lead to treatment of myelin injury of any etiology. Thus, the instant claims are rendered obvious by the reference claims U.S. Patent 10,238,664.
Claims 26, 30, 41, 43, 46, 52, are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 11,426,419 in view of Shah et al. (J. of Peds. Vol. 153, Iss. 2; 2008, pgs. 170-175). Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are directed to “treating diseases or disorders related to inflammation” by administering at least one oxysterol. Unlike the instant claims, the reference claims are limited to “promoting oligodendrogenesis”. However, the present specification sets forth the use of oxysterols for promoting oligodendrogenesis (see for example, paragraph 0025). Additionally, Shah et al. teach that necrotizing enterocolitis (recited in instant invention) is mediated by white matter injury (which itself is due to myelin injury). Consequently, treatment targeting necrotizing enterocolitis as recited in instant claim 26 would also lead to treatment of myelin injury of any etiology. Thus, the instant claims are rendered obvious by the reference claims U.S. Patent 11,426,419.
Claims 26, 30, 32, 37-39, 41, 43, 46, and 48-52 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 3-19 of U.S. Patent No. 12,029,742 in view of Shah et al. (J. of Peds. Vol. 153, Iss. 2; 2008, pgs. 170-175). Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are directed to “treating diseases or disorders related to inflammation” by administering at least one oxysterol. Unlike the instant claims, the reference claims are limited to “treating a disease characterized by myelin pathology”. However, the present specification sets forth the use of oxysterols for repairing injured myelin by promoting oligodendrogenesis (see for example, paragraph 0025). Additionally, Shah et al. teach that necrotizing enterocolitis (recited in instant invention) is mediated by white matter injury (which itself is due to myelin injury). Consequently, treatment targeting necrotizing enterocolitis as recited in instant claim 26 would also lead to treatment of myelin injury of any etiology. Thus, the instant claims are rendered obvious by the reference claims U.S. Patent 12,029742.
Claims 26, 27 and 31-44 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 18-38 of copending Application No. 18/673,022 (reference application) in view of Shah et al. (J. of Peds. Vol. 153, Iss. 2; 2008, pgs. 170-175). Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are directed to “treating diseases or disorders related to inflammation” by administering at least one oxysterol. Unlike the instant claims, the reference claims are limited to “treating a disease or disorder associated with myelin injury”. However, the present specification sets forth the use of oxysterols for repairing injured myelin (see for example, paragraph 0025). Additionally, Shah et al. teach that necrotizing enterocolitis (recited in instant invention) is mediated by white matter injury (which itself is due to myelin injury). Consequently, treatment targeting necrotizing enterocolitis as recited in instant claim 26 would also lead to treatment of myelin injury of any etiology. Thus, the instant claims are rendered obvious by the reference claims U.S. Patent Application 18/673,022. thus, the instant claims are rendered obvious by the reference claims or disclosure.
This is a provisional non-statutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 of this title, 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.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 26, 31-33, and 41-43 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Spann et al. (Nature Immunology, 2013, Vol. 14, No. 9, pgs. 893-900) in view of Yu et al. (FASEB, Mar. 2016, Vol. 30, No. 7, pgs. 2570-2579) and Kim et al. (J. of Lipid Res., 2010, Vol. 51, pgs. 3425-3433).
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.
LXR receptors are members of the nuclear receptor family of transcription factors that function to positively and negatively regulate gene expression in a ligand-dependent manner (see pg. 893, right col). LXRα is expressed mainly in adipose tissue, the liver and the intestine and has an important role in cholesterol homeostasis while LXRβ is broadly expressed and has key functions in both the central nervous system and the immune system (see pg. 893, right col.). After binding activating ligands, corepressor complexes are exchanged for coactivator complexes, which results in transcriptional activation (see pg. 893, right col.). In some cases, this mechanism of inhibition has been demonstrated to involve the tethering of LXRs to AP-1- and/or NFκB-dependent promoters, which results in inhibition of the exchange of corepressors for coactivators (see pg. 894, left col.). Importantly, the transcriptional activities of LXRs are regulated by cholesterol precursors and oxysterols that include desmosterol, 24S-hydroxycholesterol (24S-OHC), 25-hydroxycholesterol (25-OHC) and 27-hydroxycholesterol (27-OHC) (see pg. 894, left col.). In addition to positively regulating genes encoding molecules required for the homeostasis of cholesterol and fatty acids, LXRs also suppress inflammatory responses (see pg.894, left col.). Anti-inflammatory activities of synthetic LXR ligands have been suggested to underlie their beneficial effects in mouse models of various diseases in which inflammation is considered to have a pathogenic role (see pg. 894, right col.).
Spann et al. do not specifically teach a method to slow or prevent disease progression wherein the disease is ulcerative colitis. Additionally, Spann et al. do not teach measuring the level of NFkB.
Activation of LXR-mediated transcription by synthetic agonists, such as T0901317 and GW3965, attenuates progression of inflammatory disease in animal models (see abstract). Yu et al. showed that oral treatment (i.e. pharmaceutical composition) with sterol-based LXR agonists in mice significantly reduces dextran sulfate sodium colitis-induced body weight loss, which is accompanied by reduced expression of inflammatory markers in the large intestine (i.e. ulcerative colitis; see abstract). Additionally, LXR agonists suppress inflammation by transrepression of NF-κB-mediated transcriptional activity (see pg. 2570). These agonists have demonstrated preclinical efficacy in treating many diverse types of chronic inflammatory diseases, including atherosclerosis, contact dermatitis, rheumatoid arthritis, and ulcerative colitis (see pg. 2570). Additionally, LXR agonists suppress inflammation by transrepression of NF-κB-mediated transcriptional activity (see pg. 2571, left col). These agonists including DMHCA (i.e. a synthetic oxysterol) have demonstrated preclinical efficacy in treating many diverse types of chronic inflammatory diseases, including atherosclerosis, contact dermatitis, rheumatoid arthritis, and ulcerative colitis (see pg. 2571, left col.). Overall, these results provide evidence for the development of sterol-based LXR agonists as novel therapeutics for chronic inflammatory diseases (see abstract).
While Yu et al. do not specifically teach about measuring the levels of NFkB, Yu et al. did teach inhibition of NFkB suggesting an increase in diseased sample and thus repression as indicated by Yu et al. is suggested since such reduction demonstrates treatment of inflammatory diseases including ulcerative colitis.
Kim et al. teach that LXR is also involved in immune responses, including
anti-inflammatory action and T cell proliferation (see abstract). Specifically, Liver X receptor (LXR) and LXR , also known as NR1H3 and NR1H2, respectively, are members of a nuclear hormone receptor superfamily, which are implicated in metabolic homeostasis and inflammation (see pg. 3425, left col.). Importantly, Kim et al. teach LXR can be activated by certain oxygenated cholesterol derivatives (i.e. oxysterols), including 20(S)-hydroxycholesterol [20(S)-HC], 22(R)-HC, and 24HC, naturally occurring oxysterols that stimulate the expression of LXR target genes (see pg. 3425, right col.).
Thus, to one of ordinary skill in the art at the time of the invention would have found it obvious to utilize the oxysterols of Spann and Kim to slow down or prevent disease progression of ulcerative colitis given that Span and Kim et al. demonstrate that oxysterols such as 24(S)-OHC and 25-OHC can activate LXRs and LXRs are involved in modulating inflammation and in light of Yu et al. who teach that LXR agonists lead to activation of LXR and suppression of inflammation and repression of NFkB which leads to treatment of ulcerative colitis. Given the teachings of Spann, Yu, and Kim., one of ordinary skill would have been motivated to utilize oxysterols such as 25-OHC with the reasonable expectation of providing a method that is useful in regulating the levels of NFkB and suppression of inflammation as observed in ulcerative colitis.
Claims 37-39 and 49-51 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Spann et al. (Nature Immunology, 2013, Vol. 14, No. 9, pgs. 893-900) in view of Yu et al. (FASEB, Mar. 2016, Vol. 30, No. 7, pgs. 2570-2579) and Kim et al. (J. of Lipid Res., 2010, Vol. 51, pgs. 3425-3433) as applied to 26, 31-33, and 41-43 in further view of Nitzan et al. (World J. Gastroentero., 2016, Vol. 22, No. 3, pgs. 1078-1087).
The Spann, Kim, and Yu references are as discussed above and incorporated by reference herein. Spann, Kim, and Yu do not teach the use of additional therapeutic agents such as antibiotics.
Nitzan et al. teach that inflammatory bowel disease is thought to be caused by an aberrant immune response to gut bacteria in a genetically susceptible host (see abstract). The gut microbiota plays an important role in the pathogenesis and complications of the two main inflammatory bowel diseases: Crohn’s disease (CD) and ulcerative colitis (see abstract). Alterations in gut microbiota, and specifically reduced intestinal microbial diversity, have been found to be associated with chronic gut inflammation in these disorders (see abstract). Antibiotics may influence the course of these diseases by decreasing concentrations of bacteria in the gut lumen and altering the composition of intestinal microbiota (see abstract). Another study of patients assigned to ciprofloxacin and metronidazole vs. methylprednisolone for 12 wk found a larger proportion of patients in clinical remission in the steroid group (did not achieve statistical significance) (see pg. 1081, right col.). Additionally, a large trial from 2007 included 213 patients that were randomly assigned to receive a combination of clarithromycin, rifabutin and clofazimine or placebo for 2 years, in addition to 16 wk of prednisolone (see pg. 1081, right col.). The only time interval where a significant effect was noted was at 16 wk (when concomitant steroids were still given) (see pg. 1081, right col.).
Thus, to one of ordinary skill in the art at the time of the invention would have found it obvious to utilize a corticosteroid to treat ulcerative colitis given that Nitzan et al. teach that addition of prednisolone led to a significant effect in IBD patients. Given the teachings of Nitzan et al., one of ordinary skill would have been motivated to add prednisolone to the treatment of oxysterol as taught by Spann and Yu with the reasonable expectation of providing a method that is useful in enhancing the treatment of ulcerative colitis.
Objections
Claims 34-36, 47, and 54 are objected to because of the following informalities: Claims are dependent upon rejected claims. Applicant is required to incorporate all of the limitations of said claims into the independent claims. Appropriate correction is required.
Conclusion
Claims 34-36, 47,and 54 are objected but the remaining claims are not allowed.
Applicant's amendment necessitated the new ground(s) of rejection 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 Director Patricia Mallari whose telephone number is 571-272-4729. The Supervisory Primary Examiner can normally be reached on 12:00-8:00 PM EST M-F at 571-270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/SAMIRA J JEAN-LOUIS/Supervisory Patent Examiner, Art Unit 1642