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 .
Claim Status
Claims 2-34, 36-89, 91, 125-126, 128-131, and 133-140 have been cancelled and claims 1, 35, 90, 92-94, 96, 98-101, 104, 106, 108-112, 115-116, 132, and 146-147 have been amended, as requested in the amendment filed on 02/19/2026. Following the amendment, claims 1, 35, 90, 92-124, 127, 132, and 141-178 are pending in the instant application.
Claims 35, 90, 93-114, 117-124, 127, 132, 141-145, 147, and 154-178 stand as withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention and/or a non-elected species in the Response filed 09/02/2025 there being no allowable generic or linking claim.
Claims 1, 92, 115-116, 146, and 148-153 are under examination in the instant office action.
Priority
Applicant's claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or
under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged.
The later-filed application must be an application for a patent for an invention which is
also disclosed in the prior application (the parent or original nonprovisional application or
provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the
first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco
Products, Inc. V. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994). The disclosure of the prior-filed applications, PCT/US2019/012786, U.S. Application No.
16/243,020, and PRO 62/872,229 fail to provide adequate support or enablement in the manner
provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims
of this application. It is specifically noted that the identified prior-filed applications do not
disclose all of the species of the instant claims; notably PCT/US2019/012786 and U.S.
Application No. 16/243,020 do not disclose the compound of instant claim 1 wherein n > 1, and
PRO 62/872,229 nor PRO 62/937,721 disclose the compound of instant claim 1 wherein n may
be 6.
In view of the above, claims 1, 92, 115-116, 146, and 148-153 have an effective filing
date of January 8, 2020 corresponding to PCT/US2020/012798, which is the earliest prior-filed
application to disclose compounds of claim 1 wherein n = 1, 2, 3, 4, 5, or 6.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 02/19/2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Specification - Objections Withdrawn
Applicant has submitted a substitute specification wherein (i) the abstract has been amended to remove inadvertently included text and structures and (ii) proper trademark notation is added. As such, the objections to the specification are withdrawn.
Claim Objections - Withdrawn
Claim 9 was objected to for the recitation of the abbreviation “LXR” without spelling out the full term at the first encounter in the claims. Claim 93 has been amended to spell out the full term “a liver X receptor (LXR) agonist”. As such, the objection to claim 93 is withdrawn.
Claim 115 was objected to for the recitation of “a compound of claim 146”. Claim 115 has been amended to recite “the compound of claim 146 or a pharmaceutically acceptable salt thereof.” As such, the objection to claim 115 is withdrawn.
Claim Rejections - 35 USC § 112 - Withdrawn
Claim 116 was rejected under 35 USC § 112(b), second paragraph, as being indefinite for lacking antecedent basis for the limitation “the conjugated compound”. Claim 116 has been amended to recite “the compound”, which has proper antecedent basis. As such, the rejection of claim 116 under 35 USC § 112(b), second paragraph, as being indefinite is withdrawn.
Claim Rejections - 35 USC § 103 - Withdrawn
Claims 1, 92, 115-116, 146, and 148-153 were rejected under 35 U.S.C. § 103 as
being obvious over WO 2019/136487 A1 (previously cited on PTO-892; herein after referred to as "Han") in view of non-patent literature by Nakamura et. al. (J. Pharm. Pharmacol., 1992, 44, 713-716; previously cited on PTO-892; herein after referred to as "Nakamura") and non-patent literature by Vig et. al. (Advanced Drug Delivery Reviews, 2013, 65, 1370-1385; previously cited on PTO-892; herein after referred to as "Vig").
Applicant argues that Han is not prior art. Han names the same inventor as the present application. Han was published July 11, 2019. The instant application is a U.S. national stage application of PCT/US2020/012798, filed January 8, 2020, i.e., less than one year from Han's publication date. Accordingly, Han does not qualify as prior art under 35 U.S.C. § 102(a)(1) at least by virtue of the exception set forth in 35 U.S.C. § 102(b)(1)(A) and does not qualify as prior art under 35 U.S.C. § 102(a)(2) at least because Han does not name "another inventor". As such, the rejection of claims 1, 92, 115-116, 146, and 148-153 under 35 U.S.C. § 103 in view of Han, Nakamura, and Vig is withdrawn.
Double Patenting - Withdrawn
Claims 1, 92, 115-116, 146, and 148-153 were rejected over claims 1-5 of U.S. Patent No. 11,760,775 in view of Han, Nakamura, and Vig;
Claims 1, 92, 115-116, 146, and 148-153 were rejected over claims 1-3, 6-8, 10-12, 15-18, 23-28 and 32-33 of U.S. patent number 10,711,032 in view of Han, Nakamura, and Vig;
Claims 1, 92, 115-116, 146, and 148-153 were rejected over claims 1-3, 5, 7-17and 20 of U.S. patent number 12,070,506 in view of Han, Nakamura, and Vig;
Claims 1, 92, 115-116, 146, and 148-153 were rejected over claims 1-7, 9-10, 13-17 and 23 of U.S. patent number 12,377,159 in view of Han, Nakamura, and Vig;
Claims 1, 92, 115-116, 146, and 148-153 were provisionally rejected over claims 1-3, 8-42, 50-71, 73-89, 91-92, 95 and 97-98 of U.S. application number 18/670,3012 in view of Han, Nakamura, and Vig;
Claims 1, 92, 115-116, 146, and 148-153 were provisionally rejected over claims 1-3, 8-42, 50-71, 73-89, 91-92, 95 and 97-98 of U.S. application number 18/670,3143 in view of Han, Nakamura, and Vig; and
Claims 1, 92, 115-116, 146, and 148-153 were provisionally rejected over claims 1-4, 7-11, 13-14, 16-17, 20-29, 32-35, 37-38 and 44-45 of U.S. application number 19/201,0754 in view of Han, Nakamura, and Vig.
As indicated above, Han does not qualify as prior art under 35 U.S.C. § 102(a)(1) at least by virtue of the exception set forth in 35 U.S.C. § 102(b)(1)(A) and does not qualify as prior art under 35 U.S.C. § 102(a)(2) at least because Han does not name "another inventor". As such, the above-listed claim rejections under nonstatutory double patenting in view of Han, Nakamura, and Vig are withdrawn.
Claim Rejections - 35 USC § 103 - Maintained
Claims 1, 92, 146, and 148-153 stand as rejected under 35 U.S.C. § 103 as being obvious over EP 1336602 A1 (previously cited on PTO-892; herein after referred to as "Scaramuzzino") in view of non-patent literature by Nakamura et. al. (J. Pharm. Pharmacol., 1992, 44, 713-716; previously cited on PTO-892; herein after referred to as "Nakamura") and non-patent literature by Vig et. al. (Advanced Drug Delivery Reviews, 2013, 65, 1370-1385; previously cited on PTO-892; herein after referred to as "Vig").
Claims 115-116 stand as rejected under 35 U.S.C. § 103 as being obvious over EP 1336602 A1 (previously cited on PTO-892; herein after referred to as "Scaramuzzino"), non-patent literature by Nakamura et. al. (J. Pharm. Pharmacol., 1992, 44, 713-716; previously cited on PTO-892; herein after referred to as "Nakamura"), and non-patent literature by Vig et. al. (Advanced Drug Delivery Reviews, 2013, 65, 1370-1385; previously cited on PTO-892; herein after referred to as "Vig") and in further view of non-patent literature by Singh et. al. (Mol. Cancer Ther., 2016, 15(6), 1311-1320; previously cited on PTO-892; herein after referred to as “Singh”).
Double Patenting - Maintained
Claims 1, 92, 115-116, 146, and 148-153 stand as rejected over claims 1-3, 6-8, 10-12, 15-18, 23-28 and 32-33 of U.S. patent number 10,711,032 in view of Scaramuzzino, Nakamura, Vig, and Singh;
Claims 1, 92, 115-116, 146, and 148-153 stand as rejected over claims 1-5of U.S. patent number 11,760,775 in view of Scaramuzzino, Nakamura, Vig, and Singh;
Claims 1, 92, 115-116, 146, and 148-153 stand as rejected over claims 1-3, 5, 7-17 and 20 of U.S. patent number 12,070,506 in view of Scaramuzzino, Nakamura, Vig, and Singh;
Claims 1, 92, 115-116, 146, and 148-153 stand as rejected over claims 1-7, 9-10, 13-17 and 23 of U.S. patent number 12,377,159 in view of Scaramuzzino, Nakamura, Vig, and Singh;
Claims 1, 92, 115-116, 146, and 148-153 stand as provisionally rejected over claims 1-3, 29-33, 52-53, 57-58, 60-61, 63-64, 68-70, 73, 76-79, 95, and 97-98 of U.S. application number 18/670,301 in view of Scaramuzzino, Nakamura, Vig, and Singh;
Claims 1, 92, 115-116, 146, and 148-153 stand as provisionally rejected over claims 2-3, 8-9, 12, 15, 17, 26, 29, 33, 37, 50, 52, 64-65, 68-71, 73, 76-83, 88, 91-92, and 95 of U.S. application number 18/670,314 in view of Scaramuzzino, Nakamura, Vig, and Singh; and
Claims 1, 92, 115-116, 146, and 148-153 stand as provisionally rejected over claims 39-40, 43-69 of U.S. application number 19/201,075 in view of Scaramuzzino, Nakamura, Vig, and Singh.
It is noted that the above-listed provisional rejections under non-statutory double patenting have been updated to reflect the most recently amended claim sets. The crux of the rejections are the same and are therefore maintained.
Response to Arguments
With regard to the maintained claim rejections above under 35 USC § 103 and nonstatutory double patenting in view of Scaramuzzino, Nakamura, Vig, and Singh, Applicant argues the following on Pages 64-67 of Remarks (02/19/2026):
The Office has selected compounds JII and JgII of Scaramuzzino as lead compounds based solely on structural similarity to the claimed compounds rather than any evidence of compound JII and JgII's pertinent properties that would have led a person having ordinary skill in the art to select them as lead compounds; a person having ordinary skill in the art, without hindsight benefit of Applicant's disclosure, would not have selected compounds JII and JgII of the cited reference as a lead compounds.
Scaramuzzino lists hundreds, if not thousands, of different possible compounds for F of Formula I. There are over 60 pages dedicated to potential F groups in Scaramuzzino. See, pages 18-82 of Scaramuzzino. Out of the exhaustive lists of compounds, Scaramuzzino discloses several species in Examples 1-34, none of which include the structures of JII or JgII. Furthermore, Table 1, on pages 165-167 of the cited reference, provides absorption data for several exemplary compounds compared to classic nitrate vasodilators. The data shows that the compounds in Table 1 displayed 10 to 1000 times slower absorption compared to classic nitrate vasodilators, which highlights the controlled release of nitric oxide, an important therapeutic advantage of this invention. Notably, none of the compounds shown in Table 1 are of Formula JII or JgII. Accordingly, there would have been no reason for a person of ordinary skill in the art to cherry pick compounds JII and JgII as lead compounds from all the compounds disclosed by Scaramuzzino.
The definition for R4 cited by the Examiner is set forth in the Group 8B section beginning on page 67. Several of the compounds in this section, which have distinct scaffolds from JgII, have R4 groups. Scaramuzzino does not state that the definition for R4 is in the Group 8B section would apply to molecules in other sections of Scaramuzzino, including the JgII formula in Group 5B. Thus, Scaramuzzino does not clearly define R4 for the JgII formula, and there is nothing in Scaramuzzino to suggest that the R4 definition cited by the Office applies to compounds outside of Group 8B compounds.
Even if, arguendo, a person having ordinary skill in the art could conclude that the R4 definitions on page 82 apply to JgII in the earlier section, there is nothing in the reference 0that would have motivated a person of ordinary skill in the art to make the selections proposed by the Examiner from the many possible R4 groups. The Examiner asserts that one of ordinary skill in the art "could," from the definitions provided by Scaramuzzino, arrive at a structure for F; obviousness is not established by what "could" be done, but by what the prior art would have taught or suggested to a person of ordinary skill in the art. The teachings of Nakamura and Vig do not remedy these deficiencies.
The teachings of Singh do not remedy the deficiencies of Scaramuzzino, Nakamura, and Vig.
Applicant’s arguments have been fully considered, but are deemed not persuasive.
With regard to Applicant’s arguments above, it is noted that that preferred embodiments are not the only teaching of a reference. “The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain.” In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983) (quoting In re Lemelson, 397 F.2d 1006, 1009, 158 USPQ 275, 277 (CCPA 1968)).
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A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill the art, including nonpreferred embodiments. Merck & Co. v. Biocraft Laboratories, 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989). See also > Upsher-Smith Labs. v. Pamlab, LLC, 412 F.3d 1319, 1323, 75 USPQ2d 1213, 1215 (Fed. Cir. 2005)(reference disclosing optional inclusion of a particular component teaches compositions that both do and do not contain that component); < Celeritas Technologies Ltd. v. Rockwell International Corp., 150 F.3d 1354, 1361, 47 USPQ2d 1516, 1522-23 (Fed. Cir. 1998) (The court held that the prior art anticipated the claims even though it taught away from the claimed invention. “The fact that a modem with a single carrier data signal is shown to be less than optimal does not vitiate the fact that it is disclosed.”). Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). “A known or obvious composition does not become patentable simply because it has been described as somewhat inferior to some other product for the same use.” In re Gurley, 27 F.3d 551, 554, 31 USPQ2d 1130, 1132 (Fed. Cir. 1994). Furthermore, “[t]he prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed….” In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004).
Thus, while the specific, exemplary embodiments may not comprise the scaffold structures of JII or JgII, the broader disclosure of Scaramuzzino indicates that such scaffolds fall within the scope of the invention, and that notably the compounds/scaffolds of the invention falling within the scope of F are molecules/drugs useful for the treatment of inflammatory, ischemic, degenerative and proliferative diseases of musculoskeletal, tegumental, respiratory, gastrointestinal, genito-urinary and central nervous systems (Page 4, Lines 7-8). Regarding the definition of R4, it is specifically noted that Groups 1B-8B are all listed together (see, for example, Page 28, Lines 34-36); thus, absent evidence to the contrary, the listing of substituent definitions following group 8B is to be applied to each of groups 1B-8B as would be suggested by how groups 1B-8B are listed together as options for F. As such, Scaramuzzino explicitly suggests that R4 for JII and JgII include the structural groups listed on Page 82 following the list of compounds/scaffolds for group 8B. Thus, Scaramuzzino explicitly suggests a compound corresponding to structure corresponds D* of instant claim 1 comprising a hydroxyl group, R5 is oxygen, R1a, R1b, and R3 are all hydrogen; Scaramuzzino also explicitly teaches that the compounds of F of the disclosure are useful in treating inflammatory conditions (i.e., are anti-inflammatory compounds). According to the prodrugs of the invention, the F structure corresponding to instant D* would then be further modified such that it fits general Formula I, F-(X)q (i.e., the group corresponding to the NR3 group of instant claim 1, or the NH2 group of F as disclosed by Scaramuzzino, is covalently attached to a promoiety). However, it is noted that one of ordinary skill in the art would recognize that there are other promoieties that could be utilized in the development of prodrugs that are still useful for the preparation of medicines for the treatment of inflammatory diseases, for example. Such promoieties are taught/suggested by Nakamura and Vig, including promoieties comprising glycine (e.g., diglycylglycine) which when covalently attached to structure F suggested by Scaramuzzino above would read on the structure of instant claim 1 wherein (R2 and R4 are both hydrogen).
It is specifically noted that no arguments against Nakamura and Vig have been provided. As indicated in the previous Office Action (11/19/2025), one of ordinary skill in the art would have been motivated to modify the “lead compound” disclosed by Scaramuzzino (corresponding to instant D*) based on the teachings of Nakamura and Vig because (i) replacing the promoiety designated as M by Scaramuzzino with amino acid promoieties, such as glycine/glycylglycine, would yield a structure reasonably predicted to achieve improved bioavailability, solubility, permeability, metabolic stability, and reduce the generation of reactive impurities such as formaldehyde upon degradation upon storage (amide linkage versus carbamate linkage), as suggested by Nakamura and Vig, wherein such a prodrug would be reasonably expected to be useful in the treatment of, for example, inflammatory diseases as suggested by Scaramuzzino.
With regard to the argument of impermissible hindsight, it is noted that “[a]ny judgement on obviousness is in a sense necessarily a reconstruction based on hindsight reasoning, but so long as it takes into account only knowledge which was within the level of ordinary skill in the art at the time the claimed invention was made and does not include knowledge gleaned only from applicant’s disclosure, such a reconstruction is proper.” In re McLaughlin 443 F.2d 1392, 1395, 170 USPQ 209, 212 (CCPA 1971). The “lead compound” corresponding to instant D* is suggested by Scaramuzzino, and the motivation to modify such a lead compound by replacing the promoiety of Scaramuzzino with an amino acid promoiety (e.g., glycine/glycylglycine) take into account knowledge available at the time the invention was filed and within the level of ordinary skill in the art.
As such, there are no deficiencies in the combination of Scaramuzzino, Nakamura, and Vig. No arguments against Singh have been provided. As such, the above-listed claim rejections under 35 USC § 103 and nonstatutory double patenting in view of Scaramuzzino, Nakamura, Vig, and Singh are maintained.
Conclusion
Claims 1, 35, 90, 92-124, 127, 132, and 141-178 are pending. Claims 35, 90, 93-114, 117-124, 127, 132, 141-145, 147, and 154-178 are withdrawn. Claims 1, 92, 115-116, 146, and 148-153 are rejected. No claims are allowed.
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 nonprovisional extension fee (37 CFR 1.17(a)) 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 ALYSSA RAE STONEBRAKER whose telephone number is (571)270-0863. The examiner can normally be reached Monday-Thursday 7:00 am - 5:00 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis can be reached at (571)270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ALYSSA RAE STONEBRAKER/Examiner, Art Unit 1642
/SAMIRA J JEAN-LOUIS/Supervisory Patent Examiner, Art Unit 1642
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