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 .
Election/Restrictions
Applicant's election with traverse of Group I, claims 1-5, drawn to a compound of formula (I), a pharmaceutically acceptable salt or a composition thereof, as well as the species compound 1001 in the reply filed on 6/26/2025 is acknowledged. The traversal is on the ground(s) that WO2014/151634 and CZ304112B6 do not suggest the modifications made in the instant application. This is not found persuasive.
WO2014/151634 (‘634) discloses macrocyclic peptides that inhibit interactions between PD-1/PD-L1 and CD80/PD-L1. ‘634 teaches a variety of macrocyclic compounds, including several where Rx or Ry are groups other than “-H” (see Examples 6043, 6044, 6045), that can be used in methods of treating disease, particularly cancer. Thus, these positions have some degree of flexibility in terms of the identity of the Rx and Ry groups.
CZ304112B6 (‘112) teaches conjugates consisting of a biologically active group (hydrazone) and a portion enhancing bioaccessibility thereof (cholic acid). ‘112 specifically notes that the main disadvantage of hydrazones is their low solubility in water or aqueous solutions, thus resulting in low bioavailability due to incomplete absorption or pre-systemic metabolism. A covalently attached absorption modifier can be attached to the biologically active portion of the molecule to increase its bioavailability. Sterol derivatives and related structures, especially bile acid derivatives (e.g., cholic acid), are commonly used as bioavailability enhancing groups. ‘112 further teaches that the conjugates exhibit a cytostatic effect and can be used for the preparation of medicaments intended for the treatment of tumor diseases.
Thus, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of ‘634 to incorporate the teachings of ‘112 to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to do so as both references are drawn to compounds used to treat cancer. Further, one of ordinary skill in the art would have recognized that the biological activity of the compounds could be enhanced through conjugation to sterols such as cholic acid. Thus, the common technical feature among the instant claims is not a special technical feature as it does not make a contribution over the prior art in view of ‘634 and ‘112.
The requirement is still deemed proper and is therefore made FINAL.
Claim Status
Claims 1-12 are pending under examination. Claims 3, 4, 6-12 have been withdrawn as non-elected species (claims 3 and 4) and inventions (claims 6-12). Claims 5-7, 9, and 11-12 are currently amended.
Priority
The instant application is the 371 national stage entry of PCT/US2021/022474, filed 3/16/2021, which claims priority to the provisional application 62/989,940, filed 3/16/2020. The priority date of 3/16/2020 is acknowledged.
Information Disclosure Statement
The IDS submitted on 7/12/2023 is being considered.
Specification
The use of the terms Tween 60 and Span 80 ([0069]) and Tween 20 ([0093]), which are trade names or marks used in commerce, have been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the terms.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claim 1 is objected to because of the following informalities: the claim recites “O- C3-C6 cycloalkyl. O-C3-C6 cycloalkyl C1-C6 alkyl” (emphasis added). The period between these two R9 appendages should be changed to a comma such that the claim reads “O- C3-C6 cycloalkyl, O-C3-C6 cycloalkyl C1-C6 alkyl” (emphasis added). Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 2, and 5 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The steroid or steroid derivative structures listed in claims 1 and 2 include “
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” but do not indicate what this structure means or represents. For purposes of examination, the structure is being interpreted as the attachment of the Rx or Ry group to at least one of the following boxed carbon:
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Claim 5 is similarly rejected for depending on claim 1.
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 (i.e., changing from AIA to pre-AIA ) 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, 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 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.
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.
Claim(s) 1, 2, and 5 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. (WO2020/237081 A1, effectively filed 5/21/2019, on IDS filed 7/12/2023) in view of Gallop et al. (WO02/28881 A1, published 4/11/2002).
Wang teaches macrocyclic peptides that bind to PD-L1 and are capable of inhibiting the interaction of PD-L1 with PD-1 and CD80 (Abstract). Wang teaches the following compound, Example 2, wherein Rx and Ry are both H and R9 is –OC1 alkyl [0296]:
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The differences between Example 2 and the instantly claimed compound 1001 are the boxed areas below:
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Wang teaches additional compounds wherein Example 2 is further modified through the addition of fatty acid chains at the boxed positions, such as Compound 1004, 1006, 1013, 1015, and 1016 (Pg 41-52), for example:
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Wang does not teach that Rx and/or Ry are steroids or steroid derivatives.
Gallop teaches bile-acid derived compounds for providing sustained systemic concentrations of drugs after oral administration (Title). Gallop teaches that rapid clearance of drugs from the systemic circulation represents a major impediment to effective clinical use of therapeutic and/or prophylactic compounds (Pg 6, first line under “State of the Art)”. One pathway that might be exploitable for sustained oral delivery of drugs with rapid systemic clearance is the entero-hepatic circulation of bile acids. Bile acids are secreted into the intestinal lumen where they emulsify and help solubilize lipophilic substances. Bile acids are conserved in the body by active uptake from the terminal ileum via the sodium-dependent transporter IBAT and subsequent hepatic extraction by the transporter NTCP (LBAT) located in the sinusoidal membrane of hepatocytes. The bile acid pool gets recirculated multiple times a day. Several groups have explored exploitation of this pathway through conjugation of C-24 carboxylic acid, C-3, C-7, and C-12 hydroxyl groups of cholic acid (and other bile acids) as handles for chemically conjugating drugs or drug surrogates (Pg 9, lines 3-27). Specifically, Gallop teaches embodiments wherein cholic acid is conjugated to γ-aminobutyric acid (GABA) or analogs thereof (Example 1; Example 43 and Figures 9 and 10). Evaluation of the pharmacokinetics of one conjugate, prodrug 8, led to the sustained release of gabapentin following oral administration compared to administration of gabapentin alone (Example 45).
Regarding claims 1 and 2, Wang teaches the compound Example 2 can be modified by adding fatty acid chains to the boxed positions shown above. Gallop teaches the addition of bile-acid derived steroids, such as cholic acid, conjugated to drugs such as GABA can promote its sustained release. It would be prima facie obvious to conjugate bile salt derivatives, such as cholic acid, to the cyclic peptides taught by Wang, in order to improve their release kinetics and take advantage of the entero-hepatic system upon administration of the compound. One skilled in the art would have a reasonable expectation of success as it was already established by Wang that the compound Example 2 could be modified at the boxed positions shown above with fatty acid chains, which are known in the art to similarly enhance stability and half-life availability.
Regarding claim 5, Wang further teaches pharmaceutical compositions containing one or a combination of the compounds described formulated together with a pharmaceutically acceptable carrier ([0272-0273]).
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, 2 and 5 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 4-6 of copending Application No. 17/772,343 (‘343, claims filed 10/17/2022) in view of Gallop et al. (WO02/28881 A1, published 4/11/2002).
Claim 1 of copending Application No. ‘343 recites a compound of formula (I)
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or a pharmaceutically acceptable salt thereof, wherein Rx and RY are independently selected from H, -(C=O)R1, -(C=NR2)R3, -(C=O)OR4, -(C=O)NR5R6, and -(C=S)NR7R8, provided that at least one of Rx and RY is other than H; each R1 is selected from phenyl, a bicyclic carbocyclic group, a tricyclic carbocyclic group, a monocyclic heterocyclyl group, a bicyclic heterocyclyl group, and a tricyclic heterocyclyl group, wherein R1 is substituted with 0-4 R1a groups, provided that R1 is other than furanyl; each R1a is independently selected from halogen, -NO2, C1-C3alkyl, haloC1-C3alkyl, -O-C1-C10alkyl, -CO2C1-C3alkyl,-CO2H,
-C(NH)NHphenyl, -OCH2phenyl, phenyl, -O-phenyl, and a monocyclic heterocyclyl group, wherein the -O-C1-C10 alkyl, phenyl, and monocyclic heterocyclyl groups are substituted with 0-2 R1b groups; each R1b is independently selected from -CN, halogen, -OC1-C3alkyl, -C1-C3alkyl, and phenyl; R2 is H or phenyl; R3 is phenyl; R4 is selected from selected from phenyl, a bicyclic carbocyclic group, a tricyclic carbocyclic group, a monocyclic heterocyclyl group, a bicyclic heterocyclyl group, and a tricyclic heterocyclyl group, wherein R4 is substituted with 0-4 R4a groups, substituted with 0-4 R4a; each R4 a is independently selected from halogen, C1-C3alkyl, haloC1-C3alkyl, and -OC1-C10alkyl; R5 is selected from H, C1-C3alkyl, and phenyl; R6 is selected from phenyl, a bicyclic carbocyclic group, a tricyclic carbocyclic group, a monocyclic heterocyclyl group, a bicyclic heterocyclyl group, and a tricyclic heterocyclyl group, wherein R4 is substituted with 0-4 R6a groups; each R6a is independently selected from halogen, -NO2, C1-C3alkyl, haloC1-C3alkyl, -O-C1-C10alkyl, -CO2C1-C3alkyl,-CO2H, -C(NH)NHphenyl,
-OCH2phenyl, phenyl, -O-phenyl, and a monocyclic heterocyclyl group, wherein the phenyl and the monocyclic heterocyclyl group are substituted with 0-2 R6b groups; each R6b is independently selected from -CN, halogen, -OC1-C3alkyl, C1-C3alkyl, and phenyl; R7 is selected from H, C1-C3 alkyl, and phenyl; R8 is selected from phenyl, a bicyclic carbocyclic group, a tricyclic carbocyclic group, a monocyclic heterocyclyl group, a bicyclic heterocyclic group, and a tricyclic heterocyclic group,, wherein R8 is substituted with 0-4 R8a; each R8 a is independently selected from halogen, NO2, -CN, C1-C3alkyl, haloC1-C3alkyl, C3-C6cycloalkyl, -O-C1-C10alkyl, -C(=O)NH2, O-haloC1-C10alkyl, -NHCO2C1-, C10alkyl, -CO2C1-C6alkyl, O-phenyl, phenyl, and a monocyclic heterocyclyl group, wherein the heterocyclyl group is substituted with 0-2 R8b groups; each R8b is independently halogen or C1-C3alkyl; and R9 is H or C1-C3alkyl.
Dependent claims include further embodiments of the cyclic peptide (claims 4 and 5) and pharmaceutical compositions thereof (claim 6).
The difference between copending Application No. ‘343 and the instant application are that ‘343 does not teach the addition of a steroid or steroid derivative to positions Rx and Ry.
As described above, Gallop teaches conjugating bile-acid derivatives such as cholic acid to drugs or drug surrogates in order to improve release kinetics. Conjugation of cholic acid to gabapentin increases its sustained release following oral administration as compared to administration of gabapentin alone.
It would have been prima facie obvious to one of ordinary skill in the art to incorporate the teachings of Gallop into the cyclic peptide compounds of copending Application No. ‘343 thereby arriving at the instant invention. One would have been motivated to do so in order to improve the release kinetics of the compounds taught by copending Application No. ‘343. Thus, the above claims are rendered obvious in light of the teachings of copending Application No. ‘343.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claim is allowed.
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/SARA E KONOPELSKI SNAVELY/Examiner, Art Unit 1658
/FRED H REYNOLDS/Primary Examiner, Art Unit 1658