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 26, 37, and 38 are pending. Claims 26 was amended; claims 27-36 and 39-43 were canceled; and no new claims were added in the Reply filed 5/04/2026. Claims 26 and 37-38 are presently considered.
Election/Restrictions
Applicant’s election without traverse of Group I (products, original claims 26-39) and the species of JW115 in the reply filed on 11/24/2025 is acknowledged.
In the absence of clarification regarding (R) and (S) stereochemistry for JW115, the absolute stereochemistry1 is understood to correspond to CAS NO: 2744980-61-6, which is identifier for the elected species associated with the instant Application, and is understood to have the following structure:
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Accordingly, the originally elected species is understood to have a LIII linker moiety of C3 alkylene and specifically -(CH2)3-; a B corresponding to a 5- 10 membered heteroaryl group, and specifically the 5-membered heteroaryl of an imidazolyl group
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; R1 is hydrogen; R2 is
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; R3 is ethyl; R4 is methyl; R5 is -CH2CH(CH3)2; R6 is
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; and R7 is hydrogen (see, e.g., Reply filed 11/24/2025 at 2-3). Examiner notes that CsA corresponds to CAS NO. 59865-13-3.
In view of the amendments and arguments filed 5/04/2026, the originally elected species has been deemed allowable in view of the prior art. Per MPEP § 803.02(III),
If the examiner determines that the elected species is allowable over the prior art, the examination of the Markush claim will be extended. If prior art is then found that anticipates or renders obvious the Markush claim with respect to a nonelected species, the Markush claim shall be rejected; claims to the nonelected species would still be held withdrawn from further consideration. The prior art search will not be extended unnecessarily to cover all nonelected species.
Examination had previously been extended to multiple other non-elected species, including CAS NO. 2744980-60-5 (“JW4-10”) (see, e.g., Action mailed 2/03/2026 at 4-5); CAS NO. 2744980-62-7 (“JW4-21”) (see, e.g., Action mailed 2/03/2026 at 4-5); CAS NO. 2744980-63-8 (“JW4-20”) (see, e.g., Action mailed 2/03/2026 at 4-5); CAS No. 1500112-70-8 (see, e.g., Action mailed 2/03/2026 at 11-12); CAS No. 881007-73-4 (see, e.g., Action mailed 2/03/2026 at 12-14); CAS NO. 1262527-22-9 (see, e.g., Action mailed 2/03/2026 at 14-15); and each of CAS NOs. 1883278-86-1, 1883278-88-3, and 1883278-89-4 (see, e.g., Action mailed 2/03/2026 at 15-16). In the Reply filed 5/04/2026, claim 26 was amended to exclude all of these previously examined non-elected species, which has necessitated new rejections.
Accordingly, per MPEP § 803.02(III), Examination has now been extended to a non-elected species reading upon the amended claim scope as filed 5/04/2026, namely to the non-elected species of CAS NO. 162926-14-9 (Cyclosporin A, 6-[(3R,4R,6E)-6,7-didehydro-3-hydroxy-8-[(1H-imidazol-1-ylcarbonyl)oxy]-N,4-dimethyl-L-2-aminooctanoic acid]- (9CI)), which has the structure of
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Following extensive search and examination, the non-elected species of CAS NO. 162926-14-9 was deemed anticipated and/or obvious in view of the prior art as applied below. Per MPEP § 803.02(III), claims directed to other nonelected species have been withdrawn.
Claims 26 and 37-38 are presently considered.
Priority
The priority claim to GB2007106.4 (filed 5/14/2020) is acknowledged.
Information Disclosure Statement
The IDS filed 5/04/2026 is acknowledged and presently considered. The fee set forth in 37 CFR 1.17(p) was checked.
Applicant should note that one or more documents disclosed on the IDS form submitted on 5/04/2026 were not considered since they did not conform to 37 CFR 1.98(b) by providing a proper date, as 37 CFR 1.98(b) requires that each publication must be identified by publisher, author (if any), title, relevant pages of the publication, and date and place of publication. The date of publication supplied must include at least the month and year of publication, except that the year of publication (without the month) will be accepted if the applicant points out in the information disclosure statement that the year of publication is sufficiently earlier than the effective U.S. filing date and any foreign priority date so that the particular month of publication is not in issue. See MPEP 609.04(a). Here, the earliest priority claim is to GB2007106.4 (filed 5/14/2020); therefore, all documents published in 2019 or later must be accompanied by both month and year of publication.
References that were not considered have been indicated by strike-though on the attached IDS forms. Although not considered, these documents have been placed in the application file, but the information referred to therein has not been considered as to the merits. Applicant is advised that the date of any re-submission of any item of information contained in this information disclosure statement or the submission of any missing element(s) will be the date of submission for purposes of determining compliance with the requirements based on the time of filing the statement, including all certification requirements for statements under 37 CFR 1.97(e). See MPEP § 609.05(a).
Claim Interpretation and Examiner Notes
For purposes of examination, the claim scope has been interpreted as set forth below per the guidance set forth at MPEP § 2111. If Applicant disputes any interpretation, Applicant is invited to unambiguously identify any alleged misinterpretations or specialized definitions in the subsequent response to the instant action. Applicant is advised that a specialized definition should be properly supported and specifically identified (see, e.g., MPEP § 2111.01(IV), describing how Applicant may act as their own lexicographer).
Amended claim 26 is representative of the pending claim scope. Applicable claim interpretations are discussed below.
The claims are understood to be directed to Cyclosporin A (CsA) analogues. The prior art is substantial, and teaches that the amino acids of CsA are routinely referred to by position numbers 1-11:
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(see, e.g., Guada et al.2 at Fig. 1 on 271). The structure/function relationships of each position are generally known, and the unsaturated chain at position 1 and the amino acids at position 2, 3, and 11 are responsible for immunosuppressive activity (see, e.g., Guada at 270 at col II at §§ 1.1).
In the absence of specialized definitions, all chemical terms are given their normal and routine meanings in the art. Cyclosporine A (CsA) is understood to correspond to CAS No: 59865-13-3, which has the absolute stereochemistry3 shown below:
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Cyclosporin A (CsA) is a cyclic undecapeptide (comprising 11 amino acid residues), wherein the amino acids are typically numbered 1-11, starting with MeBmt¹: (4R)-4-[(E)-2-butenyl]-4,N-dimethyl-L-threonine, then Abu²: L-α-aminobutyric acid, then Sar³: Sarcosine (N-methylglycine), then MeLeu⁴: N-methyl-L-leucine, then Val⁵: L-Valine, then MeLeu⁶: N-methyl-L-leucine, then Ala⁷: L-Alanine, then D-Ala⁸: D-Alanine, then MeLeu⁹: N-methyl-L-leucine, then MeLeu¹⁰: N-methyl-L-leucine, and then MeVal¹¹: N-methyl-L-valine .
The invention is understood to be directed to analogues of CsA modified at position 1 (see, e.g., instant claim 26 at R1, LIII, B, and R2). The prior art is replete with CsA analogues modified at position 1 (see, e.g., US 2013/03244804 at US’480 at col. 33 and 84; see also US20070232532A15 at title, abs, claims; see also US 9,669,0956 at claim 1; etc. This is not an exhaustive listing).
Examiner notes that zero evidence of unexpected results commensurate in scope with the requirements of MPEP §§ 716, 716.01, and 716.02 have been placed on record at this time. Relative to the originally elected species, the only data of record at Figure 4(B), appears to show that it does not exhibit any statistically different or improved properties relative to CsA.
Accordingly, no difference in chemical properties or applications appear to distinguish the instantly claimed genera and subgenera relative to the species, subgenera, and genera taught, disclosed, and claimed by the prior art.
Additional claim interpretations and notes are provided below.
Withdrawn Claim Rejections
The rejection of claims 34-36 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite, is withdrawn as moot in view of the cancellation of claims 34-36.
The rejection of claims 26-34 and 37-38 under 35 U.S.C. 102(a)(1)/(a)(2) as being clearly anticipated by US 2013/0324480 (Dec. 5, 2013; Pettit et al.; cited in previous action), is withdrawn in view of the cancellation of claims 27-34 and amendments to claim 26 limiting the claim scope to require that Group B is a 1-imidazolyl moiety.
The rejection of claims 26-34 and 37-38 under 35 U.S.C. 102(a)(1)/(a)(2) as being clearly anticipated by US 2006/0069015 Al (Mar. 30, 2006; Molino; attached with CAS Substance Table beginning at Page 37; cited in previous action) is withdrawn in view of the cancellation of claims 27-34 and amendments to claim 26 limiting the claim scope to require that Group B is a 1-imidazolyl moiety.
The rejection of claims 26-34 under 35 U.S.C. 102(a)(1)/(a)(2) as being clearly anticipated by WO2016/027089 (attached with additional substance Table starting at page 67; cited in previous action) is withdrawn in view of the cancellation of claims 27-34 and the amendments to claim 26 limiting the claim scope to require that Group B is a 1-imidazolyl moiety.
The rejection of claims 26-33 and 37-38 under 35 U.S.C. 102(a)(1)/(a)(2) as being clearly anticipated by US 2017/0349632 Al (Dec. 7, 2017; Selwood et al; cited in previous action.) as evidenced by WO2016/027089 (attached with additional substance Table starting at page 67; cited in previous action) is withdrawn in view of the cancellation of claims 27-34 and the amendments to claim 26 limiting the claim scope to require that Group B is a 1-imidazolyl moiety.
The rejection of claims 26-32 and 34-38 under 35 U.S.C. 103 as being unpatentable over US2018/0296588A1 (Oct. 18, 2018; Foster et al.; cited in previous action) is withdrawn in view of the cancellation of claims 27-32 and the amendments to claim 26 limiting the claim scope to require that Group B is a 1-imidazolyl moiety.
The rejection of claims 26-39 under 35 U.S.C. 103 as being unpatentable over US2018/0296588A1 (Oct. 18, 2018; Foster et al.; cited in previous action) as applied to claims 26-32 and 34-38 above, and further in view of US 2016/0002299A1 (Jan. 7, 2016; Towers et al.; cited in previous action) is withdrawn in view of the cancellation of claims 27-37 and 39, and the amendments to claim 26 limiting the claim scope to require that Group B is a 1-imidazolyl moiety.
The rejection of claims 26-33 and 37-38 on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 10,494,404 B2 (corresponding to US 2017/0349632 Al; cited in previous action) as evidenced by WO2016/0270897 (attached with additional substance Table starting at page 67; cited in previous action) is withdrawn in view of the cancellation of claims 27-33 and 39, and the amendments to claim 26 limiting the claim scope to require that Group B is a 1-imidazolyl moiety.
New Claim Rejections Necessitated by Applicant Amendment
Claim Rejections - 35 USC § 112(d)
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 37 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 37 depends from independent claim 26, wherein claim 26 was amended in the Reply filed 5/04/2026 to include all limitations regarding the linker moiety LIII recited at dependent claim 37 (compare claims 26 and 37-38, noting that claim 38 narrows the linker moiety length to C1-15 moieties). Accordingly, claim 37 is rejected under 35 USC § 112(d) as failing to further limit the subject matter of the claim upon which it depends.
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 § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 26 and 37-38 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being clearly anticipated by US 5,834,266 (Crabtree et al.; Nov. 10, 1998) as evidenced by Record8 and as evidenced by Registry9
Claim interpretation: The applicable claim interpretation has been set forth in a preceding section above, and those interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below.
Regarding instant claims 26 and 37-38, US’266 discloses a cyclosporin A analog having the structure of
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(see, e.g., US’266 at Example 21A at col. 60 at lines 32-60; see also id. at Fig. 13A)10. The stereochemistry is understood to be identical to that present in cyclosporine A (see, e.g., US’266 at Example 21A at col. 60 at lines 32-60; see also id. at Fig. 13A) 11. This prior art compound satisfies the requirements of the pending claims wherein: B is
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; R1 is hydrogen; LIII is a C1-15 alkylene group wherein one -CH2- is replaced with -O- and the another is replaced with -C(O)-, namely -(CH2)-O-C(O)-; R2 is
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; R3 is ethyl; R4 is methyl; R5 is -CH2CH(CH3)2; R6 is
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; R7 is a hydrogen; and all additional positions are identical and understood to correspond to cyclosporine A (compare instant claims 26 and 37-38 with US’266 at Example 21A at col. 60 at lines 32-60, Fig. 13A). Accordingly, the cyclosporin A analog of US’266 anticipates instant claims 26 and 37-38.
Claims 26 and 37-38 are rejected.
Response to Arguments
Applicant’s arguments with respect to claims 26 and 37-38 have been fully considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
US7141648B2 (cited in prior action) discloses ways of synthesizing CsA modified at the 1-position (see, e.g., id. at title, abs, Figures, claims).
WO2017/059207 (April 6, 2017; Neville et al.; cited in IDS filed 2/20/2023 as cite No. 14) discloses and claims two CsA analogues modified at position 1, corresponding to CAS NOs: 2093328-56-2 and 2093328-55-1 (see, e.g., WO’207 at claim 49).
WO2016/073480 discloses and claims CsA analogues modified at position 1 (see, e.g., WO’480 at claim 1; cited in IDS filed 2/20/2023 as cite No. 10). These embodiments differ from the pending claim scope with respect to position R5 of instant Formula III at claim 26.
US9,669,095 B2 (cited in prior action) discloses and claims CsA analogues modified at position 1 (see, e.g., US’095 at claims). However, these embodiments differ from the pending claim scope with respect to position R5 of instant Formula III at claim 26.
US2011/0206637 (cited in prior action) discloses and claims CsA analogues modified at position 1 (see, e.g., US’637 at claims). However, these embodiments differ from the pending claim scope with respect to position R5 of instant Formula III at claim 26.
US2017/0267726A1 (Sep. 21, 2017; cited in prior action) pertains to CsA derivatives, derivatized at position 1 (see, e.g., id. at title, abs, claims).
US20070232532A1 (cited in prior action) pertains to CsA derivatives modified at position 1 used in antiviral applications (see, e.g., id. at title, abs, claims).
US20120157385 A1 (cited in prior action) pertains to CsA derivatives modified at position 1 used in antiviral applications (see, e.g., id. at title, abs, claims).
US 2013/0324480 (Dec. 5, 2013; Pettit et al.), was previously applied under 35 USC 102 in the Action mailed 2/03/2026, and is therefore pertinent to the instant Application.
US 2006/0069015 Al (Mar. 30, 2006; Molino; attached with CAS Substance Table beginning at Page 37) was previously applied under 35 USC 102 in the Action mailed 2/03/2026, and is therefore pertinent to the instant Application.
WO2016/027089 (attached with additional substance Table starting at page 67) was previously applied under 35 USC 102 in the Action mailed 2/03/2026, and is therefore pertinent to the instant Application.
US 2017/0349632 Al (Dec. 7, 2017; Selwood et al.) as evidenced by WO2016/027089 (attached with additional substance Table starting at page 67) was previously applied under 35 USC 102 in the Action mailed 2/03/2026, and is therefore pertinent to the instant Application.
US2018/0296588A1 (Oct. 18, 2018; Foster et al.) was previously applied under 35 USC 103 in the Action mailed 2/03/2026, and is therefore pertinent to the instant Application.
US 2016/0002299A1 (Jan. 7, 2016; Towers et al.) was previously applied under 35 USC 103 in the Action mailed 2/03/2026, and is therefore pertinent to the instant Application.
U.S. Patent No. 10,494,404 B2 (corresponding to US 2017/0349632 Al) as evidenced by WO2016/02708912 (attached with additional substance Table starting at page 67) was previously applied under non-statutory obviousness-type double patenting in the Action mailed 2/03/2026, and is therefore pertinent to the instant Application.
Conclusion
No claims are 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 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 RANDALL L BEANE whose telephone number is (571)270-3457. The examiner can normally be reached Mon.-Fri., 7 AM to 2 PM ET.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko G. Garyu can be reached at (571) 270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/RANDALL L BEANE/Primary Examiner, Art Unit 1654
1 This is reasonable because absolute stereochemistry (the exact 3D arrangement of atoms) requires both the visual representation (wedges/dashes) and the Cahn-Ingold-Prelog (CIP) priority rules to assign R or S configuration. In addition, utilizing CAS numbers and associated structures permits standardized searching for structures regardless of N to C or C to N differences in structural displays.
2 Guada et al., Reformulating cyclosporine A (CsA): More than just a life cycle management strategy. J Control Release. 2016 Mar 10;225:269-82. doi: 10.1016/j.jconrel.2016.01.056. Epub 2016 Jan 30. PMID: 26829101; hereafter “Guada”; cited in previous action.
3 This is reasonable because absolute stereochemistry (the exact 3D arrangement of atoms) requires both the visual representation (wedges/dashes) and the Cahn-Ingold-Prelog (CIP) priority rules to assign R or S configuration.
4 Cited in previous action.
5 Cited in previous action.
6 Cited in previous action.
7 This is the corresponding WIPO publication, and is included herein because it has an added substance Table showing CAS Numbers and corresponding chemical structures.
8 Reference Details Record for Regulated apoptosis by chimeric proteins binding to FK506-type and cyclosporin-type ligands, US5834266A, 9 pages; SciFinder-n.cas.org; https://scifinder-n.cas.org/searchDetail/reference/6a28088f3e303e12d6e503fd/referenceDetails (accessed June 6, 2026); hereafter “Record”.
9 CAS NO. 162926-14-9; a.k.a., Cyclosporin A, 6-[(3R,4R,6E)-6,7-didehydro-3-hydroxy-8-[(1H-imidazol-1-ylcarbonyl)oxy]-N,4-dimethyl-L-2-aminooctanoic acid]- (9CI); 3 pages; SciFinder-n.cas.org; Chemical Abstracts Service: Columbus, OH; https://scifinder-n.cas.org/searchDetail/substance/6a2809483e303e12d6e512e7/substanceDetails (accessed June 6, 2026); hereafter “Registry”.
10 This structure is CAS NO. 162926-14-9; a.k.a., Cyclosporin A, 6-[(3R,4R,6E)-6,7-didehydro-3-hydroxy-8-[(1H-imidazol-1-ylcarbonyl)oxy]-N,4-dimethyl-L-2-aminooctanoic acid]- (9CI). See Record and Registry, listing compounds disclosed in US 5,834,266 and showing that US’266 discloses CAS NO. 162926-14-9.
11 See prior footnote.
12 This is the corresponding WIPO publication, and is included herein because it has an added substance Table showing CAS Numbers and corresponding chemical structures.
Prosecution Insights