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 .
Current Status
This action is responsive to the amended claims of 01/20/2026. Claims 1-11 are pending. Claim 11 is withdrawn. Claims 1-10 are examined on the merits.
Election/Restrictions
The amendments/response of 01/20/2026 have overcome the prior art rejection of the prior action. Thus, the Markush search was extended. A search for the entire scope of Formula (I) (independent claim 1) did not return any prior art (see SEARCH 6 of the attached search notes). Therefore, the election requirement of 07/17/2025 is rendered moot.
The claims of Group I (claims 1-10) are still subject to rejections, necessitated by the amendments of 01/20/2026. Thus, the restriction requirement of 07/17/2025 is still in place.
Claim 11 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 07/17/2025.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
The effective filing date remains 03/02/2020.
Response to Arguments
The remarks and amendments of 01/20/2026 are acknowledged and have been reviewed by the Examiner; no new matter is found.
The objection to the specification is withdrawn because Applicant has provided structures with the conventional wavy line (i.e.,
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) to denote attachment points.
The objections to claims 1-10 are all withdrawn (¶11-18 of the prior action) because Applicant has amended in line with the Examiner’s suggestions.
The 112b rejection of claims 1-10 (¶21 of prior action) over moieties not containing the wavy line at attachment points is maintained in part and is modified to reflect Applicant’s amendments below. Many of the moieties now have the wavy line; however, a few remain undefined.
The 112b rejection of claims 1-10 (¶22 of prior action) over R15, R22, R23, R24, R36, and R37 is not withdrawn. Applicant has struck these R groups; however, in making such amendment, Applicant did not strike other R groups that were only found in the definition of R15. Thus, the amendment did not fully rectify the issue.
The 112b rejection of claims 1-10 (¶23) is withdrawn since Applicant has provided the recited structure at improved resolution.
The 112b rejection of claims 1-10 (¶24) over Y as oxygen is withdrawn since Applicant has added a proviso addressing the valence of oxygen so it is no longer violated.
The 112b rejection of claims 1-10 (¶25) is withdrawn since Applicant has struck “deoxy-forms” from the claims.
The 112b rejection of claim 2 (¶26) over Formula (V) is withdrawn since Applicant has struck RB from the claim.
The 112b rejection of claim 2 (¶27) over Formula (VIII) and (VIIIa) is not withdrawn. Applicant addressed the issue regarding Y as oxygen (above) and has defined the variable R’. However, the definition of R’ does not fall within the definition of parent variable R38 or R39, thus, there is still a lack of antecedent basis.
The 112b rejection of claim 2 (¶28) is withdrawn since Applicant added the recited structure containing the variables q, Z, RC’, or RC” to parent claim 1.
The 112b rejection of claim 3 (¶29) over the RA structures is maintained, in part. Structures 1-2, 5-7, and 9, as explained previously, cannot be found in the parent claim 1. For structures 3-4, 8, 10, and 12-14, many of the R groups are numbered differently; for example: structure 3 in claim 3
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corresponds to this structure in claim 1
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which differs in the naming of R28 vs R31. However, for structures 3-4, 8, 10, and 12-14, while the R groups may be numbered differently, they are chosen from the same variables. Thus, while the numbering is not consistent between the claims, the moieties from which the R groups are chosen is not contradictory. Thus, for structures 1-2, 5-7, and 9 the rejection is maintained below. For structures 3-4, 8, 10, and 12-14, the rejection is withdrawn and made into an objection.
The 112b rejection of claim 8 (¶30) is withdrawn since Applicant has struck “infectious” from claim 8 and its parent claim 7.
The 112d rejection of claim 2 (¶33) is not withdrawn since the issue regarding R’ still stands.
The 112d rejection of claim 2 (¶34) regarding variables q, Z, RC’, or RC” is withdrawn since they now have support in the parent claim.
The 112d rejection of claim 3 (¶35) is maintained, in part, since the structures 1-2, 5-7, and 9 are not found in parent claim 1.
The 103 rejection of claims 1-10 over WANG, POMPLUN, and SUN is withdrawn in view of Applicant’s arguments. The arguments regarding unexpected results are persuasive. The remarks (Pg. 5/6) cite the data in specification regarding the performance of (S)-methylation at the 1-position relative to the variable RA. The corresponding data found on Pg. 64 Table 1 of the specification compares the binding affinity of exemplary compounds of Formula (I) to the prior art compounds which lack the (S)-methyl group at the 1-position relative to the variable RA. The compounds of Formula (I) consistently have a lower Ki (nM) and are therefore more potent binders/inhibitors of the target molecules. Thus, the Applicant has shown superiority of a property shared with the prior art – i.e., evidence of nonobviousness (MPEP 716.02(a)(I.)). This evidence is found to be commensurate in scope with independent claim 1 since Applicant’s data covers multiple exemplary species across the genus of Formula (I).
Response to Amendment
Claim Objections
Claims 2-3 are objected to because of the following informalities. Appropriate correction is required.
Claim 2 recites “wherein the substituents RB, RC, [[RN]] and R7-R9 have the meanings as defined for formula (I)”. By amendment, the variable RN has been struck form this recitation; however, the claimed structure Formula (VIIa) recites RN. To improve claim consistency, Examiner suggests Applicant restore RN here. Note, there is no indefiniteness issue since claim 2 depends from claim 1, thus, the variables are automatically understood as defined in claim 1 formula (I).
Claim 3 recites RA is selected from 14 structures. For structures 3-4, 8, 10, and 12-14, many of the R groups are numbered differently than how they appear in the corresponding structure recited in claim 1. For example: structure 3 in claim 3
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corresponds to this structure in claim 1
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which differs in the naming of R28 vs R31. For structures 3-4, 8, 10, and 12-14, while the numbering is not consistent between the claims, the moieties from which the R groups are chosen is the same/not contradictory (i.e., definite). However, to improve consistency and readability between the claims, it is preferred if Applicant use consistent numbering of R groups between the claims. Applicant could replace the structures recited in claim 3 with the corresponding structures recited in claim 1. This way the structures are consistent across claims.
Rejections Necessitated by Amendment
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 7 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
MPEP § 2163 states that, “[n]ew or amended claims which introduce elements or
limitations which are not supported by the as-filed disclosure violate the written description requirement. See, e.g., In re Lukach, 442 F.2d 967, 169 USPQ 795 (CCPA 1971) (subgenus range was not supported by generic disclosure and specific example within the subgenus range); In re Smith, 458 F.2d 1389,1395, 173 USPQ 679, 683 (CCPA 1972) (a subgenus is not necessarily described by a genus encompassing it and a species upon which it reads).” Further, the MPEP states, “[w]hile there is no in haec verba requirement, newly added claim limitations must be supported in the specification through express, implicit, or inherent disclosure.”
By the amendment of 01/20/2026, the scope of claim 7 has been broadened from “infectious diseases” to “diseases”. The original claims do not recite a genus of disease this broad, i.e., encompassing any disease. Further, the specification does not recite a genus this broad. The specification, at its broadest, points to diseases characterized by aberrant activity of FKBP12 and FKBP12.6 (Pg. 50 final ¶). The current recitation in claim 7 is not this narrow and encompasses diseases outside of such genus.
A finding of written description support is not similar to obviousness analysis where one can assume Applicants intended to claim the instantly recited “diseases” when they filed the application based solely on a recited genus of diseases characterized by aberrant activity of FKBP12 and FKBP12.6. Applicants must actually have support for all limitations of the claims in the original disclosure. In this case, the genus of “diseases” lacks written description support in the original disclosure and hence is new matter. As such, claim 7 lacks written description support.
Note, claim 8 depends from claim 7 and recites wherein the disease is selected from a smaller genus. This smaller genus has support in the original disclosure.
Claim Rejections - 35 USC § 112(b)
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 1-10 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.
Claim 1 recites chemical structures for moieties RA:
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(Pg. 2) and RB:
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&
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(Pg. 28). The moieties do not clearly denote the point of attachment to the base Formula I. For RA, it is unclear if the annotated line is a methyl group or bond to the Formula I. For RB, it is unclear if the wavy line is a methyl group of undetermined stereochemistry or if the wavy line was meant to denote a point of attachment (by intersecting the existing structure). Therefore, the metes and bounds of the claim are undefined rendering the claim indefinite. Dependent claims 2-10 are similarly rejected since they do not rectify the issue.
To overcome: please use the conventional wavy line (i.e.,
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) to denote the point of attachment. For all structures where a wavy line has been added by amendment, please check that the wavy line fully intersects with the point of attachment to avoid structures which introduce ambiguity (e.g., the above RB).
Claim 1 recites “R17-R21” on Pg. 47. By the amendment, Applicant has struck R15 which incorporated R17-R20 (see Pg. 43). Thus, it is unclear where these variables exist within the structure of the claimed compound. Therefore, these variables lack antecedent basis in the Formula (I) and the metes and bounds of the claim are undefined rendering the claim indefinite. Dependent claims 2-10 are similarly rejected since they do not rectify the issue.
To overcome: please strike all instances R17-R20 from the claim text.
Claim 2 recites Formula (VIIIa)
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wherein RA is
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. The annotated moiety lacks antecedent basis in the claims. The variable R’ is not recited in parent claim 1 under the RA moiety -C(X)Y(R38)(R39). Neither R38 nor R39 is allowed to be R’. Further R38/R39 and R’ are chosen from different sets of chemical moieties. R’ is chosen from 6 moieties: the first 5 moieties fall under the definition of R38 and R39 as set forth in claim 1, but the 6th moiety -COCH3 is not found under the definition of R38 and R39. Thus, the definition of R’ (added in the most recent amendment) does not provide support for the claimed structure. Therefore, the metes and bounds of the claim are undefined rendering the claim indefinite.
Claim 3 recites RA is selected from a list of 14 chemical moieties. Structures 1-2, 5-7, and 9 lack antecedent basis in the claims, as follows:
Structures 1-2
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correspond to -CH2OR16 and -CH2NR38R39. Applicant has amended the claim to define R’ and R”; however, R’/R” being chosen as -COCH3 is not found under R16 and R38-R39 in parent claim 1. Further, R16 and R38-R39 are not chosen form R’/R” in parent claim 1. Thus, R’/R” as -COCH3 lacks antecedent basis.
Structures 5, 7, and 9 are not found in parent claim 1:
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,
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, and
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. Each of these structures recite a R36 which is not found in the definition of formula (I) claim 1. The claim text also recites R36 is as defined in formula (I); however, it is not found in formula (I) claim 1. Further, the closest structures in claim 1 are:
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,
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, and
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which also differ in R28-29 (claim 1) vs. R34 (claim 3). Thus, these RA moieties lack antecedent basis.
Structure 6
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is not found in claim 1. The closest moieties are:
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. These differ in both the arrangement of the N atoms and the R group numbering. Thus, this RA moiety lacks antecedent basis.
Therefore, the metes and bounds of claim 3 are undefined rendering the claim indefinite.
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 2 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 2 recites Formula (VIIIa) comprising R’ in place of R38/R39. R’ is chosen from 6 moieties: the first 5 moieties fall under the definition of R38 and R39 as set forth in claim 1, but the 6th moiety -COCH3 is not supported by the scope of parent claim 1. Thus, claim 2 does not properly further limit claim 1 since it recites a moiety outside of the scope of said claim. 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 3 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 3 recites RA is selected from a list of 14 chemical moieties. Structures 1-2, 5-7, and 9 are not found in the definition of RA as recited in parent claim 1 (see ¶35 above). Thus, claim 3 does not properly further limit claim 1 since it recites a moiety outside of the scope of said claim. 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.
Conclusion
Claims 1-10 are rejected.
The search for the compound of Formula (I) did not retrieve any prior art (see SEARCH 6 of the attached search notes). The closest art is considered: WANG (WO 2015/110271, cited in IDS of 08/29/2022). WANG teaches compound M5
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(Pg. 147 Example 9-5 & Pg. 202 claim 4 second to last compound) which is analogous to the instant elected compound 24b, except that it lacks the Me group at the annotated *C. WANG further teaches the compound as an inhibitor of FK506-binding proteins (Pg. 205 claim 5), as a pharmaceutically active agent in medicine (Pg. 205 claim 7), and in treatment of a variety of diseases overlapping with the instantly recited disease (Pg. 205 claims 8-9).
Since Applicant’s have provided evidence of unexpected results, as discussed in ¶24 above, the methylation of the annotated *C is understood as non-obvious. Since no art of record teaches methylation of a compound of Formula (I) at this position, the instant compound is not anticipated. Further, since no art of record teaches superiority of a property shared with the prior art compound by such methylation (MPEP 716.02(a)(I.)), such modification of the prior art compound is found to be non-obvious. Therefore, the claims 1-10 are free of the prior art.
Note: see the non-final rejection of 08/21/2025 (¶42) for notes about references considered, but ultimately not applied, for double patenting.
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.
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/S.E.B./Examiner, Art Unit 1625
/JOHN S KENYON/Primary Patent Examiner, Art Unit 1625
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