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 26-43 are pending. Claims 40-43 are withdrawn as directed to a non-elected species. Claims 26-39 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.
Following extensive search and examination, the originally elected species has been deemed obvious in view of the prior art of US2018/0296588A1 in view of US 2016/0002299A1, as set forth below. Per MPEP § 803.02(III)(A),
Following election, the Markush claim will be examined fully with respect to the elected species and further to the extent necessary to determine patentability. Note that where a claim reads on multiple species, only one species needs to be taught or suggested by the prior art in order for the claim to be anticipated or rendered obvious...
If the Markush claim is not allowable, the provisional election will be given effect and examination will be limited to the Markush claim and claims to the elected species, with claims drawn to species patentably distinct from the elected species held withdrawn from further consideration.
Accordingly, claims 26-39 are rejected as set forth below, and claims 40-43 are withdrawn.
Claims 40-43 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 11/24/2025.
As a courtesy to the Applicant and in pursuit of compact prosecution, although the originally elected species is rejected, the Examiner has extended Examination to (i) CAS NO. 2744980-60-5 (“JW4-10”), which has the structure of
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(ii) CAS NO. 2744980-62-7 (“JW4-21”), which has the structure of
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and (iii) CAS NO. 2744980-63-8 (“JW4-20”) having the structure of
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which were all deemed free of the prior art. The determination of allowability of CAS NO. 2744980-60-5 (“JW4-10”), CAS NO. 2744980-62-7 (“JW4-21”), and CAS NO. 2744980-63-8 (“JW4-20”) has been made in view of the unique combination of modifications at position 1 of CsA in combination with the data shown (see, e.g., Spec. filed 11/11/2022 at Example 3 at pages 82-85).
During the search and examination of the originally elected species, art pertinent to other non-elected species was incidentally discovered. Although examination has not been extended beyond the non-elected species identified above per MPEP § 803.02, as a courtesy to the Applicant, this art has been applied below, and the exact species searched are identified in the rejections set forth below; examination has not been extended beyond these species at this time.
Claims 26-39 are presently considered.
Priority
The priority claim to GB2007106.4 (filed 5/14/2020) is acknowledged.
Information Disclosure Statement
The IDS filed 2/20/2023 and 6/06/2025 are acknowledged and presently considered.
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).
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).
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 2013/0324480 at US’480 at col. 33 and 84; see also US20070232532A1 at title, abs, claims; see also US 9,669,095 at claim 1; etc. This is not an exhaustive listing).
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 .
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.
Drawings
The drawings are objected to under 37 CFR 1.83(a) because they fail to show details as described in the specification. Specifically, Figure 4(A) shows illegible structures. Any structural detail that is essential for a proper understanding of the disclosed invention should be shown in the drawing. MPEP § 608.02(d). Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Rejections
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 34-36 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.
Claims 34-36 refer to “the cyclic group”. There is insufficient antecedent basis for this limitation in the claim because these claims depend from claim 26, and claim 26 recites or refers literally, inherently, or implicitly to multiple cyclic groups at variable B and claim 26(a)-(b)(i)-(ii). For purposes of applying prior art, it is presumed that claims 34-36 are referring to “B”. Clarification is required.
Claims 34-36 are rejected.
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.
[Prior Art Rejection 01]
Claims 26-34 and 37-38 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being clearly anticipated by US 2013/0324480 (Dec. 5, 2013; Pettit et al.).
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 26-34 and 37-38, US’480 discloses the following two species:
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(see, e.g., US’480 at col. 33) and
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(see, e.g., US’480 at col. 84). These two species are understood to satisfy the instant claims relative to instant Formula (III) at claim 26 as follows: These species have an LIII that is a linker moiety of C1 or C2 alkylene and specifically -(CH2)1-2-; a B corresponding to a 6-membered heterocyclyl group; 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 (compare US’480 at col. 33 and 84 with instant claims 26-34 and 37-38).
Accordingly, claims 26-34 and 37-38 are anticipated by the prior art.
[Prior Art Rejection 02]
Claims 26-34 and 37-38 are rejected 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).
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 26-34 and 37-38, teaches and discloses a CsA analogues modified at position 1, namely cyclosporin pyrrolidine (see, e.g., US’015 at ¶[0246]), which is understood to have the structure associated with CAS No. 881007-73-4 (see US’015 at attached Substance Table at page 425). The structure of this analog is understood to be:
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(see, e.g., US’015 at ¶[0246], Substance Table at 42 showing CAS No. 881007-73-4). This substance is identical to Cyclosporin A except at position 1. Accordingly, it is understood to satisfy the limitations of instant claims 26-34 and 37-38 relative to instant Formula (III) at claim 26 as follows: These species have an LIII that is a linker moiety of C1 alkylene and specifically -(CH2)1-; a B corresponding to a 5-membered heterocyclyl group; 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 (compare US’015 at ¶[0246] and Substance Table at 42 showing CAS No. 881007-73-4with instant claims 26-34 and 37-38).
Accordingly, claims 26-34 and 37-38 are anticipated by the prior art.
[Prior Art Rejection 03]
Claims 26-34 are rejected 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).
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 26-34 and 37-38, teaches and discloses a CsA analogues modified at position 1, namely a modified cyclosporin A having the structure of
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(see, e.g., WO’089 at substance Table at 69 and pages 31-32)6. This substance is identical to Cyclosporin A except at position 1. Accordingly, it is understood to satisfy the limitations of instant claims 26-34 and 37-38 relative to instant Formula (III) at claim 26 as follows: These species have an LIII that is a direct bond; a B corresponding to a substituted 5-membered aryl group; 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 (compare WO’089 at substance Table at 69 and pages 31-32 with instant claims 26-34).
Accordingly, claims 26-34 are anticipated by the prior art.
[Prior Art Rejection 04]
Claims 26-33 and 37-38 are rejected 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.) as evidenced by WO2016/027089 (attached with additional substance Table starting at page 67).
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 26-34 and 37-38, US’632 claims CsA analogues modified at position 1 (see, e.g., US’632 at claims 1-9, 14, and 16). The claim scope is understood to read upon and encompass at least preferred Compounds 1, 3, 4, and 5 (see, e.g., US’632 at ¶¶[0058], [0080], [0094], [0097], [0103]). These compounds are understood to refer to CAS NOs. 1883278-86-1, 1883278-88-3, and 1883278-89-4 (see, e.g., WO’089 at Substance Table on 67-68, pages 19, 21-24). Accordingly, these compounds are understood to satisfy the limitations of instant claims 26-34 and 37-38 relative to instant Formula (III) at claim 26 as follows: These species have an LIII that is a C3 alkylene and specifically -(CH2)3-; a B corresponding to a substituted 10-membered heteroaryl group; 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 (compare US’632 at ¶¶[0058], [0080], [0094], [0097], [0103], corresponding to CAS NOs. 1883278-86-1, 1883278-88-3, and 1883278-89-4 as evidenced by WO’089 at Substance Table on 67-68, pages 19, 21-24 with instant claims 26-34 and 37-38).
Accordingly, claims 26-33 and 37-38 are rejected.
Claim Rejections - 35 USC § 103
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.
[Prior Art Rejection 05]
Claims 26-32 and 34-38 are rejected under 35 U.S.C. 103 as being unpatentable over US2018/0296588A1 (Oct. 18, 2018; Foster et al.).
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 26-32 and 34-38, US’588 pertains to cyclosporin A (CsA) derivatives and analogues modified at position 1 of CsA (see, e.g., US’588 at title, abs, ¶[0004], claims). US’588 is understood to reasonably inform artisans of methods of treating or preventing HBV or HIV diseases by administering any one of the equivalent compounds within the genus of Formula (I) as set forth at claim 1 (see, e.g., US’588 at claim 1, ¶[0594]):
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Regarding instant claims 26 and the general structure of CsA, the claimed embodiments of US’588 are understood to be CsA derivatives having 11 amino acids corresponding to CsA, wherein positions 4-11 as shown at Formula (I) are 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 (see, e.g., US’588 at claim 1). Regarding instant claims 26, 28, and R2 of instant formula (III), US’588 identifies that the corresponding position, R’, may be hydrogen (see, e.g., US’588 at claim 1). Regarding instant claims 26, 29, and R3 of instant formula (III), US’588 identifies that the corresponding position is ethyl (see, e.g., US’588 at claim 1). Regarding instant claims 26, 30, and R4 of instant formula (III), US’588 identifies that the corresponding position is methyl (see, e.g., US’588 at claim 1). Regarding instant claims 26, 31, and R5 of instant formula (III), US’588 identifies that the corresponding position is -CH2CH(CH3)2 (see, e.g., US’588 at claim 1). Regarding instant claims 26, and R6 of instant formula (III), US’588 identifies that the relative position for R6 is MeVal¹¹: N-methyl-L-valine (see, e.g., US’588 at claim 1). Regarding instant claims 26 and R7 of instant formula (III), US’588 identifies that the corresponding position, R23, may be an alkyl moiety (see, e.g., US’588 at claim 1, ¶¶[0336]-[0337]). Regarding instant claims 26, 37-38, and LIII of instant formula (III), US’588 teaches and discloses the corresponding position, R1, may be any saturated or unsaturated straight aliphatic carbon chain from 2 to 15 carbons in length (see, e.g., US’588 at claim 1). Accordingly, this includes an equivalent LIII moiety comprising linkers such as -(CH=CH)-(CH2)x-, where x is 0-13 (see, e.g., US’588 at ¶[0330]). Regarding instant claims 26, 34-36, and B of instant formula (III), US’588 teaches and discloses the corresponding position, R2, may be any substituted or unsubstituted aryl group or “aromatic group” (see, e.g., US’588 at claim 1, ¶¶[0330]-[0331], [0504]). Regarding potential differences in stereochemistry, US’588 pertains to cyclosporin A (CsA) derivatives and analogues modified at position 1 of CsA (see, e.g., US’588 at title, abs, ¶[0004], claims), and therefore the stereochemistry is reasonably assumed to be identical to CsA unless otherwise specified. However, even if potential differences existed, this would not weigh in favor of a determination of non-obviousness (see In re May, 574 F.2d 1082, 1093-95, 197 USPQ 601, 610-11 (CCPA 1978), noting that a genus comprising stereoisomers supports a prima facie case of obviousness over specific stereoisomers based on structural similarity).
Accordingly, the prior art differs from the pending claim scope as follows: Although US’588 teaches and discloses CsA analogues comprising aromatic moieties (e.g., imidazolyl moieties) and various linkers at position 1, US’588 does not explicitly exemplify a structurally complete species within the scope of instant claim 26.
The exemplified embodiments of US’588 are understood to differ from the instant claim scope only with respect to position 1 relative to CsA (compare instant claims with US’588 at ¶¶[0365] and [0367] with both CsA and instant claim 26, noting that only positions 1 and position 3 differ from CsA, wherein position 3 at the R7/R23 position is a methyl rather than a hydrogen, but wherein the prior art and instant claims both encompass this change to position 3). Therefore, the issue is whether or not the guidance of US’588 would reasonably direct artisans to overlapping structures.
US’588 provides additional guidance regarding the selection of “R1-R2”: exemplifies position 1 changes, which are referred to as “R1-R2” (see, e.g., US’588 at ¶[0330]), and explicitly identifies that position 1 of the CsA analogues may be
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(see, e.g., US’588 at ¶[0330]). Directly after this disclosure, US’588 exemplifies R2 as including at least
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(compare R2 of US’588 at ¶[0331] with instant B). Accordingly, in view of these disclosures (see, e.g., US’588 at ¶¶[0330]-[0331]), an artisan would appreciate that the explicitly contemplated R1 moieties included at least linkers comprising -(CH=CH)-(CH2)0-4- (compare R1-R2 of US’588 at ¶¶[0330]-[0331], claim 1 with instant claims and LIII-B). Accordingly, US’588 directs artisans to overlapping species and subgenera in common with the instantly pending claims. Regarding instant claims 26, 34-36, and the selection of an imidazolyl moiety for B in instant formula (III), US’588 informs artisans that the corresponding position of instant moiety B, namely R2 of US’588, may be any substituted or unsubstituted aryl group or “aromatic group” (see, e.g., US’588 at claim 1, ¶¶[0330]-[0331], [0504]). This is pertinent because US’588 explicitly identifies that “aryl group” and “aromatic” groups include imidazolyl (see, e.g., US’588 at ¶[0504]). Accordingly, and artisan would readily appreciate in view of this disclosure and exemplified embodiments of “R1-R2” and “R2” (see, e.g., US’588 at ¶¶[0330]-[0331], [0504]), that the aromatic and aryl moieties of the exemplified embodiments could be simply substituted with an imidazole moiety to produce an equivalent “aryl” or “aromatic” compound, reasonably predicted and expected to exhibit the same properties in view of US’588, wherein such compounds would be usable for the same predicted and expected applications and utilities taught by the prior art (see, e.g., US’588 at claim 1, ¶¶[0330]-[0331], [0504], [0511]; see also MPEP § 2144.06(II)). In sum, the prior art teaches and directs artisans to utilize species and subgenera of compounds overlapping in scope with the instantly claimed genus, wherein the prior art explicitly teaches each claimed component. Notably, the selection of prior art components according to prior art arrangements does not weigh in favor of non-obviousness, because the courts have previously noted that "[r]eading a list and selecting a known compound to meet known requirements is no more ingenious than selecting the last piece to put in the last opening in a jig-saw puzzle." (see, e.g., Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327 (1945), at 335).
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. 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.
Therefore, it would have been obvious to one of ordinary skill in the art, either before the effective filing date of the claimed invention (AIA ) or otherwise at the time the invention was made (pre-AIA ), to arrive at the instantly claimed invention in view of the prior art for at least the following reason(s): The claimed invention is obvious because it is the combination of prior art elements (e.g., chemical moieties) according to known methods and arrangements (e.g., Formula (I) of US’588) to yield predictable results, namely CsA analogues capable of use in methods of treating viral diseases, exactly as taught and disclosed by the primary reference (see, e.g., MPEP § 2143(I)(A), § 2144.06(II), § 2144.08, § 2144.09). Furthermore, each element merely performs its art-recognized function in combination as it does separately.
Furthermore, there would be a reasonable expectation of success because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). Furthermore, it is well-within the ordinary skill in the art to combine known moieties at known positions of a known compound according to known prior art formulas to arrive at equivalent CsA analogues exactly as taught and disclosed by the prior art, wherein such compounds would predictably and expectedly exhibit the properties and utilities taught and disclosed y the prior art.
Accordingly, claims 26-32 and 34-38 are rejected as obvious.
[Prior Art Rejection 06]
Claims 26-39 are rejected under 35 U.S.C. 103 as being unpatentable over US2018/0296588A1 (Oct. 18, 2018; Foster et al.) as applied to claims 26-32 and 34-38 above, and further in view of US 2016/0002299A1 (Jan. 7, 2016; Towers et al.).
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.
The teachings of US’588 as applied to claims 26-32 and 34-38 have been discussed above, and those teachings are incorporated into the instant rejection.
The teachings of US’588 differ with respect to instant claims 33 and 39 as follows: US’588 teaches and claims a genus of CsA analogs having a position R23, which corresponds to instant R7 of instant formula (III), as a methyl group (see, e.g., US’588 at claims 1, 4, ¶¶[0336]-[0337]), but instant claims 33 and 39 require the position to be a hydrogen instead of a methyl group.
US’588 is directed to CsA analogues and derivatives (see, e.g., US’588 at title, abs, ¶[0004], claims). Although US’588 requires position R23, which corresponds to instant R7 of instant formula (III), to be an alkyl moiety, and explicitly exemplifies it as a methyl group (see, e.g., US’588 at claims 1, 4, ¶¶[0336]-[0337]), US’588 does not provide an explanation of why modification at this position from native CsA is required or beneficial for antiviral activity in the claimed embodiments.
US’299 teaches and discloses a highly similar subgenus of CsA derivatives differing from US’588 primarily in that US’299 does not require the corresponding position to R23 (instant R7) to be a methyl, but instead permits the position to be a hydrogen: Specifically, US’299 teaches and discloses CsA derivatives having the structure of Formula I”:
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(see, e.g., US’299 at claims 1 and 12), wherein A (corresponding to instant R2) is
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, wherein B (corresponding to instant R4) is methyl; wherein R4 (corresponding to instant R5) is -CH2CH(CH3)2, and wherein R2 (corresponding to instant R3) is ethyl (see, e.g., US’299 at claims 1 and 12). Regarding instant claims 26, 33, 39, and position R7, US’299 teaches and discloses at claim 12 and Formula I” that the corresponding position may be hydrogen (see, e.g., US’299 at claims 1 and 12). Regarding R1 and R1* (corresponding to instant B-LIII and R1, respectively), US’299 explains that “one of R1 and R1* represents hydrogen and the other represents -L1-G1” (see, e.g., US’299 at claims 1 and 12), wherein L1 corresponds with instant variable LIII, and L1 may be a direct bond or any C1-C6 alkylene group or C2-C6 alkenylene group (see id); and wherein “G1” corresponds to instant variable “B”, and may be “a phenyl moiety which is unsubstituted or substituted” (see id).
US’588 and US’299 teach CsA analogs having substantially identical predicted and expected results, properties, and applications: Like the compounds of US’588, US’299 teaches and informs artisans that all disclosed CsA analogs and derivatives are equivalents for the purpose of treating viral infections in patients (see, e.g., US’299 at claims 1, 3-7, 12-14, ¶¶[0060]-[0063]). Accordingly, the utility and applications of the CsA analogues of US’588 and US’299 appear to be substantially identical.
Combined teachings and inferences: Accordingly, the combined teachings of US’588 and US’299 reasonably inform artisans of ways of modifying CsA to predictably obtain functional derivatives and analogues suitable for use in the treatment of viral infections (see, e.g., US’299 at claims 1, 3-7, 12-14, ¶¶[0060]-[0063]; see, e.g., US’588 at title, abs, ¶[0004], claims). More specifically, the combined references reasonably inform artisans that position 1 of CsA may be modified using linkers conjugated to phenyl or other aryl moieties (e.g., imidazolyl), and the references collectively inform artisans that position 3 of CsA (i.e., R23 of US’588, instant R7, or R3 in Formula I of US’299) may be either hydrogen or an alkyl moiety, and that such alterations would not abrogate the antiviral activity and applications of such derivatives. In sum, in view of the collective teachings and guidance of both references, an artisan would readily appreciate that the structures of US’588 could optionally have a hydrogen at position 3 relative to CsA (i.e., R23 of US’588, instant R7, or R3 in Formula I of US’299), while still producing functionally equivalent CsA derivatives and analogs for the purpose of treating viral diseases, exactly as taught and suggested by both documents.
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. 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.
Therefore, it would have been obvious to one of ordinary skill in the art, either before the effective filing date of the claimed invention (AIA ) or otherwise at the time the invention was made (pre-AIA ), to arrive at the instantly claimed invention in view of the prior art for at least the following reason(s): The claimed invention is obvious because it amounts to the simple substitution of hydrogen in place of methyl in the CsA derivatives of the primary reference at position R23 of US’588, but such hydrogen and methyl moieties were collectively known in the art at that position, and the art established that substituting hydrogen in place of methyl at that position produced predictable results, namely CsA derivatives modified at position 1, having utility in antiviral treatment applications, exactly as taught and suggested by the prior art (see, e.g., MPEP § 2143(I)(B); § 2144.06(II), § 2144.08, § 2144.09). In addition, the courts have previously determined that hydrogen and methyl substitutions may be insufficient to render a compound patentably distinct over the prior art (see In re Grunwell, 203 USPQ 1055; In re Magerlein, 202 USPQ 473; In re Wood, 199 USPQ 137; and In re Lohr, 137 USPQ 548).
Furthermore, there would be a reasonable expectation of success because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). Furthermore, it is well-within the ordinary skill in the art to combine known moieties at known positions of a known compound according to known prior art formulas to arrive at equivalent CsA analogues exactly as taught and disclosed by the prior art, wherein such compounds would predictably and expectedly exhibit the properties and utilities taught and disclosed y the prior art.
Accordingly, claims 26-39 are rejected as obvious.
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 26-33 and 37-38 are rejected 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) as evidenced by WO2016/0270897 (attached with additional substance Table starting at page 67), because although the claims at issue are not identical, they are not patentably distinct from each other because they substantially and materially overlap in scope as explained below.
Claim interpretation: The applicable claim interpretation has been set forth above in a separate section, and in preceding rejections. Those interpretations and discussions are incorporated into the instant rejection.
MPEP § 804(II)(B)(2)-(3) identifies that a Nonstatutory Double Patenting Rejection may be appropriate based upon either an anticipation analysis or an obviousness analysis (see, e.g., MPEP § 804(II)(B)(2)-(3)). The following rejection is based upon an anticipation analysis.
Regarding instant claims 26-34 and 37-38, US’404 claims CsA analogues modified at position 1 (see, e.g., US’404 at claims 1-10). The issued claim scope is understood to read upon and encompass at least preferred Compounds 1 and 3-58 (see, e.g., US’404 at col 17 at lines 1-26, col. 20 at lines 30-55, col. 21 at lines 1-30, col 22 at lines 30-60). These compounds are understood to refer to CAS NOs. 1883278-86-1, 1883278-88-3, and 1883278-89-4 (see, e.g., WO’089 at Substance Table on 67-68, pages 19, 21-24). Accordingly, these compounds are understood to satisfy the limitations of instant claims 26-34 and 37-38 relative to instant Formula (III) at claim 26 as follows: These species have an LIII that is a C3 alkylene and specifically -(CH2)3-; a B corresponding to a substituted 10-membered heteroaryl group; 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 (compare US’632 at ¶¶[0058], [0080], [0094], [0097], [0103], corresponding to CAS NOs. 1883278-86-1, 1883278-88-3, and 1883278-89-4 as evidenced by WO’089 at Substance Table on 67-68, pages 19, 21-24 with instant claims 26-34 and 37-38).
Accordingly, claims 26-33 and 37-38 are not patentably distinct relative to the issued patent of US’404 because both claim scopes read upon the overlapping embodiments.
Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
US7141648B2 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 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 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) pertains to CsA derivatives, derivatized at position 1 (see, e.g., id. at title, abs, claims).
US20070232532A1 pertains to CsA derivatives modified at position 1 used in antiviral applications (see, e.g., id. at title, abs, claims).
US20120157385 A1 pertains to CsA derivatives modified at position 1 used in antiviral applications (see, e.g., id. at title, abs, claims).
Conclusion
No claims are allowed.
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/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”.
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 This Corresponds to CAS No. 1500112-70-8, and all bond orientations are identical to the originally elected species (see search notes for CAS No. 1500112-70-8).
5US’015 also discloses CAS NOs. 881007-58-5 and 881008-21-5, as shown in the attached substance table.
6 This structure corresponds to CAS NO. 1262527-22-9 as shown in the substance table of the corresponding WIPO publication of WO2016/027089 at page 69 of WO’089.
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 See, e.g., MPEP § 804(II)(B)(1), “those portions of the specification which provide support for the reference claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application”.