Detailed Action
The present office action is in response to the remarks filed on 05 Aug 2026.
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 .
Status
Claims 37-39, 56, 59, 64, 66, 69, 73-74, 76, 78, 80, 82, 128, 150-151, 155-157, and 159 of the pending application have been examined on the merits. Claims 129-130, 132, 134-135, 137, 140, 142-144, and 146-147 remain withdrawn and claims 148-149, 152-154, and 158 are newly withdrawn (see “Response to Applicant Arguments” below). Acknowledgement is made of the amendments filed 05 Aug 2026. Acknowledgement is made of the cancellation of claims 1-36, 40-55, 57-58, 60-63, 65, 67-68, 70-72, 75, 77, 79, 81, 83-127, 131, 133, 136, 138-139, 141, and 145.
Priority
The instant application retains the priority date of 14 Apr 2021.
Response to Applicant Arguments
Acknowledgement is made of the remarks filed 05 Aug 2026.
Acknowledgement is made of newly added claims 148-159. Claims 150-151, 155-157, and 159 are under examination. Claims 148-149, 152-154, and 158 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.
Previously, examiner performed a Markush search for the applicant elected species of Formula (IIj) (below):
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A search for this species returned no art. Examiner expanded the Markush search to compound 232b:
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238
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Newly added claims 150 and 157 are not directed to the expanded Markush search, and so examiner expanded the Markush search to include the following compound:
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Which is a species of Formula (IIj) when ring C is bicyclic heteroaryl; n is 0; RA is H; RB is alkyl; J is -NH-; K is a bond; ring D is heteroaryl; LD is a bond; and R1 is a substituted alkyl group. A search for this species returned art.
The 112(d) rejection is rendered moot following applicant amendments.
The rejection of claim 39 under 35 U.S.C. § 103 over WO 2019/195720 (provided in IDS 03/04/26), hereinafter ‘720, is rendered moot following applicant amendments. Claim 39 is newly rejected under 35 U.S.C. § 103 over WO 2011/044157, hereinafter ‘157, further in view of Kumari et al. (J Med Chem, 2020, 63:12290-12358), hereinafter Kumari. This new grounds of rejection is necessitated by applicant amendments.
Regarding the rejection of claims 37-39, 56, 59, 64, 66, 69, 73, 74, 76, 78, 80, and 128 over 35 U.S.C. § 112(b), applicant arguments have been fully considered but are not persuasive.
Applicant argues on pg. 62 of the remarks that claim 37 has been amended to delete formula (II) and narrow the definition of ring A and ring B by incorporating formulae (IIg), (IIh), (IIj), (IIk), (IIm), (IIn), and (IIo), and revising the definitions of ring C and YB. Applicant argues that the bicyclic moieties defined in the newly added formulae share structural similarity that would be recognized by one of skill in the art.
This is not persuasive. Examiner acknowledges the narrowing definition of rings A and B, but the definitions of rings C and D are still so expansive as to make the Markush group improper. The amendment to claim 37 has even broadened the definition of ring C. Newly added claims 150-151, 155-157, and 159 do not remedy the deficiencies of claim 37 and are newly rejected. This rejection is necessitated by applicant amendments.
In light of the discussion above, the rejection of claims 37-39, 56, 59, 64, 66, 69, 73, 74, 76, 78, 80, 128, 150-151, 155-157, and 159 under 35 U.S.C. § 112(b) is amended for the reasons of record and restated below.
Regarding the rejection of claims 37-38, 56, 59, 64, 66, 69, 73, 74, 76, 78, 80, 82, and 128 under 35 U.S.C. § 103 over ‘720, applicant arguments have been fully considered but are not persuasive.
Applicant argues on pg. 63 of the remarks that ‘720 teaches compound 87c, a positional isomer of instantly searched compound, has an IC50 value above 10 µM for Factor D inhibition putting in the lowest activity bracket and is among the least potent compounds in the reference. Applicant argues that the person having ordinary skill in the art would not choose this compound as a starting point for further modification.
This is not persuasive. MPEP § 2144.09(I) teaches, “A prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities.” Further, MPEP § 2144.09(II) teaches, “compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2 groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties.” The person of ordinary skill in the art would modify the attachment position of the methoxy linker and the isoquinoline substituent of reference compound 87c, taught by ‘720, to facilitate a positional isomer which has a sufficiently close structural similarity that the person or ordinary skill in the art would have a presumed expectation of the compounds having similar properties. The motivation to make the instantly claimed compounds derives from the expectation that structurally similar compounds would possess similar activity (i.e., they would be pharmacologically active Factor D inhibitors) with potential for better bioavailability and lower side effects. There would be a reasonable expectation of success in producing and using the instantly claimed compounds in view of the compound taught by ‘720.
Applicant argues on pg. 64 of the remarks that nothing in the disclosure of ‘720 would lead a person skilled in the art to modify the disclosed compounds to arrive at the claimed compound and that none of the compounds of ‘720 possess the Ring C moiety and the -J-K-[Ring D] moiety attached to different rings of the bicyclic ring and that the artisan would not have been motivated to develop the claimed compounds with the described moieties bonded to different rings of the bicyclic core.
This is not persuasive. As mentioned above, positional isomers have a sufficiently close structural similarity that the artisan would have a presumed expectation that the compounds would have similar utilities and would have a reasonable expectation of success in producing the isomers.
Applicant argues that ‘720 is directed to compounds that inhibit Complement Factor D whereas the instantly claimed compounds have utility as KLK5 inhibitors and, while targets are serine proteases, that there is no expectation that the inhibitors of one serine protease would inhibit a different serine protease.
This is not persuasive. It is not necessary for the prior art to suggest the same compounds as the instant claims to achieve the same purpose. See MPEP § 2144(IV).
Newly added claims 151, 155-156, and 159 are also rejected over ‘720. This new grounds of rejection is necessitated by applicant amendment.
In light of the discussion above, the rejection of claims 37-39, 56, 59, 64, 66, 69, 73, 74, 76, 78, 80, 128, 151, 155-156, and 159 under 35 U.S.C. § 112(b) is amended for the reasons of record and restated below.
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 37-39, 56, 59, 64, 66, 69, 73, 74, 76, 78, 80, 128, 150-151, 155-157, and 159 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of rings C and D in formulae (IIg), (IIh), (IIj), (IIk), (IIm), (IIn), and (IIo):
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are improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: The claims ring C as a “bicyclic ring system” and ring D as “aryl or heteroaryl”. The specification defines arylene groups to be diradicals of aryl groups which are defined as a term of art which includes monocyclic, bicyclic, and polycyclic aromatic hydrocarbon groups (pg. 16). Further, the specification further defines heteroarylene as diradicals of heteroaryl groups which are defined as a term of art which refers to monocyclic, bicyclic, and polycyclic aromatic groups with 3-12 atoms including one or more heteroatoms (pg. 17). The variability of the definitions for each of the rings in the claimed structure of formula II results in there being no shared structural similarity that a person of ordinary skill in the art would recognize. Further, based on the breadth of the structures claimed, the artisan would have no reasonable expectation of success that all compounds claimed would have the same use.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
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) 37-38, 56, 59, 64, 66, 69, 73-74, 76, 78, 80, 82, and 128 is/are rejected under 35 U.S.C. 103 as being unpatentable over WO 2019/195720 (provided in IDS 03/04/26), hereinafter ‘720.
Applicant elected compound 247c in the reply filed on 04 Mar 2026 which is a species of formula (IIj):
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Instant claim 37 includes Formula (IIg):
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Examiner expanded the Markush search to include compound 232b (instant specification pg. 496):
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which is a species of formula (IIg) when ring AB is benzofuran, ring C is isoquinoline, J is CH2, K is O, D is phenyl, LD is CH2, R1 is H, and m, n, and p are 0.
‘720 teaches compounds that inhibit Factor D (pg. 1142-1150), including compound 87c which inhibits Factor D with an IC50 of greater than 10 µM (pg. 259; pg. 1144):
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‘720 further teaches pharmaceutical compositions comprising compounds of the reference and a pharmaceutically acceptable carrier (pg. 83). However, compound 87c differs from instant compound 232b in the attachment of the substituents to the benzofuran core and the position of attachment on the isoquinoline moiety.
MPEP § 2144.09(II) teaches, “compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2 groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties.”
The person of ordinary skill in the art would modify the attachment position of the methoxy linker and the isoquinoline substituent of reference compound 87c, taught by ‘720, to facilitate a positional isomer which has a sufficiently close structural similarity that the person or ordinary skill in the art would have a presumed expectation of the compounds having similar properties. The motivation to make the instantly claimed compounds derives from the expectation that structurally similar compounds would possess similar activity (i.e., they would be pharmacologically active Factor D inhibitors) with potential for better bioavailability and lower side effects. There would be a reasonable expectation of success in producing and using the instantly claimed compounds in view of the compound taught by ‘720.
A reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976). In light of the foregoing discussion, the examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103. From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Claim(s) 37, 39, 56, 64, 76, 78, 80, 128, 150, 156, 157, and 159 is/are rejected under 35 U.S.C. 103 as being unpatentable over WO 2011/044157, hereinafter ‘157, further in view of Patani et al. (Chem Rev, 1996, 96:3147-3176), hereinafter Patani.
Applicant elected compound 247c in the reply filed on 04 Mar 2026 which is a species of formula (IIj):
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Examiner has expanded the Markush search to include the following species of Formula (IIj):
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Which is a species of Formula (IIj) when ring C is bicyclic heteroaryl; n is 0; RA is H; RB is alkyl; J is -NH-; K is a bond; ring D is heteroaryl; LD is a bond; and R1 is a substituted alkyl group.
‘157 teaches Compound 14.2 (paragraph [00432]; and pg. 278, Table) with utility as a PDK1 inhibitor (Abstract; pg. 340, Table 2):
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‘157 teaches that Compound 14.2 inhibits PDK1 with an IC50 of less than 0.1 µM. However, Compound 14.2 differs from the instantly searched compound by having an amide bond in place of an ester bond.
MPEP § 2144.09(I) teaches, “A prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities.” Further, MPEP § 2144.09(III) teaches, “prior art structures do not have to be true homologs or isomers to render structurally similar compounds prima facie obvious. In re Payne, 606 F.2d 303, 203 USPQ 245 (CCPA 1979).”
Patani teaches that bioisosterism represents one approach used by the medicinal chemist for the rational modification of lead compounds into safe and more clinically effective agents and the concept of bioisosterism is often considered to be qualitative and intuitive (pg. 3147, columns 1-2). One such bioisostere pair is amide and ester. Patani teaches that esters have been widely used as replacement for amides and that bioisosteric replacements for the amide are important for implications in peptide chemistry (pg. 3170, column 1).
Based on the teachings of ‘157 and Patani, the person of ordinary skill in the art would modify Compound 14.2, taught by ‘157, and replace the amide moiety with an ester, as taught by Patani, to create a safe and clinically effective agent for the inhibition of PDK1. The motivation to make the instantly claimed compounds derives from the expectation that structurally similar compounds would possess similar activity (i.e., they would be pharmacologically active PDK1 inhibitors) with potential for better bioavailability and lower side effects. There would be a reasonable expectation of success in producing and using the instantly claimed compounds in view of the compound taught by ‘157.
A reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976). In light of the foregoing discussion, the examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103. From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Conclusion
No claim is 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.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jonathan D. Mahlum whose telephone number is (703)756-4691. The examiner can normally be reached 8:30 AM - 5:00 PM ET, M-F.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Andrew Kosar can be reached at (571) 272-0913. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/J.D.M./Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625
