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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 of 18/263,442
This Office Action is responsive to the claims of 07/28/2023, claims 1,10-11,14-16,18,27-34 and 52-55 are pending in the instant application, and have been reviewed on the merits.
Priority
The instant application is a national stage entry of PCT/CN2022/074172, international filing date 01/27/2022, which claims priority to Chinese Patent application No. 202110118008.8, filed 01/28/2021, and Chinese Patent application No. 202111457630.8, filed 12/01/2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 07/28/2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 10, 11, 14-16, 18, 28, 29, and 31-34 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.
Regarding claims 10, 11, 14-16, 18, 28, 29, and 31-34, the phrases "preferably", “more preferably”, “further preferably”, and “still further preferably”, render the claims indefinite because it is unclear whether the limitation(s) following the phrases are part of the claimed invention. See MPEP § 2173.05(d).
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 54 and 55 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claims do not fall within at least one of the four categories of patent eligible subject matter because the claims are directed to the “use of the compound for manufacturing a medicament for the prevention and/or treatment of diseases at least partially mediated by a TLR7 agonist.” Such a use claim does not recite a process comprising steps, nor does it recite a manufacture or composition of matter. Accordingly, the claims are not directed to a statutory category of invention.
Claim Rejections - 35 USC § 102
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 1, 11, 16, 18, and 53 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Graupe (CN 101784548 A found in IDS filed 07/28/2023, US 7968544 B2 was relied upon as an English language equivalent of the identified Chinese patent).
Graupe discloses compounds of formula I or II
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and identifies them as modulators of toll-like receptor 7 (TLR7) and discloses the use of these compounds as part of compositions (see Title and Abstract, Col 1, lines 16-19).
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is a species of formula I with the following substitutions reading on the allowed substitutions of instant claim 1. E is amino; Y is N; R3 is absent; R2 is O(R4), R4 is C4 alkyl; X is O(R20), R20 is H; n=0, L2=5-membered heterocycle; B is C1 alkyl, L1 is C6 aryl, Z is -C(R10)(R11)-, R10 and R11 are both H. These substitutions anticipate the allowed substitutions of instant claim 1. The ring structure of the species above and the selection of X being O(R20), anticipates the limitations of instant claim 11. The substituent Z being -C(R10)(R11)- anticipates the limitations of instant claim 16.
Claims 1, 10, 16, 18, and 53 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Isobe (CN 101679433, found in IDS filed 07/28/2023, US 2010/0093998 A1 was relied upon as an English language equivalent of the identified Chinese patent.)
Isobe discloses compounds of formula (1)
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(Abstract) and identifies these compounds as being excellent TLR activators (see [0007]). The reference discloses
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(see [0333]) as a species of formula (1) and corresponds to the following allowed substitutions of the instant application. E is amino; Y is N; R3 is absent; R2 is O(R4), R4 is C4 alkyl; X is O as part of a carbonyl group, n=0, L2=6-membered heterocycle; B is C1 alkyl, L1 is C6 aryl, Z is -C(R10)(R11)-, R10 and R11 are both H. These substitutions anticipate the allowed substitutions of instant claim 1. The ring structure of the species above and the selection of X being O as part of a carbonyl group, anticipates the limitations of instant claim 10. The substituent Z being -C(R10)(R11)- anticipates the limitations of instant claim 16. Claim 21 of Isobe also teaches pharmaceutical compositions comprising these compounds, anticipating instant claim 53.
Claims 27-34 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Valiante (WO 2006/031878 A2).
Valiante discloses compounds of formula (I)
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(see [0041]), further identifying
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(Claim 25) as a species of (I). The species of claim 25 has the following substations, reading on the instant application’s compound of formula (IV): RB is hydrogen (anticipating instant claim 29); Q is C (anticipating instant claim 30); RA is C3 alkyl (anticipating instant claim 28); m is zero, therefore Z is absent (anticipating instant claim 31); L1 is C3 alkyl (anticipating instant claim 33); B is a chemical bond (anticipating instant claim 32); and L2 is C1 alkyl (anticipating instant claim 34). These substitutions anticipate the allowed substitutions of instant claim 27 and the dependent claims mapped above.
Claims 1and 14-15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Dellaria (WO 2007028129).
Dellaria discloses 2-hydroxy-1H-imidazo[4,5-c]pyridine-4-amines of Formulas I, II, and III
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(pg. 1, lines 17-20). Example 1 is a species of the disclosed compounds with the following formula
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(pg. 48, line 23), which has the following substitutions according to the instant application: X is -O(R20), R20 is H; R1 is absent; E is amino; R2 is R4, R4 is C5 alkyl; Y is C, R3 is hydrogen (anticipating instant claims 14 and 15), n is 0, A is absent; m is 0, Z is absent; L1 is C1 alkyl; B is a direct bond; and L2 is C6 aryl. The species anticipates the limitations of instant claims 14 and 15, requiring Y to be C.
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.
Claim 52 is rejected under 35 U.S.C. 103 as being unpatentable over Graupe in view of Gekeler (CN 101980707, found in IDS filed 07/28/2023, US 9073913 B2 was used as the English language equivalent document for this reference).
Graupe teaches compounds of Formulae (I) and (II)
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(Col 2, lines 1-20) and discloses these compounds as activators of TLR7 (Col 1, lines 17-19). The species of formula (I) discussed in the proceeding rejection is incorporated by reference into this rejection. The species of Graupe is shown here with substituents mapped to the corresponding variables of the instant application
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. This species has an identical R2 substituent to example compounds 29, 30, 34-37, 39, 41-92, 96, and 131. The Z substituent is also found within the species of instant claim 52 in the same position (see example compounds 1 and 2). Graupe teaches varied substituents off of this position in the embodiments of the disclosure beginning at Col 26, line 47 and continuing through Col 44, line 18. The breadth of the disclosed substituents at this position demonstrates that the moiety is both tolerant to modification and is not critical to the desired TLR-activation activity. Graupe teaches that this position is suitable for routine substitution/modification. The compounds of Graupe differ from the instant claims in that they do not include an imidazoquinoline core. However, imidazoquinoline cores are well known in the art as scaffolds for TLR activation.
Gekeler teaches imidazoquinolines of formula (I)
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(Col 2, lines 50-62) and discloses that these compounds are TLR7 activators (Col 2, lines 44-50). The reference also teaches that small molecule TLR7 agonists can be broadly categorized into purine-like molecules or imidazoquinoline-type molecules (Col 1, lines 28-39). The reference further teaches that the imidazoquinoline, imiquimod is the only approved definitive TLR agonist.
The artisan would be familiar with know small-molecule TLR agonists, structure-activity relationships (SAR), and routine medicinal chemistry modifications capable of optimizing receptor activity.
Based on the teachings of the references above, the artisan would have been motivated to begin with an imidazoquinoline core when developing a small-molecule TLR agonist, as this scaffold is present in the only approved definitive TLR agonist and is well established for TLR activation. Both Graupe and Gekeler further demonstrate that substitution at the position corresponding to “Z” of the instant claims is not essential to TLR agonistic activity and represents a position amenable to structural modification for SAR exploration.
Given that Graupe teaches multiple alternatives at this corresponding position while preserving TLR agonistic activity, the artisan would have logically selected such known substituents as the starting points for modifying the imidazoquinoline scaffold. Combing a well-established TLR activator core with substituents drawn from structurally related compounds known to exhibit TLR activity represents the use of known elements according to their known functions. The artisan would reasonably expect the resulting compounds to retain TLR agonistic activity. This expectation is further supported by the fact that each reference teaches variation at the same relative positions of their respective cores. This reinforces that these positions are routinely modified in the art without negative impacts to TLR activity.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CONNOR KENNEDY ENGLISH whose telephone number is (571)270-0813. The examiner can normally be reached Monday Friday, 8 a.m. 5 p.m. ET..
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/C.K.E./Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625