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 .
DETAILED ACTION
Status of Claims
Claims 1-204 are pending.
Election/Restrictions
Applicant’s election of Group I and the following species:
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, in the reply filed on 2/9/2026 is acknowledged.
The election was made without traverse.
Claims 8-10, 14, 16-17, 26, 31-36, 41-70, 78, 84, 86, 89-91, 107-109, 113, 118-133, 136-137, 139-140, 151-152, and 168-204 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected group or species, there being no allowable generic or linking claim. Claims 1-7, 11-13, 15, 18-25, 27-30, 37-40, 71-77, 79-83, 85, 87-88, 92-106, 110-112, 114-117, 134-135, 138, 141-150, and 153-167 are under examination in the instant office action.
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 165-167 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 pre-AIA the applicant regards as the invention. All dependent claims are included.
Claims 165-167 are incomplete in themselves due to incorporation by references to “Table C1 and/or Table C2” in the specification. Here, each of the Table C1 and Table C2 contains 13 compounds and as such can easily be written out in the claim and there is no need for such incorporation by references to the Table.
Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table “is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience.” Ex parteFressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted). See MPEP 2173.05(s).
Claim Objections
Claims 4-7, 11-13, 15, 18-25, 27-30, 37-40, 71-77, 79-83, 85, 87- 88, 92-106, 114-117, 134-135, 138, 141-150, and 153-167 are objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim cannot depend from any other multiple dependent claim. See MPEP § 608.01(n). Accordingly, the claims have not been further treated on the merits.
Claims 1, 3 and 110 are objected to because of the following informalities: typographical errors.
In claim 1, the recitations, “from 1-6” in lines 7, 20, and 21 at page 1; in lines 1, 2, 3, 4, and 10 at pages 2; line 2 and 18 at page 3; line 2, 15, and 21 at page 4; “from 1-5” in line 26 at page 2; “from 1-3” in line 17 at page 3, line 6 and 25 at page 4;, “from 1-4” in line 29 at page 4 should be corrected to --from 1 to 6--; --from 1 to 5--; --from 1 to 3--; --from 1 to 4--, respectively.
In claim 1, the recitation of “integer from 1-3” in line 20 at page 2 should be corrected to --integer of from 1 to 3--.
In claim 1, the recitation, “a carbocyclic ring including from 3-8 ring atoms” in line 10 at page 4 should be corrected to -- a carbocyclic ring having from 3 to 8 atoms--.
In claim 3, the recitation, “from 1-5” in lines 3-4 should be corrected to --from 1 to 5”.
In claim 110, the word, “from 1-3” in line 11 should be corrected to --from 1 to 3”.
Claim Rejections – Improper Markush Grouping Rejection
Claims 1-3, 110-112, and 117 are rejected on the judicially-created basis that it contains an improper Markush grouping of alternatives.
In the aforementioned claim, the instantly claimed Markush group of formula I may encompass a number of independent/distinct cores which do not have a common structure and are not recognized equivalents to those skilled in the art. Thus, these claims are properly rejected under the judicially approved “improper Markush grouping” doctrine, see Supplementary Examination Guidelines for Determining Compliance with 35 U.S.C. § 112 and for Treatment of Related Issues in Patent Applications, 76 FR 7162, 7167 (Feb. 9, 2011).
In re Harnish, 206 USPQ 300, 305, says, “ …we think it should be clear from our actions in Weber and Haas II that we there recognized the possibility of such a thing as an "improper Markush grouping." The court went on to reverse the rejection, (which had been made by the Board under Rule 196(b)) but not on the lack of a specific statutory basis but rather, “Clearly, they are all coumarin compounds which the board admitted to be "a single structural similarity." We hold, therefore, that the claimed compounds all belong to a subgenus, as defined by appellant, which is not repugnant to scientific classification. Under these circumstances we consider the claimed compounds to be part of a single invention so that there is unity of invention…” Thus, the rejection was overturned because of the specific facts in the case. The Markush group was held proper in that case, as was the case also in Ex parte Price 150 USPQ 467, Ex parte Beck and Taylor, 119 USPQ 100, and Ex parte Della Bella and Chiarino 7 USPQ2d 1669. Cases where the Markush group was held improper include Ex Parte Palmer, 7 USPQ 11, In re Winnek, 73 USPQ 225, In re Ruzicka, 66 USPQ 226, Ex parte Hentrich, 57 USPQ 419, Ex parte Barnard, 135 USPQ 109, Ex parte Reid, 105 USPQ 251, Ex parte Sun and Huggins, 85 USPQ 516, In re Thompson and Tanner, 69 USPQ 148, In re Swenson, 56 USPQ 180, and In re Kingston, 65 USPQ 371.
Indeed, as was stated in Ex parte Haas, 188 USPQ 374, “The rejection of a claim as containing an improper Markush grouping has a relatively long history in Office practice. The Court of Customs and Patent Appeals, at least as far back as 1942, has recognized that a rejection may be based upon the Examiner's holding that the claim has an improper Markush group. See In re Swenson, 30 CCPA 764, 132 F.2d 336, 56 USPQ 180 , citing Ex parte Palmer, 398 OG 707, 1930 CD 3.”
It should be noted that in Harnish, there was a single heterocyclic core. That is exactly what is lacking in this case, as the genus defined by formula (I) encompasses different heterocyclic cores, depending on various structures of Ring A, Ring B, Ring C, Ring D, and Linkers L1 and L2. Also, the instant claims further recite that some of substituents on the rings can form additional rings with the atoms to which they are attached. Thus, the resulting compounds would have different heterocyclic cores with different ring size and ring members and thus will not belong to the same chemical classes due to such differences. The examiner recommends that the claim should be amended to include only species that share a single structural similarity and a common use to overcome the rejection.
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 1-3 and 110-111 are rejected under 35 U.S.C. 103 as being unpatentable over US 2019/0225604 (hereafter, YOSHINO).
The instant claims are drawn to a compound of the following formula (I), which is a GLP-1 agonist:
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.
The elected compound (
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) appears to be free of prior art. Thus, the examination and search are extended to the following scope of the compounds of formula (I); wherein Ring A is phenyl; L2 is
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; Ring D is phenyl substituted with RQB, which is -(CRhRh)q1-S(O)2-(CRhRh)q2-Rc wherein q1 and q2 is 0 and Rc is C1-6 alkyl; L1 is C(O); Ring B is
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; R8a and R8b together with a carbon atom to which they are attached forms C3 cycloalkyl ring, L4 is a bond, and R9 is
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; Ring C is
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.
YOSHINO disclose pyrazolopyridine derivatives defined by the following formula (I) as GLP-1 receptor agonist and a pharmaceutically acceptable salt thereof and a pharmaceutical composition comprising the same:
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wherein X is CH;
Y (corresponding to L1) is C(O);
Q1 (corresponding to Ring A) is C6-10 aryl (e.g., phenyl) or 5 to 10 membered heteroaryl,
Q2 (corresponding to Ring C) is 3 to 12 membered-heterocyclyl or 5 to 10 membered heteroaryl;
Z1 (corresponding to L2) is
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;
Z2 (corresponding to Ring D) can be C6-10 aryl (e.g., phenyl), which is optionally substituted with one to five substituents independently selected from Group A (corresponding to RQB), including -S(O)2-Rzh wherein Rzh is hydrogen or C1-6 alkyl;
R7 and R8 (corresponding to R8a and R8b) together with a carbon atom to which they are attached may form C3-15 cycloalkane ring (e.g., cyclopropyl); and
R9 is
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(title, abstract, claims 1, 5, 8, and 10, [0001], [0012]-[0034], [0022], [0028], [0035], [0051] and [0079]).
YOSHINO further discloses a pharmaceutical composition comprising a pharmaceutically effective amount of the compound of formula I as an active ingredient, in association with a pharmaceutically acceptable additives such as an excipient, a lubricant (a coating agent), a binding agent, a disintegrator, a stabilizer, correctives, a base, a dispersant, a diluent, a surfactant, or an emulsifier ([0306] and claim 11).
However, YOSHINO specifically discloses the following compound:
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(p35, Table 2, Compound 21). This compound is a species of the genus defined by formula (I), but it is excluded by claimed proviso (when Lª is -(CRᵇRh)q1 and q1 is 0, then -Lb-Rc is other than unsubstituted C₁-₃ alkyl).
As shown above, while the genus of YOSHINO encompasses the claimed genus and disclose the specific compound having almost identical structure as claimed except for having unsubstituted C2 alkyl for -Lb-Rc, the prior art does not disclose a specific embodiment of a compound having -S(O)2-C4-6 alkyl for RQB.
The compound of the prior art differs in that the claimed compounds are homologs differing only by the successive addition of the same chemical group –CH2- (e.g., C2 alkyl in the prior art while C4-6 alkyl in the claimed compounds. However, YOSHINO teach the compound having almost identical structure except for having -S(O)2-CH2CH3-substitution on the phenyl ring and disclose the same use of the compounds as a GLP-1 receptor agonist as claimed. Also, YOSHINO already discloses that Rzh can be C1-6 alkyl. Thus, one of ordinary skill in the art would have envisaged the claimed compounds having phenyl ring substituted with -S(O)2-C4 alkyl or -S(O)2-C5 alkyl from the teachings of the prior art. The skilled artisan would have been able to make the instantly claimed compounds by following the suggestion of the prior art or modifying the compound of the prior art on the reasonable expectation of success of getting additional GLP-1 receptor agonists.
It is well established that position isomers and homologs are prima facie structurally obvious even in the absence of a teaching to modify. The isomer is expected to be preparable by the same method and to have generally the same properties. This expectation is then deemed the motivation for preparing the adjacent homolog. This circumstance has arisen many times. Such a variation is considered obvious because of the close structural similarity. See specifically In re Shetty, 195 USPQ 753; In re Wilder, 195 USPQ 426 and Ex Parte Greshem, 121 USPQ 422, all of which feature a compound with a C2 link rejected over a compound with a C1 link. Similarly, In re Chupp, 2 USPQ2d 1437 and In re Coes, 81 USPQ 369 have a compound with a C1 link unpatentable over prior art showing C2 link. Note Ex parte Agouridas, 65 USPQ2d 1142, where a C4 chain was held obvious over a C3 chain. Note also In re Schaub, 190 USPQ 324, 326, where compounds with C5 and C6 chains were called “adjacent homologs in the classic sense”. Ex parte Ruddy, 121 USPQ 427 has a C3 link unpatentable over a C1 link. Ex parte Nathan, 121 USPQ 349 found the insertion of a C2H4 link obvious. In all of these cases, the variation was found to be obvious on the basis of close structural similarity; no secondary teaching was employed.
As was stated directly in THE GENERAL TIRE & RUBBER COMPANY v. JEFFERSON CHEMICAL COMPANY, INC., 182 USPQ 70 (1974): “If any structural change is obvious to one skilled in the art, a substitution of the next higher homolog would seem to be.” Note also In re Jones, 21 USPQ2d 1942, which states at 1943 “Particular types or categories of structural similarity without more, have, in past cases, given rise to prima facie obviousness”; one of those listed is “adjacent homologues and structural isomers”. Similar is In re Schechter and LaForge, 98 USPQ 144, 150, which states “a novel useful chemical compound which is homologous or isomeric with compounds of the prior art is unpatentable unless it possesses some unobvious or unexpected beneficial property not possessed by the prior art compounds.”
MPEP 2144.09, second paragraph, states, “Compounds which are position isomers or homologs are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties.” In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977).
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 forgoing discussion, it is concluded 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 reference, 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 before the effective filing date of the claimed invention, as evidenced by the reference, especially in the absence of evidence to the contrary.
Allowable Subject Matter
The following scope of compounds appears to be free of prior art and would be allowable:
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wherein Ring A is phenyl;
L1 is C(O);
L2 is
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;
RQB is -(CRhRh)q1-S(O)2-(CRhRh)q2-Rc wherein RQB is para relative to L2, q1 is 1 or 2, q2 is 0, Rc is C1-6 alkyl; each of Rh is independently selceted from the group consisting of H and C1-6 alkyl;
RQA is halo or C1-6 alkyl, m1 is 0, 1, or 2;
Ring E is C3-cycloalkyl;
R9 is
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R8c is slelceted from the group consisting of H and C1-6 alkyl, which is optionally substituted with 1-3 substituents selected from Rf;
Ring C is
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R1, R2, and R3 are each indepently slelceted from the group consisting of H and C1-6 alkyl which is optionally substituted with from 1-6 substituents each independently selected from the group consisting of halo, -OH, and C1-6 alkoxy; and
R4, R5, R6, and R7 are each indepently slelceted from the group consisting of H, halo, and C1-6 alkyl .
Examiner’s note
The instant application is a national stage entry of PCT/CN2021/116684 filed on 9/6/2021 and claims benefit of foreign application PCT/CN2020/113758 filed on 9/7/2020. However, it is noted that the copy submitted as a certified copy of foreign priority document is not a copy of PCT/CN2020/113758, but a copy of PCT/CN2021/116684. Also, the document No. of foreign priority document appears to be incorrect as PCT/CN2020/113758 does not exist in WIPO.
Conclusion
No claims are allowed.
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/BONG-SOOK BAEK/Primary Examiner, Art Unit 1611