DETAILED ACTION
Claims 4, 5, and 20-28 are currently pending in the instant application. Claims 4, 5, and 20-21, and 25-28 are rejected. Claims 22-24 appear allowable.
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 .
Election/Restrictions
Applicant’s election without traverse of Group I and the species of example 211:
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in the reply filed on 6 December 2023 has been previously acknowledged.
According to MPEP 803.02, the examiner has previously determined whether the elected species is allowable. Applicants’ elected species appears allowable. Therefore, the search and examination has previously been extended to the compounds of claim 22 which also appear allowable and previously further to the compound:
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which is not allowable previously in addition to the compound
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which is not allowable.
Claims 4, 5, and 20-28 have been examined to the extent that they are readable on the elected embodiment, the elected species and the above mentioned compounds.
Response to Amendment and Arguments
Applicant's amendment and arguments filed 15 July 2025 have been fully considered and entered into the instant application. In regards to the 35 USC 102 rejection, Applicant argues that the Office Action mischaracterizes the make up of formula II stating that unlike the ’34 publication, the pending claims do not provide that the NH at position X1 can be substituted as NR, where R is R6 and the pending claims do not encompass a genus where X1 is NR6. This argument is not persuasive as the instant claims define R4 as being selected from variables such as:
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wherein the R6 variable is variable attached to the ring of R4. As shown, R6 can be attached variably on the ring, which would include being variably attached on the position of X1. Any place that R6 variably exists on the ring of R4 would require the removal of a hydrogen atom to place the R6 variable. There is no limitation provided that R6 cannot be variably substituted on any position of the ring. Therefore, the 35 USC 102 rejection is maintained. In regards to the 35 USC 103 rejection, Applicant’s argue that the ‘025 publication does not make the instant claims obvious that there is no finite number of predictable solutions and that the cited reference does not indicate why a methyl group should be attempted in this combinatorial synthesis as opposed to hydrogen for R6. Applicant argues that the reference fails to show why a person having skill in the art would be motivated to modify the cites structures, particularly example 100 as the ‘025 publication does not yield a teaching or suggestion of appending a substituent to pyrrolidine, particularly where X1 is CHR6, where R6 is substituted with a hydrocarbon or otherwise. This argument is not persuasive as any known compound may serve as a lead compound when there is some reason for starting with that lead compound and modifying it to obtain the claimed compound. See Eisai Co. Ltd. V. Dr. Reddy’s Labs., Ltd., 533 F.3d 1353 (Fed. Cir. 2008). Therefore, while the ‘025 publication discloses a very large genus of formula (I), example 100 is exemplified. The compounds of the ‘025 publication are disclosed on Page 19 for the treatment of patients suffering from cardiovascular diseases, inhibition of tumor cell growth, weight loss, etc. Therefore, example 100 would qualify as a lead compound as the prior art reference provides direction to the compound of example 100 as the prior art reference exemplifies only 180 compounds out of the very large genus disclosed, discloses that Example 100 falls within formula (I) on page 3 wherein R2 can be -A-R10 wherein A can be heterocyclyl and R10 can be H or C1-10 alkyl, discloses that Example 100 is also within formula (II) on page 4 wherein R2 can be -A-R10 wherein A can be heterocyclyl and R10 can be H or C1-10 alkyl, and additionally because the compounds of the ‘025 publication are disclosed to have utility as treatment of patients suffering from cardiovascular diseases, inhibition of tumor cell growth, weight loss, etc. The reason to modify the prior art compound of example 100 is that it is well established that the substitution of methyl for hydrogen on a known compound is not a patentable modification absent unexpected or unobvious results. Additionally, the difference is the compound of example 100 of the prior art has the position equivalent to applicant’s R6 as hydrogen, whereas the instant claims can have R6 as lower alkyl. Example 100 falls within formula (I) on page 3 of US Pre-Grant Publication 2015/0252025 wherein R2 can be -A-R10 wherein A can be heterocyclyl and R10 can be H or C1-10 alkyl. Example 100 is also within formula (II) on page 4 wherein R2 can be -A-R10 wherein A can be heterocyclyl and R10 can be H or C1-10 alkyl . The difference is one of hydrogen versus a methyl. In re Wood, 199 U.S.P.Q. 137 (C.C.P.A. 1978) and In re Lohr, 137 U.S.P.Q. 548, 549 (C.C.P.A. 1963). The motivation to make the claimed compounds derives from the expectation that structurally similar compounds would possess similar activity (ie., treatment of patients suffering from cardiovascular diseases, inhibition of tumor cell growth, weight loss, etc). Additionally, according to MPEP 2144.08, compounds which are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. It is not necessary for the reasoning to be explicitly found in the prior art of record nor is it necessary for the prior art to point to only a single lead compound. See Altana Pharma AG v. Teva Pharms. USA, Inc., 566 F.3d 999 (Fed. Cir. 2009). Therefore, the 35 USC 103 rejection is maintained.
Maintained 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.
Claim(s) 4, 5, 20, 21, and 25-28 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US Pre-Grant Publication 2003/0125344.
US Pre-Grant Publication 2003/0125344 discloses the compounds of Formula I:
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on page 2 wherein A can be a ring which can be substituted with an aryl. Preferred values of A can be:
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and
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wherein R15 can be H or phenyl optionally substituted by C1-10alkyl…, page 4. A specific compound disclosed is:
compound
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on page 6, paragraph [0050]. Pharmaceutical compositions are disclosed on page 6 wherein the compounds may be administered orally, paragraphs [0052]-[0054], including with pharmaceutically acceptable carriers and in the form of tablets.
The compound
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corresponds to the instant formula II wherein L2 is N; L1 is CH; R5 is H; R2 and R3 are taken together to form a 6 membered fused ring having 0 heteroatoms and is unsubstituted; R4 is
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; X1 is NH; n is 2; a is 1; and R6 is substituted aryl. (R6)a is variably substituted on applicant’s R4 of instant formula II. The compound of the prior art corresponds to the instant claims wherein a is 1 and R6 substitutes on the position X1 of the R4 ring
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, thereby replacing the hydrogen of NH at position X1.
Maintained 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) 4, 5, 20 and 21 is/are rejected under 35 U.S.C. 103 as being unpatentable over US Pre-Grant Publication 2015/0252025.
Determination of the scope and content of the prior art (MPEP §2141.01)
US Pre-Grant Publication 2015/0252025 discloses the compound of example 100, page 51:
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.
Example 100 falls within formula (I) on page 3 of US Pre-Grant Publication 2015/0252025 wherein R2 can be -A-R10 wherein A can be heterocyclyl and R10 can be H or C1-10 alkyl. Example 100 is also within formula (II) on page 4 wherein R2 can be -A-R10 wherein A can be heterocyclyl and R10 can be H or C1-10 alkyl . Page 21 provides pharmaceutical compositions, including solid dosages for oral administration which include pharmaceutically acceptable carriers. Page 19 provides utility for the prior art compounds, such as the treatment of patients suffering from cardiovascular diseases, inhibition of tumor cell growth, weight loss, etc.
Ascertainment of the difference between the prior art and the claims (MPEP §2141.02)
This prior art compound corresponds to the instant claims, for example, as follows:
The prior art compound corresponds to the formula (II)
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of claim 4, for example, wherein R5 is H; L1 is CH; L2 is N; R2 is H; R3 is halo; R4 is
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wherein a is 0; n is 1; and X1 is CHR6. The difference is the compound of example 100 of the prior art has the position equivalent to applicant’s R6 as hydrogen, whereas the instant claims can have R6 as lower alkyl. The difference is one of hydrogen versus a methyl.
The prior art compound corresponds to the formula (IIa)
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of claim 5, for example, wherein R5 is H; R2 is H; R3 is halo; R4 is
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wherein a is 0; n is 1; and X1 is CHR6. The difference is the compound of example 100 of the prior art has the position equivalent to applicant’s R6 as hydrogen, whereas the instant claims can have R6 as lower alkyl. The difference is one of hydrogen versus a methyl.
Finding of prima facie obviousness--rational and motivation (MPEP §2142-2413)
However, it would have been obvious of one of ordinary skill in the art to replace hydrogen with methyl at the position of example 100 that is equivalent to applicants X1 as CHR6 wherein R6 is hydrogen to be X1 as CHR6 wherein R6 is methyl as the prior art provides direction in formula (I) and (II) wherein R10 can be H or C1-10 alkyl. Additionally, it is well established that the substitution of methyl for hydrogen on a known compound is not a patentable modification absent unexpected or unobvious results. In re Wood, 199 U.S.P.Q. 137 (C.C.P.A. 1978) and In re Lohr, 137 U.S.P.Q. 548, 549 (C.C.P.A. 1963). The motivation to make the claimed compounds derives from the expectation that structurally similar compounds would possess similar activity.
Conclusion
THIS ACTION IS MADE FINAL. 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to REBECCA L ANDERSON whose telephone number is (571)272-0696. The examiner can normally be reached Monday-Friday from 6am-2pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Joseph McKane can be reached on 571-272-0699. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/REBECCA L ANDERSON/Primary Examiner, Art Unit 1626 ____________________ 14 October 2025
Rebecca Anderson
Primary Examiner
Art Unit 1626, Group 1620
Technology Center 1600