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
Claims 1-12 are pending in the application. Claims 1, 2 and 4-12 are rejected. Claim 3 is objected to.
Information Disclosure Statement
The Examiner has considered the Information Disclosure Statement(s) filed on January 7th, 2025 and September 18th, 2023.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 63/321,244, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application.
The provisional application fails to disclose that the compound of formula (J) can be used in salt form as embraced by instant step (h) of each pending claim or that step (J-5) can result in a salt of formula (J) as embraced by instant claims 1 and 12.
The provisional application fails to disclose that the variable G1 can be anything besides methyl, ethyl or phenyl where instant claims 9 and 10 embrace C3-C6 alkyl groups and aryl groups besides phenyl.
The provisional further fails to disclose steps (J-2a) and (J-2b) of instant clam 12.
For these reasons, the earliest filing date for prior art purposes of each claim is March 17th, 2023.
Claim Objections
In step “f” of claim 1, the phrase “the compound of formula (K)” should be changed to “a compound of formula (K)” since it is the first mention of the formula.
In the step “d” limitation of claim 4, “methol” should be changed to “methanol”.
In the step “(J-4)” limitation of claim 4, “the mixture of solvent of xylene and methanol” should be changed to “a solvent mixture of xylene and methanol”.
In the second to last line of claim 4, the phrase “of is” should be changed to “of”.
In step “f” of claim 5, the phrase “the compound of formula (K)” should be changed to “a compound of formula (K)” since it is the first mention of the formula.
Applicant is advised that should claim 6 be found allowable, claim 11 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m). The main differences between the parent claims 5 and 9 appear to be the definitions of G1 and the preferable statement in claim 9 regarding the definition of R1. These differences, however, are rendered moot in claims 6 and 11 where both G1 and R1 are limited to the same scope. Furthermore, the lack of alternative step (g) in claim 9 does not appear to affect claim scope since it merely restates an embodiment embraced by the first recited option of step g.
In step “f” of claim 12, the phrase “the compound of formula (K)” should be changed to “a compound of formula (K)” since it is the first mention of the formula.
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 1, 2, 4, 5, 6, 8, 9, 10 and 12 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 1, 2, 4 and 8 are rejected as indefinite since steps “c” and “d” of claim 1 refer to a compound of formula (D-1) but where the two structures are different. It is unclear if one of them contains a structural error or if Applicant is implying that an additional step takes place when G1 is not methyl.
Claim 4 recites the limitation "the ratio of diastereomer (d-1) and diastereomer (d-2)" in lines 5 and 6. There is insufficient antecedent basis for this limitation in the claim. Parent claim 1 does not explicitly define the diastereomers cited in claim 4.
Claim 4 recites the limitation "the ratio of diastereomer (e-1) and diastereomer (e-2)" in lines 7 and 8. There is insufficient antecedent basis for this limitation in the claim. Parent claim 1 does not explicitly define the diastereomer (e-2) cited in claim 4.
Claim 4 recites the limitation "the salt form of Compound (f-1)" in line 10. There is insufficient antecedent basis for this limitation in the claim. Parent claim 1 does not define a formula “(f-1)”. It is unclear if applicant is attempting to refer to formula “(F-1)” or a single diastereomer.
Claims 5 and 6 are rejected as indefinite since steps “c” and “d” of claim 5 refer to a compound of formula (D-1) but where the two structures are different. It is unclear if one of them contains a structural error or if Applicant is implying that an additional step takes place when G1 is not methyl.
Claim 8 recites the limitation "the ratio of diastereomer (d-1) and diastereomer (d-2)" in lines 5 and 6. There is insufficient antecedent basis for this limitation in the claim. Parent claim 1 does not explicitly define the diastereomers cited in claim 8.
Claim 8 recites the limitation "the ratio of diastereomer (e-1) and diastereomer (e-2)" in lines 7 and 8. There is insufficient antecedent basis for this limitation in the claim. Parent claim 1 does not explicitly define the diastereomer (e-2) cited in claim 8.
Claim 8 recites the limitation "the salt form of Compound (f-1)" in line 10. There is insufficient antecedent basis for this limitation in the claim. Parent claim 1 does not define a formula “(f-1)”. It is unclear if applicant is attempting to refer to formula “(F-1)” or a single diastereomer.
Claims 9 and 10 are rejected as indefinite since steps “c” and “d” of claim 9 refer to a compound of formula (D-1) but where the two structures are different. It is unclear if one of them contains a structural error or if Applicant is implying that an additional step takes place when G1 is not methyl.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 9 recites the broad recitation “R1 is as previously defined”, and the claim also recites “is preferably hydrogen or F,” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 12 is rejected as indefinite since steps “c” and “d” of claim 12 refer to a compound of formula (D-1) but where the two structures are different. It is unclear if one of them contains a structural error or if Applicant is implying that an additional step takes place when G1 is not methyl.
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.
Claim(s) 5-7 and 9-11 is/are rejected under 35 U.S.C. 103 as being unpatentable over U.S. Patent PGPub No. 2022/0162216 A1 by Wang et al. in view of U.S. Patent No. 11,325,916 by Shen et al. and in further view of Efremov et al. J. Med. Chem. 2012, 55, 9069-9088.
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
Wang et al. teach the following compound on page 53:
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The compound corresponds to instant formula (A) where R1 is F and R2 is isobutyl, which definitions are embraced by instant claim 6. The prior art teaches in paragraph [0284] that the compound was prepared using a similar protocol to Example 42:
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The steps above correspond to step g of instant claim 5 where an analogous compound of formula (L) is converted to a compound of formula (M) (conversion of prior art compound 39-1 to prior art compound 42-1), step h of claim 5 where an analogous compond of formula (J) is reacted with an analogous compound of formula (M) (conversion of prior art compound 42-1 to prior art compound 42-2 using 4-methoxy-1H-indole-2-carboxylic acid in paragraph [0282] of the prior art), and step i of isntant claim 5 where an analogous compound of formula (N) is converted to an analogous compound of formula (A) (conversion of prior art compound 42-2 to prior art Example 42).
Regarding the preparation of prior art compound 39-1, Wang et al. teach the following conversion on page 49:
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The conversion above corresponds to instant step f of claim 5 where a compound of formula (F-1) (prior art compound 1-4) where X is Cl (recited in instant claim 7) is reacted with N-((benzyloxy)carbonyl)-N-methyl-L-leucine (prior art paragraph [0277]) which is a compound of instant formula (K) where PG1 is -Cbz (recited in instant claim 7) and R2 is isobutyl.
Regarding the preparation of prior art compound 1-4, Wang et al. teach the following conversions on page 34:
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The prior art teaches conversion of a compound of isntant Formula (B) to a compound of instant Formula (C) (conversion to prior art compound 1-1) where G1 is methyl (recited in instant claim 7), subjecting a compound of Formula (C) to rearrangement to produce a compound of formula (D-1) (conversion of prior art compound 1-1 to prior art compound 1-2), converting a compound of Formula (D-1) to a compound of formula (e-1) (conversion of prior art compound 1-2 to prior art compond 1-3) and converting a compound of formula (e-1) to a compound of formula (F-1) (conversion of prior art compound 1-3 to prior art compound 1-4 where X is Cl-), i.e. steps b-e of instnat claim 5.
Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
Wang et al. do not provide the explicit procedure that was used to prepare the following prior art compound:
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The prior art does not provide an explicit procedure corresponding to instant step a using formaldehyde.
Finding of prima facie obviousness --- rationale and motivation (See MPEP § 2141.02)
Wang et al. teach the following general conversion on page 29:
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Wang et al. further teach on page 30: “Treatment of amine (X-1) with formaldehyde affords the cyclized amine (X-2), which is converted to (X-3) using appropriate protecting group PG2 (e.g. Boc).” Accordingly, Wang et al. generally teach that the compound is prepared using formaldehyde. Furthermore, Shen et al. teach the following in column 41:
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Shen et al. refer to the disclosure of Efremov et al. Accordingly, a person having ordinary skill in the art in seeking to produce the compound of Wang et al. would have been motivated to use known procedures such as the procedure involving formaldehyde from the methoxy-protected HCl salt of the amino acid.
Regarding instant claims 9-11, the same discussion applies since the claims recite the same corresponding conversions.
Allowable Subject Matter
Claim 3 is objected to as being dependent upon an objected to base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims and amended to correct for the claim objections and rejections above.
The prior art suggests steps a-g of instant claims 1 and 12; however, arriving at the particular arrangement of steps (J-1)-(J-5) (of claims 1 and 12) would require combining multiple references to arrive the instantly claimed permutation of steps. While the instantly claimed reactions are known types of reactions, e.g. reducing an aryl carboxylic acid, oxidation a benzyl alcohol, etc., the Examiner finds that arriving at the instantly claimed permutation would entail using the instant disclosure as a roadmap to support obviousness as opposed to any rationale in the prior art regarding why a person of ordinary skill in the art would pursue the approach instantly claimed.
For instance, U.S. Patent PGPub No. 2020/0354379 A1 by Donald et al. teaches steps corresponding to instant steps (J-3) through (J-5) on page 44 where a compound of instant formula G where R1 is F is reacted with a compound of instant formula (G-1) where R3 is ethyl (paragraph [0722] of the prior art), the product is cyclized to a compound of instant formula (I) (paragraph [0723] of the prior art) followed by hydrolysis using sodium hydroxide to produce a compound of instant formula (J) (paragraph [0724] of the prior art). Donald et al., however, fail to teach the preparation of the compound of formula (G), which would entail finding additional reference(s) teaching steps (J-1) and (J-2). There is no clear reason why: (1) one would pursue the synthesis of Donald et al. in combination with Wang et al. and then (2) pursue the instantly claimed steps (J-1) and (J-2). For instance, even in locating references that disclose the corresponding aldehyde, there is no consistency in how the synthesis should proceed. WO 95/09828 A1 by Schlosser et al. discloses the following synthetic map on page 10:
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The disclosure above teaches the aldehyde of instant formula (G) and the alcohol of instant formula (G-b) but in the inverse synthetic order, i.e. the alcohol is prepared from the aldehyde instead of the aldehyde from the alcohol as instantly claimed. Given the myriad ways in which a person having ordinary skill in the art might approach the overall synthesis, the Examiner finds that the prior art is not suggesting the process as claimed but rather (in attempting to formulate an obviousness rejection) the Examiner would be using Applicant’s disclosure as a roadmap to arrive at the claimed subject matter.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MATTHEW P COUGHLIN whose telephone number is (571)270-1311. The examiner can normally be reached Monday - Friday, 10 am - 6 pm EST.
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/MATTHEW P COUGHLIN/Primary Examiner, Art Unit 1626