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 with traverse of Group I in the reply filed on 11/20/2025 is acknowledged. The traversal is on the ground(s) that there would not be serious burden to search all the claims. This is not found persuasive because Applicants arguments are not responsive to the ‘explanation’ at page 4 of previous action.
The requirement is still deemed proper and is therefore made FINAL.
Now amended process claims 1-5, 7-9, 19 and the new independent process claim 21 are examined together.
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) 1-5, 7-9, 19 and claim 21 is/are rejected under 35 U.S.C. 103 as being unpatentable over the combined teachings of GUO WO2014173289: WANG WO2018033853; Ghozlan, Journal of Heterocyclic Chemistry (2010), 47(6), 1379-1385. Petek, Bioorganic Chemistry (2019), 84, 226-238 Available online 19 November 2018.
Claim 1 (step a) and claim 21:
GUO teaches compound of instant Formula-3 at page 80, [0411].
The number [0411] refers to paragraph number at page 80.
Further in this action, hereinafter, the terms ‘compound of instant and Formula-‘ would be dropped when referring to the pictured compounds in the claims. As such
3 means compound of instant Formula-3; 1 means compound of instant Formula-1 and so on.
Thus GUO teaches 3 at page 80, [0411].
GUO teaching includes the preparation of 1 at bottom of page 133 ,
(and large number of closely related structures differing only in the piperidine part of 1, in Table 1 at page 124).
GUO’s exemplifications (working examples) does not include the
the use of 3 to make 1.
GUO does teach in generic chemistry scheme at page 31, line 1
the use of 3 to make 1.
In the above generic scheme carboxamide S-18 or nitrile S-3 are indicated as optional interchangeable intermediates to make S-36.
wherein
S-36 encompasses 1, that is 1 falls under the scope of S-36.
amide S-18 encompasses 3; that is 3 falls under the scope of S-18
nitrile S-3 encompasses BG-4 that is 3 falls under the scope of S-3.
wherein BG-4 is nitrile version of the amide 3; see more on this
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(nitrile) and
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(amide) below.
WANG teaches 4 which is BG-8 at page 9 chemistry scheme line 2 to make 1
using the above noted BG-4 (in S-3) which is the is nitrile version of the amide 3.
WANG does not teach the use of 3 to make 1.
WANG scheme at page 9 (herein after scheme)
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reacts with
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to make
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en route to 1.
In the above scheme, BG-4 and BG-9 correspond to 3 and 5 respectively, in that 3 and 5 represent replacement of
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(nitrile) in BG-9 with
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(amide).
With all the intermediates (except 5) in the step a) AND all bond forming steps explicitly taught in the prior art, there is extensive overlap in the $ubject matter of claimed method and the $ubject matter of GUO and WANG, for making the commercially important 1, Zanubrutinib.
The issue here therefore is whether making and using 5 to make 1 would be obvious$ to one of skill in the art to arrive at alternate version of prior
art to make 1.
Making of 5 (claim 21 and step a of claim 1):
5 is with P = Boc
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in lieu of
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One of skill in the art would anticipate that by replacing the starting material
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(nitrile) in BG-4 taught by WANG’s scheme (to make BG-9) with 3 taught by GUO would provide 5,
because
the underlying chemistry bond forming steps in the making of the critical intermediates ring system
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in
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of WANG’s BG-9 and in 5
is independent of the substituents on the reaction centers of the reactants pointed below with arrows for WANG’s chemistry:
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reacts
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of BG-8 to make
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That replacement of the
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substituent with the prior art GUO compound 3 having
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substituent would provide 5 is supported by the teachings of Ghozlan,
because
Ghozlan at page 1380, Scheme 1 teaches formation of the bicyclic heterocycle
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wherein the reaction centers pointed out with the arrow carry different substituents to make the same ring system
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(also in 5 and in BG-9).
Further, that
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would not participate in subsequent relevant steps such as reduction (hydrogenation) and deprotection (treatment with acid for de-Boc-ing) to make 1 as taught WANG’s scheme, is supported by the teachings of Petek in column A, page 230, Scheme 5.
Taken together, one of skill in the art would be motivated to make the replacement of
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(nitrile) with
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(amide) to make the early intermediate 5 in the multi-step synthesis of 1 (see more below), which would be consistent with the well-acknowledged desire of chemists to develop short, streamlined syntheses rather than multi-step procedures driven primarily by the need for efficiency, higher overall yields, cost reduction( and maybe environmental sustainability).
Limitation of claim b) of claim 1 and the limitation of dependent claims 1-5, 7-9, 19
Scheme of WANG page 9 is shown below:
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Thus by substituting 3, discussed for step a) limitation of claim 1, in the above scheme for BG-4, and omitting steps (crossed out below) for the conversion of
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(nitrile) to
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(amide).,
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would provide 7a (of claim 2 step b), that is
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in scheme
(which as per
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in scheme)
would make the step b
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.
Claim 2, reduction of double bonds in 5 to make 6 (step a); deprotection of 6 to make 7a (step b), see line 3 of scheme
Claim 3 (solvent for step a of claim 1) Wang page 19 paragraph 0096,
hydrocarbon solvent toluene
Claim 4 (solvent for step a of claim 2) Wang page 20, paragraph 0097,
ether solvent THF
Claim 5 (acid in step a of claim 1) see Wang page 19 paragraph 0096, acetic acid
Claim 7 (reducing agent in claim 2) see line 3 of scheme; Wang page 20 paragraph 0097, Pd/C
Claim 8 (deprotecting agent of claim 2) see line 3 of scheme; Wang page 20 paragraph 0098, hydrochloric acid
Claim 9 (conversion of product of claim 2 7a to 1) see line 4 onto line 5 of scheme, Wang page 23, paragraph 0105.
As such there is nothing unobvious in the claimed method. One of skill in the art would make the 5 using intermediates and chemical steps taught in the prior en route to 1, with reasonable expectation of success.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NIZAL S CHANDRAKUMAR whose telephone number is (571)272-6202. The examiner can normally be reached M-F 8-5 EST.
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/NIZAL S CHANDRAKUMAR/Primary Examiner, Art Unit 1625