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 .
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.
Previously presented rejection of claims 1-5, 7-9, 19 and claim 21 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 is maintained for reasons of record.
Applicant focusses on the differences, acknowledged and explicitly pointed out with highlights in the previous action. See top of page 4 and top of page 5 of previous action.
The benefits of the instant process pointed out by the Applicant at page 4 are considered. It is noted that this is what one of skill in the art of process optimization strives to do. For example, efforts to avoid chromatography, for example, is routinely practiced to avoid costs.
As explained in the previous action, nitrile and carboxamide groups play spectator role, that is, they are non-participants in the chemistry steps to make the target. See Guo teaching in this regard. The starting material Formula -3 is a known compound by Guo. It would have been obvious to one of ordinary skill in the art to modify an otherwise known process to obtain known products using analogous reagents and alternate order of conditions as the results would not have been unexpected.
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.
Obviousness can be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art.
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 foregoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a). From the teachings of the references, 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 at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
The Supreme Court in KSR International Co. v. Teleflex Inc., 550 U.S. 398, 127 S. Ct. 1727, 82 USPQ2d 1385, 1395-97 (2007) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper “functional approach” to the determination of obviousness as laid down in Graham. The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. The Supreme Court in KSR noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit.
Exemplary rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) “Obvious to try” – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Note that the list of rationales provided is not intended to be an all-inclusive list. Other rationales to support a conclusion of obviousness may be relied upon by Office personnel.
Accordingly, the claims do not recite an unobvious distinction over the prior art. Further, a reference is relevant not only for what it expressly teaches, but also for what it would have conveyed to one of ordinary skill in the art. See In re Opprecht, 12 USPQ2d 1235, 1236 (Fed. Cir. 1989); In re Bode, 193 USPQ 12 (CCPA 1976). In light of the foregoing discussion, the Examiner finds that the claimed subject matter as a whole would have been obvious to one of ordinary skill in the art at the time the invention was made, in view of the cited references and the knowledge generally available in the art. Accordingly, the claims are rejected under 35 U.S.C. § 103.
Suggestion:
Amending base claim with process parameters such that the claim clearly sets out and circumscribe the particular area with a reasonable degree of precision and particularity, that enables for the benefits of the instant process listed at Remarks at page 4. Just Amended claim consistent with working example would be a starting point for favorable action.
Following is from previous action”
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.
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 NIZAL S CHANDRAKUMAR whose telephone number is (571)272-6202. The examiner can normally be reached M-F 8-5 EST.
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, Andrew Kosar can be reached at (571) 272-0913. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/NIZAL S CHANDRAKUMAR/Primary Examiner, Art Unit 1625
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