DETAILED ACTION
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 .
Status of Claims
Claims 1-16 are pending.
Priority
Instant application 18/574,513, filed 12/27/2023 claims priority as follows:
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Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
All references from IDS(s) received 12/27/2023 have been considered unless marked with a strikethrough.
Claim Interpretation
Claims 15 and 16 are being interpreted according to MPEP 2111.02 (II), which states: “If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction”.
The recitation “used for the preparation of Enzalutamide” in claims 15 and 16 is not considered a limitation because it merely represents an intended use for the compound of formula (IIa) or formula (IIb). In view of the interpretation of claims 15 and 16 as not further limiting, see the duplicate claim warning and 112(d) rejection below.
Claim Objections
Applicant is advised that should claim 1 be found allowable, claims 15 and 16 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).
Claim 8 objected to because of the following informalities: the claim contains a typographical error. See the last two lines, reading “which optionally it is purified via crystallization”. Appropriate correction is required.
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, 3-9, and 11 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.
Claim 1 recite a Markush grouping which requires a selection (for R1 and/or R2) from an open list of alternatives. A Markush grouping is a closed group of alternatives, i.e., the selection is made from a group “consisting of” rather than “can be”. Pursuant to MPEP 2173.05(h), if a Markush grouping requires a material selected from an open list of alternatives, the claim should generally be rejected under 35 USC 112(b) as indefinite because it is unclear what other alternatives are intended to be encompassed by the claim. With respect to claim 1, the phrase “R1 and R2, each independently from the other, can be” should be replaced with the phrase “R1 and R2, each independently from the other, are selected from the group consisting of” in order to properly recite a closed grouping of alternatives. Please note that claim 2 currently includes additional groups not recited for R1 and R2 in claim 1 (fluorine, chlorine, bromine, iodine). Those groups should be introduced into the definition for R1 and R2 in claim 1 in order to avoid antecedent basis issues in the amended claim. Dependent claims 3-9 fail to resolve the issue identified above and are therefore also rejected.
Claim 8 recites the limitations “formula (IIb)” and “formula (IIIa)” in lines 2-4. There is insufficient antecedent basis for this limitation in the claim. Claim 7 provides structures for the aforementioned formulas, but claim 8 depends from claim 1, which does not contain them.
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 11 recites the broad recitation “R’’’ is selected from 4-nitrophenyl, pentafluorophenyl, 4-chlorophenyl, 2,4-dichlorophenyl or 2,4-difluorophenyl”, and the claim also recites “preferably R’’’ is selected from 4-nitrophenyl, pentafluorophenyl, 4-chlorophenyl” 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 Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 15 and 16 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claims 15 and 16 depend from claim 1 and fail to further limit the claim. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
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.
Claims 1-16 are rejected under 35 U.S.C. 103 as being unpatentable over JAIN (WO 2011106570 A1; 2011; IDS) in view of SHANGHAI (CN108069869A; 2018; IDS)
The disclosure is generally directed to a new process for preparing the nonsteroidal antiandrogen Enzalutamide. The claims are drawn to a process for preparing a compound of formula (I) by coupling formula (II) and formula (III) as represented below:
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Additional claims are drawn to the intermediate compound used in the aforementioned process (claims 10-12); and a process for preparing the intermediate compound (claims 13-14).
Close prior art is JAIN. JAIN discloses (Example 5, para. [0016] on page 46) the coupling of ester fragment A with fragment B (the aryl isothiocyanate of formula (IIIa) in recited by the instant claims) to furnish the thiohydantoin ring of enzalutamide:
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The only difference between JAIN and the claims is that the claims require an “activated” ester, wherein R’’’ in formula (II) is a phenyl ring substituted with NO2 or halide; whereas in JAIN the equivalent R’’’ group is a methyl ester.
However, SHANGHAI teaches (page 15, para. [0135]) a process for preparing apalutamide, which is a thiohydantoin drug structurally analogous to enzalutamide, by coupling a compound of formula II-7 with compound TFP-6:
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Note that compound II-7 comprises a p-nitrophenyl ester group. The intermediate compound II-7 is prepared by condensation of the corresponding carboxylic acid with p-nitrophenol (page 13, para. [0113]):
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Finding of prima facie obviousness
The Supreme Court in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 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. See MPEP 2143.
Examples of 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.
Applying KSR example rationale (G), it would have been prima facie obvious to modify the methyl ester in fragment A of JAIN to a p-nitrophenyl ester as taught by SHANGHAI. Both enzalutamide and apalutamide are thiohydantoin-based antiandrogen drugs. Both are synthesized by coupling an N-substituted amino acid ester intermediate with an aryl isothiocyanate to form the thiohydantoin ring. Activated esters are a well-established concept in organic synthesis. The structural similarity between the two drug targets and the shared mechanism of the key ring-forming step would motivate a person of ordinary skill to apply the activated ester approach of SHANGHAI to the enzalutamide synthesis of JAIN with a reasonable expectation of success. Moreover, applicant admits in the background of the application that there were known problems with the JAIN synthesis (specification, page 2, lines 7-10):
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The aforementioned problems would have motivated the person of ordinary skill to identify and attempt an alternative synthesis strategy, such as the one disclosed by SHANGHAI.
The intermediate compounds recited by claims 10-12, and the process for preparing the intermediate compound recited by claims 9, 13-13 are obvious in view of SHANGHAI’s teachings regarding the preparation of the p-nitrophenyl ester analogue intermediate II-7.
Accordingly, claims 1-16 are obvious over JAIN in view of SHANGHAI.
Conclusion
Claims 1-16 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Kyle Nottingham whose telephone number is (571)270-0640. The examiner can normally be reached M-F from 10:00 am - 6:00 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Clinton Brooks can be reached at (571) 270-7682. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/K.N./Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621