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 .
Current Status of 18 / 241186
Claims 1-20 filed 2023 August 31 are examined on the merits.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 2023 August 31 was submitted in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
Claim 2 is objected to because of the following informalities: the phrase “hydrogen atomand a halogen” should be written as --hydrogen atom and a halogen--. Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 9-13 recites the two compounds below among other compounds. There is insufficient antecedent basis for these compounds in the claims because examined variable R2 cannot be a CF3 group in a compound of formula (I). Ellermann (WO 2019025562, published 2019 February 7) describes example 135 (page 344, line 14 to page 345, line 11) is the same compound as the first compound recited in claim 12. Example 146 (page 350, line 13, to page 351, line 15) is the same compound as the second compound recited in claim 12. Applicants use the same examples as Ellermann (examined specification, page 67, table 1). Based on this teaching, the compounds lack antecedent basis. Any other examples in which examined variable R2 is other than H or halogen also lack antecedent basis.
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Example 135
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Example 146
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103(a) 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 1-20 are rejected under 35 U.S.C. 103(a) as being unpatentable over ELLERMANN (WO 2019025562, published 2019 February 7) in view of NAZIR (Experimental Cell Research, 2017, 361, 308-315) and PULKKA (Clinical Cancer Research, 2019, 25(5), 1676-1687).
Determining the scope and contents of the prior art
Ellermann describes examples 1, 4-6,17, 18, 20, 21, 24, 25-1, 25-2, 26, 30, 77-92, 119, 162, 163, 167-171, 173-189, 226-255, 264-266, and 281-318 (page 271, line 2 to page 287, line 22; page 325, line 20 to page 337, line 12; page 358, line 15 to page 359, line 19;) that inhibit PDE3A and PDE3B (page 451, table 6 to page 457, line 24; page 458, line 2 to page 460, line 14). The table below shows what each examined variable is in the compounds. Example 1 (page 271, lines 2-18) is the same compound as the first compound recited in claims 10 and 11. Example 265 (page 404, line 18, to page 495, line 18) is the same compound as the last compound recited in claim 12. Example 192 (page 369, line 19 to page 320, line 8) is a racemic mixture of 6R and 6S methyl enantiomers. Kits are described (page 163, lines 3-26). Pharmaceutical compositions are described (page 215, line 1 to page 221, line 11). Example 135 (page 344, line 14 to page 345, line 11) is the same compound as the first compound recited in claim 12. Example 146 (page 350, line 13, to page 351, line 15) is the same compound as the second compound recited in claim 12.
Example #
Variable R1 group
Variable R2 group
Variable R3 group
Variable R4 group
1, 4-6, 26
F
H
4,4-difluoropiperidin-1-yl; morpholine; 4-F-4-Me-piperidin-1-yl;4-fluoro-piperidin-1-yl; 3,3-difluoropyrrolidin-1-yl
H
17, 18
F
F
Morpholine; 3-methyl-morpholine
Me
24
H
F
2,6-dimethylmopholin-4-yl; 4-fluorophenyl
H
25-1, 25-2
F
H
Morpholine
Me
77-119, 162, 163, 167-171, 174-189
H
F
Substituted pyridine; substituted or unsubstituted phenyl; cyclopentenyl; pyrimidine;
173, 226-255
CF3
F
Indole; substituted phenyl; pyrazine; substituted piperidine; substituted amino group; substituted pyrrolidine; azetidine; 2-lambda-azaspiro[3.3]heptane-2,2-dione
Me
264
CF3
F
Morpholine
H
265-266
CF3
H
Substituted pyrazole or imidazole
Me
281-318
CF3
H
Substituted amino; 2-oxa-7-azaspiro[4.4]nonane; pyrazole; azetidine; cyclohexyl; pyrrolidine
H
Nazir describes that gastrointestinal stromal tumor (GIST), a soft tissue sarcoma, has a high expression of PDE3A (page 313, column 1, paragraph 2 to page 315, column 1; supplementary figure 4, graphs A-C).
Pulkka describes GIST expresses both PDE3A and PDE3B (abstract; page 1677, table 1; page 1685, column 1, paragraph 4 to column 2, paragraph 2).
Ascertaining the differences between the prior art and the claims at issue
Ellermann does not explicitly describe the inhibition of the growth of proliferation of a sarcoma or the control of a sarcoma.
Resolving the level of ordinary skill in the pertinent art
Those of relative skill in the art are those with level of skill of the authors of the references cited to support the examiner’s position (MD’s, PhD’s, or those with advanced degrees and the requisite experience in preparation of compounds of the elected group).
Considering objective evidence present in the application indicating obviousness or nonobviousness
When Ellermann is combined with Nazir and Pulkka, there is a reasonable expectation of success that a compound of Ellerman can inhibit the growth or the proliferation of a sarcoma due to the relationship of PDE3A and PDE3B to gastrointestinal stromal tumor. Ellermann describes compounds that inhibit PDE3A and PDE3B in vitro and in vivo. Nazir and Pulkka show that PDE3A and PDE3B are expressed in GIST. Even though Ellermann does not explicitly disclose in vitro cell testing against a sarcoma cell line, Nazir and Pulkka show that the compounds of Ellerman can be used to treat a sarcoma because of the relationship between the compounds of one, Ellerman and PDE3A and PDE3B, and two, PDE3A and PDE3B, and gastrointestinal stromal tumor. Based on the discussed linkages, there is a reasonable expectation of success that the specified compounds of Ellermann can treat a sarcoma.
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.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-13 and 16-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 11, 13, and 14 of U.S. Patent No. 12258323. Although the claims at issue are not identical, they are not patentably distinct from each other because a method of treating a disease sensitive to PDE3A or PDE3B modulation in a subject with a compound embraced by examined formula (I). A sarcoma is one of those cancers (column 152, lines 11-46; column 154, lines 33-35 and 49-51). US 12258323 describes examples 1 and 3 (column 203, line 47 to column 204, line 67).
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Allowable Subject Matter
Claims 1-20 are not allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NOBLE E JARRELL whose telephone number is (571)272-9077. The examiner can normally be reached 9:00 AM to 5:00 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Fereydoun Sajjadi can be reached at 571-272-3311. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/NOBLE E JARRELL/Primary Examiner, Art Unit 1699