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 .
Claims 1-21 are currently pending.
Priority
The instant application claims priority as follows:
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Claims 1-21 were fully searched and considered for patentability. Claims 1-21 are the subject of this Office action.
Claim interpretation
Claim 1 recites that variable Y is an acyclic hydrocarbon chain of 2 to 20 carbon atoms. Y only consists of hydrogen and carbon atoms and is unsubstituted, and. This is in accordance with how all other variables are being claimed in the claims.
If this is not the case, the examiner requests Applicant to clarify the definition for Y since additional prior art rejections may be applicable.
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 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 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 1-2, 7-8, 10, 12 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Estephane (Bioorganic & Medicinal Chemistry Letters 18 (2008) 4321-4324) in view of Kerns, Edward et al, Goosen et al., Fourie et al. and Rautio et al.
Determination of the scope and content of the prior art (MPEP §2141.01)
Estephan teaches the genus of compounds 5-10
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, which are useful as inhibitors of bacterial quorum sensing. These were in pharmaceutical carriers, evaluated for their ability to inhibit the natural ligand of LuxR in the V. fischeri QS system.
Ascertainment of the difference between the prior art and the claims (MPEP §2141.02)
The difference between compounds of the instant claims and compounds 5 and 6 of the prior art is a H vs. CH3 on the nitrogen atom.
Finding of prima facie obviousness--rational and motivation (MPEP §2142-
2413)
It is well established that position isomers and homologs are prima facie structurally obvious even in the absence of a teaching to modify. The isomer is expected to be preparable by the same method and to have generally the same properties.
Such a variation is considered obvious because of the close structural similarity. See In re Hoeksema, 154 USPQ 169; Ex parte Weston, 121 USPQ 428; Ex parte Bluestone, 135 USPQ 199; In re Doebel, 174 USPQ 158. As was stated directly in THE GENERAL TIRE & RUBBER COMPANY v. JEFFERSON CHEMICAL COMPANY, INC., 182 USPQ 70 (1974): “If any structural change is obvious to one skilled in the art, a substitution of the next higher homolog would seem to be.”
In addition, the secondary references explicitly teach the known advantages of adding a methyl group (alkyl group) to a nitrogen atom. Permeability is the velocity of molecule passage through a membrane barrier, and thus is an important determinant of intestinal absorption, passage through blood-organ barriers, penetration into cells containing the therapeutic target and oral bioavailability. “The best way to improve permeability is structural modification”, and one way to do that is to add lipophilicity, as is taught by Kerns, Edward et al, Drug-like Properties: Concepts, Structure Design and Methods: from ADME to Toxicity Optimization, (Elsevier, 2008) pages 92-93. The reference gives an example which is based on the fact that replacing a H with a methyl group on an amine improves the lipophilicity, so that in that particular case, the in vivo oral bioavailability rose from 24% to 84%.
Adding a methyl group to a secondary amine can be expected to improve its solubility. The reference Goosen et al., Pharmaceutical Research Volume 19, Number 1, 13-19 (January 2002) shows that methylation of the amine thalidomide produced a sharp increase (5 fold to as much as 20 fold) in its solubility in both water (Table III) and in a range of alcohols (Table IV).
In addition, the reference Fourie, International Journal of Pharmaceutics Volume 279, Issues 1-2, 26 July 2004, Pages 59-66 showed that methylation of the amine carbamazepine significantly improved its aqueous solubility (Table 1) and tripled its transdermal flux (Table 2).
In the reference Edwards, J. Med. Chem. 39 (1996), pp. 1112–1124, methylation of the amine improved the in vitro Human Neutrophil Elastase inhibitory activities in both series of compounds (see Table 2, comparing a with b in both columns)
The reference Rautio, Eur. J. Pharm. Sci. 11:157–163 (2000) showed that the methylation of the N atom in 4b to produce 4c produced a marked improvement in flux and permeability values (see Table 3) and indeed, the prodrug 4c was deemed the most promising of the compounds studied. This was attributed to the “simultaneously high aqueous solubility and lipophilicity”.
Accordingly, one is well motivated to add a methyl group to nitrogen, because there is a reasonable expectation of improved properties.
It would have been obvious to treat a bacterial infection caused by a gram-negative bacterium from the order of Vibrionalles because the compounds are inhibitors of Vibrionalles fischeri QS system.
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 1-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of U.S. Patent No. 10,744,111. Although the claims at issue are not identical, they are not patentably distinct from each other because the compounds, compositions and method as claimed in the rejected claims are prima facie obvious and covered by claims 1-21 of the patent. Particularly, claims 1-4 and 6-17 of the patent in which R4 is alkyl group anticipate the subject matter of the instant claims.
In addition, it would have been prima facie obvious to one of ordinary skill in the art to select the compounds of the claims wherein R4 is alkyl, such as any of the alkyl groups described for R4 in the patent since these are the embodiments that provide support to and fall within the scope of the claims of the patent.
Finding of prima facie obviousness--rational and motivation
The ordinary skilled artisan would have been motivated to make the compounds wherein R4 is a C1-C3 substituted alkyl group (see column 4 of the patent), wherein Y is an acyclic carbon chain of 2 or 4 carbon atoms (column 5), and use them in the manner described in the specification of the patent. These compounds were covered by the claims of the patent because of the particular definitions for the variables and substituents which provide support for the claims.
This rejection is proper under MPEP 804 II. B. 2. (a):
Further, those portions of the specification which provide support for the reference claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application (as distinguished from an obvious variation of the subject matter disclosed in the reference patent or application). In re Vogel, 422 F.2d 438, 441-42, 164 USPQ 619, 622 (CCPA 1970). The court in Vogel recognized "that it is most difficult, if not meaningless, to try to say what is or is not an obvious variation of a claim," but that one can judge whether or not the invention claimed in an application is an obvious variation of an embodiment disclosed in the patent or application which provides support for the claim. According to the court, one must first "determine how much of the patent disclosure pertains to the invention claimed in the patent" because ONLY "[t]his portion of the specification supports the patent claims and may be considered." The court pointed out that "this use of the disclosure is not in contravention of the cases forbidding its use as prior art, nor is it applying the patent as a reference under 35 U.S.C. 103, since only the disclosure of the invention claimed in the patent may be examined." In AbbVie Inc. v. Kennedy Institute of Rheumatology Trust, 764 F.3d 1366, 112 USPQ2d 1001 (Fed. Cir. 2014), the court explained that it is also proper to look at the disclosed utility in the reference disclosure to determine the overall question of obviousness in a nonstatutory double patenting context. See Pfizer, Inc. v. Teva Pharm. USA, Inc., 518 F.3d 1353, 86 USPQ2d 1001 (Fed. Cir. 2008); Geneva Pharmaceuticals Inc. v. GlaxoSmithKline PLC, 349 F3d 1373, 1385-86, 68 USPQ2d 1865, 1875 (Fed. Cir. 2003).
Telephonic Inquiry
Any inquiry concerning this communication or earlier communications from the examiner should be directed to VALERIE RODRIGUEZ-GARCIA whose telephone number is (571)270-5865. The examiner can normally be reached Monday-Friday 9:30am-4:30pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Joseph K McKane can be reached at 571-272-0699. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/VALERIE RODRIGUEZ-GARCIA/Primary Examiner, Art Unit 1621