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 .
Application Status
The amendment filed on 7/22/2026 in response to the Non-Final Rejection of 4/22/2026 is acknowledged and has been entered.
Claims 1, 12-16, 18-22, 24-31 and 35 are currently pending and under consideration.
Claim Interpretation
The majority of the independent method claims recite the limitation a method of treating a disease or a condition in which activation of AT2 receptors is desired or required, but in which inhibition of CYPs is not desired. While the specification and claims (dependent ) appear to provides examples of diseases or conditions, this does not appear to be an exhaustive list. A careful review of the literature recognizes that CYP 450 metabolic enzymes are an important system for metabolism of drug substances in the body, wherein inhibition of these enzymes could lead to reduced metabolism of other drugs that might lead to unwanted side effects or toxicity. (See Mahalingam et al./Bioorg. Med. Chem. 18 (2010) 4570-4590, IDS, specific citation to page 4571, 1st column, half way down bridging paragraph). Accordingly, it would see reasonable to interpret that CYP inhibition would not be desired for any disease or disorder. As such, the diseases or disorders are being interpreted as those in which AT2 action is desired or required.
Rejections Maintained:
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1, 13-16, 19-20, 22, 24-26, 28-29 and 31 remain rejected under 35 U.S.C. 103 as being unpatentable over Vicore Pharma AB (WO2016/139475A1, 9/9/2016, IDS) in view of Wan et al. (J. Med. Chem. 2004, 47, 5995-6008, IDS) and Mahalingam (Bioorg. Med. Chem. 18 (2010) 4570-4590, IDS) as evidenced by Sica (Clin. Pharmacokinetics 2005; 44(8); 797-814).
Vicore Pharma teaches a method of treating pulmonary fibrosis, in particular idiopathic pulmonary fibrosis (IPF), comprising administering to a person in need thereof a therapeutically effective amount of a compound capable of stimulating AT2 receptors (AT2 receptor agonists)(page 4, lines 11-19). With regards to the compound, the WO document teaches that the compounds are agonist of AT2 receptor where they bind selectively to the AT2 receptor in an affinity ration for the relevant compound (AT2:AT1) is at least 100:1, more preferably 10000:1 (page 14, lines 18-25). Specifically, the WO document teaches a compound referred to as C21 having the structure
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. which differs from the instantly claimed compound of formula I, wherein R1 is a hydrogen (C21) vs. a C1-3 alkyl (compound of formula I) (Fig 1, page 4, lines 8-9). The WO document further teaches a pharmaceutical composition comprising a compound of the invention, in admixture with a pharmaceutically acceptable adjuvant, diluent or carrier (page 16, line 24 to page 17, line 1). Moreover, the WO document teaches that the compounds of the invention may also be administered in combination with other AT2 agonist that are known in the art, in combination with AT1 receptor antagonist such as losartan, ACE inhibitors, as well as, established therapies for IPF such as pirfenidone (page 17, lines 3-16). Lastly, the WO document teaches a kit of parts comprising components: (a) a pharmaceutical formulation comprising an AT2 receptor agonist, (b) a pharmaceutical formulation including an AT1 antagonist and/or an ACE inhibitor, which components (a) and (b) are provided in a form that is suitable for administration in conjunction with the other (page 18, lines 20 to page 19, line 4) . While the WO document does not specifically teach that losartan is a drug metabolized by a CYP enzyme, as evidenced by Sica, the major metabolic pathway for losartan is by the cytochrome P450 3A4, 2C9 and 2c10 isoenzymes (page 798, 1st full paragraph).
The WO document does not specifically teach that the AT receptor antagonist has a substantially similar structure to compound 21, wherein there is a C1-C3 alkyl, specifically a methyl, between the two nitrogen’s on the imidazole ring. Moreover, the WO document does not specifically teach that the kit of components contains pirfenidone in combination with the AT2 receptor agonist.
Wan et a. teaches the design, synthesis and biological evaluation of the first selective Nonpeptide AT2 receptor agonist (Title). Specifically, Wan et al. teach the first druglike selective angiotensin II receptor agonist referred to as compound 21 which has a Ki value of 0.4nM for the AT2 receptor and a Ki>10 mM for the AT1 receptor (Abstract). Compound 21 has the following formula:
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, which differs from the instantly claimed compound of formula I, wherein R1 is a hydrogen (compound 21) vs. a C1-3 alkyl (compound of formula I). In addition to the compound of 21, Wan et al. teach other compounds having the core structure:
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which vary by the R substituent including wherein R is
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as well as their Ki values for AT1 and AT2. As such, Wan et al. teach a compound 20 which reads on the instantly claimed compound wherein R1 is a methyl (page 5998, Table 5).
Mahalingam et al. teach selective angiotensin II AT2 receptor agonist with reduced CYP450 inhibition (Title). Specifically, Mahalingam teaches that the first non-peptidic selective AT2 receptor agonist M024 has recently been reported, wherein the unsubstituted imidazole provided a good moiety to obtain high affinity, AT1/AT2 selectivity, as well as, agonist (page 4570, 2nd column, first full paragraph). Compound M024 has the structure
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which differs from the instantly claimed compound of formula I, wherein R1 is a hydrogen (compound M024) vs. a C1-3 alkyl (compound of formula I) (Figure 1). Mahalingam further teaches that while M024 high affinity and selectivity towards the AT2 receptor, it was found to be an inhibitor of CYP 450 metabolic enzyme system which could lead to reduced metabolism of other drugs that might lead to unwanted side effects of toxicity (page 4571, 1st column (bridging paragraph). As such, Mahalingam teaches other compounds which have been modified at the imidazole in an attempt to eliminate the unwanted CYP 450 inhibition but maintain the other properties (page 4571, 1st column (bridging paragraph). For example, Mahalingam tested the binding affinities (Ki) for AT2 and At1, as well as, the CYP450 inhibition as shown below:
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Of interest, Mahalingam et al. teach that the un-substituted imidazole lead structure 1 (M024) showed a significant inhibition to most of the tested CYP450, which could be decreased by introducing substituents on the imidazole ring (page 4575, 1st column, 2nd paragraph).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to substitute compound 21 within the method/pharmaceutical composition and kit taught by the WO document for compound 20 of Wan (previously Wu) et al. in view of the teachings of Wan (previously Wu) et al. and Mahalingam et al.. One of ordinary skill in the art would have been motivated to make such a substitution, with a reasonable expectation of success, because:
-The WO document teaches that ATII receptor antagonists suitable for the method of treatment include those which selectively bind AT2 receptor with an affinity over AT1 at 100:1, preferably 10,0000 to 1,
- Wan (previously Wu) et al. teach a an AT2 receptor agonist, compound 20, which is structurally similar to compound 21, wherein compound 20 has a selectively to AT2 over AT1 of >20,000 and,
- Mahalingam et al. reports that that the un-substituted imidazole lead structure 1 (M024) showed a significant inhibition to most of the tested CYP450, which could be decreased by introducing substituents on the imidazole ring.
Moreover, it would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to have included pirfenidone in the kit in combination with the AT receptor agonist. One of ordinary skill in the art would have been motivated to make such a substitution, with a reasonable expectation of success, because:
- the WO document teaches that the compounds of the invention may also be administered in combination with other AT2 agonist that are known in the art, in combination with AT1 receptor antagonist such as losartan, ACE inhibitors, as well as, established therapies for IPF such as pirfenidone.
In response to this rejection, Applicants contend that while Wan reports that compounds 20 and 21 possess similar AT2 receptor activity and selectivity, neither Wan nor Dahlof, Mahalingam, or Sica appear to establish that the specific compound now recited in the independent claims would have been expected to exhibit the advantageous combination of properties demonstrated for the first time in the present application. In particular, Applicants contend, surprisingly, the compound claimed in the independent claims is not only a selective AT2 receptor agonist but it is also more potent, has a significantly improved stability to metabolic hydrolysis and/or exhibits less inhibition of CYP enzymes when compared to C21 (see specification at page 5, lines 23-28 and page 33, lines 6-19).
These arguments have been carefully considered but are not found persuasive.
As noted in the previous office action, the Examiner acknowledges that Applicants assert that surprising they have found that certain chemically modified compounds are not only selective AT2 receptor agonist, but are also more potent, have a significantly improved stability to metabolic hydrolysis and/or exhibit less inhibition of CYP enzymes, compared to C21 (see page 5, 4th full paragraph of specification as originally filed). However, the Examiner recognizes that compound 20 has already been shown in Wan et al. to have similar activity to compound 21, and further, in view of Mahalingam et al. it would be reasonably to expect a decrease in CYP activity because of the methyl substitution of the imidazole ring. For example, Mahalingam et al. reports that that the un-substituted imidazole lead structure 1 (M024) showed a significant inhibition to most of the tested CYP450, which could be decreased by introducing substituents on the imidazole ring. "Expected beneficial results are evidence of obviousness of a claimed invention, just as unexpected results are evidence of unobviousness thereof." In re Gershon, 372 F.2d 535, 538, 152 USPQ 602, 604 (CCPA 1967) See MPEP 716.02(C).
With regards to the citation of Mahalingam in paragraph bridging page 10-11 of the Non-Final rejection for the teachings of introducing substituents on the imidazole ring may reduce CYP450 inhibition, Applicants contend that Mahalingam teaches that the imidazole itself is responsible for CYP inhibition and highlights that replacing the imidazole ring with alternative heterocycles can virtually eliminate CYP inhibition. As such, Applicants contend that this teaches away from a substituted imidazole.
These arguments have been carefully considered, but are not found persuasive.
In response to Applicant arguments, the Examiner does not dispute that Mahalingam teaches that almost all of the inhibitory effect was eliminated by replacing the imidazole ring with a pyrazole (page 4575, 1st column, last sentence). However, as noted above in the office action, Mahalingam specifically teaches that the strong inhibition can also be decreased by introducing substitutes ON the imidazole ring (68 and 62). Further, "the prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed…." In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004) See MPEP 2145(X)(D)(1).
Claim(s) 12, 23 and 35 remain rejected under 35 U.S.C. 103 as being unpatentable over Vicore Pharma AB (WO2016/139475A1, 9/9/2016, IDS) in view of Wan et al. (J. Med. Chem. 2004, 47, 5995-6008, IDS) and Mahalingam (Bioorg. Med. Chem. 18 (2010) 4570-4590, IDS) as evidenced by Sica (Clin. Pharmacokinetics 2005; 44(8); 797-814), as applied to claims 1, 13-16, 19-20, 22, 24-26, 28-29 and 31 above, in further view of Wu et al. (J. Med. Chem. 2006, 49, 7160-7168).
The combination of Vicore Pharma AB referred to as the WO document in view of Wan et al. and Mahalingam as evidenced by Sica et al. has been described above and incorporated herein. In short, the combination teaches a method of treating pulmonary fibrosis, in particular idiopathic pulmonary fibrosis (IPF), comprising administering to a person in need thereof a therapeutically effective amount of a compound capable of stimulating AT2 receptors (AT2 receptor agonists), wherein the compound is a compound having the formula
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.
The combination does not specifically teach that the methyl on the imidazole ring is an ethyl or separately that the ester is not a butyl, but instead an ethyl. Moreover, the combination does not specifically teach a method of making said compounds, wherein the process involves:
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Wu et al. teach structural modifications in the 2- and 5- positions of the first drug-like selective angiotensin II AT1 receptor agonist (1) have been performed (Abstract). Specifically, Wu et al. teach the synthesis of these compounds which involve the scheme below:
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, wherein to obtain compounds 5-9 deprotection of compound 4 by TFA or by BCl3 delivered the primary sulfonamide that was subsequently reacted with acyl chlorides or alkyl chloroformates, at ambient temperature, in pyridine with 4-pyrrolindin-1-ylpyridine nucleophilic catalyst, to afford the target compound 5-9 (page 7161, Scheme 1, 1st column). In summary, Wu et al. teaches that all variations gave good AT2 receptor affinities and retained high AT2/AT1 selectivity (page 7165, 1st column, Conclusion).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to modify the length of the carbon chain on the imidazole or ester of compound 20 of the combination in view of the teachings of Wu et al.. One of ordinary skill in the art would have been motivated to make such a modification, with a reasonable expectation of similar properties, because:
- Wu et al. teaches that all variations gave good AT2 receptor affinities and retained high AT2/AT1 selectivity (page 7165, 1st column, Conclusion).
Moreover, compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977). See also In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978) (stereoisomers prima facie obvious); Aventis Pharma Deutschland v. Lupin Ltd., 499 F.3d 1293, 84 USPQ2d 1197 (Fed. Cir. 2007) (5(S) stereoisomer of ramipril obvious over prior art mixture of stereoisomers of ramipril.).
In response to this rejection, Applicants assert Wu fails to overcome the above-noted deficiencies of Dahlof, Wan, Mahalingam, and Sica with respect to the compound recited in independent claims 12 and 35 for the reasons noted above in the response to the preceding rejection.
These arguments have been carefully considered, but are not found persuasive for the reasons set forth above.
Claim(s) 18 and 27 remain rejected under 35 U.S.C. 103 as being unpatentable over Vicore Pharma AB (WO2016/139475A1, 9/9/2016, IDS) in view of Wan et al. (J. Med. Chem. 2004, 47, 5995-6008, IDS) and Mahalingam (Bioorg. Med. Chem. 18 (2010) 4570-4590, IDS) as evidenced by Sica (Clin. Pharmacokinetics 2005; 44(8); 797-814), as applied to claims 1, 13-16, 19-20, 22, 24-26, 28-29 and 31 above, in further view of Vicore Pharma AB (WO02/096883A1, 5/12/2002, IDS) referred to herein as Vicore 2.
The combination of Vicore Pharma AB referred to as the WO document in view of Wan et al. and Mahalingam as evidenced by Sica et al. has been described above and incorporated herein. In short, the combination teaches a method of treating pulmonary fibrosis, in particular idiopathic pulmonary fibrosis (IPF), comprising administering to a person in need thereof a therapeutically effective amount of a compound capable of stimulating AT2 receptors (AT2 receptor agonists), wherein the compound is a compound having the formula
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.
The combination does not specifically teach that the disease is chronic obstructive lung disease, pulmonary hypertension, myocardial infarction, autoimmune disorders, diabetes, diabetic nephropathy or myocardial infarction.
Vicore 2 teaches agonist of the AT2 receptor which are useful in the treatment of conditions where AT2 receptors are expressed and their stimulation is required (page 25, lines 19-21). Specifically, Vicore 2 teaches that such conditions include, but are not limited to, chronic obstructive lung disease, pulmonary hypertension, myocardial infarction, autoimmune disorders, diabetes, diabetic nephropathy or myocardial infarction (page 27, line 8 to page 28, line 22).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to substitute pulmonary fibrosis as taught by the combination for another condition where AT2 receptors are expressed as described above in view of Vicore 2. One of ordinary skill in the art would have been motivated to make such a substitution, with a reasonable expectation of success, because:
-Vicore 2 teaches that such conditions are treatable with AT2 receptor agonists.
In response to this rejection, Applicants assert Hallberg fails to overcome the above-noted deficiencies of Dahlof, Wan, Mahalingam, and Sica with respect to the compound recited in independent claims 13 and 14 for the reasons noted above in the response to the preceding rejection.
These arguments have been carefully considered, but are not found persuasive for the reasons set forth above and incorporated herein
Claim(s) 21 and 30 remain rejected under 35 U.S.C. 103 as being unpatentable over Vicore Pharma AB (WO2016/139475A1, 9/9/2016, IDS) in view of Wan et al. (J. Med. Chem. 2004, 47, 5995-6008, IDS) and Mahalingam (Bioorg. Med. Chem. 18 (2010) 4570-4590, IDS) as evidenced by Sica (Clin. Pharmacokinetics 2005; 44(8); 797-814), as applied to claims 1, 13-16, 19-20, 22, 24-26, 28-29 and 31 above, in further view of Fex et al. (US2022/0388994A1, Published 12/8/2022, priority to 11/20/2019).
The combination of Vicore Pharma AB referred to as the WO document in view of Wan et al. and Mahalingam as evidenced by Sica et al. has been described above and incorporated herein. In short, the combination teaches a method of treating pulmonary fibrosis, in particular idiopathic pulmonary fibrosis (IPF), comprising administering to a person in need thereof a therapeutically effective amount of a compound capable of stimulating AT2 receptors (AT2 receptor agonists), wherein the compound is a compound having the formula
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The combination does not specifically teach that the disease is sarcoidosis.
Fex et al. teaches agonist of the AT2 receptor which are useful in the treatment of conditions where AT2 receptors are expressed and their stimulation is required (paragraph 0135). Specifically, Fex et al. teaches that such conditions include, but are not limited to, chronic obstructive lung disease, pulmonary hypertension, myocardial infarction, all which are currently claimed including sarcoidosis (paragraph 0161).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to substitute pulmonary fibrosis as taught by the combination for another condition where AT2 receptors are expressed as described above in view of Fex et al.. One of ordinary skill in the art would have been motivated to make such a substitution, with a reasonable expectation of success, because:
-Fex et al. teaches that such conditions are treatable with AT2 receptor agonists.
In response to this rejection, Applicants assert Fex fails to overcome the above-noted deficiencies of Dahlof, Wan, Mahalingam, and Sica with respect to the compound recited in independent claims 12 and 35 for the reasons noted above in the response to the preceding rejection.
These arguments have been carefully considered, but are not found persuasive for the reasons set forth above and incorporated herein.
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 remains rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 11123329 in view of in view of Wan et al. (J. Med. Chem. 2004, 47, 5995-6008, IDS) and Mahalingam (Bioorg. Med. Chem. 18 (2010) 4570-4590, IDS).
U.S. Patent No. 11123329 claims a method of treating damage, injury or dysfunction of respiratory tract mucosal tissue caused by a severe acute respiratory syndrome (SARS) coronavirus in a subject in need of such treatment, which method comprises administering N-butyloxycarbonyl-3-(4-imidazol-1-ylmethylphenyl)-5-isobutylthiophene-2-sulfonamide which has the structure
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. which differs from the instantly claimed compound of formula I, wherein R1 is a hydrogen (C21) vs. a C1-3 alkyl (compound of formula I) (claim 1). The patent further claims that the treating includes symptoms of the respiratory disease caused by SARS coronavirus (claim 8), wherein the symptoms include pneumonia (Claim 9).
The US Patent does not claim a compound of formula I, wherein R1 is a C1-C3 alkyl, specifically a methyl, between the two nitrogen’s on the imidazole ring.
Wan et a. teaches the design, synthesis and biological evaluation of the first selective Nonpeptide AT2 receptor agonist (Title). Specifically, Wan et al. teach the first druglike selective angiotensin II receptor agonist referred to as compound 21 which has a Ki value of 0.4nM for the AT2 receptor and a Ki>10 mM for the AT1 receptor (Abstract). Compound 21 has the following formula:
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, which differs from the instantly claimed compound of formula I, wherein R1 is a hydrogen (compound 21) vs. a C1-3 alkyl (compound of formula I). In addition to the compound of 21, Wan et al. teach other compounds having the core structure:
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which vary by the R substituent including wherein R is
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as well as their Ki values for AT1 and AT2. As such, Wan et al. teach a compound 20 which reads on the instantly claimed compound wherein R1 is a methyl (page 5998, Table 5).
Mahalingam et al. teach selective angiotensin II AT2 receptor agonist with reduced CYP450 inhibition (Title). Specifically, Mahalingam teaches that the first non-peptidic selective AT2 receptor agonist M024 has recently been reported, wherein the unsubstituted imidazole provided a good moiety to obtain high affinity, AT1/AT2 selectivity, as well as, agonist (page 4570, 2nd column, first full paragraph). Compound M024 has the structure
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which differs from the instantly claimed compound of formula I, wherein R1 is a hydrogen (compound M024) vs. a C1-3 alkyl (compound of formula I) (Figure 1). Mahalingam further teaches that while M024 high affinity and selectivity towards the AT2 receptor, it was found to be an inhibitor of CYP 450 metabolic enzyme system which could lead to reduced metabolism of other drugs that might lead to unwanted side effects of toxicity (page 4571, 1st column (bridging paragraph). As such, Mahalingam teaches other compounds which have been modified at the imidazole in an attempt to eliminate the unwanted CYP 450 inhibition but maintain the other properties (page 4571, 1st column (bridging paragraph). For example, Mahalingam tested the binding affinities (Ki) for AT2 and At1, as well as, the CYP450 inhibition as shown below:
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Of interest, Mahalingam et al. teach that the un-substituted imidazole lead structure 1 (M024) showed a significant inhibition to most of the tested CYP450, which could be decreased by introducing substituents on the imidazole ring (page 4575, 1st column, 2nd paragraph).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to substitute the compound claimed in the US Patent for compound 20 of Wu et al. in view of the teachings of Wu et al. and Mahalingam et al.. One of ordinary skill in the art would have been motivated to make such a substitution, with a reasonable expectation of success, because:
-Wu et al. teach a an AT2 receptor agonist, compound 20, which is structurally similar to compound 21 (compound claimed in the US Patent), wherein compound 20 has a selectively to AT2 over AT1 of >20,000 and,
- Mahalingam et al. reports that that the un-substituted imidazole lead structure 1 (M024) showed a significant inhibition to most of the tested CYP450, which could be decreased by introducing substituents on the imidazole ring.
In response to this rejection, Applicants contend that the ‘329 patent recite the compound C21, which is structurally different from the compound claimed in the independent claims in that it contains a methyl substituted imidazole group. As such, Applicants assert that this feature would not have been obvious over the claims of the ‘329 Patent in view of Wan and Mahalingam for essentially the same reasons discussed above over the combination of Dahlof in view of Wan and Mahalingam, as evidenced by Sica.
These arguments have been carefully considered, but are not found persuasive for the reasons set forth above.
Note: All remaining rejections of claim 1 on the ground of nonstatutory double patenting have been traversed for substantially the same reason as noted above with respect to the nonstatutory double patenting rejection over the claims of the ‘329 Patent.
These arguments have been carefully considered, but are not found persuasive for the reasons set forth above and incorporated herein. As such, the nonstatutory double patenting rejections set forth below are maintained.
Claim 1 remains rejected on the ground of nonstatutory double patenting as being unpatentable over claims 21-23 of U.S. Patent No. 11,654,115 in view of in view of Wan et al. (J. Med. Chem. 2004, 47, 5995-6008, IDS) and Mahalingam (Bioorg. Med. Chem. 18 (2010) 4570-4590, IDS).
U.S. Patent No. 11,654,115 claims a method of treating of interstitial lung disease which method comprises orally administering a pharmaceutical dosage form of N-butyloxycarbonyl-3-(4-imidazol-1-ylmethylphenyl)-5-isobutylthiophene-2-sulfonamide which has the structure
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. which differs from the instantly claimed compound of formula I, wherein R1 is a hydrogen (C21) vs. a C1-3 alkyl (compound of formula I) to a patient in need of such treatment (claim 21), wherein the interstitial lung disease is idiopathic pulmonary fibrosis (claim 22) or sarcoidosis (claim 23).
The US Patent does not claim a compound of formula I, wherein R1 is a C1-C3 alkyl, specifically a methyl, between the two nitrogen’s on the imidazole ring.
Wan et a. teaches the design, synthesis and biological evaluation of the first selective Nonpeptide AT2 receptor agonist (Title). Specifically, Wan et al. teach the first druglike selective angiotensin II receptor agonist referred to as compound 21 which has a Ki value of 0.4nM for the AT2 receptor and a Ki>10 mM for the AT1 receptor (Abstract). Compound 21 has the following formula:
PNG
media_image2.png
186
217
media_image2.png
Greyscale
, which differs from the instantly claimed compound of formula I, wherein R1 is a hydrogen (compound 21) vs. a C1-3 alkyl (compound of formula I). In addition to the compound of 21, Wan et al. teach other compounds having the core structure:
PNG
media_image3.png
71
154
media_image3.png
Greyscale
which vary by the R substituent including wherein R is
PNG
media_image4.png
437
413
media_image4.png
Greyscale
as well as their Ki values for AT1 and AT2. As such, Wan et al. teach a compound 20 which reads on the instantly claimed compound wherein R1 is a methyl (page 5998, Table 5).
Mahalingam et al. teach selective angiotensin II AT2 receptor agonist with reduced CYP450 inhibition (Title). Specifically, Mahalingam teaches that the first non-peptidic selective AT2 receptor agonist M024 has recently been reported, wherein the unsubstituted imidazole provided a good moiety to obtain high affinity, AT1/AT2 selectivity, as well as, agonist (page 4570, 2nd column, first full paragraph). Compound M024 has the structure
PNG
media_image5.png
202
161
media_image5.png
Greyscale
which differs from the instantly claimed compound of formula I, wherein R1 is a hydrogen (compound M024) vs. a C1-3 alkyl (compound of formula I) (Figure 1). Mahalingam further teaches that while M024 high affinity and selectivity towards the AT2 receptor, it was found to be an inhibitor of CYP 450 metabolic enzyme system which could lead to reduced metabolism of other drugs that might lead to unwanted side effects of toxicity (page 4571, 1st column (bridging paragraph). As such, Mahalingam teaches other compounds which have been modified at the imidazole in an attempt to eliminate the unwanted CYP 450 inhibition but maintain the other properties (page 4571, 1st column (bridging paragraph). For example, Mahalingam tested the binding affinities (Ki) for AT2 and At1, as well as, the CYP450 inhibition as shown below:
PNG
media_image6.png
379
343
media_image6.png
Greyscale
PNG
media_image7.png
449
703
media_image7.png
Greyscale
Of interest, Mahalingam et al. teach that the un-substituted imidazole lead structure 1 (M024) showed a significant inhibition to most of the tested CYP450, which could be decreased by introducing substituents on the imidazole ring (page 4575, 1st column, 2nd paragraph).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to substitute the compound claimed in the US Patent for compound 20 of Wu et al. in view of the teachings of Wu et al. and Mahalingam et al.. One of ordinary skill in the art would have been motivated to make such a substitution, with a reasonable expectation of success, because:
-Wu et al. teach a an AT2 receptor agonist, compound 20, which is structurally similar to compound 21 (compound claimed in the US Patent), wherein compound 20 has a selectively to AT2 over AT1 of >20,000 and,
- Mahalingam et al. reports that that the un-substituted imidazole lead structure 1 (M024) showed a significant inhibition to most of the tested CYP450, which could be decreased by introducing substituents on the imidazole ring.
Claim 1 remains rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 10 of U.S. Patent No. 12,121,614 in view of in view of Wan et al. (J. Med. Chem. 2004, 47, 5995-6008, IDS) and Mahalingam (Bioorg. Med. Chem. 18 (2010) 4570-4590, IDS).
U.S. Patent No. 12,121,614 claims a method of treating of pulmonary fibrosis comprising administering to the gastrointestinal tract of a patient a composition comprising N-butyloxycarbonyl-3-(4-imidazol-1-ylmethylphenyl)-5-isobutylthiophene-2-sulfonamide which has the structure
PNG
media_image1.png
316
288
media_image1.png
Greyscale
. which differs from the instantly claimed compound of formula I, wherein R1 is a hydrogen (C21) vs. a C1-3 alkyl (compound of formula I) to a patient in need of such treatment (claim 1), wherein the pulmonary fibrosis is idiopathic pulmonary fibrosis (claim 10).
The US Patent does not claim a compound of formula I, wherein R1 is a C1-C3 alkyl, specifically a methyl, between the two nitrogen’s on the imidazole ring.
Wan et a. teaches the design, synthesis and biological evaluation of the first selective Nonpeptide AT2 receptor agonist (Title). Specifically, Wan et al. teach the first druglike selective angiotensin II receptor agonist referred to as compound 21 which has a Ki value of 0.4nM for the AT2 receptor and a Ki>10 mM for the AT1 receptor (Abstract). Compound 21 has the following formula:
PNG
media_image2.png
186
217
media_image2.png
Greyscale
, which differs from the instantly claimed compound of formula I, wherein R1 is a hydrogen (compound 21) vs. a C1-3 alkyl (compound of formula I). In addition to the compound of 21, Wan et al. teach other compounds having the core structure:
PNG
media_image3.png
71
154
media_image3.png
Greyscale
which vary by the R substituent including wherein R is
PNG
media_image4.png
437
413
media_image4.png
Greyscale
as well as their Ki values for AT1 and AT2. As such, Wan et al. teach a compound 20 which reads on the instantly claimed compound wherein R1 is a methyl (page 5998, Table 5).
Mahalingam et al. teach selective angiotensin II AT2 receptor agonist with reduced CYP450 inhibition (Title). Specifically, Mahalingam teaches that the first non-peptidic selective AT2 receptor agonist M024 has recently been reported, wherein the unsubstituted imidazole provided a good moiety to obtain high affinity, AT1/AT2 selectivity, as well as, agonist (page 4570, 2nd column, first full paragraph). Compound M024 has the structure
PNG
media_image5.png
202
161
media_image5.png
Greyscale
which differs from the instantly claimed compound of formula I, wherein R1 is a hydrogen (compound M024) vs. a C1-3 alkyl (compound of formula I) (Figure 1). Mahalingam further teaches that while M024 high affinity and selectivity towards the AT2 receptor, it was found to be an inhibitor of CYP 450 metabolic enzyme system which could lead to reduced metabolism of other drugs that might lead to unwanted side effects of toxicity (page 4571, 1st column (bridging paragraph). As such, Mahalingam teaches other compounds which have been modified at the imidazole in an attempt to eliminate the unwanted CYP 450 inhibition but maintain the other properties (page 4571, 1st column (bridging paragraph). For example, Mahalingam tested the binding affinities (Ki) for AT2 and At1, as well as, the CYP450 inhibition as shown below:
PNG
media_image6.png
379
343
media_image6.png
Greyscale
PNG
media_image7.png
449
703
media_image7.png
Greyscale
Of interest, Mahalingam et al. teach that the un-substituted imidazole lead structure 1 (M024) showed a significant inhibition to most of the tested CYP450, which could be decreased by introducing substituents on the imidazole ring (page 4575, 1st column, 2nd paragraph).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to substitute the compound claimed in the US Patent for compound 20 of Wu et al. in view of the teachings of Wu et al. and Mahalingam et al.. One of ordinary skill in the art would have been motivated to make such a substitution, with a reasonable expectation of success, because:
-Wu et al. teach a an AT2 receptor agonist, compound 20, which is structurally similar to compound 21 (compound claimed in the US Patent), wherein compound 20 has a selectively to AT2 over AT1 of >20,000 and,
- Mahalingam et al. reports that that the un-substituted imidazole lead structure 1 (M024) showed a significant inhibition to most of the tested CYP450, which could be decreased by introducing substituents on the imidazole ring.
Claim 1 remains rejected on the ground of nonstatutory double patenting as being unpatentable over claims 15-17 of U.S. Patent No. 11,844,868 in view of in view of Wan et al. (J. Med. Chem. 2004, 47, 5995-6008, IDS) and Mahalingam (Bioorg. Med. Chem. 18 (2010) 4570-4590, IDS).
U.S. Patent No. 11,844,868 claims a method of treating of interstitial lung disease which method comprises administering a pharmaceutical dosage form of N-butyloxycarbonyl-3-(4-imidazol-1-ylmethylphenyl)-5-isobutylthiophene-2-sulfonamide which has the structure
PNG
media_image1.png
316
288
media_image1.png
Greyscale
. which differs from the instantly claimed compound of formula I, wherein R1 is a hydrogen (C21) vs. a C1-3 alkyl (compound of formula I) to a patient in need of such treatment (claim 15), wherein the interstitial lung disease is idiopathic pulmonary fibrosis (claim 16) or sarcoidosis (claim 17).
The US Patent does not claim a compound of formula I, wherein R1 is a C1-C3 alkyl, specifically a methyl, between the two nitrogen’s on the imidazole ring.
Wan et a. teaches the design, synthesis and biological evaluation of the first selective Nonpeptide AT2 receptor agonist (Title). Specifically, Wan et al. teach the first druglike selective angiotensin II receptor agonist referred to as compound 21 which has a Ki value of 0.4nM for the AT2 receptor and a Ki>10 mM for the AT1 receptor (Abstract). Compound 21 has the following formula:
PNG
media_image2.png
186
217
media_image2.png
Greyscale
, which differs from the instantly claimed compound of formula I, wherein R1 is a hydrogen (compound 21) vs. a C1-3 alkyl (compound of formula I). In addition to the compound of 21, Wan et al. teach other compounds having the core structure:
PNG
media_image3.png
71
154
media_image3.png
Greyscale
which vary by the R substituent including wherein R is
PNG
media_image4.png
437
413
media_image4.png
Greyscale
as well as their Ki values for AT1 and AT2. As such, Wan et al. teach a compound 20 which reads on the instantly claimed compound wherein R1 is a methyl (page 5998, Table 5).
Mahalingam et al. teach selective angiotensin II AT2 receptor agonist with reduced CYP450 inhibition (Title). Specifically, Mahalingam teaches that the first non-peptidic selective AT2 receptor agonist M024 has recently been reported, wherein the unsubstituted imidazole provided a good moiety to obtain high affinity, AT1/AT2 selectivity, as well as, agonist (page 4570, 2nd column, first full paragraph). Compound M024 has the structure
PNG
media_image5.png
202
161
media_image5.png
Greyscale
which differs from the instantly claimed compound of formula I, wherein R1 is a hydrogen (compound M024) vs. a C1-3 alkyl (compound of formula I) (Figure 1). Mahalingam further teaches that while M024 high affinity and selectivity towards the AT2 receptor, it was found to be an inhibitor of CYP 450 metabolic enzyme system which could lead to reduced metabolism of other drugs that might lead to unwanted side effects of toxicity (page 4571, 1st column (bridging paragraph). As such, Mahalingam teaches other compounds which have been modified at the imidazole in an attempt to eliminate the unwanted CYP 450 inhibition but maintain the other properties (page 4571, 1st column (bridging paragraph). For example, Mahalingam tested the binding affinities (Ki) for AT2 and At1, as well as, the CYP450 inhibition as shown below:
Claims 1 remains rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of U.S. Patent No. 11,819,494 in view of in view of Wan et al. (J. Med. Chem. 2004, 47, 5995-6008, IDS) and Mahalingam (Bioorg. Med. Chem. 18 (2010) 4570-4590, IDS).
U.S. Patent No. 11,819,494 claims a method of improving lung function in a patient having idiopathic pulmonary fibrosis which comprises administering a pharmaceutical dosage form of N-butyloxycarbonyl-3-(4-imidazol-1-ylmethylphenyl)-5-isobutylthiophene-2-sulfonamide which has the structure
PNG
media_image1.png
316
288
media_image1.png
Greyscale
. which differs from the instantly claimed compound of formula I, wherein R1 is a hydrogen (C21) vs. a C1-3 alkyl (compound of formula I) to a patient in need of such treatment (claim 21), wherein the interstitial lung disease is idiopathic pulmonary fibrosis (claim 22) or sarcoidosis (claim 23).
The US Patent does not claim a compound of formula I, wherein R1 is a C1-C3 alkyl, specifically a methyl, between the two nitrogen’s on the imidazole ring.
Wan et a. teaches the design, synthesis and biological evaluation of the first selective Nonpeptide AT2 receptor agonist (Title). Specifically, Wan et al. teach the first druglike selective angiotensin II receptor agonist referred to as compound 21 which has a Ki value of 0.4nM for the AT2 receptor and a Ki>10 mM for the AT1 receptor (Abstract). Compound 21 has the following formula:
PNG
media_image2.png
186
217
media_image2.png
Greyscale
, which differs from the instantly claimed compound of formula I, wherein R1 is a hydrogen (compound 21) vs. a C1-3 alkyl (compound of formula I). In addition to the compound of 21, Wan et al. teach other compounds having the core structure:
PNG
media_image3.png
71
154
media_image3.png
Greyscale
which vary by the R substituent including wherein R is
PNG
media_image4.png
437
413
media_image4.png
Greyscale
as well as their Ki values for AT1 and AT2. As such, Wan et al. teach a compound 20 which reads on the instantly claimed compound wherein R1 is a methyl (page 5998, Table 5).
Mahalingam et al. teach selective angiotensin II AT2 receptor agonist with reduced CYP450 inhibition (Title). Specifically, Mahalingam teaches that the first non-peptidic selective AT2 receptor agonist M024 has recently been reported, wherein the unsubstituted imidazole provided a good moiety to obtain high affinity, AT1/AT2 selectivity, as well as, agonist (page 4570, 2nd column, first full paragraph). Compound M024 has the structure
PNG
media_image5.png
202
161
media_image5.png
Greyscale
which differs from the instantly claimed compound of formula I, wherein R1 is a hydrogen (compound M024) vs. a C1-3 alkyl (compound of formula I) (Figure 1). Mahalingam further teaches that while M024 high affinity and selectivity towards the AT2 receptor, it was found to be an inhibitor of CYP 450 metabolic enzyme system which could lead to reduced metabolism of other drugs that might lead to unwanted side effects of toxicity (page 4571, 1st column (bridging paragraph). As such, Mahalingam teaches other compounds which have been modified at the imidazole in an attempt to eliminate the unwanted CYP 450 inhibition but maintain the other properties (page 4571, 1st column (bridging paragraph). For example, Mahalingam tested the binding affinities (Ki) for AT2 and At1, as well as, the CYP450 inhibition as shown below:
PNG
media_image6.png
379
343
media_image6.png
Greyscale
PNG
media_image7.png
449
703
media_image7.png
Greyscale
Of interest, Mahalingam et al. teach that the un-substituted imidazole lead structure 1 (M024) showed a significant inhibition to most of the tested CYP450, which could be decreased by introducing substituents on the imidazole ring (page 4575, 1st column, 2nd paragraph).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to substitute the compound claimed in the US Patent for compound 20 of Wu et al. in view of the teachings of Wu et al. and Mahalingam et al.. One of ordinary skill in the art would have been motivated to make such a substitution, with a reasonable expectation of success, because:
-Wu et al. teach a an AT2 receptor agonist, compound 20, which is structurally similar to compound 21 (compound claimed in the US Patent), wherein compound 20 has a selectively to AT2 over AT1 of >20,000 and,
- Mahalingam et al. reports that that the un-substituted imidazole lead structure 1 (M024) showed a significant inhibition to most of the tested CYP450, which could be decreased by introducing substituents on the imidazole ring.
Claim 1 remains rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 of U.S. Patent No. 12,128,029 in view of in view of Wan et al. (J. Med. Chem. 2004, 47, 5995-6008, IDS) and Mahalingam (Bioorg. Med. Chem. 18 (2010) 4570-4590, IDS).
U.S. Patent No. 12,128,029 claims a method of treating of idiopathic pulmonary fibrosis in a patient in need thereof administering a pharmaceutical dosage form of N-butyloxycarbonyl-3-(4-imidazol-1-ylmethylphenyl)-5-isobutylthiophene-2-sulfonamide which has the structure
PNG
media_image1.png
316
288
media_image1.png
Greyscale
. which differs from the instantly claimed compound of formula I, wherein R1 is a hydrogen (C21) vs. a C1-3 alkyl (compound of formula I) to a patient in need of such treatment (claim 1).
The US Patent does not claim a compound of formula I, wherein R1 is a C1-C3 alkyl, specifically a methyl, between the two nitrogen’s on the imidazole ring.
Wan et a. teaches the design, synthesis and biological evaluation of the first selective Nonpeptide AT2 receptor agonist (Title). Specifically, Wan et al. teach the first druglike selective angiotensin II receptor agonist referred to as compound 21 which has a Ki value of 0.4nM for the AT2 receptor and a Ki>10 mM for the AT1 receptor (Abstract). Compound 21 has the following formula:
PNG
media_image2.png
186
217
media_image2.png
Greyscale
, which differs from the instantly claimed compound of formula I, wherein R1 is a hydrogen (compound 21) vs. a C1-3 alkyl (compound of formula I). In addition to the compound of 21, Wan et al. teach other compounds having the core structure:
PNG
media_image3.png
71
154
media_image3.png
Greyscale
which vary by the R substituent including wherein R is
PNG
media_image4.png
437
413
media_image4.png
Greyscale
as well as their Ki values for AT1 and AT2. As such, Wan et al. teach a compound 20 which reads on the instantly claimed compound wherein R1 is a methyl (page 5998, Table 5).
Mahalingam et al. teach selective angiotensin II AT2 receptor agonist with reduced CYP450 inhibition (Title). Specifically, Mahalingam teaches that the first non-peptidic selective AT2 receptor agonist M024 has recently been reported, wherein the unsubstituted imidazole provided a good moiety to obtain high affinity, AT1/AT2 selectivity, as well as, agonist (page 4570, 2nd column, first full paragraph). Compound M024 has the structure
PNG
media_image5.png
202
161
media_image5.png
Greyscale
which differs from the instantly claimed compound of formula I, wherein R1 is a hydrogen (compound M024) vs. a C1-3 alkyl (compound of formula I) (Figure 1). Mahalingam further teaches that while M024 high affinity and selectivity towards the AT2 receptor, it was found to be an inhibitor of CYP 450 metabolic enzyme system which could lead to reduced metabolism of other drugs that might lead to unwanted side effects of toxicity (page 4571, 1st column (bridging paragraph). As such, Mahalingam teaches other compounds which have been modified at the imidazole in an attempt to eliminate the unwanted CYP 450 inhibition but maintain the other properties (page 4571, 1st column (bridging paragraph). For example, Mahalingam tested the binding affinities (Ki) for AT2 and At1, as well as, the CYP450 inhibition as shown below:
PNG
media_image6.png
379
343
media_image6.png
Greyscale
PNG
media_image7.png
449
703
media_image7.png
Greyscale
Of interest, Mahalingam et al. teach that the un-substituted imidazole lead structure 1 (M024) showed a significant inhibition to most of the tested CYP450, which could be decreased by introducing substituents on the imidazole ring (page 4575, 1st column, 2nd paragraph).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to substitute the compound claimed in the US Patent for compound 20 of Wu et al. in view of the teachings of Wu et al. and Mahalingam et al.. One of ordinary skill in the art would have been motivated to make such a substitution, with a reasonable expectation of success, because:
-Wu et al. teach a an AT2 receptor agonist, compound 20, which is structurally similar to compound 21 (compound claimed in the US Patent), wherein compound 20 has a selectively to AT2 over AT1 of >20,000 and,
- Mahalingam et al. reports that that the un-substituted imidazole lead structure 1 (M024) showed a significant inhibition to most of the tested CYP450, which could be decreased by introducing substituents on the imidazole ring.
Conclusion
Therefore, no claim is allowed.
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 BRANDON J FETTEROLF whose telephone number is (571)272-2919. The examiner can normally be reached M-F 6AM-4PM.
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/BRANDON J FETTEROLF/Primary Examiner, Art Unit 1626
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