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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on June 11, 2025 has been entered.
Priority
This application is a 371 of PCT/IB2020/055034 05/27/2020, which claims benefit of 62/858,009 06/06/2019.
Claim Status
Claims 2-3 and 13-14 are canceled. Claim 24 is new. Therefore, claims 1, 4-12 and 15-24 are examined on the merits herein.
Withdrawn Objections and Rejections
With respect to the objections and/or rejections mailed in the final office action on March 11, 2025:
The objection of claims 18-23 is withdrawn in view of Applicant’s amendment to claims 18-23.
Response to Arguments
(I) The rejection of claims 1, 4-12 and 15-23 under 35 U.S.C. 103; and
(II) The rejection of claims 1, 4-12 and 15-23 on the ground of nonstatutory double patenting, are maintained.
With respect to the 103 rejection above, Applicant argues:
(A) Leoni is not directed toward the discovery of new imidazoquinoline scaffolds but provides a reach-through genus of imidazoquinolines that might be solubilized with lactic acid and polaxamers, see Applicant’s remarks, pg. 8, paragraph 2.
(B) Resiquimod is not covered by the disclosed genus and nothing in Leoni would motivate the skilled artisan to select and combine any variables with the disclosed genus, or variables found elsewhere such as with Resiquimod with any expectation of improving activity, reducing systemic effects or the like, see Applicant’s remarks, pg. 8, paragraph 2.
(C) The present disclosure confirms R1 of formula (I) of claim 1 is involved in the activation of TLRs when the N1-substituent is 2-hydroxyalkyl; resiquimod derivatives are not required to be something other than hydrogen when considering R2 of formula (I) of claim 1 and therefore R1 of formula (I) of claim 1 rescues the reliance on R2 of formula (I) of claim 1 for TLR activation, see Applicant’s remarks, pg. 9, paragraph 1.
(D) There is not enough data available to adequately conduct a thorough structure activity relationship for imidazoquinolines such that the activity of any new structure is predictable and that a laundry list disclosure like Leoni, used as prior art, could effectively shut down research, see Applicant’s arguments, pg. 9, paragraph 2.
(E) The data clearly shows that Example 9 substantially outperforms comparative example 2 in the production of IFN-α, IFN-γ and TLR-7, while maintaining production of TNF-α. Additionally, from this data is its further clear the stereochemistry at R1 is exceptionally important as evidenced between enantiomers Example 9 and Example 10, wherein Example 10 is far poorer than both Example 9 and Comparative Example 2 in inducing cytokine biosynthesis based on the data disclosed within the specification in Table 16b on pg. 76 and Table 17b on pp. 77-78.
Thus, there is nothing within Leoni’s disclosure that would suggest this unique activity attributed to R1 and certainly nothing that would motivate a skilled artisan to expect this dependency on stereochemistry, see Applicant’s remarks, pg. 9, last paragraph of the page.
(F) It could not have been obvious to insert a substituent (i.e. R1) so close to the active site and expect non-interference, enhanced activity or any activity at all in the absence of R2 substitution; and nothing in the Leoni disclosure specifically teaches substitution at the R1 position and nothing within the Leoni disclosure would have motivated a skilled artisan to expect the R1 to not only be tolerated, but that it could rescue the absence of n-butyl/n-pentyl substitution at the R2 position, see Applicant arguments, see pg. 15, last paragraph of the page – pg. 16, first paragraph.
With respect to Applicant’s arguments (A)-(F), the Examiner respectfully notes instant claims 1, 4-12 and 15-23 are compound claims.
Leoni teaches the present invention encompasses any racemic, optically active, polymorphic, or stereoisomeric form, or mixtures thereof of imidazoquinolin(amines) or their derivatives as defined within the 103 rejection below and Leoni discloses it being well known in the art how to prepare optically active forms for example, by synthesis from optically-active starting materials or by chiral synthesis as discussed in the 103 rejection below.
The Examiner respectfully notes the removal of the compound resiquimod from the 103 and double patenting rejections below.
The Examiner respectfully notes Leoni already teaches their disclosed imidazoquinolin(amines) or derivatives thereof encompasses any stereoisomeric form, which the Examiner respectfully points out encompasses the S-configuration within R1 of formula (I) of claim 1 as exemplified by Example 10 as discussed above.
Furthermore, Applicant’s arguments (A)-(F) as discussed above are not found persuasive because the Examiner respectfully notes Leoni teaches the compound of formula (II) of claim 1 as discussed below as Leoni defines “alkyl” to be preferably straight or branched C1-C10 alkyl groups and further exemplifies a 1-methylpropyl, where the 1-methyl corresponds to the C1-alkyl of R1 in Formula (II) of claim 1 as discussed in the 103 rejection below. Therefore, Applicant’s argument of an unexpectedly improved result or a superior result which is discussed particularly in arguments (E)-(F)above are not found persuasive as Leoni teaches the compound of formula (II) of claim 1 as discussed in greater detail in the 103 rejection below
Applicant further argues:
(G) Leoni does not teach or suggest “a substituted straight or branched chain alkyl containing one to about ten carbon atoms” where it is implied that the substitution could be -OH, see Applicant’s remarks, pg. 13, last paragraph of the page.
(H) It is clear that said substituent can only be a C3-C6 cycloalkyl or a C3-C6 cycloalkyl further substituted with a C1-4 alkyl, see Applicant’s argument, pg. 14, second paragraph from the bottom of the page.
With respect to Applicant’s arguments (G)-(H), the Examiner respectfully notes, imiquimod is taught as a preferred embodiment of Leoni which is encompassed by formula (I) of Leoni where R3 can be a branched chain alkyl containing one to about ten carbon atoms, and wherein paragraph [0147] of Leoni defines “alkyl” can be optionally substituted with one more substituents, including hydroxyl.
With particular attention to Applicant’s argument (H) as mentioned above, the Examiner reasonably interprets paragraph [0052] of Leoni as an exemplification in view of how Leoni defines “alkyl” in paragraph [0147] as discussed above.
With respect to the double patenting rejection above, Applicant argues:
(I) Nothing in U.S. Patent No. 12,024,514 teaches or suggests that R1 being C1-6 alkyl would maintain activity or afford any activity benefit, and Leoni does not cure the deficiencies for the reasons provided above, see Applicant’s arguments, pg. 16, last paragraph from the bottom of the page.
The Examiner respectfully notes Leoni teaches as discussed above. Leoni further teaches a substitution of a C1-6 alkoxy C1-6 alkyl corresponding to R1 of formula (II) of reference claim 1 for a lower alkyl exemplified as methyl, ethyl, propyl, butyl, and 2-methylpropyl (e.g. isobutyl) is a known consideration in the prior art as taught by Leoni and discussed in further detail in the double patenting rejection below.
Furthermore, the Examiner respectfully notes ‘514 discloses TLR activation of TLR 8 using examples 1-14 which are encompassed by the compounds of Formula (II) of reference claim 1 and demonstrates activation in the micromolar range of TLR 8 in Table 23, see Col. 53, Table 23, wherein 5 out of 14 examples (e.g. 36% of the examples) had a MEC equal to 30 µM, and 5 out of 14 (e.g. 36% of the examples) had MEC greater than 30 µM. Therefore, 10 out of 14 (e.g. about 71%) of the examples discussed above had a MEC of ≥ 30 µM.
The Examiner further respectfully notes within Applicant’s remarks, on pg. 10, the table displayed on this page shows the MEC to produce TLR 8 activation within the micromolar range of Example 9 and Comparative Example 2 is >30 µM.
Therefore, based on the considerations of the previous two paragraphs the Examiner reasonably interprets the substitution of R1 is X-O-Y as recited in formula (II) of reference claim 1 within ‘514 as compared to R1 being a methyl group as taught by Leoni above would maintain activity as argued by Applicant above.
Thus, Applicant’s arguments (A)-(I) have been fully considered but are not found persuasive.
Claim Objections
Claims 10 and 24 are objected to because of the following informalities:
Claim 10, line 3, recites “R2 is Hydrogen” unnecessarily capitalizing the word hydrogen which is grammatically incorrect. Thus, to promote clarity the Examiner suggests replacing “Hydrogen” with “hydrogen” as discussed above.
Claim 24, line 11, recites “R3 and R4 are independently selected from” which is grammatically incorrect when referring to multiple positions on the compound of formula (II). Thus, to promote clarity the Examiner suggests inserting the word “each” immediately before the word “independently” as discussed above.
Appropriate correction is required.
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.
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.
Claims 1, 4-12 and 15-24 are rejected under 35 U.S.C. 103 as being unpatentable over Leoni et al. (Published 14 January 2016, US-20160008477-A1, PTO-892 mailed 08/21/2024).
Regarding claims 1, 4-12, and 15-24, Leoni teaches in the field of modulators of the innate immune system, particularly pharmaceutical compositions comprising imidazoquinolin(amines) and derivatives thereof suitable for local administration, such as, intravesical administration; the use of imidazoquinolin(amines) and derivatives thereof for intravesical treatment of bladder diseases, such as, for example, bladder cancer and cystitis; and treatment for these diseases, see abstract.
Leoni teaches a pharmaceutical composition suitable to comprise immune modifiers, in particular imidazoquinolin(amin)es, such as imiquimod, in therapeutically effective amounts, see paragraph [0024]. Leoni teaches the pharmaceutical composition may be used for human and also veterinary medical purposes, preferably for human medical purposes, see paragraph [0189].
Leoni teaches the pharmaceutical composition may further comprise a pharmaceutically acceptable carrier, see paragraph [0182]. Leoni teaches the pharmaceutical composition may comprise an adjuvant. In this context, an adjuvant may be understood as any compound, which is suitable to initiate or increase an immune response of the innate immune system, i.e. a non-specific immune response. Such an adjuvant may be selected from any adjuvant known to a skilled person and suitable for the present case, i.e. supporting the induction of an innate immune response in a mammal. Preferably, the adjuvant may be selected from the group consisting of, without being limited thereto, any of the following including cholera toxin, see paragraph [0185].
Leoni teaches the composition comprises imidazoquinolin(amines) selected from the following formula (I), see paragraph [0050];
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, wherein R2 can be hydrogen, a straight chain alkyl containing one to about ten carbon atoms; or an alkoxyalkyl, wherein the alkoxy moiety contains one to about four carbon atoms and the alkyl moiety contains one to about six carbon atoms (e.g. R2 as recited in formula (II) of claim 1 and claim 24); R3 can be a branched chain alkyl containing one to about ten carbon atoms, see paragraph [0052]; R4 is hydrogen, halo, C1-C8 alkoxy or C1-C8 alkyl (e.g. R and n as recited in formula (II) of claim 1 or in formula (II) of claim 24), see paragraph [0057]; Ra and Rb are each independently hydrogen, see paragraph [0059]; and the dashed lines in the five-membered ring of formula (I) above denote an optional bond that connects a nitrogen of the five-membered ring to the carbon that is between the two nitrogen of the five-membered ring, and when the bond is present, R1 is absent, see paragraph [0060].
Leoni defines “alkyl” preferably straight or branched C1-C10 alkyl groups can be e.g. 1-methylpropyl, see paragraph [0132].
The Examiner notes the 1-methylpropyl exemplified by Leoni reads on the limitation of “branched chain alkyl containing one to about ten carbon atoms” as taught by Leoni above, where the Examiner respectfully notes 1-methylpropyl is a branched chain alkyl containing four carbon atoms. Also, the Examiner respectfully notes the 1-methylpropyl corresponds to when R1 is C1-alkyl and R3 or R4 is a C1-alkyl as defined in formula (II) of either claim 1 or claim 24.
Leoni teaches “alkyl” as defined herein can be optionally substituted with one or more substituents, wherein the substituents are the same or different, and include lower alkyl and hydroxyl, see paragraph [0147], where Leoni defines “lower alkyl” preferably includes straight or branched C1-C6 alkyl groups, e.g., methyl, ethyl, propyl, butyl, and 2-methylpropyl (e.g. isobutyl), see paragraph [0133].
Therefore, based on the teachings discussed above the Examiner respectfully notes the teachings wherein R3 is a branched chain alkyl containing one to about ten carbon atoms as taught by Leoni above encompass the compounds recited in instant claims 1 and 18-24, as the Examiner respectfully notes since Leoni teaches the 1-methylpropyl, e.g. said “alkyl”, can be substituted with methyl, ethyl, propyl, butyl, and 2-methylpropyl (e.g. isobutyl) it would correspond to the R1, R3 or R4 positions of formula (II); and when substituted with hydroxyl (e.g. -OH) correspond to the R5 position of formula (II) and together these teachings would encompass the compounds as recited in instant claim 1 or instant claim 24 or the recited compounds of instant claims 18-23.
The Examiner further respectfully notes the compounds recited in instant claims 18-23 contain a branched chain alkyl containing between 5 and 8 carbon atoms when R1, R3 and R4 are chosen and a hydroxyl when R5 is chosen as recited in formula (II) of instant claim 1.
Leoni teaches the present invention encompasses any racemic, optically active, polymorphic, or stereoisomeric form, or mixtures thereof, of imidazoquinolin(amines) or their derivatives as defined above and that it is well known in the art how to prepare optically active forms (for example, by resolution of the racemic form by recrystallization techniques, by synthesis from optically-active starting materials, by chiral synthesis, or by chromatography separation using a chiral stationary phase), see paragraph [0148].
Although, Leoni does not exemplify the structures recited in instant claims 18-23.
However, Leoni teaches a preferred embodiment known as imiquimod (also known as 1-isobutyl-1H-imidazo[4,5-c]quinolin-4-amine) with the structure,
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, see paragraph [0125].
The Examiner respectfully notes that imiquimod is covered by the imidazoquinolin(amines) of the genus of formula (I) of Leoni when R4 is hydrogen; Ra and Rb are each independently hydrogen; R1 is absent; R2 is hydrogen; and R3 is a branched chain alkyl containing 4 carbon atoms as discussed above.
Additionally, as previously noted, Leoni teaches an alkyl, exemplified as the branched chain alkyl containing 4 carbon atoms of imiquimod above, can be optionally substituted with one or more substituents, wherein the substituents are the same or different, and include lower alkyl and hydroxyl, see paragraph [0147], and wherein Leoni defines “lower alkyl” preferably includes straight or branched C1-C6 alkyl groups, e.g., methyl, ethyl, propyl, butyl, and 2-methylpropyl (e.g. isobutyl), see paragraph [0133].
Therefore, the Examiner respectfully notes when substituting the alkyl exemplified by imiquimod above with the substituents taught by Leoni above one of ordinary skill in the art would arrive at the claimed compounds of either formula (II) of instant claim 1 or instant claim 24 or the recited compounds within instant claims 18-23 based on the teachings of Leoni as discussed above.
Thus, it would have been prima facie obvious to one of ordinary skill in the art before the invention was filed to have used the teachings of Leoni as discussed above, by particularly using formula (I) as recited by Leoni above as a starting point in view of the preferred embodiment of imiquimod and to have used formula (I) to further substitute the branched chain alkyl depicted in imiquimod which is a 2-methylpropyl in order to create 1,2-methylpropyl as Leoni exemplifies a methyl at that position when reciting the 1-methylpropyl as discussed above; and to further substitute the 1,2-methylpropyl with either methyl, ethyl, propyl, butyl, 2-methylpropyl and/or hydroxyl as discussed above and thus arrive at any of the recited compounds required in any of instant claims 18-23 as combining prior art elements within the scope of the artisan as Leoni explicitly teaches those substitutions are within the scope of R3 of formula (I) of Leoni when R3 is a branched chain alkyl containing one to about ten carbon atoms as discussed above.
One of ordinary skill would have been motivated to provide pharmaceutical compositions comprising imidazoquinolin(amines) and derivatives thereof for use in treating bladder diseases, such as, for example, bladder cancer as taught by Leoni as discussed above.
One of ordinary skill in the art would have had a reasonable expectation of success to have modified formula (I) of Leoni in the way discussed above, as Leoni teaches pharmaceutical compositions comprising an imidazoquinolin(amine) or a derivative thereof; that it is well known in the art how to prepare optically active forms of imidazoquinolin(amines) by synthesis from optically-active starting materials or by chiral synthesis; and Leoni explicitly teaches those substitutions as discussed above.
Thus, the claimed invention as a whole would have been prima facie obvious over the teachings of the prior art.
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, 4-12 and 15-24 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 6-7 and 19-22 of U.S. Patent No. 12,024,514 (Applicant: Solventum Intellectual Properties Company, PTO-892 mailed 08/21/2024) in view of Leoni et al. (Published 14 January 2016, US-20160008477-A1, PTO-892 mailed 08/21/2024). Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are directed to compounds of formula (II).
Reference claim 1 recites a compound of formula (II) or a salt thereof,
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, which reads on instant claims 1, 7 and 10. Reference claims 2, 3, 6-7, 19, 20 and 21-22 read on instant claims 4, 5, 8, 11, 12 and 15-16 respectively.
Although, ‘514 does not recite R1 is a C1-C6 alkyl, required in instant claims 1, 6, 9-10 and 18-24.
However, in the same field of endeavor of imidazoquinolin(amines) and derivatives thereof, Leoni teaches the composition comprises imidazoquinolin(amines) selected from the following formula (I), see paragraph [0050];
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, wherein R2 can be hydrogen, a straight chain alkyl containing one to about ten carbon atoms; or an alkoxyalkyl, wherein the alkoxy moiety contains one to about four carbon atom and the alkyl moiety contains one to about six carbon atoms (e.g. R2 as recited in formula (II) of instant claim 1 and instant claim 24); R3 can be a branched chain alkyl containing one to about ten carbon atoms, see paragraph [0052]; R4 is hydrogen, halo, C1-C8 alkoxy or C1-C8 alkyl (e.g. R and n as recited in formula (II) of instant claim 1 or in formula (II) of instant claim 24), see paragraph [0057]; Ra and Rb are each independently hydrogen, see paragraph [0059]; and the dashed lines in the five-membered ring of formula (I) above denote an optional bond that connects a nitrogen of the five-membered ring to the carbon that is between the two nitrogen of the five-membered ring, and when the bond is present, R1 is absent, see paragraph [0060].
Leoni defines “alkyl” preferably straight or branched C1-C10 alkyl groups can be e.g. 1-methylpropyl, see paragraph [0132].
The Examiner respectfully notes the 1-methylpropyl exemplified by Leoni above reads on the limitation of “branched chain alkyl containing one to about ten carbon atoms”, where said 1-methylpropyl is a branched chain alkyl containing four carbon atoms. Also, the Examiner respectfully notes the 1-mehylpropyl corresponds to when R1 is C1-alkyl and R3 or R4 is a C1-alkyl as defined in formula (II) of either instant claim 1 or instant claim 24.
Leoni also teaches “alkyl” as defined herein can be optionally substituted with one or more substituents, wherein the substituents are the same or different, and include lower alkyl, hydroxyl and C1-6 alkoxy C1-6 alkyl, see paragraph [0147], and wherein Leoni defines “lower alkyl” preferably includes straight or branched C1-C6 alkyl groups, e.g., methyl, ethyl, propyl, butyl, and 2-methylpropyl (e.g. isobutyl), see paragraph [0133].
Therefore, based on the teachings of Leoni as discussed above the Examiner respectfully notes the teachings of Leoni wherein R3 is a branched chain alkyl containing one to about ten carbon atoms encompasses the compounds recited in instant claims 1 and 18-24.
As the Examiner respectfully notes since Leoni teaches said “alkyl” can be substituted with methyl, ethyl, propyl, butyl, and 2-methylpropyl (e.g. isobutyl) which would correspond to the R1, R3 or R4 positions of formula (II) of the instant claims and when substituted with hydroxyl (e.g. -OH) would correspond to the R5 position of formula (II) of the instant claims and when put together these teachings would encompass the compounds as recited in instant claim 1 or instant claim 24 or the recited compounds of instant claims 18-23; as the Examiner further respectfully notes the compounds recited in instant claims 18-23 contain a branched chain alkyl containing between 5 and 8 carbon atoms when R1, R3 and R4 are chosen and a hydroxyl when R5 is chosen as recited in formula (II) of instant claim 1.
Leoni teaches in the field of modulators of the innate immune system, particularly pharmaceutical compositions comprising imidazoquinolin(amines) and derivatives thereof suitable for local administration; and the use of imidazoquinolin(amines) and derivatives thereof for intravesical treatment of bladder diseases, such as, for example, bladder cancer and cystitis; and treatment for these diseases, see abstract.
Leoni teaches the present invention encompasses any racemic, optically active, polymorphic, or stereoisomeric form, or mixtures thereof, of imidazoquinolin(amines) or their derivatives as defined above and that it is well known in the art how to prepare optically active forms (for example, by resolution of the racemic form by recrystallization techniques, by synthesis from optically-active starting materials, by chiral synthesis, or by chromatography separation using a chiral stationary phase), see paragraph [0148].
Although, Leoni does not exemplify the structures recited in instant claims 18-23.
However, Leoni teaches a preferred embodiment known as imiquimod (also known as 1-isobutyl-1H-imidazo[4,5-c]quinolin-4-amine) with the structure,
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, see paragraph [0125].
The Examiner respectfully notes that imiquimod is covered by the imidazoquinolin(amines) of the genus of formula (I) of Leoni when R4 is hydrogen; Ra and Rb are each independently hydrogen; R1 is absent; R2 is hydrogen; and R3 is a branched chain alkyl containing 4 carbon atoms as discussed above.
Additionally, as previously noted, Leoni teaches an “alkyl”, exemplified as the branched chain alkyl containing 4 carbon atoms of imiquimod above, can be optionally substituted with one or more substituents, wherein the substituents are the same or different, and include lower alkyl, hydroxyl and C1-6 alkoxy C1-6 alkyl, see paragraph [0147], and wherein Leoni defines “lower alkyl” preferably includes straight or branched C1-C6 alkyl groups, e.g., methyl, ethyl, propyl, butyl, and 2-methylpropyl (e.g. isobutyl), see paragraph [0133].
Therefore, the Examiner respectfully notes when substituting the alkyl exemplified by imiquimod with the substituents taught by Leoni above, one of ordinary skill in the art would arrive at the claimed compounds of either formula (II) of instant claim 1 or instant claim 24 or the recited compounds within instant claims 18-23 based on the teachings of Leoni as discussed above.
Additionally, the Examiner respectfully notes in formula (II) of reference claim 1 of ‘514 above when R1 is X is C1 alkylene and Y is C1 alkyl and R3=R4=R5=CH3, the resulting structure creates a branched alkyl chain containing 6 carbon atoms, wherein one of those carbon atoms (e.g. R1 wherein X is C1 alkylene) is further substituted with a methoxy (e.g. R1 wherein Y is C1 alkyl).
Therefore, the Examiner respectfully notes the C1-6 alkoxy C1-6 alkyl limitation taught by Leoni above meets the structural limitation at the R1 of formula (II) of ‘514 wherein R1 is —X—O—Y where X is a C1-3 alkylene and Y is a C1-3 alkyl.
Thus, it would have been prima facie obvious to one of ordinary skill in the art before the invention was filed to have modified formula (II) as recited in ‘514 with the teachings of Leoni above, by substituting the R1 limitation recited within formula (II) of ‘514 with a methyl, ethyl, propyl, butyl, or 2-methylpropyl (e.g. isobutyl) as taught by Leoni above as combining prior art elements within the scope of the artisan as Leoni explicitly teaches a branched alkyl chain comprising 6 carbons that can be substituted with a lower alkyl, hydroxyl and/or C1-6 alkoxy C1-6 alkyl as discussed above that encompasses the structure of formula (II) of ‘514 corresponding to R1, R3, R4, R5 and any structural elements connecting those groups as recited in formula (II) of reference claim 1 of ‘514 as discussed above .
One of ordinary skill would have been motivated to provide pharmaceutical compositions comprising imidazoquinolin(amines) and derivatives thereof for use in treating bladder diseases, such as, for example, bladder cancer as taught by Leoni as discussed above.
One of ordinary skill in the art would have had a reasonable expectation of success to make the modification as discussed above, as both Leoni and ‘514 are drawn to pharmaceutical compositions comprising an imidazoquinolin(amine) or a derivative thereof and methods of treating neoplastic disease; wherein Leoni teaches that it is well known in the art how to prepare optically active forms of imidazoquinolin(amines) by synthesis from optically-active starting materials or by chiral synthesis; and wherein Leoni teaches a substitution of a C1-6 alkoxy C1-6 alkyl corresponding to R1 of formula (II) of reference claim 1 for a lower alkyl exemplified as methyl, ethyl, propyl, butyl, and 2-methylpropyl (e.g. isobutyl) as discussed above is a known consideration in the prior art as discussed above.
Therefore, the claimed invention as a whole would have been prima facie obvious over the combined recitations of ‘514 and the teachings of the prior art.
Conclusion
No claims are allowed in this action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JARET J CREWS whose telephone number is (571)270-0962. The examiner can normally be reached Monday-Friday: 9:00am-5:30pm EST.
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/JARET J CREWS/Examiner, Art Unit 1691
/RENEE CLAYTOR/Supervisory Patent Examiner, Art Unit 1691