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 .
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. In particular, applicant has an embedded hyperlink and/or other form of browser-executable code on page 29 line 13 of the specification. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Objections
Claim 9 is objected to because of the following informalities: missing commas between the structures of the claim. Appropriate correction is required.
Claim 9 is objected to because of the following informalities: missing a conjunction between the last two structures of the claim. Appropriate correction is required.
Claim 10 is objected to because of the following informalities: missing commas between the structures of the claim. Appropriate correction is required.
Claim 10 is objected to because of the following informalities: missing a conjunction between the last two structures of the claim. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 9, and 20 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 9 recites, “the compound according to claim 1, wherein A is selected from the group consisting of: […]
PNG
media_image1.png
200
400
media_image1.png
Greyscale
; but fails to end the claim with a period. Each claim begins with a capital letter and ends with a period. (MPEP 608.01(m)). Thus, the lack of a period at the end of the claim after the last structure renders the claim indefinite because it is unclear whether the claim comprises more structures then what is recited in the claim. Are only compounds listed in the claim included with the scope of the claim or does the claim encompass unrecited structures? As a consequence, one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Specifically one of ordinary skill in the art would not be reasonably apprised of what compounds are included within the scope of claim 9 and which are not.
Moreover, Claim 9 recites, the compounds in a list without commas between the structures and without a conjunction between the last two structures; thus, the claim recites a non-closed list of alternatives. As a consequence, one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Specifically one of ordinary skill in the art would not be reasonably apprised of whether only the recited compounds are included within the scope of the claim or whether any compound of claim 1 falls within the scope of the invention. Therefore, given the uncertainty around what compounds or included in claim 9 due to the lack of ending punction and conjunction; claim 9 is rejected under 35 U.S.C. 112(b).
Regarding claim 20, the phrase "including" renders the claim indefinite because it is unclear whether the limitations following the phrase are required limitations of the claimed invention or preferred embodiments of the invention. See MPEP § 2173.05(d).
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 factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1 – 7, 9, and 16 – 20 are rejected under 35 U.S.C. 103 as being unpatentable over International Publication Number WO 2005/054239 A1 to Sato et. al. (Sato’239; cited on IDS dated September 5th, 2024) in view of Altenbach et. al., ((2008), Structure-activity studies on a series of a 2-aminopyrimidine-containing histamine H4 receptor ligands, J. Med. Chem., 51, 6571 – 6580; cited on IDS dated September 5th, 2024).
Regarding claims 1 – 7, 9, and 16 – 20, Sato’239 teach novel 2-aminopyrimidine derivatives with unexpectedly excellent antagonistic activity to histamine H4 receptor. See page 5 lines 15 – 17. In particular, Sato’239 teach compound species 1 – 3 of structure
PNG
media_image2.png
182
268
media_image2.png
Greyscale
. See page 33. See claim 1 limitation for a compound of formula (1) where X = N; where the C1-3 alkyl group of R1 cyclizes back onto the ring to which NHR1 is attached to form a second ring; and n is 2. See claim 2 limitation where X = N. See claim 17 limitation for a compound of formula (2c). See claim 19 limitation where the C1-3 alkyl group of R1 cyclizes back onto the ring to which NHR1 is attached to form a second ring.
Furthermore, Sato’239 teach compound species 2 – 4 of structure
PNG
media_image3.png
274
414
media_image3.png
Greyscale
. See page 44. See claim 1 limitation for a compound of formula (1) where X = N; R1 = CH3; R2 = H; and n is 1. See claim 2 limitation where X = N. See claim 3 limitation where R1 = CH3. See claim 4 limitation where R2 = H. See claim 5 limitation where the compound is of formula (2d). See claim 18 limitation where n is 1. And Sato’239 teach compound species 2 – 19 of structure
PNG
media_image4.png
204
288
media_image4.png
Greyscale
. See pages 33, 44, and 48. See claim 1 limitation for a compound of formula (1) where X = N; R1 = CH3; R2 = H; and n is 1. See claim 2 limitation where X = N. See claim 3 limitation where R1 = CH3. See claim 4 limitation where R2 = H. See claim 5 limitation where the compound is of formula (2d). See claim 18 limitation where n is 1.
Additionally, Sato’239 teach that the compounds of the disclosure, that include compound 2 – 4, are useful as effective anti-inflammatory agents, further teaching that the use of compounds in the disclosure in the treatment of asthma and rheumatoid arthritis. See abstract and page 5 line 11. See claim 20 limitation for a method of treating an inflammatory disorder. Moreover, Sato’239 teach that compounds of the disclosure which include compound 2 – 4 can be prepared in pharmaceutical compositions comprising pharmaceutically acceptable excipients including carriers, diluents, flavoring agents. See page 23 lines 20 – 27. See claim 16 limitation for a pharmaceutical composition comprising a compound of claim 1 and pharmaceutically acceptable excipient. Moreover, Sato’239 teach that compound 1 – 4 had an IC50 = 20 nM, compound 2 – 4 had an IC50 = 20 nM, and compound 2 – 19 had an IC50 = 20 nM of CHO cells transfected with Human H4 receptor (CHO-H4 stable cells) in a buffer comprising 50 mM Tris (pH = 7.5) and 5 mM EDTA. See page27 lines 10 – 11 and page 28 line 20. See claim 16 limitation for a pharmaceutical composition comprising a compound of claim 1 and pharmaceutically acceptable excipient.
However, Sato’239 fails to teach a compound of formula (1) where A = a pyrazole ring linked to the ring containing X by a carbon-carbon bond. See claim 1 limitation. Moreover, Sato’239 fails to teach a pyrazole selected from
PNG
media_image5.png
200
400
media_image5.png
Greyscale
;
PNG
media_image6.png
200
400
media_image6.png
Greyscale
;
PNG
media_image7.png
200
400
media_image7.png
Greyscale
where R3 = H. See claim 6 limitation. Additionally, Sato’239 fail to teach a compound where R3 = H on the pyrazole ring. See claim 7 limitation. Furthermore, where the selected A is
PNG
media_image8.png
200
400
media_image8.png
Greyscale
. See claim 9 limitation.
Nevertheless, Altenbach et. al. teach a library of compounds based on the generic 2-aminopyrimidine scaffold as histamine H4 receptor modulators of structures
PNG
media_image9.png
154
420
media_image9.png
Greyscale
. See page 6571 abstract and Figure 1. Specifically, Altenbach et. al. teach both compound 63 and 99 with a generic scaffold of structure
PNG
media_image10.png
258
358
media_image10.png
Greyscale
where compound 63 has the structure
PNG
media_image11.png
252
420
media_image11.png
Greyscale
where A is a phenyl, and compound 99 has the structure
PNG
media_image12.png
258
422
media_image12.png
Greyscale
where A is a pyrazol-4-yl. See page 6574 Table 4.
Additionally, Altenbach et. al. teach that Compound 63 has a pEC50 of 8.39 ± 0.39 and Compound 99 has a pEC50 of 8.38 ± 0.14 HEK-293 cells expressing human H4 receptors using a cell-based Ca2+-influx assay FLIPR. See page 6574 Table 4. Accordingly, Altenbach et. al. suggest that both compound 63 and compound 99 have similar biological properties in regards to H4 receptors. Thus given the amount of structural overlap between compound 63 of structure
PNG
media_image11.png
252
420
media_image11.png
Greyscale
and compound 99 of structure
PNG
media_image12.png
258
422
media_image12.png
Greyscale
, and similar biological efficacy prior art compound 63 and compound 99 are structural homologs that differ only in the structural limitation of ring A.
Furthermore, Altenbach et. al. teach that both compound 63 and compound 99 possess equivalent potencies for human H4 receptor around 4 nM. See page 6574 column 2 paragraph 1, page 6575 column 1 paragraph and column 2 paragraph 1. Moreover, Altenbach et. al. further suggest that the pyrazole ring and the phenyl ring as ring equivalents; and structural features capable of interacting with human H4 receptor. Thus, Altenbach et. al. suggest the structural feasibility of substituting a pyrazole for a phenyl to maintain affinity levels while conducting a structure activity study for H4R modulators.
Therefore it would have been obvious to one of ordinary skill in the art before the effective filing date of the instant application to modify the structure of compound species 1 – 4, 2 – 4, and/or 2 – 19 of Sato’239 in view of Altenbach et. al., that is to substitute the phenyl rings taught in Sato’239 for the equivalent pyrazole ring. One of ordinary skill in the art would be motivated to make this modification to maintain potency levels while diversifying the scaffold. One of ordinary skill in the art would have a reasonable expectation of success because the compounds with similar core scaffolds with either a phenyl or a pyrazole demonstrated equivalent potencies at 4 nM for H4 receptors.
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over International Publication Number WO 2005/054239 A1 to Sato et. al. (Sato’239; cited on IDS dated September 5th, 2024) and Altenbach et. al., ((2008), Structure-activity studies on a series of a 2-aminopyrimidine-containing histamine H4 receptor ligands, J. Med. Chem., 51, 6571-6580; cited on IDS dated September 5th, 2024) as applied to claims 1 – 7, 9, and 16 – 20 above, and further in view of Meanwell ((2011), Synopsis of Some Recent Tactical Application of Bioisosteres in Drug Design, J. Med. Chem., 54, 2529 – 2591).
The teachings of Sato’239 and Altenbach et. al. as they relate to claims 1, and 6, from which claim 8 depends, are given previously in this office action and are fully incorporated here.
However, the prior art of Sato’239 and Altenbach et. al. fail to teach a compound of claim 6 where R4 and/or R5 is methyl or fluoro. See claim 8 limitation.
Nevertheless, Meanwell teach that in the contemporary practice of medicinal chemistry, the development and application of bioisosteres have been adopted as a fundamental tactical approach useful to address a number of aspects associated with the design and development of drug candidates. See page 2529 column 1 paragraph 1. Additionally, Meanwell teach that bioisosteres are typically less than exact structural mimetics and are often more alike in biological rather than physical properties. See page 2529 column 1 paragraph 1. Moreover, Meanwell teach that H, F, OH, NH2, and CH3 are classical monovalent bioisosteres. See page 2530 column 1 Table 1. Thus Meanwell suggest the ability to substitute the H atom for a F or CH3 with a reasonable expectation that compounds with either H, F and/or CH3 would have similar biological properties.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filling date of the instant application to modify the structure of compound species 1 – 4, 2 – 4, and/or 2 – 19 of Sato’239 in view of Altenbach et. al., that is to substitute the phenyl rings taught in Sato’239 for the equivalent pyrazole ring, in further view of Meanwell, that is to replace the H for either a F atom or a CH3 group. One of ordinary skill in the art would be motivated to make this modification and have a reasonable expectation of success because F, H, and CH3 are classical monovalent bioisosteres and would be reasonable expected to at least have the same biological properties.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over International Publication Number WO 2005/054239 A1 to Sato et. al. (Sato’239; cited on IDS dated September 5th, 2024) and Altenbach et. al., ((2008), Structure-activity studies on a series of a 2-aminopyrimidine-containing histamine H4 receptor ligands, J. Med. Chem., 51, 6571-6580; cited on IDS dated September 5th, 2024) as applied to claims 1 – 7, 9, and 16 – 20 above, and further in view of Meanwell ((2011), Synopsis of Some Recent Tactical Application of Bioisosteres in Drug Design, J. Med. Chem., 54, 2529 – 2591).
The teachings of Sato’239 and Altenbach et. al. as they relate to claim 1, from which claim 10 depends, are given previously in this office action and are fully incorporated here.
However, the prior art of Sato’239 and Altenbach et. al. fail to teach a selected compound of claim 1 that is
PNG
media_image13.png
200
400
media_image13.png
Greyscale
. See claim 10 limitation.
Nevertheless, Meanwell teach that in the contemporary practice of medicinal chemistry, the development and application of bioisosteres have been adopted as a fundamental tactical approach useful to address a number of aspects associated with the design and development of drug candidates. See page 2529 column 1 paragraph 1. Additionally, Meanwell teach that bioisosteres are typically less than exact structural mimetics and are often more alike in biological rather than physical properties. See page 2529 column 1 paragraph 1. Moreover, Meanwell teach that H, F, OH, NH2, and CH3 are classical monovalent bioisosteres. See page 2530 column 1 Table 1. Thus Meanwell suggest the ability to substitute the H atom for a CH3 with a reasonable expectation that compounds with either H or CH3 would have similar biological properties.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filling date of the examined application to modify the structure of compound species 1 – 4, 2 – 4, and/or 2 – 19 of Sato’239 in view of Altenbach et. al., that is to substitute the phenyl rings taught in Sato’239 for the equivalent pyrazole ring, in further view of Meanwell, that is to replace the H for a CH3 group. One of ordinary skill in the art would be motivated to make this modification and have a reasonable expectation of success because F, H, and CH3 are classical monovalent bioisosteres and would be reasonable expected to at least have the same biological properties. One of ordinary skill in the art would be motivated to make this modification to maintain potency levels while diversifying the scaffold. One of ordinary skill in the art would have a reasonable expectation of success because the compounds with similar core scaffolds with either a phenyl or a pyrazole demonstrated equivalent potencies at 4 nM for H4 receptors.
Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over International Publication Number WO 2005/054239 A1 to Sato et. al. (Sato’239; cited on IDS dated September 5th, 2024) and Altenbach et. al., ((2008), Structure-activity studies on a series of a 2-aminopyrimidine-containing histamine H4 receptor ligands, J. Med. Chem., 51, 6571-6580; cited on IDS dated September 5th, 2024) as applied to claims 1 – 7, 9, and 16 – 20 above, and further in view of Meanwell ((2011), Synopsis of Some Recent Tactical Application of Bioisosteres in Drug Design, J. Med. Chem., 54, 2529 – 2591).
The teachings of Sato’239 and Altenbach et. al. as they relate to claim 1, from which claim 15 depends, are given previously in this office action and are fully incorporated here.
However, the prior art of Sato’239 and Altenbach et. al. fail to teach compound of claim 1 that is
PNG
media_image14.png
200
400
media_image14.png
Greyscale
. See claim 15 limitation.
Nevertheless, Meanwell teach that in the contemporary practice of medicinal chemistry, the development and application of bioisosteres have been adopted as a fundamental tactical approach useful to address a number of aspects associated with the design and development of drug candidates. See page 2529 column 1 paragraph 1. Additionally, Meanwell teach that bioisosteres are typically less than exact structural mimetics and are often more alike in biological rather than physical properties. See page 2529 column 1 paragraph 1. Moreover, Meanwell teach that H, F, OH, NH2, and CH3 are classical monovalent bioisosteres. See page 2530 column 1 Table 1. Thus Meanwell suggest the ability to substitute the H atom for a CH3 with a reasonable expectation that compounds with either H or CH3 would have similar biological properties.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filling date of the examined application to modify the structure of compound species 1 – 4, 2 – 4, and/or 2 – 19 of Sato’239 in view of Altenbach et. al., that is to substitute the phenyl rings taught in Sato’239 for the equivalent pyrazole ring, in further view of Meanwell, that is to replace some of the H atoms for either F atoms. One of ordinary skill in the art would be motivated to make this modification and have a reasonable expectation of success because F, and H, are classical monovalent bioisosteres and would be reasonable expected to at least have the same biological properties. One of ordinary skill in the art would be motivated to make this modification to maintain potency levels while diversifying the scaffold. One of ordinary skill in the art would have a reasonable expectation of success because the compounds with similar core scaffolds with either a phenyl or a pyrazole demonstrated equivalent potencies at 4 nM for H4 receptors.
Claims 11 – 14 are rejected under 35 U.S.C. 103 as being unpatentable over International Publication Number WO 2005/054239 A1 to Sato et. al. (Sato’239; cited on IDS dated September 5th, 2024) and Altenbach et. al., ((2008), Structure-activity studies on a series of a 2-aminopyrimidine-containing histamine H4 receptor ligands, J. Med. Chem., 51, 6571-6580; cited on IDS dated September 5th, 2024) as applied to claims 1 – 7, 9, and 16 – 20 above, and further in view of Meanwell ((2011), Synopsis of Some Recent Tactical Application of Bioisosteres in Drug Design, J. Med. Chem., 54, 2529 – 2591) and Savall et. al., ((2014), Discovery and SAR of 6-alkyl-2,4-diaminopyrimidines as Histamine H4 Receptor Antagonists, J. Med. Chem., 57, 2429 – 2439; cited on IDS dated September 5th, 2024).
The teachings of Sato’239 and Altenbach et. al. as they relate to claim 1, from which claims 11 - 14 depend, are given previously in this office action and are fully incorporated here.
However, the prior art of Sato’239 and Altenbach et. al. fail to teach compound of claim 1 that is
PNG
media_image15.png
200
400
media_image15.png
Greyscale
. See claim 11 limitation. Moreover, the prior art of Sato’239 and Altenbach et. al. fail to teach compound of claim 1 that is
PNG
media_image16.png
200
400
media_image16.png
Greyscale
. See claim 12 limitation. Additionally, the prior art of Sato’239 and Altenbach et. al. fail to teach compound of claim 1 that is
PNG
media_image17.png
200
400
media_image17.png
Greyscale
. See claim 13 limitation. Furthermore, the prior art of Sato’239 and Altenbach et. al. fail to teach compound of claim 1 that is
PNG
media_image18.png
200
400
media_image18.png
Greyscale
. See claim 14 limitation.
Nevertheless, given that the prior art teach compound Furthermore, Sato’239 teach compound species 2 – 4 of structure
PNG
media_image3.png
274
414
media_image3.png
Greyscale
. See page 44. See claim 1 limitation for a compound of formula (1) where X = N; R1 = CH3; R2 = H; and n is 1. See claim 2 limitation where X = N. See claim 3 limitation where R1 = CH3. See claim 4 limitation where R2 = H. See claim 5 limitation where the compound is of formula (2d). See claim 18 limitation where n is 1. And Sato’239 teach compound species 2 – 19 of structure
PNG
media_image4.png
204
288
media_image4.png
Greyscale
. See pages 33, 44, and 48. See claim 1 limitation for a compound of formula (1) where X = N; R1 = CH3; R2 = H; and n is 1. See claim 2 limitation where X = N. See claim 3 limitation where R1 = CH3. See claim 4 limitation where R2 = H. See claim 5 limitation where the compound is of formula (2d). See claim 18 limitation where n is 1.
Given that the only difference between the prior art compound of Sato’239 that is species 2 – 4 of structure
PNG
media_image3.png
274
414
media_image3.png
Greyscale
, and species 2 – 19 of structure
PNG
media_image4.png
204
288
media_image4.png
Greyscale
and the examined application compound species of
PNG
media_image15.png
200
400
media_image15.png
Greyscale
,
PNG
media_image16.png
200
400
media_image16.png
Greyscale
,
PNG
media_image17.png
200
400
media_image17.png
Greyscale
, and
PNG
media_image18.png
200
400
media_image18.png
Greyscale
in the introduction of a -CH2- unit in the 4 membered N containing heterocyclic ring; the compounds of the prior art and the examined claims species are structural homologs of each other. Moreover, the prior art compound of Sato’239 that is species 2 – 4 of structure
PNG
media_image3.png
274
414
media_image3.png
Greyscale
, and species 2 – 19 of structure
PNG
media_image4.png
204
288
media_image4.png
Greyscale
and the examined application compound species of
PNG
media_image15.png
200
400
media_image15.png
Greyscale
,
PNG
media_image16.png
200
400
media_image16.png
Greyscale
,
PNG
media_image17.png
200
400
media_image17.png
Greyscale
, and
PNG
media_image18.png
200
400
media_image18.png
Greyscale
are classified as 2,4-diaminopyridine derivatives having H4 receptor activity. Compounds which are 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 MPEP 2144.09 (II).
However, the prior art of Sato’239 and Altenbach et. al. fail to teach compound of claim 1 that is
PNG
media_image15.png
200
400
media_image15.png
Greyscale
where one H atom on the pyrazolyl ring is substituted with a CH3 group. See claim 11 limitation. Moreover, the prior art of Sato’239 and Altenbach et. al. fail to teach compound of claim 1 that is
PNG
media_image16.png
200
400
media_image16.png
Greyscale
where two H atoms on the pyrazolyl ring is substituted with a CH3 group. See claim 12 limitation. Additionally, the prior art of Sato’239 and Altenbach et. al. fail to teach compound of claim 1 that is
PNG
media_image17.png
200
400
media_image17.png
Greyscale
where one H atom on the pyrazolyl ring is substituted with a Cl atom. See claim 13 limitation. Furthermore, the prior art of Sato’239 and Altenbach et. al. fail to teach compound of claim 1 that is where all 3 H atoms on the methyl group on the pyrazolyl ring is substituted with F atoms.
PNG
media_image18.png
200
400
media_image18.png
Greyscale
. See claim 14 limitation.
Nevertheless, Meanwell teach that in the contemporary practice of medicinal chemistry, the development and application of bioisosteres have been adopted as a fundamental tactical approach useful to address a number of aspects associated with the design and development of drug candidates. See page 2529 column 1 paragraph 1. Additionally, Meanwell teach that bioisosteres are typically less than exact structural mimetics and are often more alike in biological rather than physical properties. See page 2529 column 1 paragraph 1. Moreover, Meanwell teach that H, F, Cl, OH, NH2, and CH3 are classical monovalent bioisosteres. See page 2530 column 1 Table 1. Furthermore, Meanwell suggest the ability to substitute the H atom for a CH3 with a reasonable expectation that compounds with either H or CH3 would have similar biological properties; and substitute H atom for a F atom and then a Cl atom.
However, the prior art of Sato’239 and Altenbach et. al. fail to teach compound of claim 1 that is
PNG
media_image15.png
200
400
media_image15.png
Greyscale
with the R stereochemistry. See claim 11 limitation. Moreover, the prior art of Sato’239 and Altenbach et. al. fail to teach compound of claim 1 that is
PNG
media_image16.png
200
400
media_image16.png
Greyscale
with the R stereochemistry. See claim 12 limitation. Additionally, the prior art of Sato’239 and Altenbach et. al. fail to teach compound of claim 1 that is
PNG
media_image17.png
200
400
media_image17.png
Greyscale
with the R stereochemistry. See claim 13 limitation. Furthermore, the prior art of Sato’239 and Altenbach et. al. fail to teach compound of claim 1 that is
PNG
media_image18.png
200
400
media_image18.png
Greyscale
with the R stereochemistry. See claim 14 limitation.
Nevertheless, Savall et. al. teach a library of compounds based on the generic 6-alkyl-2,4-diaminopyridine scaffold, as histamine H4 receptor modulators that were assessed using recombinant histamine H4 receptors. See page 2432 column 1 Table 1. Savall et. al. teach compound 20 where n = 1, compound 19 where n = 2 with S stereochemistry, and compound 18 where n = 2 with R stereochemistry. See page 2432 Table 1. Hence, Savall et. al. teach compounds 18, 19, and 20 that differ only differ by the diamine ring; and are thus, structural homologs. Moreover, Savall et. al. teach that compound 20 had a Ki of 5.5 nM, compound 19 had a Ki of 36 nM, and compound 18 had a Ki of 0.92 nM. See page 2432 Table 1. Consequently, Savall et. al. teach an improvement in pharmacokinetic profiles when n increases to 2 in combination with R stereochemistry; as highlighted by prior art compound 18 which had the lowest Ki value. Furthermore, Savall et. al. teach that a compounds pharmacokinetic profile can be improved by defining the stereochemistry in combination with increasing n to 2. Hence it would have been obvious to increase n to 2 and have the amine of the diamine in the R stereo configuration if the desire is to modulate receptor activity with the lowest drug concentration.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filling date of the examined application to modify the structure of compound species 1 – 4, 2 – 4, and/or 2 – 19 of Sato’239 in view of Altenbach et. al., that is to substitute the phenyl rings taught in Sato’239 for the equivalent pyrazole ring, in further view of Meanwell, that is to substitute the H atom for a CH3; and/or substitute H atom for a F atom and then a Cl atom even further in view of Savall et. al. to increase n to 2 and define the stereochemistry in the R stereochemistry. One of ordinary skill in the art would be motivated to increase n to 2 and define the stereochemistry in the R stereochemistry to improve the compounds therapeutic properties. One of ordinary skill in the art would have a reasonable expectation of success because when n is 2 and has a R stereochemistry there was an improvement in the Ki value 36 nM to 0.92 nM.
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 – 15, and 17 – 19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 17 of U.S. Patent No. US 12234227 B2 to Brown et. al. (Brown’227).
Although the claims at issue are not identical, they are not patentably distinct from each other because the invention of Brown’227 and the examined application direct to 2-aminopyrimidine derivatives compounds of the formula (I)
PNG
media_image19.png
176
232
media_image19.png
Greyscale
. See reference claim 1. See examined claim 1. Moreover, Brown’227 recites compound species that overlapping structural features as further defined in dependent reference claims 2 – 17. See examined claims 1 – 15, and 17 – 19.
Claims 1, 16, and 20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 17 of U.S. Patent No. US 12234227 B2 to Brown et. al. (Brown’227) in view of International Publication Number WO 2005/054239 A1 to Sato et. al. (Sato’239; cited on IDS dated September 5th, 2024).
Brown’227 recite a compound of the formula (I)
PNG
media_image19.png
176
232
media_image19.png
Greyscale
. See reference claim 1. See examined claim 1. Moreover, Brown’227 recites compound species that overlapping structural features as further defined in dependent reference claims 2 – 17.
However, Brown’227 fails to recite a pharmaceutical composition comprising a compound of (examined) claim 1 and a pharmaceutically acceptable excipient. See examined claim 16. Moreover, Brown’227 fails to recite a method of treating an inflammatory disorder comprising administering the compound of (examined) claim 1. See examined claim 20.
Nevertheless, the prior art teachings of Sato’239 as they relate to the prior art rejections of examined claims 1, 16, and 20 are given previously in this office action and are fully incorporated here.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the examined application to use the compounds of invention Brown’227 in view of Sato’239 to make pharmaceutical compositions that can be further used in methods of treating inflammatory disease. One of ordinary skill in the art would have been motivated to make the modification to modulate H4 receptors. One of ordinary skill in the art would have had a reasonable expectation of success because Sato’239 taught example 2-aminopyrimidine derivatives that were effective H4 receptor modulators.
Claims 1 – 9, 16, and 18 – 19 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 4, 6 – 7, 9 – 11, and 21 – 30 of copending Application No. 17/920583 to Congreve et. al. (reference application; Congreve’583).
Although the claims at issue are not identical, they are not patentably distinct from each other because both copending applications direct to 2-aminopyrimidine derivatives compounds. See reference claim 1. See examined claim 1. Moreover, Congreve’583 recite compound species that anticipates the genus of compounds of examined Formula (1) of structure
PNG
media_image20.png
270
398
media_image20.png
Greyscale
overlapping structural features as further defined in dependent reference claims 1 –2, 6 – 7, 9 – 11. See examined claims 1 – 9, 16, and 18 – 19. For example, Congreve’583 recite compound species
PNG
media_image21.png
128
212
media_image21.png
Greyscale
. See reference claim 1 – 2, and 6 – 7. See examined claims 1 – 9, and 18. Furthermore, Congreve’583 recite a pharmaceutical composition comprising a compound of (reference) claim 1 and a pharmaceutically acceptable excipient. See reference claims 3 – 4, and 9 – 11. See examined claim 19. Additionally, Congreve’583 recite a method for treating an inflammatory disorder. See reference claims 21 – 30. See examined claims 20.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 10 – 15, and 17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 4, 6 – 7, and 9 – 11, of copending Application No. 17/920583 to Congreve et. al. (reference application; Congreve’583) in view of International Publication Number WO 2005/054239 A1 to Sato et. al. (Sato’239; cited on IDS dated September 5th, 2024), Altenbach et. al., ((2008), Structure-activity studies on a series of a 2-aminopyrimidine-containing histamine H4 receptor ligands, J. Med. Chem., 51, 6571-6580; cited on IDS dated September 5th, 2024), Meanwell ((2011), Synopsis of Some Recent Tactical Application of Bioisosteres in Drug Design, J. Med. Chem., 54, 2529 – 2591), and Savall et. al., ((2014), Discovery and SAR of 6-alkyl-2,4-diaminopyrimidines as Histamine H4 Receptor Antagonists, J. Med. Chem., 57, 2429 – 2439; cited on IDS dated September 5th, 2024).
Congreve’583 recite compound species that anticipates the genus of compounds of examined Formula (1) of structure
PNG
media_image20.png
270
398
media_image20.png
Greyscale
overlapping structural features as further defined in dependent reference claims 1 –2, 6 – 7, 9 – 11.
However, Congreve’583 fail to recite a selected compound of (examined) claim 1 that is
PNG
media_image13.png
200
400
media_image13.png
Greyscale
. See examined claim 10. Additionally, Congreve’583 fail to recite a compound of (examined) claim 1 that is
PNG
media_image15.png
200
400
media_image15.png
Greyscale
. See examined claim 11. Moreover, Congreve’583 fail to recite a compound of (examined) claim 1 that is
PNG
media_image16.png
200
400
media_image16.png
Greyscale
. See examined claim 12. Additionally, the Congreve’583 fail to recite a compound of (examined) claim 1 that is
PNG
media_image17.png
200
400
media_image17.png
Greyscale
. See examined claim 13. Furthermore Congreve’583 fail to recite a compound of (examined) claim 1 that is
PNG
media_image18.png
200
400
media_image18.png
Greyscale
. See examined claim 14. Moreover, Congreve’583 fail to recite a compound of (examined) claim 1 that is
PNG
media_image14.png
200
400
media_image14.png
Greyscale
. See examined claim 15. Additionally, Congreve’583 fail to recite a compound of (examined) claim 1 that is a compound of formula (2c). See examined claim 17.
Nevertheless, the prior art teachings of Sato’239, Altenbach et. al., Meanwell, and Savall et. al., as they relate to the prior art rejections of examined claims 1, 10 – 15, and 17 are given previously in this office action and are fully incorporated here.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the examined application to modify the compounds of copending Congreve’583 in view of Sato’239, Altenbach et. al., Meanwell, and Savall et. al., that is for the compounds as recited above. One of ordinary skill in the art would be motivated to increase n to 2 and define the stereochemistry in the R stereochemistry to improve the compounds therapeutic properties. One of ordinary skill in the art would have a reasonable expectation of success because when n is 2 and has a R stereochemistry there was an improvement in the Ki value 36 nM to 0.92 nM.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Claims 1 – 20 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DAWANNA S WHITE whose telephone number is (703)756-4687. The examiner can normally be reached 7:00 am - 5:00 pm [EST] M - Th.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Kortney Klinkel can be reached on 571-270-5239. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/DAWANNA SHAR-DAY WHITE/Examiner, Art Unit 1627
Prosecution Insights