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 .
Election/Restrictions
Applicant's election with traverse of Group I, drawn to a compound of formula I, a pharmaceutical composition comprising the compound, a device comprising the pharmaceutical composition, or a combination of the compound with one or more active ingredients; and the following species:
the compound of Example 1 that is a single enantiomer compound: (R)-2-fluoro-4-(3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)pyrrolidin-1-yl)benzonitrile as the elected compound species of formula I;
lactose as the elected species of carrier/excipient in the pharmaceutical composition;
a dry powder inhaler as the elected device; and
corticosteroid as the elected active ingredient in the combination
in the reply filed on February 13, 2026 is acknowledged. The traversal is on the ground(s) that restriction is only proper if the claims of the restricted groups are independent or patentably distinct and there would be a serious burden placed on the examiner. Applicant further argues there are no reasons or examples to support a conclusion that the species are indeed patentably distinct; and the claims was not interpreted in light of the description when determining the groups are lacking unity. This is not found persuasive because interpreting the claims in light of the description is not required for unity of invention restriction analysis; and search burden is not a requirement for unity of invention. As stated in the previous Office Action, the technical features shared between the groups of inventions is the compound of Formula I, said technical feature is not a special technical feature in view of CAS Registry Number 2248077-03-2 (cited in the previous Office Action). The species are lacking a priori, because they are not trivial features of the claims and required to be search along with the compound of Formula I. In other words, the groups of species do not share a common technical feature without a need to consult prior arts.
The requirement is still deemed proper and is therefore made FINAL.
Please note applicant elects “lactose” as the species of carriers or excipients in the pharmaceutical composition. It is noted that the claims submitted on September 14, 2023 does not have claims drawn to the elected lactose as the species of carrier or excipients, thus, the examiner limits examination to any pharmaceutically acceptable carriers or excipients. However, to the extent that Applicant amends the claims to include said species, it would require further search and consideration.
Claim 7 is withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on February 13, 2026.
Expansion of Election of Species Requirement
A reasonable and comprehensive search of the elected compound species of Formula I conducted by the Examiner determined that the prior art at the time of the present invention was such that it did not anticipate or render obvious the elected compound species: (R)-2-fluoro-4-(3-(methyl(7H-pyrrolo[2,3-d] pyrimidin-4-yl) amino) pyrrolidin-1-yl) benzonitrile. In light of this discovery, the search is expanded to the subject matter of the subgenus of the elected compound species of Formula I, i.e., the compound having the structure of
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,
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and
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, such that it does not encompass the full scope of the claims.
Status of Claims
Acknowledgement is made of the receipt and entry of the amendment to the claims filed on September 14, 2023, wherein claims 1-5, 7-8 are amended; claim 6 is cancelled; and claim 9 is newly added.
Claims 1-5 and 7-9 are pending. Claim 7 is withdrawn.
Claims 1-5 and 8-9 are under examination in accordance with the elected species along with the expanded compound species sets forth in the Expansion of Election of Species Requirement above.
Priority
The instant application 18/282,068 filed on September 14, 2023 is a 371 of PCT/EP2022/056552 filed on March 14, 2022, which claims priority to, and the benefits of Foreign Application No.
EP21162525.6 filed on March 15, 2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on September 14, 2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Interpretation
The claimed term “(R)-2-fluoro-4-(3-(methyl(7H-pyrrolo[2,3-d] pyrimidin-4-yl) amino) pyrrolidin-1-yl) benzonitrile”, when reasonably construed in light of page 15 of the specification, is a compound having the structure of:
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.
The claimed phrase “suitable to be administered by inhalation, selected from an inhalable powder, a propellant-containing metering aerosol or a propellant-free inhalable formulation” in claim 4 is reasonably construed to be an intended use of the pharmaceutical composition. Since the claim is interpretated to be a product, the intended use of the pharmaceutical composition does not further limit the structural components; and therefore, if the prior art(s) meet the structural limitation of the claimed product, it is capable of performing the intended use.
The claimed phrase “used in the treatment of respiratory disorders” in claim 8 is reasonably construed to be an intended use of the one or more active ingredients. Since the claim is interpretated to be a product, the intended use of the one or more active ingredients does not further limit the structural components of the one or more active ingredients; and therefore, if the prior art(s) meet the structural limitation of the claimed product, it is capable of performing the intended use.
Claim Objections
Claims 4 and 8 are objected to because of the following informalities:
Regarding claims 4 and 8, the comma is missing in between the claim number and the phrase that follows, for example, “… according to claim 3 suitable to” in claim 4 should read –according to claim 3, suitable--.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 8-9 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Instant claim 8 recites “[a] combination of the compound, enantiomer, diastereoisomer or mixture thereof, or pharmaceutically acceptable salt or solvate thereof according to claim 1 with one or more active ingredients selected from the classes currently used in the treatment of respiratory disorders, and known to the skilled person”; and claim 9 recites “wherein the one or more active ingredients are selected from the group consisting of a beta2-agonist, an antimuscarinic agent, a corticosteroid, a mitogen-activated kinase (P38 MAP kinases) inhibitor, a nuclear factor kappa-B kinase subunit beta inhibitor (IKK2), a human neutrophil elastase (HNE) inhibitor, a phosphodiesterase 4 (PDE4) inhibitor, a leukotriene modulator, a non-steroidal anti-inflammatory agent (NSAID), and a mucus regulator”. The specification fails to disclose any species of one or more active ingredients. There is insufficient written basis for any species of beta2-agonist, antimuscarinic agent, corticosteroid, mitogen-activated kinase inhibitor, nuclear factor kappa-B kinase subunit beta inhibitor (IKK2), human neutrophil elastase (HNE) inhibitor, phosphodiesterase 4 (PDE4) inhibitor, leukotriene modulator, non-steroidal anti-inflammatory agent (NSAID), and a mucus regulator encompassed by the instant claims.
Regarding the requirement for adequate written description of chemical entities, Applicant's attention is directed to the MPEP §2163. In particular, Regents of the University of California v. Eli Lilly & Co., 119 F.3d 1559, 1568 (Fed. Cir. 1997), cert. denied, 523 U.S. 1089, 118 S. Ct. 1548 (1998), holds that an adequate written description requires a precise definition, such as by structure, formula, chemical name, or physical properties, "not a mere wish or plain for obtaining the claimed chemical invention." Eli Lilly, 119 F.3d at 1566. The Federal Circuit has adopted the standard set forth in the Patent and Trademark Office ("PTO") Guidelines for Examination of Patent Applications under the 35 U.S.C. 112.I "Written Description" Requirement ("Guidelines"), 66 Fed. Reg. 1099 (Jan. 5,2001), which state that the written description requirement can be met by "showing that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics," including, inter alia, "functional characteristics when coupled with a known or disclosed correlation between function and structure ..." Enzo Biochem, Inc. v. Gen-Probe Inc., 296 F.3d 316, 1324-25 (Fed. Cir. 2002) (quoting Guidelines, 66 Fed. Reg. at 1106 (emphasis added)). Moreover, although Eli Lilly and Enzo were decided within the factual context of DNA sequences, this does not preclude extending the reasoning of those cases to chemical structures in general. Univ. of Rochester v G.D. Searle & Co., 249 Supp. 2d 216, 225 (W.D.N.Y. 2003).
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof.
In the present case, the only factor present in the claims is a recitation of “one or more active ingredients” in claim 8; and the recitation of “a beta2-agonist, an antimuscarinic agent, a corticosteroid, a mitogen-activated kinase (P38 MAP kinases) inhibitor, a nuclear factor kappa-B kinase subunit beta inhibitor (IKK2), a human neutrophil elastase (HNE) inhibitor, a phosphodiesterase 4 (PDE4) inhibitor, a leukotriene modulator, a non-steroidal anti-inflammatory agent (NSAID), and a mucus regulator” in claim 9. The specification does not provide any structural characteristics, chemical formula, name(s) or physical properties of one or more active ingredients, aside from a broad recitation that they are “currently used in the treatment of respiratory disorders, and known to the skilled person, such as beta2-agonists, antimuscarinic agents, corticosteroids mitogen-activated kinases (P38 MAP kinases) inhibitors, nuclear factor kappa-B kinase subunit beta inhibitors (IKK2), human neutrophil elastase (HNE) inhibitors, phosphodiesterase 4 (PDE4) inhibitors, leukotriene modulators, non-steroidal anti-inflammatory agents (NSAIDs) and mucus regulators” (see page 13, line15-21 of the specification). In other words, the specification does not provide sufficient description of a representative number of species of the claimed genus, aside from a broad recitation that these drug classes are contemplated for use as the one or more active ingredients in the claimed invention.
Accordingly, in the absence of sufficient description of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus. Therefore, based on the limited disclosure provided, it is not apparent that the Applicant was actually in possession of the entire scope of one or more active ingredients instantly claimed.
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 1 and 8-9 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.
Regarding claim 1,
the recitation of “[a] compound of formula I…R3 is….; a single enantiomer, diastereoisomer or mixture thereof, or a pharmaceutically acceptable salt or solvate thereof” is missing a coordinating conjunction proceeding the phrase of “; a single enantiomer” to connect the independent clauses. It is not clear if applicant is intending to claim that (i) the compound of formula I is a single enantiomer, diastereoisomer or mixture thereof; or (ii) R3 of formula I is a single enantiomer, diastereoisomer or mixture thereof.
the recitation of “R2 is selected from the group consisting of a phenyl, phenylmethyl, pyridinyl and pyrimidinyl group optionally substituted by one or more group selected from the group consisting of -CN, F, Cl, (thiazol-2-yl)aminocarbonyl, (methoxy)carbonyl, and (hydroxy)carbonyl” lacks clarity as it can be interpreted in various ways. It is not clear if applicant is intending to claim (i) each of the phenyl, the phenylmethyl, the pyridinyl and the pyrimidinyl group can be optionally substituted, or (ii) (R2 is selected from the group consisting of a phenyl, phenylmethyl, pyridinyl) and (pyrimidinyl group optionally substituted by one or more group selected from the group consisting of -CN, F, Cl, (thiazol-2-yl)aminocarbonyl, (methoxy)carbonyl, and (hydroxy)carbonyl), such that only pyrimidinyl group can be optionally substituted. The lack of clarify renders the claims indefinite since the resulting claims do not clearly set forth the metes and bounds of the patent protection desired.
In order to advance prosecution, the Examiner is examining the claim 1 to the extent that the compound of formula I is a single enantiomer, diastereoisomer or mixture thereof; and each of the phenyl, the phenylmethyl, the pyridinyl and the pyrimidinyl group can be optionally substituted.
Regarding claim 8,
the term “currently” and “known” in the phrase of “selected from the classes currently used in the treatment of respiratory disorders, and known to the skilled person” are relative terms which renders the claim indefinite. The term “currently” and the term “known” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. In the present case, it is not clear what is considered a known classes and an unknown class as this depends on the context and the knowledge of the person using it. In addition, the term “currently” is a relative adverb of time that depends entirely on the context of when the applicant is referring to; thus, the metes and bounds of the claimed subject matter cannot be determined.
the claims recite the term “the classes” in the phase of “the classes currently used in the treatment of respiratory disorders, and known to the skilled person”. There is insufficient antecedent basis for said term in the claim, because said term is not recited prior to said phrase. It is not clear what said term is being referred to by the Applicant; and therefore, the recitation of “the classes currently used in the treatment of respiratory disorders, and known to the skilled person” is indefinite, because it lacks clear definition or known boundaries. The metes and bounds of said phrase cannot be determined.
In order to advance prosecution, the Examiner is interpretating the claim such that the limitation of “with one or more active ingredients selected from the classes currently used in the treatment of respiratory disorders, and known to the skilled person” is drawn to the elected corticosteroid.
Regarding claim 9,
a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, the claim recites the broad recitation “a mitogen-activated kinase”, and the claim also recites “(P38 MAP kinases)” which is the narrower statement of the range/limitation. It is noted that P38 MAP kinases is a subgroup of mitogen-activated protein kinase. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. In addition, the narrow statement recited in the parenthesis renders the claim indefinite, because it is unclear whether the limitation recites therein is part of the claimed invention.
Claims 1-5 and 8-9 are rejected on the judicially-created basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). The improper Markush grouping includes species of the claimed invention that do not share both a substantial structural feature and a common use that flows from the substantial structural feature.
A Markush claim contains an “improper Markush grouping” if: (1) The species of the Markush group do not share a single structural similarity,” or (2) the species do not share a common use. Members of a Markush group share a "single structural similarity” when they belong to the same recognized physical or chemical class or to the same recognized physical or chemical class or to the same art-recognized class. Members of a Markush group share a common use when they are disclosed in the specification or known in the art to be functionally equivalent (see Federal Register, Vol. 76, No. 27, Wednesday, February 9, 2011, p. 7166, left and middle columns, bridging paragraph).
The Markush grouping of compounds of formula I is improper because the alternatives defined by the Markush grouping do not share a single structural similarity and a common use for the following reasons:
Instant claim 1 recites “[a] compound of formula I
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…”. The Markush grouping of the compound species are improper, because the alternatives embraced by the Markush grouping do not share a substantial structure feature, and the alternated compound species do not share a common use that flows from the substantial structure feature.
For instance, the Markush grouping of compounds of formula I include a variety of
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, such as pyrrolo[2,3-d]pyrimidin
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and thieno[3,2-b]pyridine
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; and they do not share any single structural similarity and do not belong to the same chemical or physical class. The Markush grouping of compound species of formula I includes a variety of compound species, such as (R)-6-(3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)pyrrolidin-1-yl)-N-(thiazol-2-yl )nicotinamide (i.e., the compound of Example 3 having the structure of:
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according to page 16 of the specification); ethyl 7-((1-(4-cyano-3-fluorophenyl)pyrrolidin-3-yl)amino)thieno[3,2-b]pyridine-6-carboxylate (i.e., the compound of Example 7 having the structure of:
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according to page 18 of the specification); and methyl 2-(4-chloro-2-fluorophenyl)-2-(3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)pyrrolidin-1-yl)acetate (i.e., the compound of Example 5 having the structure of:
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according to page 17 of the specification) that do not share a substantial structure feature. These compound species only share the aminopyrrolidine ring (
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) in common, and does not constitute a significant portion of the compound as a whole. According to Frazee et al. (WO 2007/065093 A2), compound represented by the formula I
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is a progesterone receptor modulator useful for treating a patient with endometriosis or uterine fibroids (see e.g., p. 1, line 3-4; abstract). Even though the compound taught by Frazee et al. share the same technical feature (
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), said compounds are taught to have progesterone receptor modulating activity rather than inhibiting JAK kinases. Therefore, it is not apparent that this common structure alone (
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) contributes to the substantial structure feature essential for the compound of formula I to give the desired property of inhibiting JAK kinases.
Each of these findings demonstrate that not all members recited in the Markush groupings share a substantial structural feature and a common use that flows from the substantial structural feature. Therefore, the Markush groupings of the compound of formula I recites in the claims drawn to the pharmaceutical composition, the device, and the combination are also improper for the same reasons set forth herein.
In response to this rejection, Applicant should either amend the claim(s) to recite only individual species or grouping of species that share a substantial structural feature as well as a common use that flows from the substantial structural feature, or present a sufficient showing that the species recited in the alternative of the claims(s) in fact share a substantial structural feature as well as a common use that flows from the substantial structural feature. This is a rejection on the merits and may be appealed to the Board of Patent Appeals and Interferences in accordance with 35 U.S.C. §134 and 37 CFR 41.31(a)(1) (emphasis provided).
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim 1 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by CAS Registry Number 2248077-03-2 (Entered STN Registry on November 13, 2018; cited in the previous Office Action mailed on December 15, 2025).
CAS Registry Number 2248077-03-2 teaches a compound having the structure :
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.
Said compound is a compound of formula I instantly claimed
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, wherein R1 is H; R2 is
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(i.e., pyridinyl substituted with a fluoro); W is
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.
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.
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 1-5 and 8-9 are rejected under 35 U.S.C. 103 as being unpatentable over Blumenkopf et al. (WO 02/00661 A1), as evidenced by CAS Registry Number 384336-88-3 (Entered STN Registry on January 19, 2002).
Blumenkopf et al. teaches a compound of Example 171, 4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-5'-carbonitrile, is an exemplary compound of the formula I useful as inhibitor of protein kinases, such as the enzyme Janus Kinase 3 (see e.g., claim 21; p. 55, line 26-29; abstract). Please note the compound of Example 171 taught by Blumenkopf et al. is a compound having the structure of:
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, as evidenced by CAS Registry Number 384336-88-3. Blumenkopf et al. further teaches a compound of the formula
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, wherein R1 is a group of the formula
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; R5 is (C2-C9)heterocycloalkyl wherein the heterocyclcolakyl group must be substituted by one to three groups selected from, inter alia, (C1-C6)alkyl and a group of the formula (II)
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(see e.g., claims 1-2), wherein a is 0, 1, 2, 3, or 4; b, c, e, f are each independently 0 or 1; d is 0, 1, 2, or 3; R12 is (C6-C10)aryl or (C2-C9)heteroaryl, wherein the aryl or heteroaryl group is optionally substituted by one to four groups consisting of, inter alia, halo and cyano (see e.g., claim 20). Blumenkopf et al. further teaches (C2-C9)heteroaryl refers to, inter alia, pyridyl (see e.g., p. 7, line 6-17). Blumenkopf et al. further teaches a pharmaceutical composition comprising an amount of the compound of formula I or a pharmaceutically acceptable salt thereof and a pharmaceutical acceptable carrier (see e.g., claim 22; page 11, line 29 to page 12, line 3). Blumenkopf et al. further teaches capsules and cartridges (made, for example, from gelatin) for use in an inhaler or insufflator may be formulated containing a powder mix of a compound of the invention and a suitable powder base (see e.g., p. 26, line 5-8). Blumenkopf et al. further teaches aerosol formulations for treatment of the conditions (e.g., asthma) in the average adult human are preferably arranged so that each metered dose or “puff” of aerosol contains 20 µg to 1000 µg of the compound of the invention; and administration may be several times daily, for example 2, 3, 4 or 8 times, giving for example, 1, 2 or 3 doses each times (see e.g., p. 26, line1 4-19). Blumenkopf et al. further teaches the compound of formula (I) administered in a pharmaceutically acceptable form either alone or in combination with one or more additional agents which modulate a mammlian immune system or with antiinflammatory agents, agents which may include but are not limited to antiinflmmatory steroids (e.g. prednisolone or dexamethasone); and such agents may be administered as part of the same or separate dosage forms, via the same or different routes of administration, and on the same or different administration schedules according to standard pharmaceutical practice (see e.g., p. 26, line 20-30).
Regarding claim 1, the difference between the compound of Example 171 of Blumenkopf et al. and the expanded compound species of formula I is that the prior art compound has methyl-substituted piperidinyl rather than pyrrolidinyl in the core shown below:
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.
It would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to select the compound of Example 171 of Blumenkopf et al., and then modify said compound by substituting the piperidinyl with pyrrolidinyl, and removes methyl as the substituent at R5 to arrive at the claimed invention. One would have been motivated to do so, because Blumenkopf et al. teaches R5 can be a (C2-C9)heterocycloalkyl substituted by one to three groups selected from (C1-C6)alkyl and a group of the formula (II), wherein the (C2-C9)heterocycloalkyl can be a pyrrolidinyl or a piperidinyl to arrive at the compound of formula I useful as inhibitor of protein kinases. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the modified compound of Example 171 of Blumenkopf et al., which substituted the piperidinyl with pyrrolidinyl and removes methyl as one of the two substituents at R5 would have successfully arrive at a compound useful for inhibiting protein kinases. Please note the modified compound of Example 171 of Blumenkopf et al. sets forth above is a compound of formula I
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, wherein R1 is methyl; R2 is
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(i.e., pyridinyl substituted with -CN); W is
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Regarding the limitation of “[a] pharmaceutical composition comprising the compound…in admixture with one or more pharmaceutically acceptable carriers or excipients” in claim 3, and “[t]he pharmaceutical composition… suitable to be administered by inhalation, selected from an inhalable powder” in claim 4, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to arrive at the pharmaceutical composition comprising the modified compound of Example 171 of Blumenkopf et al. sets forth above with a pharmaceutical acceptable carrier. One would have been motivated to do so, because Blumenkopf et al. teaches a pharmaceutical composition comprising an amount of the compound of formula I and a pharmaceutical acceptable carrier. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the modified compound of Example 171 of Blumenkopf et al. sets forth above in admixture with a pharmaceutical acceptable carrier would have successfully arrive at a pharmaceutical composition; and therefore, the limitation of “suitable to be administered by inhalation, selected from an inhalable powder” would necessarily present in said pharmaceutical composition.
Regarding the limitation of “[a] device comprising the pharmaceutical composition… selected from the group consisting of single- or multi-dose dry powder inhaler” in claim 5, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to arrive at a single- or multi-dose dry powder inhaler comprising the pharmaceutical composition of Blumenkopf et al. sets forth above. One would have been motivated to do so, because Blumenkopf et al. teaches capsules and cartridges for use in an inhaler may be formulated containing a powder mix of the compound of formula I and a suitable powder base, and the aerosol formulations may administer several times daily giving 1, 2 or 3 doses each time. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the pharmaceutical composition of Blumenkopf et al. sets forth above can be formulated into a powder mix used in an inhaler that delivers a single or multiple doses each time, and said inhaler renders obvious the limitation instantly claimed. Please note the powder mix in an inhaler is a dry powder.
Regarding the limitation of “[a] combination of the compound…with one or more active ingredients selected from the classes currently used in the treatment of respiratory disorders, and known to the skilled person” in claim 8, and the limitation of “the one or more active ingredients are selected from the group consisting of…a corticosteroid” in claim 9, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to combine the modified compound of Example 171 of Blumenkopf et al. sets forth above with prednisolone as the anti-inflammatory agent. One would have been motivated to do so, because Blumenkopf et al. teaches the compound of formula (I) may be in combination with anti-inflammatory agents, including anti-inflammatory steroids such as prednisolone. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected the modified compound of Example 171 of Blumenkopf et al. sets forth above with prednisolone as the anti-inflammatory agent can successfully form a combination without any appreciable loss of activity.
Regarding the limitation of “the compound is selected from the group consisting of…5-(3-(methyl(7H-pyrrolo[2,3-d] pyrimidin-4-yl) amino) pyrrolidin-1-yl)picolinonitrile” in claim 2, the difference between the modified compound of Example 171 of Blumenkopf et al. sets forth above and the claimed compound is the position of nitrogen atom in the pyridine ring shown below (see shaded):
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It would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to further modify the modified compound of Example 171 of Blumenkopf et al. sets forth above by changing the position of nitrogen atom in the pyridine ring at R12 of the Formula I. One would have been motivated to do so, because Blumenkopf et al. teaches R12 of Formula I includes pyridyl as the (C2-C9) heteroaryl. One would have reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that by connecting the pyridyl ring at R12 through any position of said ring, including the claimed position, in the modified compound of Example 171 of Blumenkopf et al. would have successfully arrive at a compound of formula I that is similarity useful for inhibiting protein kinases.
Therefore, the claimed invention is prima facie obvious to one of ordinary skill in the art at the time the application was filed, absent factual evidence to the contrary.
Conclusion
No claims are allowed.
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/CHIHYI LEE/Examiner, Art Unit 1628 /JEAN P CORNET/Primary Examiner, Art Unit 1628