DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
Claims 1-4, 6, 8-11, 14-17, 19-22, and 28-30 are pending. Claims 5, 7, 12, 13, 18, and 23-27 are cancelled.
Status of Priority
The present application is a 35 U.S.C. § 371 national stage patent application of International patent application PCT/IB2022/057491, filed on August 11, 2022. This application also claims the benefits of foreign priority to IN202111036319, filed on August 11, 2021.
Election/Restrictions
Examiner previously required a restriction of the claimed inventions. The requirement filed on April 13, 2026 is now withdrawn and the prosecution will continue with a first non-final office action on the merits addressing the entire claim set.
Specification - Abstract
The abstract of the disclosure is objected to because of the following informalities:
The abstract discloses a compound represented by Formula I, but does not provide a structure of Formula I.
In chemical patent abstracts for compounds or compositions, the general nature of the compound or composition should be given as well as its use, e.g., “The compounds are of the class of alkyl benzene sulfonyl ureas, useful as oral anti-diabetics.” Exemplification of a species could be illustrative of members of the class. For processes, the type of reaction, reagents and process conditions should be stated, generally illustrated by a single example unless variations are necessary.
Appropriate correction is required.
Specification - Disclosure
The specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Claim Objections
Claim 28 is objected to because of the following informalities:
In claim 28, for grammatical consistency:
“…(STING) protein in a subject, the, the method comprising…” should read“…(STING) protein in a subject, the method comprising…”
Appropriate correction is required.
Claim Rejections – Improper Markush Grouping’
Claims 1-4, 6, 8-11, 14-17, 19-20, 22, and 28-30 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 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 members of the improper Markush grouping do not share a substantial feature and/or a common use that flows from the substantial structural feature for the following reasons:
The fused heterocyclic ring systems depicted below:
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represent only some of the numerous core structures a compound of instant Formula (I) can possess. However, these core structures exhibit no discernible structural similarity. The rings in each of these fused ring structures are all different.
Clearly no ‘‘single structural similarity’’ can be seen.
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 an ejection 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 CFR41.31 (a) (1) (emphasis provided).
Claims 2-4, 6, 8-11, 14-17, 19-20, 22, and 28-30, which are dependent on claim 1, are also rejected for further requiring and/or reciting the improper Markush grouping of claim 1.
Claim Rejections - 35 USC § 112(a)
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.
Scope of Enablement
Claims 1-4, 6, 8-11, 14-17, 19-20, 22, and 28-30 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for:
A compound of formula (I):
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wherein
R4 = H
R5 = benzyl optionally substituted with one or more halo; or phenyl
X6 = C=O or CR7R8 (wherein R7 = R8 = H)
Z = CR9R10 (wherein R9 = R10 = H)
n = 1
X7 = S, O, or S=O
X1 = CR1 (wherein R1 = H)
X2 = CR2 and X3 = CR3
One of R2 and R3 is -A-NR17-C(O)-NR18-R15 and the other of R2 and R3 is H
A =
Unsubstituted C2-C6 alkenylene or
C1-C6 alkylene optionally substituted with one or more of the following:
oxo, OH,
5-6 membered heterocyclyl optionally substituted with one OH
NR20R21 wherein R20 and R21 may each independently be selected from the group consisting of H; C1-C6 alkyl optionally substituted with OH or C1-C6 alkoxy; C1-C6 alkoxy; C3-C6 cycloalkyl; and 6-membered heteroaryl
Although R20 and R21 are not defined in instant claim 6, Examiner refers to the instant specification on pg. 10, lines 10-19 for the definition of R20 and R21
R17 = R18 = H
R15 =
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or
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or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof;
A pharmaceutical composition comprising a compound according to point (1) above, or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof, and a pharmaceutically acceptable vehicle;
A method for modulating the STimulator of INterferon Genes (STING) protein in a subject, the method comprising administering, to a subject in need of such treatment, a therapeutically effective amount of a compound of formula (I), as defined by point (1) above, or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof;
A method of treating or ameliorating a disease selected from liver fibrosis, fatty liver disease, non-alcoholic steatohepatitis (NASH), pulmonary fibrosis, lupus, sepsis, rheumatoid arthritis (RA), type I diabetes, STING-associated vasculopathy with onset in infancy (SAVI), Aicardi-Goutieres syndrome (AGS), familial chilblain lupus (FCL), systemic lupus erythematosus (SLE), retinal vasculopathy, neuroinflammation, systemic inflammatory response syndrome, pancreatitis, cardiovascular disease, renal fibrosis, stroke and age-related macular degeneration (AMD); the method comprising administering, to a subject in need of such treatment, a therapeutically effective amount of a compound of formula (I), as defined by point (1) above, or a pharmaceutically acceptable salt, solvate, tautomeric form or polymorphic form thereof;
The method of point (4) above, wherein the disease is fibrosis or fatty liver disease, and the fibrosis is selected from the group consisting of liver fibrosis, pulmonary fibrosis or renal fibrosis, and the fatty liver disease is non-alcoholic (or simple) fatty liver or non-alcoholic steatohepatitis (NASH);
does not reasonably provide enablement for elements that are outside the scope of the enabling elements listed above. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make the invention commensurate in scope with these claims.
As stated in the MPEP 2164.01(a), “There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue.”
In evaluating the enablement question, several factors are to be considered. According to In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988), these factors include:
1) The nature of the invention,
2) the state of the prior art,
3) the predictability or lack thereof in the art,
4) the amount of direction or guidance present,
5) the presence or absence of working examples,
6) the breadth of the claims, and
7) the quantity of experimentation needed to make and use the invention based on the content of the disclosure, and
8) the level of the skill in the art.
In the instant case, the Wands factors are relevant for the following reasons:
The nature of the invention
The nature of the invention claims compounds of formula (I). The compounds may be used to antagonize the Stimulator of Interferon Genes (STING) protein and may thereby treat liver fibrosis, fatty liver disease, non-alcoholic steatohepatitis (NASH), pulmonary fibrosis, lupus, sepsis, rheumatoid arthritis (RA), type I diabetes, STING-associated vasculopathy with onset in infancy (SAVI), Aicardi-Goutieres syndrome (AGS), familial chilblain lupus (FCL), systemic lupus erythematosus (SLE), retinal vasculopathy, neuroinflammation, systemic inflammatory response syndrome, pancreatitis, cardiovascular disease, renal fibrosis, stroke and age-related macular degeneration (AMD).
State of the prior art and the predictability or lack thereof in the art
The prior art discloses compounds encompassed by the scope of the instant claims. However, these previously disclosed compounds have been reported in the prior art as antagonists of MCP-1 function (see abstract of WO 02/070509 A2) rather than antagonists of STING. Thus, the prior art does not provide a predictable structure-activity relationship from which a POSITA could reasonably determine which combinations of substituents, substitution patterns, or substitution positions would result in compounds having STING inhibitory activity. Accordingly, the prior art demonstrates that STING inhibitor activity within the claimed genus is unpredictable.
See “Claim Rejections - 35 USC § 102” section below for examples of compounds encompassed by the scope of the instant claims.
Prior art referenced: Decout et al. (Decout) (Decout, A. et al. The cGAS–STING pathway as a therapeutic target in inflammatory diseases. Nature Reviews Immunology 2021, 21, 548-569. Published online April 8, 2021 - see line after “Outlook and future perspective” section on pg. 566).
The STING inhibitors disclosed in Decout possess core scaffolds that are structurally distinct from those of the compounds of the instant application (see Table 3 on pg. 563-564 of Decout). Accordingly, the prior art does not reasonably predict that the compounds of the instant application would exhibit STING inhibitory activity based solely on the known STING inhibitors.
The level of the skill in the art
The level of ordinary skill in the art is relatively high. A person of ordinary skill would typically have formal training in medicinal chemistry and organic synthesis and would be familiar with standard methods for evaluating therapeutic efficacy of compounds.
The breadth of the claims
The claims are broad insofar as the instant claims recite a compound of general formula (I) wherein the compound can possess a structurally diverse range of chemical groups wherein the chemical groups can further be optionally substituted with any substituent.
The presence or absence of working examples
The instant specification provides 37 specific examples of compounds encompassed by instant formula (I) (see pg. 95-99). The working examples do not adequately represent the full breadth of the claimed genus. For example, R1, (R2 or R3), R4, R7, R8, R9, R10, R17, and R18 are consistently hydrogen throughout the working examples and the exemplified value of “n” is 1. Furthermore, the instant claims allow R5 to be any of the options listed in instant claim 1, however, R5 is consistently either phenyl or benzyl that is optionally substituted with one or more halo. Likewise, the instant claims allow R15 to be any of the options listed in instant claim 1, however, R15 is consistently an indole moiety within the working examples. Accordingly, significant portions of the claimed structural space remain unexplored by the working examples. The examples, therefore, provide only limited information regarding how variations in substituent identity, substituent number, and substituent position affect THP-1(HAQ) activity (see pg. 99 for results from biological assay) across the full scope of the claimed genus.
The amount of direction or guidance present and the quantity of experimentation needed to make and use the invention based on the content of the disclosure
Although the specification provides synthetic procedures for the specific examples encompassed by the instant claims, it provides limited direction and guidance regarding which structural features are responsible for STING inhibitory activity and how modifications to the claimed variables affect such activity. For example, formula (I) permits R1, (R2 or R3), R4, R7, R8, R9, R10, R17, and R18 to be substituents selected from a broad list of chemical groups recited in instant claim 1. However, the working examples only show specific compounds wherein R1, (R2 or R3), R4, R7, R8, R9, R10, R17, and R18 are hydrogen only. The specification does not provide guidance regarding the effect of changing R1, (R2 or R3), R4, R7, R8, R9, R10, R17, or R18 to be a substituent other than hydrogen nor does it provide a structure-activity relationship that would allow a POSITA to predict whether compounds with other substituents (as defined in instant claim 1) would retain STING inhibitory activity.
Likewise, the specification does not provide guidance regarding how changes in the identity, position, and combination of substituents affect STING inhibitory activity. Variations in substituent number and placement can substantially alter steric properties, conformational preferences, electronic distribution, intermolecular interactions, and protein-binding characteristics. The specification does not identify which of these features are important for achieving the claimed activity, nor does it provide predictive principles by which a POSITA could distinguish operative compounds from inoperative compounds across the breadth of the claims.
Because the claims encompass numerous variables, each having multiple permissible values, the required experimentation would involve not merely routine verification of activity but extensive exploration of the claimed genus to identify operative species which involves undue experimentation. Although a POSITA possesses expertise in medicinal chemistry and organic synthesis, such expertise cannot substitute for the absence of guidance in the specification. The issue is not whether a POSITA is capable of synthesizing and testing compounds encompassed by the claims. Rather, the issue is that the specification provides insufficient information to identify which structural modifications (e.g., which combinations of substituents, substitution patterns, and number of substitution) preserve STING inhibitory activity and which modifications destroy such activity. Consequently, a POSITA would be required to undertake a substantial medicinal chemistry research program to establish the relevant structure-activity relationships before the full scope of the claimed genus could be practiced.
Furthermore, claim 29 encompasses prophylactic administration of the compounds of instant claim 1 to subjects who do not yet have any one of the diseases listed in instant claim 29 as a method to prevent the disease onset. The specification only contains in vitro reporter assay data obtained from cGAMP-stimulated THP1-Dual cells. The specification provides no in vivo prophylactic studies (e.g., no animal models evaluating prevention of disease onset), no identification of at-risk patient populations, and no evidence that administration of the disclosed compounds prior to disease onset prevents any of the diseases recited in instant claim 29. Therefore, the amount of experimentation required to identify whether prophylactic administration of a compound of instant claim 1 would prevent disease onset would be undue in view of the limited guidance provided in the specification, the absence of prophylactic administration efficacy data, the unpredictable nature of the invention, and the breadth of the diseases encompassed by the claims. Accordingly, the specification does not enable a method of preventing a disease as recited in instant claims 29 and 30.
Claims 2-4, 6, 8-11, 14-17, 19-20, 22, and 28-30, which are dependent on claim 1, are also rejected for further requiring and/or reciting elements that are outside the scope of the enabling elements listed above.
Written Description
Claims 1-4, 6, 8-11, 14-17, 19-20, 22, and 28-30 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.
The breadth of the claims
See “4. The breadth of the claims” subsection from the “Scope of Enablement” section discussed above.
The presence or absence of working examples
See “5. The presence or absence of working examples” subsection from the “Scope of Enablement” section discussed above.
State of the prior art and the predictability or lack thereof in the art
See the “2. State of the prior art and the predictability or lack thereof in the art” subsection from the “Scope of Enablement” section discussed above as well as the prior art discussed below:
Prior art referenced:
Hong et al. (Hong, Z. et al. STING inhibitors target the cyclic dinucleotide binding pocket. PNAS 2021, 118, e2105465118.; Published June 7, 2021 – see last line of 1st page)
Hong discloses that:
“Although several STING antagonists—including C-176, C-178, H-151, Astin C, compound 18, and endogenous nitro-fatty acids (NO2-FAs)—have been identified, they all have limited potential for therapeutic applications because of low affinity, inactivity against human STING, and probable lack of specificity” (pg. 2, left col., 1st paragraph, last sentence);
C-176 and C-178 are inactive against human STING and NO2-FAs, Astin C, and compound 18 have low bioactivity against human STING (see pg. 9, left col., 1st full paragraph, 1st sentence)
Therefore, Hong specifically states that “a specific STING inhibitor that binds to the STING CDN-binding pocket is a promising lead compound for STING-driven disease” (abstract, last sentence).
Therefore, Hong does not demonstrate that a compound exhibiting in vitro STING inhibitory activity, irrespective of its mechanism of inhibition, binding site, or level of inhibitory activity, necessarily translates into efficacy for the treatment of all of the STING-related diseases recited in instant claims 29 and 30.
The instant specification does not demonstrate that the inventor(s), at the time the application was filed, had possession of the claimed invention
According to MPEP § 2163:
“Satisfactory disclosure of a ‘representative number’ depends on whether one of skill in the art would recognize that the inventor was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are ‘representative of the full variety or scope of the genus,’ or by the establishment of ‘a reasonable structure-function correlation.’ Such correlations may be established ‘by the inventor as described in the specification,’ or they may be ‘known in the art at the time of the filing date.’ See AbbVie, 759 F.3d at 1300-01, 111 USPQ2d 1780, 1790-91 (Fed. Cir. 2014).
The instant specification does not reasonably convey to one of ordinary skill in the art that the inventor(s) were in possession of the full scope of the claimed genus of the compounds having STING antagonistic activity. The limited disclosure of a narrow subset of compounds in an unpredictable art does not adequately reflect the structural diversity of the claimed genus and, therefore, does not provide adequate written description of a genus which embraces widely variant species as explained in MPEP § 2163.
The instant specification also does not reasonably convey to one of ordinary skill in the art that the inventor(s) were in possession, as of the effective filing date, of methods for treating the full scope of the pathologically diverse diseases recited in instant claims 29 and 30.
Although Hong discloses C-176, C-178, H-151, Astin C, compound 18, and endogenous nitro-fatty acids (NO2-FAs) as known STING antagonists, Hong also states that “they all have limited potential for therapeutic applications because of low affinity, inactivity against human STING, and probable lack of specificity” (pg. 2, left col., 1st paragraph, last sentence). Therefore, the state of the prior art establishes that STING antagonistic activity alone is not reasonably predictive of therapeutic efficacy across different diseases. Thus, the prior art establishes that STING protein modulation does not necessarily translates into efficacy for the treatment of diseases such as those listed in instant claims 29 and 30.
In view of the state of the prior art, the instant specification’s disclosure of 37 specific compound examples and results from a reporter gene expression assay in THP-1 cells, without any experimental evidence demonstrating therapeutic efficacy or prevention for any of the numerous diseases recited in instant claims 29 and 30, does not reasonably convey to one of ordinary skill in the art that the inventors were in possession of methods for treating the full breadth of the claimed diseases.
Claims 2-4, 6, 8-11, 14-17, 19-20, 22, and 28-30, which are dependent on claim 1, are also rejected for further requiring and/or reciting non-enabling elements as described above.
Claim Rejections - 35 USC § 112(b)
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 4 and 6 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 claims 4 and 6, the phrase "preferably" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 6 further recites the variables “R20” and “R21.” However, these variables have not been previously introduced in claim 1 (i.e., wherein claim 6 is dependent upon) and are not defined in claim 6. Thus, there is insufficient antecedent basis for this limitation in the claim and the claim is rendered indefinite.
Note on 35 USC § 102 and § 103 Rejections
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.
Claim Rejections - 35 USC § 102
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.
Rejection Part 1:
Claims 1-4, 6, 8-11, 15, 16, 19, and 22 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by:
Laborde et al. (Laborde) (WO 02/070509 A2; published September 12, 2002)
Laborde discloses the following compound:
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(herein, referred to as Laborde-compound-141; see pg. 54, Table 8). Laborde-compound-141 is a compound of instant formula (I) wherein:
R4 = H
R5 = Me
X6 = CR7R8 (wherein R7 = R8 = H)
Z = CR9R10 (wherein R9 = R10 = H)
n = 1
X7 = O
X1 = CR1 (wherein R1 = H)
X2 = CR2 (wherein R2 = H)
X3 = CR3 wherein
R3 = -A-NR17-C(O)-NR18-R15
A = C1 alkylene substituted with an oxo
R17 = R18 = H
R15 = C6 aryl (i.e., phenyl) substituted with two Cl’s
and anticipates instant claims 1-4, 6, 8-11, 15, 16, and 19.
Laborde also discloses a pharmaceutical composition comprising Laborde-compound-141 (i.e., a compound of instant claim 1) and a pharmaceutically acceptable vehicle:
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(see example 10 on pg. 64). Therefore, Laborde also anticipates instant claim 22.
Rejection Part 2:
Claims 1-4, 6, 8-10, 17, 19, and 22 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by:
Laborde et al. (Laborde) (WO 02/070509 A2; published September 12, 2002)
Laborde also discloses the following compound:
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(herein, referred to as Laborde-compound-137; see pg. 54, Table 7). Laborde-compound-137 is a compound of instant formula (I) wherein:
R4 = R5 = H
X6 = (C=O)
Z = CR9R10 (wherein R9 = R10 = H)
n = 1
X7 = O
X1 = CR1 (wherein R1 = H)
X2 = CR2 (wherein R2 = H)
X3 = CR3 wherein
R3 = -A-NR17-C(O)-NR18-R15
A = C1 alkylene substituted with an oxo
R17 = R18 = H
R15 = C6 aryl (i.e., phenyl) substituted with one Cl
and anticipates instant claims 1-4, 6, 8-10, 17, and 19.
Laborde also discloses a pharmaceutical composition comprising Laborde-compound-137 (i.e., a compound of instant claim 1) and a pharmaceutically acceptable vehicle:
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(see example 10 on pg. 64). Therefore, Laborde also anticipates instant claim 22.
Rejection Part 3:
Claim 1-4, 6, 8-11, 14-17, and 19 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by:
Wu et al. (Wu) (Wu, Y.-J. et al. Bioorganic & Medicinal Chemistry Letters 2004, 14, 1991-1995.)
Wu teaches the following compound:
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(pg. 1992, scheme 2, compound 11) which is a compound of instant formula (I) wherein:
R4 = H
R5 = L1-L2-R16
wherein L1 = unsubstituted C1 alkylene
L2 = absent
R16 = unsubstituted C3 cycloalkyl
X6 = CR7R8 (wherein R7 = R8 = H)
Z = CR9R10 (wherein R9 = R10 = H)
n = 1
X7 = O
X1 = CR1 (wherein R1 = H)
X2 = CR2 (wherein R2 = H)
X3 = CR3 wherein
R3 = -A-NR17-C(O)-NR18-R15
A = C2 alkylene
R17 = R18 = H
R15 = C6 aryl (i.e., phenyl) substituted with two Cl’s.
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 29 and 30 are rejected under 35 U.S.C. 103 as being unpatentable over:
Laborde et al. (Laborde) (WO 02/070509 A2; published September 12, 2002)
Laborde discloses compounds that are encompassed by instant formula (I) (specifically: Laborde-compound-137 and Laborde-compound-141; see the “Claim Rejections - 35 USC § 102” section above for details). Laborde further teaches that compounds of the invention are useful in methods for treating chronic or acute inflammatory or autoimmune diseases such as asthma, atherosclerosis, diabetic nephropathy, glomerulonephritis, inflammatory bowel disease, Crohn's disease, multiple sclerosis, pancreatitis, pulmonary fibrosis, psoriasis, restenosis, rheumatoid arthritis, or a transplant rejection in mammals in need thereof (pg. 14, 3rd to last paragraph, paragraph starts with “A fourth embodiment…”; note: the diseases bolded and underlined are also recited in instant claims 29 and/or 30).
Thus, Laborde expressly teaches both:
compounds encompassed by instant formula (I) including Laborde-compound-137 and Laborde-compound-141, and
methods of treating pulmonary fibrosis, rheumatoid arthritis, or pancreatitis by administering “a therapeutically effective amount of at least one compound of this invention” to a subject (pg. 14, 3rd to last paragraph, paragraph starts with “A fourth embodiment…”).
Although Laborde does not explicitly disclose a method of treating pulmonary fibrosis, rheumatoid arthritis, or pancreatitis in a subject by administering a therapeutically effective amount of Laborde-compound-137 or Laborde-compound-141 to the subject, these two compounds are disclosed embodiments of “this invention.”
Accordingly, Laborde would have reasonably conveyed to one of ordinary skill in the art that Laborde-compound-137 and Laborde-compound-141 were suitable for use in the disclosed therapeutic methods. Therefore, a person of ordinary skill in the art would have found it prima facie obvious before the effective filing date of the claimed invention to administer compounds encompassed by instant formula (I), including Laborde-compound-137 and Laborde-compound-141, to a subject for the treatment of pulmonary fibrosis, rheumatoid arthritis, or pancreatitis in the subject.
A POSITA would have been motivated to administer Laborde-compound-137 or Laborde-compound-141 to a subject for the treatment of pulmonary fibrosis, rheumatoid arthritis, or pancreatitis in the subject because Laborde explicitly teaches that compounds of the invention are useful for treating pulmonary fibrosis, rheumatoid arthritis, or pancreatitis in a subject and identifies Laborde-compound-137 and Laborde-compound-141 as embodiments of those compounds.
Allowable Subject Matter
Claim 21 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims from which it depends.
Conclusion
Claims 1-4, 6, 8-11, 14-17, 19, 20, 22, and 28-30 are rejected. Claim 21 is objected to. Any inquiry concerning this communication or earlier communications from the examiner should be directed to KRISTEN ROMERO whose telephone number is (571)272-6478. The examiner can normally be reached M-F 9:30 AM - 6:00 PM ET.
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/KRISTEN W ROMERO/Examiner, Art Unit 1624
/JEFFREY H MURRAY/Supervisory Patent Examiner, Art Unit 1624
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