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 .
Status of the Claims and Response to Restriction Requirement
Claims 21-40 are pending as of the response filed 01/30/2026. Claims 1-20 are cancelled. Applicant’s election of a species of compound of formula I for use in a method of treating or preventing Dirofilaria infection/a disease or condition caused by Dirofilaria infection in a mammal shown below is acknowledged.
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Claims 21-38 and 40 encompass the elected species. Claim 39 is withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no allowable generic or linking claim. Claims 21-38 and 40 have been examined to the extent to which they are readable on the above identified elected species.
Because Applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Prior art that renders the use of the elected species in the method of the instant claims was found, as discussed below. In view of the pending claims, the following objections and rejections are made.
Priority
This application is a 371 of PCT/EP22/50922 filed 01/17/2022 and claims foreign priority to UNITED KINGDOM 2100635.8 filed 01/18/2021.
Acknowledgment is made of applicant's claim for foreign priority based on an application filed in the UNITED KINGDOM on 01/18/2021.
The subject matter of claims 21-38 and 40 are supported by the foreign application and accordingly, have an effective filing date of 01/18/2021.
Information Disclosure Statement
The information disclosure statements submitted on 03/20/2025, 12/20/2024, 04/08/2024 and 10/16/2023 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
References that have a strike through have not been considered either because they are illegible or irrelevant to the instant invention.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code on Pg. 89 and Pg. 91 of the instant specification (three hyperlinks total). 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
Claims 37-38 are objected to because of the following informalities:
In claim 37, the limitation “C3-6 cycloalkyl” in the definition of the variable “Rb and Re” is repeated twice. It is suggested that the second occurrence of “C3-6 cycloalkyl” be removed from the claim.
In claim 38, on page 13 of the claim set dated 01/30/2026, there is a numbering in the middle that appears to be extraneous (highlighted below) and should be removed.
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Each claim begins with a capital letter and ends with a period. See MPEP 608.01(m).
Appropriate correction is required.
Claim Rejections - 35 USC § 112 - Written Description
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 21-37 and 40 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.
Claim 21 and claim 29 are drawn to a method of treating or preventing a Dirofilaria infection/a disease or condition caused by a Dirofilaria infection in a mammal comprising administering to said mammal an effective amount of a compound of formula I, or a pharmaceutically acceptable salt or solvate thereof, wherein the variables are as defined in claims 21 and 29.
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The genus of compounds according to formula I claimed encompass a highly divergent variety of functional groups, which includes species that do not share both a substantial structural feature and a common function that flows from the substantial feature. For instance, Q is defined to be a group selected from an C3-11 cycloalkyl optionally substituted by one or more Rb, 3-15 membered heterocycloalkyl optionally substituted by one or more Rb, C6-11 aryl group optionally substituted with by one or more Rb, 5-15 membered heteroaryl optionally substituted by one or more Rb, wherein Rb is defined to be selected from hydroxyl, =O, halogen, CN, C1-6 haloalkyl,
C1-6 haloalkoxy, C1-6 alkyl, O-C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, -C(=O)Rd2, -C(=O)ORd2, -C(=O)NRc2Rd2, etc., wherein the C3-6 cycloalkyl, C1-6 alkyl, 3-7 membered heterocycloalkyl, are optionally further substituted. R7 and R7’ are defined to be selected from hydrogen, C3-6 cycloalkyl and C1-C6 alkyl, which can be optionally substituted by one or more Ra, wherein each Ra is independently selected from hydroxyl, halogen, CN, C1-6 haloalkyl,
C1-6 haloalkoxy, C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, wherein said C3-6 cycloalkyl, 3-7 membered heterocycloalkyl, can further be optionally substituted. Additionally, R7 and R7’, together with the carbon to which they are attached form a 3-7 membered cycloalkyl ring, optionally substituted with one or more Ra, or R7 and R7’, together with the carbon to which they are attached form a carbonyl group. The compounds further include a pharmaceutically acceptable salt or solvate thereof.
The myriad of compounds embraced by the claims would be presumed by one of ordinary skill in the art to have different physical properties (e.g. solubility, stability, etc.) that would lead to different activities (e.g. ADME and PK/PD, efficacy, toxicity, etc.). In consideration of the unpredictability in the field of filarial treatments driven by emerging parasite resistance, one of ordinary skill in the art would not expect this diverse array of compounds to show adequate anti-filarial activity against Dirofilaria infection. Specifically, the specification discloses the anti-filarial activity of a limited number of species of compounds of formula I. The instant specification discloses the efficacy of four compounds, Compounds A-D (Table A) against D. immitis L4 (Table 3A, Table 3B). The instant specification indicates the compounds of formula I and salts and solvates thereof may be prepared using synthetic techniques that are known in the art with PCT publication WO 2018/134685 incorporated by reference for methods of preparation.
These are not viewed as being reasonably representative of the genus of compounds in its claimed scope because no readily apparent combination of identifying characteristics is provided, other than the disclosure of those specific species as examples of the claimed genus for use in a method of treatment of Dirofilaria infection or diseases therefrom. It is not readily apparent that the genus of compounds according to formula I claimed have a structural entity in common, that leads to said anti-filarial activity.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the Application. Whether the specification shows that the inventor was in possession of the claimed invention is not a single, simple determination, but rather is a factual determination reached by considering a number of factors. Factors to be considered in determining whether there is sufficient evidence of possession include the level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. See MPEP 2163 (II) 3 (a) (i).
A chemical genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. If the genus has substantial variance, the disclosure must describe a sufficient number of species to reflect the variation within that genus. The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice (see i)(A) above), reduction to drawings (see i)(B) above), or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the inventor was in possession of the claimed genus (see i)(C) above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure "indicates that the patentee has invented species sufficient to constitute the gen[us]." See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615. "A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed. See MPEP 2163 (II) 3 (a) (ii).
In the instant case, there is no evidence Applicants had possession of the full genus of compounds according to formula I recited in the method claims at the time of filing, because the specification does not conclusively demonstrate the structure-activity relationship of the claimed vast array of compounds, towards their anti-filarial activity. The instant specification does not describe enough species of compounds having said anti-filarial activity within the scope of the claimed invention. Thus, the written description requirement for the claimed genus of anti-filarial compounds has not been met.
In response to this rejection, the Applicant can amend the claim(s) to recite only individual species or grouping of species that share a substantial structure as well as a common function that flows from the substantial structural feature, or present a sufficient showing that the species recited in the alternative of the claim(s) in fact share a common function that flows from the substantial structural feature.
Claims 22-28, 30-37 and 40 depend from the rejected base claim 21 AND claims 30-33 depend from the rejected base claim 29 and are similarly rejected.
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 21-37 and 40 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 21, the claim recites “R6 and R7, together with the atoms to which they are attached form a 3-7 membered heterocyclic ring”. The variable R6 is defined to be selected from hydrogen and C1-C6 alkyl; the variable R7 is defined to be selected from hydrogen, C3-6 cycloalkyl and C1-C6 alkyl, which can be optionally substituted. It is not clear how R6 and R7, together with the atoms to which they are attached can join to form a heterocyclic ring, when there are no options for heteroatoms present in R6 and R7. Therefore, the metes and bounds of the claim are indefinite. (note that the Para. [0040] of the instant specification defines “cycloalkyl” to refer to non-aromatic carbocyclic ring system).
Moreover, claim 21 defines in the last section of the claim, “R3, R4 and R5 are independently selected from hydrogen, hydroxyl, …”. R3 does not appear to be a variable present within the structure of formula I, further rendering the scope of the claim indefinite.
Claims 22-28, 34-37 and 40 depend from claim 21 and are similarly rejected.
Regarding claim 29, the claim recites “R6 and R7, together with the atoms to which they are attached form a 3-7 membered heterocyclic ring”. The variable R6 is defined to be selected from hydrogen and C1-C6 alkyl; the variable R7 is defined to be selected from hydrogen, C3-6 cycloalkyl and C1-C6 alkyl, which can be optionally substituted. It is not clear how R6 and R7, together with the atoms to which they are attached can join to form a heterocyclic ring, when there are no options for heteroatoms present in R6 and R7. Therefore the metes and bounds of the claim are indefinite. (note that the Para. [0040] of the instant specification defines “cycloalkyl” to refer to non-aromatic carbocyclic ring system).
Moreover, claim 29 defines in the last section of the claim, “R3, R4 and R5 are independently selected from hydrogen, hydroxyl, …”. R3 does not appear to be a variable present within the structure of formula I, further rendering the scope of the claim indefinite.
Claims 30-33 depend from claim 29 and are similarly rejected.
For the purpose of applying prior art, claim 21 and claim 29 have been interpreted to read without the limitation “R6 and R7, together with the atoms to which they are attached form a 3-7 membered heterocyclic ring” and the variable R3 appearing in the claims.
Regarding claim 32, the claim recites “wherein the disease or condition is selected from heartworm associated respiratory disease (HARD)”. It is unclear if other diseases were intended to be included within the scope of the claim. Therefore, the metes and bounds of the claim are indefinite.
For the purpose of applying prior art, claim 32 has been interpreted to read “wherein the disease or condition is [[selected from ]]heartworm associated respiratory disease (HARD)”.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 37 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Regarding claim 37, the claim depends from claim 21 and recites “R7 is selected from hydrogen, =O, C3-6 cycloalkyl, C1-6 alkyl, …”. However, claim 21 does not allow for R7 to be =O. This broadens the scope of the claim, which is improper.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 21-23, 26-31, 33-38 and 40 are rejected under 35 U.S.C. 103 as being unpatentable over Ward et al. (WO 2018/134685 A2, 26 July 2018, hereinafter Ward, in the IDS) in view of Bakowski et al. (Advances in Antiwolbachial Drug Discovery for Treatment of Parasitic Filarial Worm Infections, 18 July 2019, hereinafter Bakowski, in the IDS).
Regarding instant claims 21-23, 26-27, 29, 33 and 37-38, Ward teaches compounds of Formulae (I) and (II) and salts and solvates thereof for use in a method of the treatment or prevention of filarial worm infection, as well as other diseases or conditions in which filarial worm infection is implicated (Abstract; Para. [0004]; Para. [0031]), with variables as defined (Para. [0065]).
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Ward teaches an embodiment of a method of treating or preventing a filarial worm infection in a subject, said method comprising administering to a subject a therapeutically effective amount of a compound of Formula I or Formula II or a salt or solvate thereof (Para. [0066], paragraph 89; Para. [00107]). Ward teaches an embodiment of a method of treating or preventing a disease or condition mediated by a filarial worm infection, said method comprising administering to a subject in need thereof a therapeutically effective amount of a compound of Formula II or a salt or solvate thereof (Para. [0066], paragraph 91; Para. [00108]). Ward teaches the subject refers to a mammal, in particular humans (Para. [0059]). Ward teaches an exemplary compound of Formula II, N2-isopropyl-N2-methyl-N4-((2-(trifluoromethyl)pyridin-3-yl)methyl)pyrido[2,3-d]pyrimidine-2,4-diamine, Compound 162 (Para. [0066], paragraph 76 (page 49); Table 1 (page 144)) having the following structure.
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Compound 162 of Ward falls within the scope of formula I of instant claims 21 and 29, and represents the instantly elected species of compound, wherein,
Q is C5-15 membered heteroaryl (pyridinyl) substituted with one Rb, Rb being C1-6 haloalkyl (CF3);
n is 1;
R6 is hydrogen;
R7 and R7’ are each hydrogen;
R4 and R5 are each hydrogen;
R2 is NRc1Rd1, Rc1 and Rd1 are both C1-6 alkyl (methyl and isopropyl).
Compound 62 further reads on the limitations of claims 37 and 38.
Ward teaches Compound 162 showed excellent anti-Wolbachia activity with an EC50 of 1nM-10nM (Para. [00189], Table 2 (page 220)).
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Ward teaches the mesylate salt of Compound 162 brought about a 99.99% reduction of Wolbachia in a Brugia malayi larval infection model (Para. [00196], Table 4) and a 99.4% reduction of Wolbachia in a Brugia malayi adult infection model (Para. [00198], Table 5A).
Ward do not teach treating or preventing a Dirofilaria infection OR treating or preventing a disease or condition caused by a Dirofilaria infection.
Bakowski teaches that in infected filarial nematode species, Wolbachia is a genus of gram-negative bacteria, which is a maternally inherited endosymbiont required by the worms for their viability and reproduction (Pg. 6, last paragraph; Pg. 8, second paragraph). Bakowski teaches optimizing antiwolbachial therapy through drug discovery efforts as a promising option to treat filarial infections (Abstract). Bakowski teaches parasitic filarial nematodes pertinent to the antiwolbachial approach to include Dirofilaria immitis and Dirofilaria repens (Table 1). Bakowski teaches Wolbachia strains of filarial nematodes of clinical relevance and ones used for antiwolbachial drug discovery include Dirofilaria immitis (Table 4). Bakowski teaches a concerted effort has been undertaken to identify shorter, safer and more effective antiwolbachial therapies for the treatment of filarial infections (Pg. 9, continued paragraph).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, in view of the teachings of Ward and Bakowski, to have modified the method of Ward to treat a mammal afflicted with a Dirofilaria infection, specifically, a D. immitis or D. repens infection, to arrive at the method of the instant claims with a reasonable expectation of success. Ward teaches a method of the treatment or prevention of filarial worm infection, as well as other diseases or conditions in which filarial worm infection is implicated comprising administering to a subject a therapeutically effective amount of a compound of Formula I or Formula II or a salt or solvate thereof. Ward teaches the subject refers to a mammal, in particular humans. Ward teaches an exemplary compound of Formula II, Compound 162 (the instantly elected species of compound). Ward teaches Compound 162 showed excellent anti-Wolbachia activity with an EC50 of 1nM-10nM. Ward teaches the mesylate salt of Compound 162 brought about a 99.99% reduction of Wolbachia in a Brugia malayi larval infection model and a 99.4% reduction of Wolbachia in a Brugia malayi adult infection model. Bakowski teaches that in infected filarial nematode species, Wolbachia is a genus of gram-negative bacteria, which is a maternally inherited endosymbiont required by the worms for their viability and reproduction. Bakowski teaches optimizing antiwolbachial therapy through drug discovery efforts as a promising option to treat filarial infections. Bakowski teaches parasitic filarial nematodes pertinent to the antiwolbachial approach to include Dirofilaria immitis and Dirofilaria repens. Bakowski teaches a concerted effort has been undertaken to identify shorter, safer and more effective antiwolbachial therapies for the treatment of filarial infections.
Therefore, one of ordinary skill in the art would have been motivated to apply the method of Ward that results in significant antiwolbachial activity in a mammal afflicted with a filarial nematode, in the treatment or prevention of a Dirofilaria infection, specifically, a D. immitis or D. repens infection, with a reasonable expectation of success in treating such a condition. The motivation being to provide shorter, safer and more effective antiwolbachial therapies for the treatment of filarial infections (Bakowski, Pg. 9, continued paragraph).
Therefore, the combined teachings of Ward and Bakowski render the method of instant claims 21-23, 26-27, 29, 33 and 37-38, prima facie obvious.
Regarding instant claims 28 and 30-31, the combined teachings of Ward and Bakowski render the method of treating or preventing a Dirofilaria infection OR treating or preventing a disease or condition caused by a Dirofilaria infection, as in instant claims 21 and 29, respectively, prima facie obvious.
Ward does not teach wherein the mammal is a dog; wherein the disease or condition is selected from heartworm disease (HWD), heartworm associated respiratory disease (HARD) or a dermatological condition and the mammal is a dog.
Bakowski teaches the disease caused by D. immitis or D. repens infection is known as dirofilariasis/dirofilariosis, aka. heartworm disease (Table 1). Bakowski teaches the common host for the D. immitis or D. repens nematodes are companion animals such as dogs, cats, ferrets and wild animals such as wolves, coyotes, foxes, pinnipeds, raccoons (Table 1). Bakowski teaches the antiwolbachial approach has been applied to the treatment of heartworm infections in dogs (Pg. 9, continued paragraph; Table 4).
Given the teachings of Ward and Bakowski, it would have been prima facie obvious to one of ordinary skill in the art to have applied the method of Ward in the treatment of heartworm disease in dogs. The motivation being to broaden the scope of antiwolbachial treatment to the treatment of Dirofilaria infection in other mammals.
Regarding instant claims 34-35, the combined teachings of Ward and Bakowski render the method of treating or preventing a Dirofilaria infection, as in instant claim 21, prima facie obvious. Ward teaches that dosages and dosing regimens may vary with the type and severity of the condition to be alleviated, and may include the administration of single or multiple doses, i.e. QD (once daily), BID (twice daily), etc., over a particular period of time (days or hours) (Para. [0097]; Paras. [00195]-[00198]). Ward teaches appropriate dosage(s) and dosing regimen(s) are well-known in the relevant art and would readily be ascertained by the skilled artisan (Para. [0097]). Ward teaches there is a need for alternative and/or improved anti-Wolbachia treatments, such as those providing a shorter treatment regimen (e.g., 7 days or less) (Para. [0018]).
According to MPEP 2144.05(II)(A), "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Therefore, it would have taken no more than the relative skills of one of ordinary skill in the art through routine experimentation to have arrived at the claimed treatment regimen of 7 consecutive days per month or less OR 1 or 2 consecutive days per month or less, in the absence of any criticality of these regimens.
Regarding instant claim 36, the combined teachings of Ward and Bakowski render the method of treating or preventing a Dirofilaria infection, as in instant claim 21, prima facie obvious. Ward teaches the compounds may be administered orally (Paras. [0092]-[0093]; Para. [0123] Paras. [00195]-[00198]).
Regarding instant claim 40, the combined teachings of Ward and Bakowski render the method of treating or preventing a Dirofilaria infection, as in instant claim 21, prima facie obvious. Ward teaches a combination composition with one or more additional therapeutic agents (Para. [0029]; Para. [0031]). Bakowski teaches current treatments against filarial worms (ivermectin, diethylcarbamazine (DEC), albendazole), alone or in combination, are only partially effective against the long-lived macrofilariae (Pg. 4, last paragraph). Bakowski teaches additional microfilaricidal agents serve as important transmission-blocking preventive chemotherapies (Pg. 4, last paragraph). Therefore, it would have been prima facie obvious to one of ordinary skill in the art to have used combination therapy as instantly claimed, for effective filarial worm treatments.
Claims 24-25 and 32 are rejected under 35 U.S.C. 103 as being unpatentable over Ward et al. (WO 2018/134685 A2, 26 July 2018, hereinafter Ward, in the IDS) in view of Bakowski et al. (Advances in Antiwolbachial Drug Discovery for Treatment of Parasitic Filarial Worm Infections, 18 July 2019, hereinafter Bakowski, in the IDS) as applied to claims 21-23, 26-31, 33-38 and 40 above, and further in view of Bondesen et al. (WO 2016/161369 A1, 06 October 2016, hereinafter Bondesen).
The teachings of Ward and Bakowski are set forth in the obviousness rejection above and incorporated herein by reference.
Regarding instant claims 24-25, the combined teachings of Ward and Bakowski render the method of treating or preventing a Dirofilaria infection, as in instant claim 21, prima facie obvious.
Ward do not teach wherein the Dirofilaria infection is infection with Dirofilaria microfilariae, Dirofilaria third stage (L3) larvae, Dirofilaria fourth stage (L4) larvae, Dirofilaria fifth stage (L5) larvae, an adult dirofilarial worm or a combination thereof; wherein the Dirofilaria infection is infection with D. immitis microfilariae (mf), L3 larvae, L4 larvae or a combination thereof.
Bakowski teaches the general filarial worm life cycle and infection biology to involve microfilariae and infectious larvae (Pg. 4, second paragraph).
Bondensen teaches one type of endoparasite which seriously harms mammals is Dirofilaria immitis, also known as heartworm, mainly affecting dogs and cats. Bondensen teaches the infection biology of D. immitis to involve the third-stage larva (L3), fourth-stage larva (L4) and microfilariae (or LI) (Pg. 1, last paragraph – Pg. 2, continued paragraph). Bondensen teaches heartworm infection is a severe and life-threatening disease transmitted by mosquitoes. Bondensen teaches preventative therapy by interrupting the third-stage larva (L3), as well as the young and maturing fourth-stage larva (L4) development is widely used and prioritized, over the costly and risky treatment (Pg. 2, first full paragraph; Claim 22).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, in view of the teachings of Ward, Bakowski and Bondensen, to have specifically targeted the larval or microfilarial stages of the D. immitis infection, to arrive at the instant method claims with a reasonable expectation of success. The motivation being to kill the larval stages of D. immitis so that they do not mature into adult worms (Claim 22).
Regarding instant claim 32, the combined teachings of Ward and Bakowski render the method of treating or preventing a disease or condition caused by a filarial worm infection, as in instant claim 29, prima facie obvious.
Ward and Bakowski do not teach wherein the disease or condition is selected from heartworm associated respiratory disease (HARD) and the mammal is a cat.
Bakowski teaches the common host for the D. immitis or D. repens nematodes are companion animals such as dogs, cats, ferrets and wild animals such as wolves, coyotes, foxes, pinnipeds, raccoons (Table 1).
Bondensen teaches treating parasitic infection in dogs and cats (Pg. 15, seventh paragraph) and wherein the parasitic infection causes heartworm associated respiratory disease in the mammal (Pg. 16, second full paragraph; Claim 23).
Given the teachings of Ward, Bakowski and Bondensen, it would have been prima facie obvious to one of ordinary skill in the art to have applied the method of Ward in the treatment of heartworm associated respiratory disease in cats. The motivation being to broaden the scope of antiwolbachial treatment to the treatment of Dirofilaria infection in other mammals.
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 21-37 and 40 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-4, 7-8 and 10 of U.S. Patent No. 12,545,675 B2 in view of Ward et al. (WO 2018/134685 A2, 26 July 2018, hereinafter Ward, in the IDS), Bakowski et al. (Advances in Antiwolbachial Drug Discovery for Treatment of Parasitic Filarial Worm Infections, 18 July 2019, hereinafter Bakowski, in the IDS) and Bondesen et al. (WO 2016/161369 A1, 06 October 2016, hereinafter Bondesen).
Although the claims at issue are not identical, they are not patentably distinct from each other because both set of claims are drawn to a pyrido[2,3-d]pyrimidine compound with substantial overlap in scope.
The instant claims are drawn to a method of treating or preventing a Dirofilaria infection in a mammal/a disease or condition caused by a Dirofilaria infection, comprising administering to a subject an effective amount of a compound of formula I, or a pharmaceutically acceptable salt or solvate thereof.
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The claims of the reference ‘675 patent are drawn to a compound of formula I or a salt or solvate thereof.
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The compounds of the reference patent and the compounds of the instant claims are obvious variants of each other because there is substantial overlap in the scope of the R2, R4, R5, R6, R7, R7’ and Q variables.
The claims of the reference ‘675 patent do not teach a method of treating or preventing a filarial worm infection in a subject, said method comprising administering to a subject a therapeutically effective amount of a compound, or a pharmaceutically acceptable salt or solvate thereof OR a method of treating or preventing a disease or condition mediated by a filarial worm infection, said method comprising administering to a subject in need thereof a therapeutically effective amount of a compound, or a pharmaceutically acceptable salt or solvate thereof and the limitations of the dependent claims.
Ward teaches compounds of Formulae (I) and (II) and salts and solvates thereof for use in a method of the treatment or prevention of filarial worm infection, as well as other diseases or conditions in which filarial worm infection is implicated (Abstract; Para. [0004]; Para. [0031]), with variables as defined (Para. [0065]). The compounds of Ward anticipate the instant compounds. Ward teaches the compounds showed excellent anti-Wolbachia activity for an exemplary compound, Compound 162, with an EC50 of 1nM-10nM (Para. [00189], Table 2 (page 220)). Ward teaches that dosages and dosing regimens may vary with the type and severity of the condition to be alleviated, and may include the administration of single or multiple doses, i.e. QD (once daily), BID (twice daily), etc., over a particular period of time (days or hours) (Para. [0097]; Paras. [00195]-[00198]). Ward teaches appropriate dosage(s) and dosing regimen(s) are well-known in the relevant art and would readily be ascertained by the skilled artisan (Para. [0097]). Ward teaches there is a need for alternative and/or improved anti-Wolbachia treatments, such as those providing a shorter treatment regimen (e.g., 7 days or less) (Para. [0018]).
According to MPEP 2144.05(II)(A), "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Therefore, it would have taken no more than the relative skills of one of ordinary skill in the art through routine experimentation to have arrived at the claimed dosage regimen.
Bakowski teaches that in infected filarial nematode species, Wolbachia is a genus of gram-negative bacteria, which is a maternally inherited endosymbiont required by the worms for their viability and reproduction (Pg. 6, last paragraph; Pg. 8, second paragraph). Bakowski teaches optimizing antiwolbachial therapy through drug discovery efforts as a promising option to treat filarial infections (Abstract). Bakowski teaches parasitic filarial nematodes pertinent to the antiwolbachial approach to include Dirofilaria immitis and Dirofilaria repens (Table 1). Bakowski teaches Wolbachia strains of filarial nematodes of clinical relevance and ones used for antiwolbachial drug discovery include Dirofilaria immitis (Table 4). Bakowski teaches a concerted effort has been undertaken to identify shorter, safer and more effective antiwolbachial therapies for the treatment of filarial infections (Pg. 9, continued paragraph). Bakowski teaches the disease caused by D. immitis or D. repens infection is known as dirofilariasis/dirofilariosis, aka. heartworm disease (Table 1). Bakowski teaches the common host for the D. immitis or D. repens nematodes are companion animals such as dogs, cats, ferrets and wild animals such as wolves, coyotes, foxes, pinnipeds, raccoons (Table 1). Bakowski teaches the antiwolbachial approach has been applied to the treatment of heartworm infections in dogs (Pg. 9, continued paragraph; Table 4). Bondensen teaches one type of endoparasite which seriously harms mammals is Dirofilaria immitis, also known as heartworm, mainly affecting dogs and cats.
Bondensen teaches the infection biology of D. immitis to involve the third-stage larva (L3), fourth-stage larva (L4) and microfilariae (or LI) (Pg. 1, last paragraph – Pg. 2, continued paragraph). Bondensen teaches preventative therapy by interrupting the third-stage larva (L3), as well as the young and maturing fourth-stage larva (L4) development is widely used and prioritized, over the costly and risky treatment (Pg. 2, first full paragraph; Claim 22). Bondensen teaches treating parasitic infection in dogs and cats (Pg. 15, seventh paragraph) and wherein the parasitic infection causes heartworm associated respiratory disease in the mammal (Pg. 16, second full paragraph; Claim 23).
Given the teachings of the reference ‘675 patent, Ward, Bakowski and Bondensen, it would have been prima facie obvious to have applied the method of the reference ‘760 patent in the treatment of Dirofilaria infection OR a diseases caused by a Dirofilaria infection. The motivation being to broaden the scope of antiwolbachial treatment in the treatment of Dirofilaria infection in other mammals.
As discussed in the 103 rejection above, all dependent instant claims are rendered prima facie obvious in view of the reference ‘675 patent, Ward, Bakowski and Bondensen.
The instant claims 21-37 and 40 and claims 1, 3-4, 7-8 and 10 of U.S. Patent No. 12,545,675 B2 are therefore not patentably distinct.
This is a nonstatutory double patenting rejection.
Claims 21-38 and 40 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 7, 9, 13 and 16 of U.S. Patent No. 11,518,760 B2 in view of Bakowski et al. (Advances in Antiwolbachial Drug Discovery for Treatment of Parasitic Filarial Worm Infections, 18 July 2019, hereinafter Bakowski, in the IDS), Bondesen et al. (WO 2016/161369 A1, 06 October 2016, hereinafter Bondesen) and Ward et al. (WO 2018/134685 A2, 26 July 2018, hereinafter Ward, in the IDS).
Although the claims at issue are not identical, they are not patentably distinct from each other because both set of claims are drawn to a method of treating or preventing a filarial worm infection in a subject, said method comprising administering to a subject a therapeutically effective amount of a compound, or a pharmaceutically acceptable salt or solvate thereof OR a method of treating or preventing a disease or condition mediated by a filarial worm infection, said method comprising administering to a subject in need thereof a therapeutically effective amount of a compound, or a pharmaceutically acceptable salt or solvate thereof, wherein the compound is a pyrido[2,3-d]pyrimidine compound.
The instant claims are drawn to a method of treating or preventing a Dirofilaria infection in a mammal/a disease or condition caused by a Dirofilaria infection, comprising administering to a subject an effective amount of a compound of formula I, or a pharmaceutically acceptable salt or solvate thereof.
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The claims of the reference ‘760 patent are drawn to a method of treating or preventing a filarial worm infection in a subject/a disease or condition mediated by a filarial worm infection in a subject, said method comprising administering to a subject a therapeutically effective amount of a compound of formula Ia, or a pharmaceutically acceptable salt or solvate thereof.
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Claim 7 and claim 16 of the reference ‘760 patent anticipates a species of compound recited in instant claim 38.
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According to MPEP 2112.01(II), “Products of identical chemical composition can not have mutually exclusive properties.” Any properties exhibited by or benefits from are not given any patentable weight over the prior art provided the composition is inherent. A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the disclosed properties are necessarily present. In re Spada, 911 F.2d 705, 709, 15 USPQ 1655, 1658 (Fed. Cir. 1990). Thus, the above species of compound, by virtue of its inherent property exhibits antiwolbachial activity.
The claims of the reference ‘760 patent do not teach the infection to be a Dirofilaria infection, wherein the Dirofilaria infection is infection with one or more parasite selected from D. immitis, D. repens and D. tenuis or the limitations of dependent claims.
Bakowski teaches that in infected filarial nematode species, Wolbachia is a genus of gram-negative bacteria, which is a maternally inherited endosymbiont required by the worms for their viability and reproduction (Pg. 6, last paragraph; Pg. 8, second paragraph). Bakowski teaches optimizing antiwolbachial therapy through drug discovery efforts as a promising option to treat filarial infections (Abstract). Bakowski teaches parasitic filarial nematodes pertinent to the antiwolbachial approach to include Dirofilaria immitis and Dirofilaria repens (Table 1). Bakowski teaches Wolbachia strains of filarial nematodes of clinical relevance and ones used for antiwolbachial drug discovery include Dirofilaria immitis (Table 4). Bakowski teaches a concerted effort has been undertaken to identify shorter, safer and more effective antiwolbachial therapies for the treatment of filarial infections (Pg. 9, continued paragraph). Bakowski teaches the disease caused by D. immitis or D. repens infection is known as dirofilariasis/dirofilariosis, aka. heartworm disease (Table 1). Bakowski teaches the common host for the D. immitis or D. repens nematodes are companion animals such as dogs, cats, ferrets and wild animals such as wolves, coyotes, foxes, pinnipeds, raccoons (Table 1). Bakowski teaches the antiwolbachial approach has been applied to the treatment of heartworm infections in dogs (Pg. 9, continued paragraph; Table 4).
Bondensen teaches one type of endoparasite which seriously harms mammals is Dirofilaria immitis, also known as heartworm, mainly affecting dogs and cats. Bondensen teaches the infection biology of D. immitis to involve the third-stage larva (L3), fourth-stage larva (L4) and microfilariae (or LI) (Pg. 1, last paragraph – Pg. 2, continued paragraph). Bondensen teaches preventative therapy by interrupting the third-stage larva (L3), as well as the young and maturing fourth-stage larva (L4) development is widely used and prioritized, over the costly and risky treatment (Pg. 2, first full paragraph; Claim 22). Bondensen teaches treating parasitic infection in dogs and cats (Pg. 15, seventh paragraph) and wherein the parasitic infection causes heartworm associated respiratory disease in the mammal (Pg. 16, second full paragraph; Claim 23).
Ward teaches that dosages and dosing regimens may vary with the type and severity of the condition to be alleviated, and may include the administration of single or multiple doses, i.e. QD (once daily), BID (twice daily), etc., over a particular period of time (days or hours) (Para. [0097]; Paras. [00195]-[00198]). Ward teaches appropriate dosage(s) and dosing regimen(s) are well-known in the relevant art and would readily be ascertained by the skilled artisan (Para. [0097]). Ward teaches there is a need for alternative and/or improved anti-Wolbachia treatments, such as those providing a shorter treatment regimen (e.g., 7 days or less) (Para. [0018]).
According to MPEP 2144.05(II)(A), "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Therefore, it would have taken no more than the relative skills of one of ordinary skill in the art through routine experimentation to have arrived at the claimed dosage regimen.
Given the teachings of the reference ‘760 patent and Bakowski, it would have been prima facie obvious to have applied the method of the reference ‘760 patent in the treatment of a Dirofilaria infection or a disease or condition caused by a Dirofilaria infection. The motivation being to broaden the scope of antiwolbachial treatment in the treatment of Dirofilaria infection in other mammals.
As discussed in the 103 rejection above, all dependent instant claims are rendered prima facie obvious in view of the reference ‘760 patent, Bakowski, Bondensen and Ward.
The instant claims 21-38 and 40 and claims 7, 9, 13 and 16 of U.S. Patent No. 11,518,760 B2 are therefore not patentably distinct.
This is a nonstatutory double patenting rejection.
Miscellaneous
The examiner would like to bring Applicant’s attention to the following:
An inventor’s oath or declaration signed by the inventors is not present in the application file.
A power of attorney document is not present in the application file.
Conclusion
Claims 21-38 and 40 are rejected.
Claims 37-38 are objected to.
No claims are allowed.
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/PADMAJA S RAO/Examiner, Art Unit 1627