DETAILED ACTION
The present application is a national stage entry of PCT/EP2022/070898, filed 26 July 2022, which claims foreign priority to EP21188311.1, filed 28 July 2021.
The preliminary amendment filed 15 August 2024 is acknowledged. Claims 1-17 are pending in the current application.
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 Velagliflozin as a First species of SGLT-2 inhibitor; heart failure due to (myxomatous) mitral valve disease [(M)MVD] as a second species of cardiac diseases; and pimobendan as a third species of active pharmaceutical ingredients in the reply filed on 28 May 2026 is acknowledged. The traversal is on the ground(s) that searching all the designated species would not be an undue burden.
This is not found persuasive because a search burden is not a requirement when making a restriction between multiple inventions in a 35 U.S.C. §371 application.
The requirement is still deemed proper and is therefore made FINAL.
Although the elected species of Velagliflozin as a species of SGLT-2 inhibitor is rejected under 35 U.S.C. §102(a)(1)/(a)(2) and 35 U.S.C. §103(a), to advance prosecution of this application, the Examiner has included a search of Bexagliflozin as a species of SGLT-2 inhibitor.
Due to the indefiniteness of the elected species of “heart failure due to (myxomatous) mitral valve disease [(M)MVD]” (see rejection under 35 U.S.C. §112b, below), the Examiner has included a search of the species heart failure due to mitral valve disease and heart failure due to myxomatous mitral valve disease as a species of heart failure.
Claim Objections
Claim 6 is objected to because of the following informalities:
It is respectfully suggested that the compounds recited in claim 6 be separated by semi-colons. The structure for some of the compounds are difficult to read, especially the compound of formulas (4), (6), (10), (16) and (20). Increasing the size of the font of the atoms may improve the readability of the structures.
The compound of formula (21) is easy to read. Thus, whatever method was used to insert the compound of formula (21) might help improve the readability of the formulas identified above.
It is noted that compound of formula (22) in claim 6 is missing. It is not required, however, it is recommended the claim include it to be consistent with the other compounds listed.
The recitation “(7-1)” and “(9-1)” in claim 6 seems to be in error.
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.
Claims 1-17 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 treating one or more cardiac diseases in a canine, does not reasonably provide enablement for treating any non-human mammal, or preventing one or more cardiac diseases in a non-human mammal. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The Applicant’s attention is drawn to In re Wands, 8 USPQ2d 1400 (CAFC1988) at 1404 where the court set forth eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors: (1) The nature of the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary.
The nature of the invention: The nature of the invention is administering an SGLT-2 inhibitor for the treatment of heart failure in canine.
The state of the prior art: Prevent is defined as “keep from happening or existing”. See provided definition of prevent (definition of prevent, Merriam-Webster, cited in PTO-892). There is no prior art disclosing how to keep heart failure from happening.
The relative skill of those in the art: The relative skill of those in the art in treating the claimed conditions is high.
The predictability or unpredictability of the art: Each of the claimed conditions have multiple possible causes.
Risk factors for heart failure include diabetes, congenital heart disease, viral infections, certain medications, and aging (Mayo Clinic, “Heart failure”, cited in PTO-892).
Thus, the risk factors for the claimed disorders/conditions vary. They include additional factors that cannot necessarily be changed or controlled, e.g. medications, diabetes, congenital heart disease, and aging. Thus, it is not deemed possible to prevent the claimed conditions, let alone with a single composition.
The breadth of the claims: The breadth of the claims includes preventing heart failure.
The amount of direction or guidance presented: The presence or absence of working examples: There is no teaching or guidance on how one would administer the claimed composition to prevent heart failure.
(8) The quantity of experimentation necessary: In order to practice the invention with the full range of all possible treatment methods beyond those known in the art, one skilled in the art would undertake a novel and extensive research program to show any and all forms of heart disease could be prevented.
In order to determine the efficacy of the claimed therapies in the absence of any existing in vivo data, one skilled in the art would undertake animal testing in order to practice the invention. Animal experiments include, induction of the disease state, administration of the potential pharmaceutical compound and collection and analysis of data, additional burdens associated with compliance with animal welfare regulations, care, feeding and other maintenance of the animals, dissection of dead animals to collect data, and dispose of the dead animals after the research is finished. These trials would need to be run separately and repeatedly for each disorder to be treated, and success in treating each and every disorder would still not be definitive. The experimentation involved would therefore be significant, undue and unpredictable.
Genentech, 108 F.3d at 1366, sates that, “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion.” And “patent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable.”
Therefore, in view of the Wands factors, as discussed above, particularly the breadth of the claims, Applicants fail to provide information sufficient to practice the claimed invention for preventing a cardiac disease in a non-human mammal.
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 2-4, 6, 7, and 13-15 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.
With respect to claims 2-4, the term “myxomatous” is always used inside parenthesis. It is unclear if the claims are drawn towards mitral valve disease AND myxomatous mitral valve disease, or simply myxomatous valve disease. One of ordinary skill in the art would not be appraised of the metes and bounds of the conditions being treated.
Similarly, the term “aortic stenosis (valvular, supravalvular and/or subvalvular)” in claim 2 should be amended to recite each term without parenthesis. As written, it is unclear if the claim includes any form of aortic stenosis, or if it requires it to be selected from aortic valvular stenosis, supravalvular aortic stenosis, and/or subvalvular aortic stenosis. The parenthesis should be removed (except in the case where it is the first instance of an abbreviation). The conditions could be written out as aortic stenosis, aortic valvular stenosis, supravalvular aortic stenosis, and/or subvalvular aortic stenosis.
Claim 14 similarly recites “(low molecular weight) heparin”. It is unclear if the claim is directed to heparin, and/or low molecular weight heparin, or just low molecular weight heparin.
Claim 15 recites “characterized by an increased ratio of [cardiac output/metabolic substrate consumed]”, “[cardiac output/oxygen consumed]”; “i.e. hydroxybutyrylcarnitine”, “amino acids (valine, leucine and isoleucine)”, etc. Claim 15 uses parenthesis, “i.e.”, “e.g.”, and “such as” throughout the claim, all of which render the claim herein indefinite.
In claim 6, for formula (14), the recitation “wherein R denotes methoxy, trifluoromethoxy, ethoxy, ethyl, isopropyl or tert. butyl;” renders the claim herein indefinite. It appears the claim ends after “tert”. This period should be deleted. “Each claim begins with a capital letter and ends with a period. Periods may not be used elsewhere in the claims except for abbreviations. See Fressola v. Manbeck, 36 USPQ2d 1211 (D.D.C. 1995)”. See MPEP 608.01 (m).
In claim 6, the structure of formula (11A) is missing hydrogen atoms for the hydroxy groups of the carbohydrate at the C2, C3 and C4 positions; the structure of formula (16) is missing hydrogen atoms for the hydroxy groups of the carbohydrate at the C2, C3 and C4 positions; the structure of formula (19) is missing hydrogen atoms for the hydroxy groups of the carbohydrate at the C2, C3, C4 and C6 positions;
Regarding claims 7, 14 and 15, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 13 refers to claim 12 and claim 1. It is unclear which claim it actually refers to, since this appears to be in error.
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(s) 1, 5-12 and 14-17 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Hadd et al. (WO2021/092341, cited in Office Action mailed 21 April 2026).
Hadd et al. teach a method for treating heart failure (HF) in a companion animal, comprising administering to the companion animal in need thereof a therapeutically effective amount of a compound that inhibits a sodium-dependent glucose transporter (SGLT) or prodrug thereof (claim 1). The companion animal is a canine (claim 10). The companion animal is a canine with HF, wherein the canine is diagnosed with mitral valve disease (MVD), (claim 16). The most common form of MVD in dogs is a chronic condition called myxomatous degeneration (para [0059]). The total daily dosage ranges from 10-4,000 µg/kg, which is equivalent to 0.01 mg to 4 mg/kg (claim 11). The total daily dosage is 1,000 µg/kg, which is equivalent to 1 mg/kg (claim 14). The total daily dosage is selected from 50 µg/kg, 100 µg/kg, 200 µg/kg, 400 µg/kg, 800 µg/kg, 1,000 µg/kg, 1,600 µg/kg, and 3,200 µg/kg (claim 13). The composition can be administered one to four times a day (claims 32-35). The composition is administered as an oral liquid dosage form (claim 36). The compound includes velagliflozin, third compound listed in claim 39 (total 22 compounds). Hadd et al. exemplify administering bexagliflozin, in the form of a proline co-crystal, to dogs (example 2). They also administered them to dogs with HF (example 5). The bexagliflozin can be administered in combination with pimobendane, for the management of HF (p.72:14-15; see also para [0062]-[0064]). Pimobendan is a potentiator of myocardial contraction, and has been shown to extend the survival of dogs with stage C and stage B heart failure (para [0062]-[0064]). Class II HF is characterized by fatigue, shortness of breath, coughing, etc. (para [0058]). Other symptoms include severe exercise intolerance, dysponea, fluid retention, and reduced longevity (see para [0062], [0067]; Example 1). Most specifically, Hadd et al. teach bexagliflozin had a positive effect on HF in fluid retention model (example 1).
Hadd et al. expressly disclose administering bexagliflozin in the form of a proline co-crystal drug to a canine with HF. Hadd et al. also expressly disclose administering velagliflozin to canines with HF. And Hadd et al. expressly disclose treating a canine with HF, wherein the canine is diagnosed with MVD. The number of possible SGLT inhibitors disclosed by Hadd is small, and includes a total of 22 compounds. One of ordinary skill in the art could at once envisage administering velagliflozin or bexagliflozin proline co-crystal to a canine with heart failure, including wherein the canine is diagnosed with MVD. The dosage of SGLT inhibitor disclosed by Hadd et al. lies in the range of present claim 10.
The recitation “improved cardiometabolic efficiency…” in claim 15, necessarily occurs upon performing the positively recited step.
The symptoms listed in claim 17 are all described by Hadd et al. as symptoms of HF, and bexagliflozin was expressly tested for its effects on fluid retention in a HF model.
Thus, the disclosure of Hadd et al. anticipates claims 1, 5-12 and 14-17 of the present application.
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.
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.
Claim(s) 1-17 are rejected under 35 U.S.C. 103 as being unpatentable over Hadd et al. (WO2021/092341, cited above).
Hadd et al. teach as discussed above. Hadd et al. further teach “the valvular heart disease of the present disclosure includes valvular insufficiencies such as aortic regurgitation, aortic stenosis, mitral regurgitation and mitral stenosis.” (para [0109]). Hadd et al. teach [(M)MVD] results in mitral regurgitation (para [0059]).
While Hadd et al. teach treating HF in a canine diagnosed with MVD, Hadd et al. do not expressly disclose treating HF due to myxomatous MVD [(M)MVD].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to administer velagliflozin or bexagliflozin treat a canine diagnosed with HF due to myxomatous mitral valve disease [(M)MVD].
The ordinary artisan would have been motivated to administer velagliflozin or bexagliflozin treat a canine diagnosed with HF due to MVD, because they are one of two compounds from a small list of 22 SGLT inhibitors for treating a canine diagnosed with HF due to MVD.
According to Hadd et al., the most common form of MVD in dogs is a chronic condition called myxomatous degeneration. While Hadd et al. do not expressly identify the MVD canines as suffering from myxomatous degeneration, the ordinary artisan would have been motivated to treat them with a reasonable expectation of success, because Hadd et al. teach [(M)MVD] is the most common form of MVD. The ordinary artisan would have had a reasonable expectation of success because [(M)MVD] results in mitral regurgitation, and Hadd et al. teach their method includes treating mitral regurgitation.
The ordinary artisan would have been motivated to combine pimobendan with either velagliflozin or bexagliflozin, because pimobendan is a potentiator of myocardial contraction, and has been shown to extend the survival of dogs with stage C and stage B HF. The ordinary artisan would have had a reasonable expectation of success, because Hadd et al. teach the bexagliflozin can be administered in combination with pimobendane for the management of HF. While Hadd et al. do not expressly disclose the order of administration (i.e. SGLT2 and pimobendan), the ordinary artisan would have been motivated to administer the SGLT in any order, i.e. before, after or concomitantly with pimobendan.
The skilled artisan would have been motivated to administer just velagliflozin as the SGLT-2 inhibitor, because Hadd et al. exemplify administering a single SGLT2 inhibitor. Since velagliflozin and bexagliflozin are both recognized as SGLT inhibitors for the treatment of heart failure in canines, one having ordinary skill in the art would have been motivated to substitute one for the other, i.e. just administer velagliflozin to canines suffering from HF (caused by MVD, or [(M)MVD].
The ordinary artisan would have been motivated to administer either of the SGLT inhibitors as a proline co-crystal salt, because Hadd et al. teach and exemplify administering bexagliflozin as a proline co-crystal salt.
According to Hadd et al., the total daily dosage is selected from 50 µg/kg, 100 µg/kg, 200 µg/kg, 400 µg/kg, 800 µg/kg, 1,000 µg/kg, 1,600 µg/kg, and 3,200 µg/kg. These dosages include amounts that lie within the range of present claim 12.
Thus, the claimed invention as a whole is prima facie obvious over the combined teaching of the prior art.
Conclusion
In view of the rejections to the pending claims set forth above, no claim is allowed.
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/BAHAR CRAIGO/
Primary Examiner
Art Unit 1699
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