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 .
Priority
The instant application is a domestic application filed on 05/17/2024. Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The instant application claims foreign priority to European Patent Application No. EP23175197.5, filed on 05/24/2023. Receipt is acknowledged of a certified copy of foreign application.
Status of Claims
Claims 1-25 were originally presented on 05/17/2024. Applicant’s preliminary amendments to the claims received on 08/02/2024 are acknowledged and entered. Claim 3 is cancelled and claims 1-2 and 4-25 are amended.
Claims 1-2 and 4-25 are pending.
Information Disclosure Statement
Thirteen separate Information Disclosure Statements (“IDSs”) have been submitted, one on 06/10/2026, one on 08/12/2024, eight on 08/07/2025, two on 01/27/2026, and one on 03/25/2026. The IDSs are in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDSs have been considered by the examiner.
Claim Objections
Claim 7 objected to because of the following informalities:
Several chemical structures are blurry. See, e.g., chemical structures for formulas (3), (4), (6), (7), (10), (11A), (16), and (20).
Further, there are extraneous markings aside the chemical structures for formulas
(12) – see marking (7-1);
(14) – see marking (9-1); and
(24) – it appears the structure was not fully cropped, as there are markings at the bottom center.
Claim 24 objected to because of the following informalities: typographical errors. See “thaty” recited in the preamble.
Appropriate correction is required.
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.
Rejection Statement
Claims 6-8, 16-20, and 22-24 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.
Representative Claim
The instant claim 1 is representative of the instant claims. It recites:
A method of prevention and/or treatment of one or more cardiac diseases in a non-human mammal comprising administering to the non-human mammal a pharmaceutical composition comprising one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and/or telmisartan or pharmaceutically acceptable forms thereof.
Instant claim 1.
Claims 6, 8, 16, and 24 Indefinite – “preferably” or “such as” or “e.g.”
Regarding claims 6, 16, the phrases "preferably" and/or “more preferably” and/or “even more preferably”, are recited. Regarding claims 8 and 24, the phrase "such as" is recited. Further, regarding claim 24, the phrase “e.g.” is recited. These phrases render the claims indefinite because it is unclear whether the limitation(s) following the phrases are part of the claimed invention. Preferences and examples are properly set forth in the Specification. See MPEP § 2173.05(d).
Accordingly, claims 6, 8, 16, and 24 are rejected as indefinite.
Claims 7 Indefinite – Unclear which Species/Compounds are Encompassed by the Claim
Claim 7 recites “The method of claim 1, wherein the one or more SGLT-2 inhibitors is selected from the group consisting of: [at least 24 distinct Markush structures, “derivatives” of compounds, and/or named compounds].”
First, the claim itself lacks the required “and/or” designation required properly set forth a Markush grouping. See between compounds (23) and (24), and note that there is no “and” between these compounds. As a result, it is unclear if the group recited in claim 7 is closed, or encompasses more compounds than those specifically depicted. See also, MPEP 2117, subsection I.
Second, the claim recites the compound named “Wanpagliflozin”; however, the Specification does not provide a structure for this compound, and the examiner cannot find a chemical structure associated with this compound. While the CAS registry provides the registry number 2690310-28-0 for “Wanpagliflozin”, the CAS analysts also have yet to identify what chemical it refers to.
Third, the claim repeatedly uses the word “derivative” with reference to certain chemical structures, but never explains what it means for a compound to be a “derivative”. For example, see item (12):
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There are an infinite number of ways that one could make a “a thiophene derivative of the formula (12), wherein R denotes methoxy or trifluoromethoxy”. One of skill in the art could not determine the metes and bounds of such a “derivative” alone due to an inability to envision all of the compounds defined by such a grouping. Compare also, items (1) and (18). For (1), it recites a derivative that includes derivatives:
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For (18), it recites a “compound” that is presumably some narrowed grouping of the “derivatives” of (1), that also includes more derivatives.
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It is unclear what “derivative” means in the many occurrences in this claim.
Last, for all of these compounds or derivatives, it is unclear if they must actually inhibit SGLT-2, and if so, whether they must inhibit only SGLT-2 selectively, or if non-selective/dual SGLT-1/2 inhibition is permitted. Moreover, it is unclear in what species of “non-human” mammals they must inhibit SGLT-2. Applicant provides no “non-human” species-specific SGLT-2 activity assays for the enormous number of compounds and derivatives listed in the claim. As a result, it is unclear in which species of non-human mammals that these compounds inhibit SGLT-2 in. Non-human mammals includes elephants, giraffes, platypus, orca whales, vampire bats, and so on. Reference is made to U.S. Patent Application Publication No. US20230000816A1 (“US’816”), which is discussed later in this office action. Its inventors understood the distinction between species-dependent SGLT selectivity and highlighted it in their invention. See US’816 at cols. 9-10, paragraph [0199]:
Many of the SGLT inhibitors are selective for human SGLT2 compared to human SGLT1. Others have lower selectivity, such as licogliflozin or sotagliflozin, and some are more active against SGLT1 than SGLT2, such as mizagliflozin. Selectivity can be species-dependent, so that high selectivity for human SGLT2 does not necessarily indicate high selectivity for, for example, cat or dog SGLT2. And depending on the disease indication a greater or lesser degree of inhibition of one or the other SGLT protein may be desirable.
US’816 at cols. 9-10, paragraph [0199].
It is unclear if that level of selectivity is required here, or if Applicant simply means administer one of the many compounds/derivatives listed in the claim. The examiner notes that the preceding excerpt from US’816 discusses the compound “sotagliflozin”, which is recited in the instant claim as item (16).
As a result of these issues, claim 7 is rejected as indefinite because it is unclear which species/compounds are encompassed by the claim.
Claims 17, 18, 19, 20, 22 and 23 Indefinite – Broad Ranges combined with Narrow Ranges
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c).
In the present instance, claim 17 recites the broad recitation of administration of one or more SGLT-2 inhibitors “at a dose of 0.01 mg/kg bodyweight to 10 mg/kg bodyweight per day”, and the claim also recites “or at a dose of 0.01 mg/kg bodyweight to 0.3 mg/kg bodyweight per day” which is the narrower statement of the range/limitation.
In the present instance, claim 18 recites the broad recitation of administration of one or more SGLT-2 inhibitors “once per day”, and the claim also recites “or twice per day”, which is the narrower statement of the range/limitation.
In the present instance, claim 19 recites the broad recitation of administration of pimobendan “at a dose of 0.1 mg/kg bodyweight to 1 mg/kg bodyweight per day”, and the claim also recites “or 0.2 mg/kg bodyweight to 0.6 mg/kg bodyweight per day”, which is the narrower statement of the range/limitation.
In the present instance, claim 20 recites the broad recitation of administration of pimobendan “once per day”, and the claim also recites “or twice per day”, which is the narrower statement of the range/limitation.
In the present instance, claim 22 recites the broad recitation recites the broad recitation of administration of telmisartan “at a dose of 0.01 to 10 mg/kg of bodyweight per day”, and the claim also recites “or 0.75 to 1.5 mg/kg of bodyweight per day”, which is the narrower statement of the range/limitation.
In the present instance, claim 23 recites the broad recitation of administration of telmisartan “once per day”, and the claim also recites “or twice per day”, which is the narrower statement of the range/limitation.
The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Accordingly, claims 17-20 and 22-23 are rejected as indefinite.
Claim Interpretation
The instant claim 1 is representative of the instant claims. It recites:
A method of prevention and/or treatment of one or more cardiac diseases in a non-human mammal comprising administering to the non-human mammal a pharmaceutical composition comprising one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and/or telmisartan or pharmaceutically acceptable forms thereof.
Instant claim 1.
In view of the many animal species, actives, and diseases recited in the many claims, the examiner tabulated their scope in the following table.
Actives
Animal Species and Claims
“SLGT-2 Inhibitor”
Required Combination
Dogs
Cats
Any non-human mammal
Any
pimobendan and/or telmisartan
5
6
1, 2, 4, 7, 8, 9, 16-20 and 22-25
Any
pimobendan and telmisartan
21
Velagliflozin
pimobendan and/or telmisartan
10, 12
11, 13
9
Velagliflozin
pimobendan
14
15
As the examiner interprets the claims, they are drawn to the addition of one or more SGLT-2 inhibitors to standard protocols of treating one or more cardiac diseases in a non-human mammals. The claimed methods require combination with at least pimobendan and/or telmisartan. All standard treatments are encompassed by these methods due to the methods “comprising” administering the recited actives. Further, the specification listed no exclusion criteria for the methods. Because the claims are drawn to veterinary methods of treatment, the actives, patient populations, dosing and routes of administration, and the therapeutic endpoints must be construed.
Regarding the actives, the claims are primarily drawn to administration of combinations of the actives pimobendan and/or telmisartan with velagliflozin. Applicant reports from various field studies and/or laboratory experiments, that certain combinations of the actives achieved cardiac related therapeutic endpoints in canines and/or felines. Regarding the actives, their structures and representative roles are shown below. Applicant reports no data for any other SGLT-2 inhibitor other than velagliflozin, nor for “more [than] one SGLT-2 inhibitor”:
Name
Structure
Representative role
pimobendan
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Inodilator (calcium sensitizer and phosphodiesterase III inhibitor)1
telmisartan
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Angiotensin II receptor blocker2
velagliflozin
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Sodium-glucose cotransporter 2 (SGLT2) inhibitor3
At the time of filing, pimobendan was marketed in the US under the trade names Vetmedin and Vetmedin®-CA1, and was indicated for the treatment of congestive heart failure (“CHF”) in dogs with AVVI, DCM and related conditions,4 and MMVD.5 The labels supported “concurrent therapy for congestive heart failure (e.g., furosemide, etc.) as appropriate on a case-by-case basis.”6
At the time of filing, telmisartan was marketed in the US under the trade name Semintra®, and was indicated “[f]or the control of systemic hypertension in cats”.7
Regarding velagliflozin, it received approval for veterinary use shortly after the effective filing date of the instant application (the Senvelgo® US date of approval was 08/10/2023).
Regarding the patient populations, Applicant tested its combinations on canines and felines with heart diseases/heart failure. Specifically, claims 1, 2, 4, 7, 8, 9, and 16-25 are generic for this patient population. The are also generic for any non-human mammal, such as orca whales, vampire bats, platypus, horses, and so on.
Regarding canines and felines, the examiner notes that Applicant tested only domesticated dogs and cats. That is, Applicant did not test its combinations on wolves, coyotes, racoons, foxes, jackals or tigers, lions, cheetahs, lynx, wildcats, cougars, and so on.
Claims 5, 10, 12, and 14 are specific to canines with heart diseases that cause heart failure. In particular, these claims recite canines with heart diseases that cause heart failure in forms of Dilated Cardiomyopathy (DCM) or mitral valve disease (MVD).
Claims 6, 11, 13, and 15 are specific to felines with heart diseases that cause heart failure. In particular, these claims recite felines with heart diseases that cause heart failure in the form of Hypertrophic Cardiomyopathy (HCM).
The examiner interprets DCM, MVD, and HCM as forms of “heart disease” that cause “chronic heart failure” for the following reasons. First, Applicant defines “heart disease” as synonymous with “cardiac disease” and states that it includes “cardiomyopathies” in the Specification at [0155].
Next, Applicant defines “heart failure” to mean “congestive heart failure” and states that such diseases are “mostly … chronic”. See Specification at [0156] (defining “heart failure” to mean “congestive heart failure”, abbreviated as (“CHF”) and stating that “[i]t is mostly a chronic disease due to a chronic work overload of the heart or developed after an acute hemodynamic stress due to fluid overload, a valvular dysfunction or a myocardial infarction.”) (emphases added).
Regarding HCM, see Specification at [0157] (stating that “the term “cardiomyopathy” refers to a group of diseases that affect the heart muscle being the most common form of heart disease seen in cats, and the most common cause of heart failure. Cardiomyopathies are described according to the effect they have on the structure and function of the cardiac muscle. Types of cardiomyopathy include: hypertrophic cardiomyopathy (HCM)….”) (emphasis added).
See also, Specification at [0159] (stating that “HCM” affects “all ages” of cats, is suggested to have “a genetic influence”, and that “[t]he left heart is predominately affected and clinical signs manifested as sudden death or, more commonly, acute left heart failure due to diastolic dysfunction.”). The examiner interprets Applicant’s statements here as explaining that HCM in cats is a persistent, underlying condition that has “clinical signs” that “manifest” in the acute phase, e.g., “sudden death”.
Regarding DCM and MVD, see Specification at [0005], explaining that DCM and MVD cause heart failure in animals (“Pimobendan is a well-known compound for the treatment of congestive heart failure (CHF) originating for example from dilated cardiomyopathy (DCM) or mitral valve disease (MVD) in animals, especially dogs.”). See also, Specification at [0165-0166] (explaining that MVD and DCM cause CHF).
Regarding the dosing and routes of administration, Applicant’s disclosure summarizes approximately 16 separate field trials and one laboratory trial (see captions from Specification at 45-65). For the majority of the trials, the data disclosed are unfortunately limited to conclusions from the trials (i.e., no figures, PK/PD, dosing methods, or statistics reported). While all routes of administration are contemplated by the claims, the “data” appear to be drawn mainly from oral (“PO”) administration.
See, e.g., Specification at 46 for an example of the data disclosed:
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Specification at 46.
The examiner notes that Applicant does not disclose the form(s) in which the combination(s) of the actives were administered in the many trials, nor the dosages. Therefore, it is unclear if the oral administrations were through liquid formulations, fast dissolving tablets, or extended release capsules. It is also unclear in the many examples if the actives were administered simultaneously as one “pharmaceutical composition”, or as separate administrations of different pills and/or oral solutions. Moreover, in the many trials reported, dosages are never specified, PK/PD are not discussed, and no data are provided to explain the conclusions drawn to how any therapeutic endpoint was “significant” compared to administration of these known actives used for treating various cardiac conditions in dogs and cats. Accordingly, when Applicant recites in the claims the administration of a “pharmaceutical composition” comprising the actives, the examiner interprets such “pharmaceutical composition” as either individual pills/liquid formulations, or as a combined compounded medication.
Further, the most specific guidance regarding dosing of the combinations appears in Example 16, Specification at 61 and 62, which teaches for dogs with DCM or MVD, administration of velagliflozin (0.5 mg/kg bodyweight PO q.d.), with pimobendan (0.5 mg/kg bodyweight PO q.d., timing unspecified, but at two separate administrations), with optional furosemide (1 mg/kg bodyweight PO b.i.d.). See Specification at 61:
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Specification at 61, and see Specification at 62:
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Specification at 62.
Regarding the therapeutic endpoints, the plain and ordinary meaning of “prevention and/or treatment” is sufficient. Several standard endpoints are recited specifically in claim 24.
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.
Claims 1-2 and 4-25 Anticipated by US’816 as evidenced by References
Claim(s) 1-2 and 4-25 is/are rejected under both 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by US’8168 as evidenced by References.9
Regarding claims 1-2 and 4-15, US’816 teaches that during the development of SGLT inhibitors for treating diabetes, its inventors discovered that such inhibitors could be used for treating other conditions in companion animals, including heart failure. US’816 uses the term “companion animal” to particularly include felines and canines in the context of treating heart failure, placing the invention of US’816 squarely in the field of art as the instant claims. See, e.g., US’816 at 9, paragraph [0114]:
[0114] As mentioned above, the current application is drawn to the discovery that despite their initial development for the use in treating metabolic disorders such as type 2 diabetes, sodium-glucose linked transporter (SGLT) inhibitors can be used in the management of hypertension, renal disease (e.g., chronic kidney disease) or heart failure in companion animals (in particular, felines and canines).
US’816 at 9, paragraph [0114] (emphasis added).
Accordingly, US’816 at 32, claim 1, teaches the instantly claimed the treatment axis comprising administering a SGLT inhibitor to “a companion animal”:
1. A method for the treatment of heart failure 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.
US’816 at 32, claim 1.
US’816 at 33, claim 38, teaches selectivity for SGLT2:
38. The method of any one of claims 1-36, wherein the compound that inhibits an SGLT selectively inhibits SGLT2.
US’816 at 33, claim 38.
US’816 teaches the “prevention” axis as well. See, e.g., US’816 at 23:
[0241] In some embodiments, administration of a therapeutically effective amount of a compound that inhibits an SGLT prevents the progression of heart failure such that the New York Heart Association (NYHA) functional classification of the companion animal does not change. In some embodiments, administration of a therapeutically effective amount of a compound that inhibits an SGLT improves the NYHA functional classification of the companion animal.
[0242] The treatments described herein can be administered prophylactically to prevent or delay the onset or progression of heart failure, or therapeutically to relieve the symptoms of heart failure for a sustained period of time
US’816 at 23.
Velagliflozin is a preferred embodiment of the SGLT inhibitors administered. See, e.g., US’816 at 33-34, claim 39, 3rd compound recited; see also US’816 at 10-11, marked paragraphs below:
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US’816 at 10-11.
US’816 at 26, paragraph [0276], teaches the instantly claimed combination therapies with telmisartan and/or pimobendan. See US’816 at 26, paragraph [0276]:
[0276] Combination therapy is also contemplated herein. In some embodiments, a companion animal with heart failure, hypertension, or chronic kidney disease receives an additional therapeutic agent. The additional therapeutic agent includes, but is not limited to, angiotensin-converting enzyme inhibitors (ACE inhibitors, such as enalapril, lisinopril and benazepril); angiotensin receptor blockers (such as valsartan and telmisartan); neprilysin inhibitors (such as sacubitril); diuretics, e.g. loop diuretics (such as furosemide and torsemide), thiazide diuretics (such as chlorthalidone and hydrochlorothiazide), and potassium-sparing diuretics (such as spironolactone); vasodilators (such as nitroglycerine, hydralazine and sodium nitroprusside); beta blockers (such as atenolol, metoprolol and propanolol); mixed β and α receptor antagonists (such as carvedilol); calcium channel blockers (such as amlodipine or diltiazem); mixed β-adrenergic receptor and potassium channel blockers (such as sotalol); and positive inotropes (such as pimobendan, digoxin, milrinone and dobutamine).
US’816 at 26, paragraph [0276] (emphases added).
US’816 exemplifies its methods using bexagliflozin in dogs with heart failure (see, e.g., US’816 at 30-31, Example 5), as well as in cats with heart failure (see, e.g., US’816 at 31, Example 6). Both RAS blocking agents, which include ARBs, i.e., telmisartan (see US’816 at 5, paragraph [0053]) and pimobendan are explicitly taught for canine and feline heart failure combination treatments. See last sentence of the representative Examples 5 and 6 of US’816.
US’816 at 9, paragraph [0109] defines heart failure as follows (the examiner bolded MVD, DCM, and HCM because these conditions appear to be the conditions Applicant also tested in its disclosed examples, and are also the conditions recited in instant claims 4 and 5):
[0109] As used herein, the term “heart failure” refers to a condition that can result from any structural or functional cardiac disorder that impairs the ability of the heart to fill with or pump a sufficient amount of blood throughout the body. Heart failure can develop following many conditions or events, for example following chronic adrenergic stimulation, or as a result of genetic factors, as a consequence of infection by cardiotropic viruses, as a manifestation of advanced trypanosomal disease, as an outcome of irreversible ischemic damage, such as follows a myocardial infarction, as a result of deterioration of function of the mitral or aortic valve, as a result of autoimmune disease, such as an autoimmune myocarditis, or as a result of poorly understood spontaneous syndromes, such as hypertrophic cardiomyopathy. Recognized forms of heart failure include, but are not limited to valvular heart disease (such as mitral valve disease, aortic valve disease, or atrioventricular valvular insufficiency), ischemic heart diseases, congenital heart diseases, dilated cardiomyopathy, hypertrophic cardiomyopathy, atrial septal defect, ventricular septal defect and symptomatic heart disease. Specifically, the valvular heart disease of the present disclosure includes valvular insufficiencies such as aortic regurgitation, aortic stenosis, mitral regurgitation and mitral stenosis.
US’816 at 9, paragraph [0109] (emphases added).
See also, US’816 at 23, paragraph [0240] (teaching HCM and MVD); see also, id. at 30-31, paragraphs [0315] and [0316] (teaching DCM in dogs and cats); see also, claim 16 (canines with MVD), and claim 27 (felines with HCM).
All pharmaceutically acceptable forms are taught, including prodrugs, and relevant to claim 8, crystalline complexes are taught. See, e.g., US’816 at 19, paragraphs [0204]-[0205]. Proline co-crystals were exemplified in US’816 at 28, paragraph [0298], Example 2.
Accordingly, claims 1-2 and 4-15 are anticipated by US’816.
Regarding claim 16, the same administration routes are all taught in US’816 at 26, section F beginning at paragraph [0277]. See, e.g., paragraph [0279] (teaching the overlapping administration routes).
Accordingly, claim 16 is anticipated by US’816.
Regarding claim 17, dosing methods are taught in US’816 at 25, beginning at section E, paragraph [0263].
US’816 teaches that it is routine to optimize dosing based upon the amount, frequency, disease treatment, etc. See, e.g., US’816 at 25, paragraph [0265]:
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US’816 at 25, paragraph [0265].
Further, US’816 teaches PK and PD parameters using bexagliflozin as an example. See US’816 at 27-28, Example 1 (rat model of heart failure), and at 28-30, Example 2 (PK and PD of bexagliflozin in dogs discussed, with discussion of crossover to cats). These parameters are relevant hereto because they show that veterinary clinicians of ordinary skill in the art at the time of filing understood how to assess relevant parameters such as AUC and determine dose proportionality over entire dosing ranges. See, e.g., US’816 at 28-30, paragraphs [0298]-[0300]. As such, it teaches that the dose of the active administered was a known result-effective variable that could be tuned by routine optimization.
US’816 exemplifies its dosing using bexagliflozin in dogs with heart failure (see, e.g., US’816 at 30-31, Example 5), as well as in cats with heart failure (see, e.g., US’816 at 31, Example 6).
The dosages are adjustable by body mass. See, e.g., US’816 at 26 paragraph [0280]. See also, US’816 at 30-31, Examples 5 and 6 (first sentence of each, teaching “dose adjusted for body mass”).
The taught doses relevant to each SGLT inhibitor or prodrug thereof all overlap with those recited in the instant claim 17. See, e.g., US’816 at 25, paragraph [0266] (for canines, lowest dose is about 10 μg kg-1 daily (i.e., 0.01 mg/kg)); see also, US’816 at 25, paragraph [0269] (for cats, lowest dose is about 100 μg kg-1 daily (i.e., 0.1 mg/kg)). Moreover, as discussed above, the dosages are adjustable based upon the desired outcome. See US’816 at 25, paragraph [0265].
Accordingly, claim 17 is anticipated by US’816.
Regarding claim 18, US’816 further teaches that the frequency of administration may change, e.g., q.d., b.i.d., or divided into portions throughout the day. See, e.g., US’816 at 26, paragraph [0273].
[0273] In some embodiments, the therapeutically effective amount is one-time daily. In some embodiments, the therapeutically effective amount is two-times (twice) daily. In some embodiments, the therapeutically effective amount is three-times daily. In some embodiments, the therapeutically effective amount is four-times daily. Thus, dosages may be divided into equal or unequal portions administered at various time throughout the day.
US’816 at 26, paragraph [0273].
See also, US’816 at 31, paragraph [0316] (exemplifying for cats, that “The fixed dosage can also be divided into equal portions for b.i.d. dosing if desired.”).
See also, US’816 at 33, claim 32-33 (teaching q.d. and b.i.d. dosing).
Accordingly, claim 18 is anticipated by US’816.
Regarding claims 19 and 20, US’816 at 6, paragraph [0063], cites Häggström et al., 2008, J Vet Intern Med 22:1124, which it incorporates by reference (see US’816 at 32, paragraph [0321]). Häggström 2008 at Abstract teaches off-label use of pimobendan at 0.4-0.6 mg/kg/d. See also, Häggström 2008 at 1126 (“The pimobendan group received pimobendanb PO at a dose of 0.4–0.6 mg/kg/d. The calculated daily dose was divided in two and adjusted to a suitable number of 1.25 or 2.5mg capsules. Owners were instructed to administer the drug in the morning and evening, approximately 12 hours apart, and approximately 1 hour before feeding.”). See also, US’816 at 5, paragraph [0059], citation to Beaumier et al., 2018, J Vet Intern Med 32: 944, which is also incorporated by reference. Beaumier 2018 teaches standard dosages for pimobendan for dogs with heart failure at 947, Table 2. Both Häggström 2008 and Beaumier 2018 cite Vetmedin as the source of pimobendan.
Accordingly, claims 19 and 20 are anticipated by US’816 as evidenced by Häggström 2008 and Beaumier 2018.
Regarding claim 21, US’816 does not require specific dosing frequency for the actives administered with the SGLT inhibitor. Instead, it states specifically that “the frequency of dosing depends on a number of factors including” “the disease being treated”, “the severity of the disease”, “the compound that inhibits a … SGLT”[], “the route of administration”, “the companion animal receiving treatment”, “as well as the size of the companion animal.” Therefore, US’816 teaches the method wherein the SGLT-2 inhibitor is administered before, after or concomitantly with administering pimobendan and telmisartan or pharmaceutically acceptable forms thereof.
Accordingly, claim 21 is anticipated by US’816.
Regarding claims 22-23, US’816 at 4, paragraph [0048], cites Sent et al., 2015 J Vet Intern Med 29:1479, which it incorporates by reference (see US’816 at 32, paragraph [0321]. Sent 2015 at Abstract and at 1480 (right column) teaches off-label use of telmisartan at 1 mg/kg. See Sent 2015 at 1480 (“An solution of telmisartana was administered PO by the cat owner at a dosage of 1 mg/kg (0.25 mL/kg) q24 h.”). The cite is to the Semintra label (see Semintra listed as Footnote a, page 1485, bottom right).
Accordingly claims 22-23 are anticipated by US’816 as evidenced by Sent 2015.
Regarding to claim 24, therapeutic endpoints are also taught. See US’816 at 30-31, both Examples 5 and 6 (teaching that the dogs and cats will not succumb to death as quickly when treated according to the methods developed by the inventors of US’816).
Accordingly, claim 24 is anticipated by US’816.
Regarding claim 25, fixed dosage forms, relevant to claim 25, are taught. See, e.g., US’816 at 26, paragraph [0271]. See also, US’816 at 27 paragraph [0286] (teaching an example of fixed dosage liquid formulation of a SGLT-2 inhibitor). Further, US’816 at paragraph [0279] teaches that “Compounds or prodrugs that inhibit an SGLT (or a pharmaceutically acceptable form thereof) can be incorporated into a variety of formulations for therapeutic administration.” US’816 expressly teaches therapeutic administrations with respect to combination therapies with pimobendan and/or telmisartan, as discussed previously.
Continuing, US’816 at 26, paragraph [0280] teaches (“As recognized in the art, drugs for companion animals can be administered by a variety of means and in a variety of dosage forms. In some embodiments, oral dosage forms, such as oral liquid dosage forms, oral semi-solid dosage forms and oral solid dosage forms, including medicated foods and dosage forms are used. Because of the wide range in body masses of cats and dogs, oral liquid or semi-solid dosage forms that readily permit dosage adjustment for the mass of the animal are contemplated in the current disclosure.”). US’816 at paragraph [0281] specifically states that “Oral liquid dosage forms are often provided as a bottle plus a dispensing syringe or a calibrated dropper or if the medication is to be dispensed dropwise the bottle assembly may contain a narrow apical orifice and a flexible bottom portion allowing the contents to be expelled in drops by squeezing when the bottle is inverted.”
US’816 at 26, paragraph [0283] teaches oral liquid dosage forms such as “syrups” and “elixirs” using “agents to improve palatability ”.
US’816 at 27 continues to discuss in paragraphs [0285]-[0286] that companion animals, and in particular cats and dogs, are known to exhibit “evasive or aversive responses” in response to medications.
The examiner interprets these statements in US’816 as teaching a compounded medication for the respective patients in a fixed-dosage form or liquid formulation, and that the compounded medication comprises the active SGLT inhibitor with pimobendan, and/or telmisartan. Alternatively stated, one of skill in the art, reading US’816, would “at once envisage” a compounded medication the active SGLT inhibitor with pimobendan, and/or telmisartan because of the consistent teachings in US’816 for using telmisartan and/or pimobendan in the context of treating heart failure,10 combined with US’816 teaching that companion animals, and in particular cats and dogs, are known to exhibit “evasive or aversive responses” in response to medications.
Accordingly, claim 25 is anticipated by US’816.
Claims 1-2, 4, 6-9, 11, 13, 15-18, 20, 21 and 23-25 Anticipated by US’090
Claim(s) 1-2, 4, 6-9, 11, 13, 15-18, 20, 21 and 23-25 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US’090.11
Regarding claims 1 and 2, US’090 teaches a method of prevention and/or treatment of one or more cardiac disease in felines comprising administering to the feline a pharmaceutical composition comprising one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and/or telmisartan or pharmaceutically acceptable forms thereof.
See, e.g., US’090 at claim 13. The examiner notes that the combination therapies taught in claim 13 of US’090 apply to claims 1-12 of US’090 by dependency.
See also, US’090 at 6, paragraph [0080], which teaches combination treatments comprising administration of pimobendan and/or telmisartan, each provided as the only example of an ARB and a positive inotrope:
[0080] In yet another aspect, the present invention also concerns the one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof for the uses as herein disclosed and/or claimed, wherein the one or more SGLT-2 inhibitors are to be administered before, after or concomitantly with administering one or more other active pharmaceutical ingredients, preferably diuretics, such as furosemide, torasemide or spironolactone; beta-blockers, such as atenolol or propranolol; calcium-channel blockers, such as diltiazem; ACE inhibitors, such as benazepril, ramipril or enalapril; angiotensin receptors blockers, such as telmisartan; antiarrhythmic agents, such as flecainide; platelet agglutination inhibitors, such as clopidogrel; nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin; anticoagulants, such as coumarins (vitamin K antagonists), (low molecular weight) heparin, synthetic pentasaccharide inhibitors of factor Xa, as well as direct factor Xa inhibitors and/or direct thrombin inhibitors; and/or calcium-channel sensitizers and/or positive inotropes, such as pimobendan and/or digitalis alkaloids.
US’090 at 6, paragraph [0080] (emphases added).
Accordingly, claims 1 and 2 are anticipated by US’090.
Regarding claims 4 and 6, the same patient populations are taught in claims US’090 at 2-3. Further, US’090 exemplifies its methods with velagliflozin. See, e.g., US’090 at 15 Example 1, paragraph [0203]-[0206] (teaching 1 mg/kg oral q.d. bw velagliflozin for cats “with every possible phenotype of cardiomyopathy (HCM, RCM, UCM, DCM and ARVC) with or without clinical symptoms (e.g. congestive heart failure) ….”) (emphasis added). Regarding the disclosed Example 1, US’090 at 15, paragraph [0202] states “The following examples serve to further illustrate the present invention; but the same should not be construed as a limitation of the scope of the invention disclosed herein.”
Accordingly, claims 4 and 6 are anticipated by US’090.
Regarding claim 7, overlapping SGLT-2 inhibitors are taught in US’090 at claim 6.
Accordingly, claim 7 is anticipated by US’090.
Regarding claim 8, US’090 at 5, paragraph [0068] teaches L-proline co-crystals of the SGLT-2 inhibitors. See also, US’090 at 13, paragraph [0181]-[0182], and at claim 7.
Accordingly, claim 8 is anticipated by US’090.
Regarding claims 9 and 11, US’090 teaches the administration of a single SGLT-2 inhibitor in its combination therapies. See, e.g., US’090 at claims 12 and 13.
Accordingly claims 9 and 11 is anticipated by US’090.
Regarding claims 13 and 15, US’090 teaches the administration of a single SGLT-2 inhibitor in its combination therapies for the same patient populations. See, e.g., US’090 at claims 12, 13, and 4.
Accordingly, claims 13 and 15 are anticipated by US’090.
Regarding claim 16, the same routes of administration are taught in claim 9.
Accordingly, claim 16 is anticipated by US’090.
Regarding claim 17, the same dosages of SGLT-2 inhibitors are taught in US’090 at 15, paragraph [0199]. See also, US’090 at claims 10 and 12.
Accordingly, claim 17 is anticipated by US’090.
Regarding claim 18, US’090 teaches the same dosing frequency. See, e.g., US’090 at claim 11.
Accordingly, claim 18 is anticipated by US’090.
Regarding claims 20-21 and 23, US’090 teaches the combination therapy “concomitantly” with administration of the active SGLT-2 inhibitors. See, e.g., US’090 at claim 13. Applying the combination therapy “concomitantly” as taught with respect to the frequencies taught in US’090 at claims 11 and 12 results in the subject matter of claims 20, 21 and 23.
Accordingly, claims 20-21 and 23 are anticipated by US’090.
Regarding claim 24, US’090 at 6-7, paragraphs [0082]-[0099] teaches the same therapeutic endpoints (e.g., longer time of survival and higher quality of life). See also, US’090 at claim 14, which applies to claim 13 by dependency.
Accordingly, claim 24 is anticipated by US’090.
Regarding claim 25, US’090 teaches solid or liquid compositions comprising the active ingredient. See, e.g., US’090 at 14-15 [0191]-[0200]. US’090 at 6, paragraph [0080], designates telmisartan and pimobendan as “active pharmaceutical ingredients” that may be administered “concomitantly”. The examiner interprets these statements as at least teaching fixed-dosage-combinations in either solid or liquid formulations. Alternatively stated, one of skill in the art, reading US’090, would “at once envisage” a compounded medication comprising the active SGLT2 inhibitor with pimobendan, and/or telmisartan because of its express teachings of “concomitantly” administering the active SGLT2 inhibitor with pimobendan, and/or telmisartan.
Accordingly, claim 25 is anticipated by US’090.
Claims 1, 2, 4-18 and 23-25 Anticipated by US’830
Claim(s) 1, 2, 4-18 and 23-25 rejected under 35 U.S.C. 102(a)(1) as being anticipated by US’830.12
Regarding claim 1, US’830 at cols. 39-40, Example XXIV(1), teaches velagliflozin. US’830 at col. 22 teaches effective dosages and dosing frequencies, and formulations with “other active substances”. US’830 at col. 23 teaches “combinations with drugs for influencing high blood pressure, chronic heart failure or atherosclerosis” including “telmisartan”, and the combination with an Angiotensin II receptor antagonist is “preferably used for the treatment or prevention of high blood pressure”:
See US’830 at col. 23:
Moreover, combinations with drugs for influencing high blood pressure, chronic heart failure or atherosclerosis such as e.g. A-II antagonists or ACE inhibitors, ECE inhibitors, diuretics, β-blockers, Ca-antagonists, centrally acting antihypertensives, antagonists of the alpha-2-adrenergic receptor, inhibitors of neutral endopeptidase, thrombocyte aggregation inhibitors and others or combinations thereof are suitable. Examples of angiotensin II receptor antagonists are candesartan cilexetil, potassium losartan, eprosartan mesylate, valsartan, telmisartan, irbesartan, EXP-3174, L-158809, EXP-3312, olmesartan, medoxomil, tasosartan, KT-3-671, GA-0113, RU-64276, EMD-90423, BR-9701, etc. Angiotensin II receptor antagonists are preferably used for the treatment or prevention of high blood pressure and complications of diabetes, often combined with a diuretic such as hydrochlorothiazide.
US’830 at col. 23.
Turning to the claims of US’830, col. 62, claim 1 teaches SGLT-2 inhibitors including velagliflozin (see wherein R3 is propyl); see also, claim 7 (indicating SGLT-2). US’830 at col. 62, claim 5 teaches “A method of treating a disease or a condition which can be influenced by inhibiting the sodium-dependent glucose cotransporter SGLT said method comprised of the steps of administering to a patient in need thereof a therapeutically effective amount of a compound according to claim 1 wherein said a disease or a condition is selected from the group consisting of … high blood pressure, chronic heart failure, ….”.
Felines and canines are patients of veterinarians. Those with high blood pressure or chronic heart failure are “patients in need”. Chronic heart failure is encompassed by the instant claims as discussed in the claim interpretation section, and hypertension prevention is a therapeutic endpoint recited specifically in claim 24.
Accordingly, US’830 at claim 5 teaches a method of treatment of one or more cardiac diseases in a non-human mammal comprising administering to the nonhuman mammal a pharmaceutical composition comprising one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with telmisartan.
As such, claims 1, 2, 4-6 (at least the “heart failure” indication), 7 and 9 are anticipated by US’830. This is consistent with the Specification, as discussed in the claim interpretation section, which defines “heart failure” as “congestive heart failure”, and states that most forms are “chronic”.
Regarding claim 8, US’830 at 19 teaches crystalline complexes with amino acids, including proline (“Moreover, the compounds obtained may be converted into mixtures, for example 1:1 or 1:2 mixtures with amino acids, particularly with alpha-amino acids such as proline or phenylalanine, which may have particularly favourable properties such as a high crystallinity.”). In this section, US’830 designates the mixtures obtained as “compounds”, which the examiner interprets as compounds of the invention of US’830.
US’830 at col. 23 teaches pharmaceutical compositions comprising compounds of the invention and the use of such pharmaceutical compositions for the treatment or prevention of diseases or conditions which can be affected by inhibiting the sodium-dependent glucose cotransporter SGLT:
Therefore, in another aspect, this invention relates to the use of a compound according to the invention or a physiologically acceptable salt of such a compound combined with at least one of the active substances described above as a combination partner, for preparing a pharmaceutical composition which is suitable for the treatment or prevention of diseases or conditions which can be affected by inhibiting the sodium-dependent glucose cotransporter SGLT. These are preferably metabolic diseases, particularly one of the diseases or conditions listed above, most particularly diabetes or diabetic complications.
US’830 at col. 23.
US’830 at claim 5 specifically teaches that high blood pressure and chronic heart failure are diseases or conditions which can be affected by inhibiting the sodium-dependent glucose cotransporter SGLT.
Continuing, US’830 at col. 24 specifically teaches “a pharmaceutical composition which comprises a compound according to the invention or a physiologically acceptable salt of such compound and at least one of the active substances described above, optionally together with one or more inert carriers and/or diluents.” (emphasis added). US’830 at 24 continues to specifically teach pharmaceutical compositions with at least one angiotensin II receptor antagonist. See US’830 at 24:
Thus, for example, a pharmaceutical composition according to the invention comprises a combination of a compound according to the invention or a physiologically acceptable salt of such a compound and at least one angiotensin II receptor antagonist optionally together with one or more inert carriers and/or diluents.
US’830 at 24.
As such, US’830 explicitly teaches pharmaceutical compositions comprising a compound according to the invention and at least one angiotensin II receptor antagonist, and that the compound is a crystalline complex between the one or more SGLT-2 inhibitors and one or more amino acids, such as proline. As discussed, telmisartan is explicitly taught in US’830 as an angiotensin II receptor antagonist.
Accordingly, the method of treatment recited in claim 5 of US’830 encompasses administering such pharmaceutical compositions, and therefore claim 8 is anticipated by US’830.
Regarding claims 10, 12, and 14, they are drawn to the intended use of prevention and/or treatment of DCM or MVD in canines. Further, regarding claims 11, 13, and 15, they are drawn to the intended use of prevention and/or treatment of HCM in felines.
As discussed in the claim interpretation section, the examiner interprets these forms of heart disease as forms of heart disease that cause chronic heart failure.
Accordingly, claims 10-15 are anticipated by US’830 in view of the reasons previously discussed.
Regarding claim 16, US’830 teaches at least oral and intravenous administration. See US’830 at col. 22 (excerpt provided below with respect to the instant claim 17).
Accordingly, claim 16 is anticipated by US’830.
Regarding claim 17, the dosages taught in US’830 encompass those not only the dosages used by Applicant, but also those recited in the instant claim 17. See US’830 at col. 22:
The dosage required to achieve the corresponding activity for treatment or prevention usually depends on the compound which is to be administered, the patient, the nature and gravity of the illness or condition and the method and frequency of administration and is for the patient's doctor to decide. Expediently, the dosage may be from 1 to 100 mg, preferably 1 to 30 mg, by intravenous route, and 1 to 1000 mg, preferably 1 to 100 mg, by oral route, in each case administered 1 to 4 times a day. For this purpose, the compounds according to the invention may be formulated, optionally together with other active substances….
US’830 at col. 22.
The “preferably 1 to 100 mg, by oral route” teaching in US’830, with a lower end of 1 mg per day, encompasses the recited dosing in the instant claim 17 (“0.01 mg/kg bodyweight to 0.3 mg/kg bodyweight per day”), for any canine of feline weighing over 3.34 kg.
Accordingly, claim 17 is anticipated by US’830.
Regarding claims 18 and 23, US’830 teaches administration of the actives at 1, 2, 3, or 4 times a day. See above excerpt from US’830 at col. 22. US’830 at cols. 23-34 further teaches administering the other actives concomitantly or at staggered times. See US’830 at cols. 23-24:
The use of the compound according to the invention, or a physiologically acceptable salt thereof, in combination with another active substance may take place simultaneously or at staggered times, but particularly within a short space of time. If they are administered simultaneously, the two active substances are given to the patient together; while if they are used at staggered times the two active substances are given to the patient within a period of less than or equal to 12 hours, but particularly less than or equal to 6 hours.
See US’830 at cols. 23-24.
Accordingly, claims 18 and 23 are anticipated by US’830.
Regarding claim 24, US’830 at col. 23 explicitly teaches that combinations with “Angiotensin II receptor antagonists are preferably used for the treatment or prevention of high blood pressure and complications of diabetes, often combined with a diuretic such as hydrochlorothiazide.” Therefore, US’830 teaches that the combination with an Angiotensin II receptor antagonist treats or prevents hypertension. Prevention of hypertension is included in the list of “clinical and/or biochemical parameters” recited in claim 24.
Accordingly, claim 24 is anticipated by US’830.
Regarding claim 25, US’830 explicitly teaches fixed-dose-combinations of one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof and telmisartan and the FDS is a solid formulation or a liquid formulation. See US’830 at col. 24, and the discussion of claim 8. See also, US’830 at col. 22, and the discussion of the instant claim 17. See also, US’830 at cols. 59-62 (teaching examples of fixed dose combinations in solid and liquid formulations containing “active substance”, which is defined at col. 59 to include not only “one or more compounds according to the invention… [but also in] the case of the combinations with one or additional active substances as described previously, the term “active substances” also includes the additional active substances.”).
Accordingly, claim 25 is anticipated by US’830.
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 1-2 and 4-25 were Obvious over US’816 as evidenced by References in view of US’090, in further view of US’830, US’894, and US’570
Claim(s) 1-2 and 4-25 is/are rejected under 35 U.S.C. 103 as being unpatentable over US’816 as evidenced by References13 in view of US’090,14 in further view of US’830,15 US’894,16 and US’570.17
The findings of fact and rejections of claims under 35 U.S.C. 102 with respect to US’816 as evidenced by References, US’090, and US’830 are incorporated herein.
As discussed with respect to US’816 as evidenced by References, it teaches a method of prevention and/or treatment of one or more cardiac diseases in a non-human mammal comprising administering to the non-human mammal a pharmaceutical composition comprising a SGLT-2 inhibitor or pharmaceutically acceptable forms thereof in combination with pimobendan and/or telmisartan or pharmaceutically acceptable forms thereof.
Continuing, US’816 as evidenced by References specifically teaches the HCM, DCM, and MVD cardiac diseases in a non-human mammal as the patient population, and exemplifies such treatments in cats and dogs.
Further, as discussed, the dosages of the active SGLT-2 inhibitor administered, and the dosages of pimobendan and telmisartan as taught in US’816 as evidenced by References encompass the dosages of these actives recited in the instant claims.
Moreover, as discussed, US’816 as evidenced by References exemplifies Bexagliflozin as the active SGLT-2 administered, and teaches proline co-crystals. See also, Fig. 5 of US’816 for a dose-dependence relationship its inventors taught for the administration “of 1:2 bexagliflozin:proline co-crystal is plotted as a function of bexagliflozin dose in mg kg−1.” US’816 at 1, paragraph [0016].
That figure is evidence that the “dose” of the active SGLT-2 administered was a result-effective variable that one of ordinary skill in the art at the time of filing could modify through routine experimentation. Indeed, as a preface to its disclosed examples, US’816 as evidenced by References states at 27, paragraph [0287] “The following examples are offered for illustrative purposes, and are not intended to limit the disclosure in any manner. Those of skill in the art will readily recognize a variety of noncritical parameters which can be changed or modified to yield essentially the same results.” Even though bexagliflozin was exemplified, velagliflozin is a preferred embodiment of the SGLT inhibitors administered, and it is indeed the third compound recited in claim 39 and listed in paragraph [0135].
To the extend the claims require combination of the actives as a single compounded medication, as discussed US’816 teaches that animals exhibit “evasive or aversive responses” in response to medications, and one of skill in the art, reading US’816 as evidenced by References would at once envision such a compounded medication to simply administration to the patients.
It would take only ordinary and routine experimentation working within the context of US’816 as evidenced by References to arrive at the entire scope claimed invention, outside of the “more [than] SGLT-2 inhibitor” administration, because it is not exactly clear if US’816 as evidenced by References specifically teaches the administration of “more [than] SGLT-2 inhibitor” at a time. The instant claims permit such combinations, but never exemplifies them in the specification.
However, as discussed, US’090 teaches a method of prevention and/or treatment of one or more cardiac disease in felines comprising administering to the feline a pharmaceutical composition comprising one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and/or telmisartan or pharmaceutically acceptable forms thereof.
As discussed, in US’090, the disclosed dosages of one or more SGLT-2 inhibitors, which specifically include velagliflozin, overlap with those recited in the instant claims. Further, the dosages were consistent with those taught in US’816 as evidenced by References.
Accordingly, telmisartan and pimobendan as taught by both US’816 and US’090, were known to be effective in combination with one or more SGLT-2 inhibitors for treating one or more cardiac diseases in a non-human mammal.
Moreover, and in further view of US’830, the express combination of a SGLT-2 inhibitor with an Angiotensin II receptor antagonist was explicitly taught in pharmaceutical combinations for treating high blood pressure and chronic heart failure. US’830 explicitly states that it was preferred to include an Angiotensin II receptor antagonist for the treatment or prevention of high blood pressure. US’830 specifically lists telmisartan as an Angiotensin II receptor antagonist to include in its pharmaceutical combinations.
Moreover, and in further view of US’894, the administration of pimobendan was known to be effective for treating symptomatic and asymptomatic heart failure in dogs, cats, horses, and other non-human mammals (see, e.g., US’894 at claims 1-7), which was exemplified with a “a daily dose of 0.4–0.6 mg/kg” pimobendan. US’894 at col. 9, example 2. The scope of the invention of US’894 further comprised “symptomatic” heart failure, and listed DVM. See US’894 at col. 1, “Technical Field”, and US’894 at col. 4, lines 56-60 (listing DVM), and US’894 at col 8, last paragraph (“The study was done in symptomatic dogs.”). While not claimed in US’894, combination with telmisartan was explicitly taught for this treatment method. See US’894 at col. 6, lines 5-10. Pimobendan was taught to prolong the outset of clinical symptoms (see, e.g., US’894 at col. 12, last paragraph and claims 1 and 8), and reduce heart size in such patients (see, e.g., US’894 at Abstract and at claims 7 and 13).
Moreover, and in further view of US’570, the administration of pimobendan was known to be effective for treating asymptomatic (occult, preclinical) heart failure due to mitral valve disease (MVD) or myxomatous mitral valve disease (MMVD) in in dogs, cats, horses, and other non-human mammals (see, e.g., US’570 at claims 1-8), and end stage in combination with diuretics (see claims 20-21, reciting ISACHC Class D3). While not claimed in US’570, combination with telmisartan was explicitly taught for this treatment method. See US’570 at col. 9, lines 7-11.
Accordingly, one of ordinary skill in the art at the time of filing would have a reasonable expectation of success in preventing and/or treating of one or more cardiac diseases in a non-human mammal comprising administering to the non-human mammal a pharmaceutical composition comprising one or more SGLT-2 inhibitors or pharmaceutically acceptable forms thereof in combination with pimobendan and/or telmisartan or pharmaceutically acceptable forms thereof, because the exact combinations and dosages were taught for such patient populations (US’816 as evidenced by References and US’090), and the combinations were taught to at least further reduce blood pressure (US’830), and prolong the time until onset of symptoms of heart failure in the patients (US’894 and US’570).
The combination results in the subject matter of claims 1, 2 and 4-25.
Accordingly, claims 1, 2 and 4-25 were obvious at the time of filing.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
NDSP over US’378 in view of US’816 as evidenced by References
Claims 1-2 and 4-25 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 14, 15, 16, and 17 of U.S. Patent No. 11,826,378 B2, hereinafter (“US’378”)18 in view of US’816 as evidenced by References.19
The findings of fact and discussions of US’816 as evidenced by References in the sections regarding 102 and 103 are fully incorporated herein.
US’378, in claims 4 and 14-16 teaches a method of treatment of one or more cardiac diseases in a feline animal (HCM and heart failure due to HCM) comprising administering a single SGLT-2 inhibitor or a pharmaceutically acceptable form thereof (Velagliflozin, overlapping dosages) before, after or concomitantly with one or more other active pharmaceutical ingredients, including pimobendan and telmisartan. Pimobendan and telmisartan are the only examples of the ARB and/or positive inotropes administered in the combination therapy. US’378, in claim 17, teaches the method of claim 4 for extended patient populations (felines with DCM, etc).
US’378 at claim 1 teaches a method of treatment of one or more cardiac diseases in a feline animal comprising administering to the feline animal one or more SGLT-2 inhibitors, and selects velagliflozin as active administered.
US’816 as evidenced by References expressly teaches a method of prevention and/or treatment of one or more cardiac diseases in a non-human mammal comprising administering to the non-human mammal a pharmaceutical composition comprising a SGLT-2 inhibitor or pharmaceutically acceptable forms thereof in combination with pimobendan and/or telmisartan or pharmaceutically acceptable forms thereof, as discussed.
As discussed, US’816 as evidenced by References teaches one or more SGLT-2 inhibitors suitable for treating one or more cardiac diseases in a non-human mammal.
One of ordinary skill in the art at the time of filing of the patent application that resulted in the grant of the US’378 patent, and in possession of its subject matter, would have a reasonable expectation of success in incorporating one or more SGLT-2 inhibitors from US’816 as evidenced by References and utilizing them in the instantly claimed methods because the one or more SGLT-2 inhibitors from US’816 as evidenced by References were taught to be effective for the prevention and/or treatment of one or more cardiac diseases in a non-human mammal.
Accordingly, claims 1-2 and 4-25 were obvious over claims 1, 4, 14, 15, 16, and 17 of US’378, in view of US’816 as evidenced by References.
NDSP over US’017 in view of WO’295 and US’373
Claims 1-2, 4, 6-7, 9, 11, 13, 15-25 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 14, 18 and 27 of U.S. Patent No. 10,220,017 B2, hereinafter (“US’017”)20 in view of WO’295,21 and US’373.22
US’017, in claims 1, 14, 18 and 27 teaches a method of treating hypertension in horses and canines and Syndrome X (metabolic syndrome) in canines and felines comprising administering a liquid pharmaceutical composition comprising at least one SGLT-2 inhibitor (velagliflozin). The route of administration is oral or parenteral administration (claim 18).
US’017 does not define Syndrome X (metabolic syndrome), nor does it require a combination therapy with pimobendan and telmisartan. The methods taught however permit such combinations because the pharmaceutical compositions taught are “comprising”, and not “consisting of”.
However, WO’295 at 21-22 defines Syndrome X (metabolic syndrome), and states that it is “a combination of medical disorders that increase the risk of developing cardiovascular disease and diabetes,” which is also called “CHAOS”, which means “Coronary artery disease, Hypertension, Atherosclerosis, Obesity, and Stroke”. WO’295 at 22, lines 25-31, states that “drug treatment is frequently required) and lists diuretics and ACE inhibitors to treat the hypertension. WO’295 was filed by the same Applicant, and it is reasonable to interpret “Syndrome X (metabolic syndrome)” using Applicant’s chosen definition.
Accordingly, Syndrome X (metabolic syndrome) is a metabolic disease that manifests as cardiovascular disease and diabetes, and may require treatment with a drug to treat hypertension. The instant specification defines “cardiac disease” to “refer to any disorder and deformities of the heart itself, which affect the heart’s structure and function”. The examiner interprets the definition of Syndrome X (metabolic syndrome) from WO’295 which includes “Coronary artery disease” as referring to “a disorder and deformit[y] of the heart itself, which affect[s] the heart’s structure and function”, because the coronary arteries are part of the heart.
Further, the examiner notes that WO’295 at claim 16 also teaches the administration of one or more SGLT-2 inhibitors, which it refers to as “another pharmaceutically active compound”. Regarding the claim term “another pharmaceutically active compound”, WO’295 at 31 states that “Such compounds are described in the art and can be incorporated into respective pharmaceutical compositions by a person skilled in the art by methods which are basically known.” On pages 32-35, WO’295 specifically discusses the SGLT-2 inhibitors, and discusses “staggered” administration at 32, lines 24-28.
One of ordinary skill in the art at the time of filing, and in possession of the subject matter of US’017, would have a reasonable expectation of success in adding telmisartan and pimobendan in such a treatment regimen for felines because US’373 teaches a method of treatment of feline systemic disease including hypertension comprising administering telmisartan (claims 1 and 3, and 7) in combination with at least one other drug (claim 5), including cardiotonic-Ca-sensitising agents (claim 6). The specification lists Pimobendan and Levosimendan as cardiotonic-Ca-sensitising agents. See US’373 at 6, paragraphs [0046]-[0049] (stating that a preferred kit for treating systemic disease includes telmisartan and one or more of a list that includes cardiotonic-Ca-sensitising agents (Pimobendan and Levosimendan)). US’373 at paragraphs [0050]-[0051] specifically lists patients with DCM, mitral valve insufficiency (MI), HCM, hypertension, “metabolic disorders like diabetes mellitus”, and other cardiac diseases as preferred patient populations. The “metabolic disorders like diabetes mellitus” indication overlaps with the definition in WO’295 at 22, for Syndrome X (metabolic syndrome).
The dose of telmisartan is “most preferred about 0.75 to about 1.5 mg/kg of body weight”, US’373 at 4, paragraph [0029], consistent with the instant claim 22. US’373 at 4, paragraphs [0028]-[0031] teaches other dosages consistent with those recited in the instant claim 22 (see, e.g., paragraph [0028] (about 10 lines down) “the range is 0.01 to about 10 mg/kg bodyweight”, and at last sentence (indicating the dose is per day)).
Furthermore, the examiner notes that US’373 at col. 2, paragraph [0015], specifically states that telmisartan had been tested in dogs since 1994, and that the information had been reported in “Investigator brochure 1994, data on file”. The examiner interprets those statements as teaching that veterinary clinicians understood that telmisartan was safe to administer to dogs for treating at least hypertension by the filing date of the US’373 patent. However, it is not clear to the extent that information was public based on US’373 itself.
Therefore, it would have been obvious for one of ordinary skill in the art at the time of filing, and in possession of the subject matter of US’017, to include telmisartan and pimobendan in the method of treating feline Syndrome X (metabolic syndrome) as taught by US’373. Any benefit to the feline patients with feline Syndrome X (metabolic syndrome) and underlying DCM, MI, HCM, hypertension and other related heart diseases would have been a clear benefit to an ordinary veterinarian at the time of filing.
Regarding the dosages of the SGLT-2 inhibitors, pimobendan and telmisartan and frequency of administration (claims 17-23), MPEP 2144.05, subjection IIA states “… 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, the amounts of SGLT-2 inhibitors (recited in the instant claim 17) and the amounts of pimobendan (recited in the instant claim 19) are not inventive over the prior art, since the administration of the SGLT-2 inhibitors (US’017 and WO’295) and pimobendan (at least US’373) were known for the same patients (felines with one or more cardiac diseases, including Syndrome X (metabolic syndrome)). The amounts of telmisartan taught in US’373 specifically overlap with those recited in the instant claim 22. Further, staggered/simultaneous dosing frequencies (claims 18, 20, 21, and 23) were known for the actives (WO’295 at 32, lines 24-28, and US’373 at 4, paragraph [0029], last sentence (teaching once, twice or trice a day dosage)). Therefore, the amounts and frequency of administration would require only ordinary and routine experimentation to optimize.
Regarding claim 24, both US’017 and US’373 teach that the administration would treat hypertension, and US’373 teaches the “prevention” axis at title.
Accordingly, claims 1-2 and 4-25 were obvious over claims 1, 14, 18 and 27 of US’017, in view of WO’295, and US’373.
NDSP over US’683 in view of WO’295 and US’373
Claims 1-2, 4, 6-7, 9, 11, 13, 15-25 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 19 and 28 of U.S. Patent No. 10,709,683 B2, hereinafter (“US’683”)23 in view of WO’295, and US’197.
US’683, in claims 1, 4, 19 and 28 teaches a method of treating hypertension in horses and canines and Syndrome X (metabolic syndrome) in canines and felines comprising administering a liquid pharmaceutical composition comprising at least one SGLT-2 inhibitor (velagliflozin). The route of administration is oral or parenteral administration (claim 19).
The preceding discussion of WO’295 and US’373 in the above NDSP rejection over US’017 in view of WO’295 and US’373 is fully incorporated herein. US’683 is in family with US’017.
One of ordinary skill in the art at the time of filing, and in possession of the subject matter of US’017, would have a reasonable expectation of success in adding telmisartan and pimobendan in such a treatment regimen for felines because US’373 teaches a method of treatment of feline systemic disease including hypertension comprising administering telmisartan (claims 1 and 3, and 7) in combination with at least one other drug (claim 5), including cardiotonic-Ca-sensitising agents (claim 6). The specification lists Pimobendan and Levosimendan as cardiotonic-Ca-sensitising agents. See US’373 at 6, paragraphs [0046]-[0049] (stating that a preferred kit for treating systemic disease includes telmisartan and one or more of a list that includes cardiotonic-Ca-sensitising agents (Pimobendan and Levosimendan)). US’373 at paragraphs [0050]-[0051] specifically lists patients with DCM, mitral valve insufficiency (MI), HCM, hypertension, “metabolic disorders like diabetes mellitus”, and other cardiac diseases as preferred patient populations. The “metabolic disorders like diabetes mellitus” indication overlaps with the definition in WO’295 at 22, for Syndrome X (metabolic syndrome).
The dose of telmisartan is “most preferred about 0.75 to about 1.5 mg/kg of body weight”, US’373 at 4, paragraph [0029], consistent with the instant claim 22. US’373 at 4, paragraphs [0028]-[0031] teaches other dosages consistent with those recited in the instant claim 22 (see, e.g., paragraph [0028] (about 10 lines down) “the range is 0.01 to about 10 mg/kg bodyweight”, and at last sentence (indicating the dose is per day)).
Furthermore, the examiner notes that US’373 at col. 2, paragraph [0015], specifically states that telmisartan had been tested in dogs since 1994, and that the information had been reported in “Investigator brochure 1994, data on file”. The examiner interprets those statements as teaching that veterinary clinicians understood that telmisartan was safe to administer to dogs for treating at least hypertension by the filing date of the US’373 patent. However, it is not clear to the extent that information was public based on US’373 itself.
Therefore, it would have been obvious for one of ordinary skill in the art at the time of filing, and in possession of the subject matter of US’683, to include telmisartan and pimobendan in the method of treating feline Syndrome X (metabolic syndrome) as taught by US’373. Any benefit to the feline patients with feline Syndrome X (metabolic syndrome) and underlying DCM, MI, HCM, hypertension and other related heart diseases would have been a clear benefit to an ordinary veterinarian at the time of filing.
Regarding the dosages of the SGLT-2 inhibitors, pimobendan and telmisartan and frequency of administration (claims 17-23), MPEP 2144.05, subjection IIA states “… 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, the amounts of SGLT-2 inhibitors (recited in the instant claim 17) and the amounts of pimobendan (recited in the instant claim 19) are not inventive over the prior art, since the administration of the SGLT-2 inhibitors (US’017 and WO’295) and pimobendan (at least US’373) were known for the same patients (felines with one or more cardiac diseases, including Syndrome X (metabolic syndrome)). The amounts of telmisartan taught in US’373 specifically overlap with those recited in the instant claim 22. Further, staggered/simultaneous dosing frequencies (claims 18, 20, 21, and 23) were known for the actives (WO’295 at 32, lines 24-28, and US’373 at 4, paragraph [0029], last sentence (teaching once, twice or trice a day dosage)). Therefore, the amounts and frequency of administration would require only ordinary and routine experimentation to optimize.
Regarding claim 24, both US’683 and US’373 teach that the administration would treat hypertension, and US’373 teaches the “prevention” axis at title.
Accordingly, claims 1-2 and 4-25 were obvious over claims 1, 4, 19 and 28 of US’683, in view of WO’295, and US’373.
Provisional NDSP over US 18/321,117 in view of US’816 as evidenced by References
Claims 1-2 and 4-25 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2, 35 and 38 of copending Application No. 18/321,117 (the reference application)24 in view of US’816 as evidenced by References.25
The findings of fact and discussions regarding US’816 as evidenced by References in the previous 102 section are fully incorporated herein.
The reference application teaches, in claims 2, 35, and 38 a method of prevention and/or treatment of one or more cardiac diseases in a non-human mammal comprising administering to the non-human mammal a pharmaceutical composition comprising one or more SGLT-2 inhibitors.
The reference application does not teach the method comprising the administration of pimobendan and/or telmisartan.
However, US’816 as evidenced by References teaches the combination of pimobendan and/or telmisartan with SGLT-2 inhibitors for treating one or more cardiac diseases in a non-human mammals.
One of ordinary skill in the art at the time of filing, and in possession of the subject matter of the reference application, would have a reasonable expectation of success in adding pimobendan and/or telmisartan in its method of treating one or more cardiac diseases in a non-human mammal because US’816 as evidenced by References teaches the combination of pimobendan and/or telmisartan with SGLT-2 inhibitors for treating one or more cardiac diseases in a non-human mammals.
Accordingly, claims 1-2 and 4-25 were obvious over claims 2, 35 and 38 of the reference application in view of US’816 as evidenced by References
This is a provisional nonstatutory double patenting rejection.
Provisional NDSP over US 18/594,627 in view of US’816 as evidenced by References
Claims 1-2 and 4-25 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 17, 18, 20, and 21 of copending Application No. 18/594,627 (the reference application)26 in view of US’816 as evidenced by References.27
The findings of fact and discussions regarding US’816 as evidenced by References in the previous 102 section are fully incorporated herein.
The reference application teaches, in claims 17, 18, 20, and 21 a method of prevention and/or treatment of one or more cardiac diseases in a non-human mammal comprising administering to the non-human mammal a pharmaceutical composition comprising one or more SGLT-2 inhibitors.
The reference application does not teach the method comprising the administration of pimobendan and/or telmisartan.
However, US’816 as evidenced by References teaches the combination of pimobendan and/or telmisartan with SGLT-2 inhibitors for treating one or more cardiac diseases in a non-human mammals.
One of ordinary skill in the art at the time of filing, and in possession of the subject matter of the reference application, would have a reasonable expectation of success in adding pimobendan and/or telmisartan in its method of treating one or more cardiac diseases in a non-human mammal because US’816 as evidenced by References teaches the combination of pimobendan and/or telmisartan with SGLT-2 inhibitors for treating one or more cardiac diseases in a non-human mammals.
Accordingly, claims 1-2 and 4-25 were obvious over claims 17, 18, 20, and 21 of the reference application in view of US’816 as evidenced by References.
This is a provisional nonstatutory double patenting rejection.
Provisional NDSP over US 18/578,205
Claims 1-2 and 4-25 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17, 19, and 20 of copending Application No. 18/578,205 (the reference application).28 Although the claims at issue are not identical, they are not patentably distinct from each other.
The reference application teaches, in claims 1-17, 19, and 20 a method of prevention and/or treatment of one or more cardiac diseases in a non-human mammal comprising administering to the non-human mammal a pharmaceutical composition comprising one or more SGLT-2 inhibitors. The one or more cardiac diseases are hypertension in a non-human mammal. The combination with telmisartan and pimobendan are expressly taught in claim 14.
One of ordinary skill in the art at the time of filing, and in possession of the subject matter of the reference application, would have a reasonable expectation of success in treating or preventing one or more cardiac diseases other than hypertension in a non-human mammal comprising administering to the non-human mammal a pharmaceutical composition comprising one or more SGLT-2 inhibitors combined with telmisartan and/or pimobendan because hypertension is a symptom of one or more cardiac sought to be treated in the instant patient populations. Treating and preventing the hypertension by administering the same compositions to the same patients would reasonably treat or prevent the underling one or more cardiac diseases by addressing the underlying problems.
Accordingly, although the claims at issue are not identical, they are not patentably distinct from each other because they teach administration of the same compositions to the same patient populations, and the same compositions would inherently produce the same biological effects when administered in the same way to the same patients.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Provisional NDSP over US 18/666,922 in view of US’816 as evidenced by References
Claims 1-2 and 4-25 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17, 19, and 20 of copending Application No. 18/666,922 (the reference application)29 in view of US’816 as evidenced by References.30
The findings of fact and discussions regarding US’816 as evidenced by References in the previous 102 section are fully incorporated herein.
The reference application teaches, in claims 1, 2, and 6-25 a method of prevention and/or treatment of one or more cardiac diseases in a non-human mammal comprising administering to the non-human mammal a pharmaceutical composition comprising one or more SGLT-2 inhibitors. The one or more cardiac diseases are hypertension in a non-human mammal. Moreover, heart disease is expressly recited in claim 7. The combination with telmisartan is expressly taught in claim 1.
The reference application does not teach the method comprising the administration of pimobendan.
However, US’816 as evidenced by References teaches the combination of pimobendan and/or telmisartan with SGLT-2 inhibitors for treating one or more cardiac diseases in a non-human mammals.
One of ordinary skill in the art at the time of filing, and in possession of the subject matter of the reference application, would have a reasonable expectation of success in adding pimobendan and/or telmisartan in its method of treating one or more cardiac diseases in a non-human mammal because US’816 as evidenced by References teaches the combination of pimobendan and/or telmisartan with SGLT-2 inhibitors for treating one or more cardiac diseases in a non-human mammals.
Accordingly, claims 1-2 and 4-25 were obvious over claims 1, 2, and 6-25 of the reference application in view of US’816 as evidenced by References.
This is a provisional nonstatutory double patenting rejection.
Provisional NDSP over US 18/578,207 in view of US’816 as evidenced by References
Claims 1-2 and 4-25 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, and 4-19 of copending Application No. 18/578,207 (the reference application)31 in view of US’816 as evidenced by References.32
The findings of fact and discussions regarding US’816 as evidenced by References in the previous 102 section are fully incorporated herein.
The reference application teaches, in claims 1, 2, and 6-25 a method of prevention and/or treatment of one or more cardiac diseases in a non-human mammal comprising administering to the non-human mammal a pharmaceutical composition comprising one or more SGLT-2 inhibitors. The one or more cardiac diseases are chronic kidney disease causing high blood pressure in a non-human mammal (see claim 18). The combination with pimobendan and/or telmisartan is expressly taught in claim 14.
The reference application does not expressly teach the administration for one or more cardiac diseases other than chronic kidney disease causing high blood pressure in a non-human mammal.
However, US’816 as evidenced by References teaches the combination of pimobendan and/or telmisartan with SGLT-2 inhibitors for treating one or more cardiac diseases in a non-human mammals.
One of ordinary skill in the art at the time of filing, and in possession of the subject matter of the reference application, would have a reasonable expectation of success in adding pimobendan and/or telmisartan in its method of treating one or more cardiac diseases in a non-human mammal because US’816 as evidenced by References teaches the combination of pimobendan and/or telmisartan with SGLT-2 inhibitors for treating one or more cardiac diseases in a non-human mammals.
Accordingly, claims 1-2 and 4-25 were obvious over claims 1, and 4-19 of the reference application in view of US’816 as evidenced by References.
This is a provisional nonstatutory double patenting rejection.
Provisional NDSP over US 18/482,334 in view of US’816 as evidenced by References
Claims 1-2 and 4-25 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 and 16-22 of copending Application No. 18/482,334 (the reference application)33 in view of US’816 as evidenced by References.34
The findings of fact and discussions regarding US’816 as evidenced by References in the previous 102 section are fully incorporated herein.
The reference application teaches, in claims 1-14 and 16-22 a method of prevention and/or treatment of one or more cardiac diseases in a felines comprising administering to the non-human mammal a pharmaceutical composition comprising one or more SGLT-2 inhibitors. The one or more cardiac diseases DCM, HCM, etc (see claim 2). The combination with pimobendan and/or telmisartan is expressly taught in claim 19.
The reference application does not expressly teach the administration for one or more cardiac diseases in non-human mammals other than felines.
However, US’816 as evidenced by References teaches the combination of pimobendan and/or telmisartan with SGLT-2 inhibitors for treating one or more cardiac diseases in a non-human mammals.
One of ordinary skill in the art at the time of filing, and in possession of the subject matter of the reference application, would have a reasonable expectation of success in adding pimobendan and/or telmisartan in its method of treating one or more cardiac diseases in a non-human mammal because US’816 as evidenced by References teaches the combination of pimobendan and/or telmisartan with SGLT-2 inhibitors for treating one or more cardiac diseases in a non-human mammals.
Accordingly, claims 1-2 and 4-25 were obvious over claims 1-14 and 16-22 of the reference application in view of US’816 as evidenced by References.
This is a provisional nonstatutory double patenting rejection.
Provisional NDSP over US 18/578,118 in view of US’816 as evidenced by References
Claims 1-2 and 4-25 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of copending Application No. 18/578,118 (the reference application)35 in view of US’816 as evidenced by References.36
The findings of fact and discussions regarding US’816 as evidenced by References in the previous 102 section are fully incorporated herein.
The reference application teaches, in claims 1-17 a method of prevention and/or treatment of one or more cardiac diseases in a non-human mammal (excluding felines) comprising administering to the non-human mammal a pharmaceutical composition comprising one or more SGLT-2 inhibitors. The one or more cardiac diseases DCM, HCM, etc (see claim 2). The combination with pimobendan and/or telmisartan is expressly taught in claim 14.
The reference application does not expressly teach the administration for one or more cardiac diseases in felines.
However, US’816 as evidenced by References teaches the combination of pimobendan and/or telmisartan with SGLT-2 inhibitors for treating one or more cardiac diseases in a non-human mammals.
One of ordinary skill in the art at the time of filing, and in possession of the subject matter of the reference application, would have a reasonable expectation of success in adding pimobendan and/or telmisartan in its method of treating one or more cardiac diseases in a non-human mammal because US’816 as evidenced by References teaches the combination of pimobendan and/or telmisartan with SGLT-2 inhibitors for treating one or more cardiac diseases in a non-human mammals.
Accordingly, claims 1-2 and 4-25 were obvious over claims 1-17 of the reference application in view of US’816 as evidenced by References.
This is a provisional nonstatutory double patenting rejection.
Prior Art Cited but not Applied
The prior art made of record and not relied upon is considered pertinent to applicant’s disclosure.
Kley, Saskia and Riche, Dania Birte, “Treatment of metabolic disorders in canine animals”, U.S. Patent No. US 10603300 B2, published 2020-03-31, assignee Boehringer Ingelheim Vetmedica GmbH, hereinafter “US’300”.
US’300 teaches the exact dosages of SGTL-2 inhibitors to administer to canines for treating metabolic conditions. The dosages all overlap, and velagliflozin is exemplified. The metabolic conditions include Syndrome X. The specification expressly states that Syndrome X causes hypertension and cardiomyopathy. Accordingly, US’300 provides direct evidence of treating a “cardiac disease” in canines using velagliflozin. Further, the Specification is broad enough to permit combination therapies at least with telmisartan, in view of it incorporating WO 2007/128749 in its entirety.
Han, Donghyun and Jung, Dong-In, “Long term effects after telmisartan administered for cardiovascular-renal axis disorder in cats”, J. Biomed Transl Res, vol. 20, no. 4, pp. 99-104.
Teaches telmisartan for cats with HCM in the context of the cardiorenal syndrome and the cardiovascular-renal axis disorder.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Christopher Evan Redwood whose telephone number is (571) 272-8882. The examiner can normally be reached Monday - Friday 6:15 AM - 4:45 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey S. Lundgren can be reached at 571-272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/C.E.R./Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
1 See, e.g., VETMEDIN FOIA Summary, dated April 30, 2007, at pdf page 2.
2 See, e.g., Semintra FOIA Summary, dated May 15, 2018, pdf page 3.
3 See, e.g., Eckhardt, Matthias, et al., “Glucopyranosyl-substituted Benzonitrile Derivatives, Pharmaceutical Compositions Containing Such Compounds, Their Use And Process For Their Manufacture”, U.S. Patent No. US 7776830 B2, published 2010-08-17, filed 2007-05-01, assignee Boehringer Ingelheim International GmbH, hereinafter “US’830”, at cols. 39-40 (Example XXIV), cols. 22-23 (dosages and combinations), and cols. 62-63 (claims 1-7).
4 See, e.g., VETMEDIN FOIA Summary, dated April 30, 2007, at pdf page
5 See, e.g., Vetmedin®-CA1 FOIA Summary, dated June 16, 2022, at pdf page 1.
6 See, e.g., VETMEDIN FOIA Summary, dated April 30, 2007, at pdf page 2.
7 See, e.g., Semintra FOIA Summary, dated May 15, 2018, pdf page 4.
8 Hadd, Michael, et al., “SODIUM-GLUCOSE LINKED TRANSPORTER INHIBITORS FOR THE MANAGEMENT OF CHRONIC KIDNEY DISEASE, HYPERTENSION, AND HEART FAILURE IN COMPANION ANIMALS”, U.S. Patent Application Publication No. US 20230000816 A1, published 2023-01-05, applicant INCREVET, INC., hereinafter “US’816”. US’816 claims priority to U.S. Provisional Patent Application No. 62/932,395, filed 11-07-2019.
9 US’816 incorporates its cited references in their entirety. See US’816 at 32, paragraph [0321]. The following references are discussed in the rejection as they provide dosages of telmisartan and pimobendan.
Sent, U., et al. "Comparison of efficacy of long-term oral treatment with telmisartan and benazepril in cats with chronic kidney disease." Journal of veterinary internal medicine 29.6 (2015): 1479-1487, hereinafter “Sent 2015”.
Häggström, J., et al. "Effect of pimobendan or benazepril hydrochloride on survival times in dogs with congestive heart failure caused by naturally occurring myxomatous mitral valve disease: the QUEST study." Journal of Veterinary Internal Medicine 22.5 (2008): 1124-1135, hereinafter “Häggström 2008”.
Beaumier, Amelie, et al. "Clinical findings and survival time in dogs with advanced heart failure." Journal of veterinary internal medicine 32.3 (2018): 944-950, hereinafter “Beaumier 2018”.
10 Telmisartan - ARBs are specifically disclosed for routine treatment of heart failure. See, e.g., US’816 at 5, paragraph [0053], and Examples 5 and 6 (discussed as RAS blocking agents). Telmisartan itself had disclosed use in companion animals. See US’816 at 4, paragraph [0048]. Further, it is one of two listed ARBs. See US’816 at 26, paragraph [0276].
Pimobendan – US’816 specifically discussed pimobendan for dogs and cats in the context of heart failure. See, e.g., US’816 at 6, paragraphs [0062]-[0064], [0066], and Examples 5 and 6.
11 Kroh, Carla, et al., “USE OF SGLT-2 INHIBITORS FOR THE PREVENTION AND/OR TREAT-MENT OF CARDIAC DISEASES IN FELINES”, US Patent Application Publication No US 20210260090 A1, published 2021-08-26, applicant BOEHRINGER INGELHEIM VETMEDICA GMBH, hereinafter “US’090”.
12 Cited previously in the claim interpretation section. Citation repeated here: Eckhardt, Matthias, et al., “Glucopyranosyl-substituted Benzonitrile Derivatives, Pharmaceutical Compositions Containing Such Compounds, Their Use And Process For Their Manufacture”, U.S. Patent No. US 7776830 B2, published 2010-08-17, filed 2007-05-01, assignee Boehringer Ingelheim International GmbH, hereinafter “US’830”.
13 Previously cited in 102 Section.
14 Previously cited in 102 Section.
15 Previously cited in 102 Section.
16 Daemmgen, Juergen et al., “Use of PDE III inhibitors for the treatment of asymptomatic (occult) heart failure”, U.S. Patent No. US 8980894 B2, published 2015-03-17, assignee BOEHRINGER INGELHEIM VETMEDICA GMBH, hereinafter “US’894”.
17 Schummer, Christoph and Joens, Olaf, “Use of pimobendan for the reduction of heart size and/or the delay of onset of clinical symptoms in patients with asymptomatic heart failure due to mitral valve disease”, U.S. Patent No. US 10537570 B2, published 2020-01-21, assignee BOEHRINGER INGELHEIM VETMEDICA GMBH, hereinafter “US’570”.
18 US’378 is the patent granted from US’090, referenced in the sections regarding 102 and 103. The full citation for US’378 is Kroh, Carla, et al., “USE OF SGLT-2 INHIBITORS FOR THE PREVENTION AND/OR TREAT-MENT OF CARDIAC DISEASES IN FELINES”, U.S. Patent No. US 11826378 B2, published 2023-11-28, priority to EP 20157761, filed 2020-02-17, applicant BOEHRINGER INGELHEIM VETMEDICA GMBH, hereinafter “US’378”.
19 Previously cited in the 102 and 103 sections. US’816 is available as prior art to US’378 because US’816 was filed on 11-07-2019.
20 The full citation for US’017 is Weiler, Cladius, et al., “Liquid pharmaceutical compositions comprising SGLT-2 inhibitors”, U.S. Patent No. US 10220017 B2, published 2019-03-05, priority to EP 15182715, filed 2015-08-27, applicant BOEHRINGER INGELHEIM VETMEDICA GMBH, hereinafter “US’017”.
21 Thomas, Leo, et al., “1-[(3-cyano-pyridin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(r)-amino-piperidin-1-yl]-xanthine for the treatment of a metabolic disorder of a predominantly carnivorous non-human animal”, International Publication No. WO 2011117295 A1, published 2011-09-29, applicant Boehringer Ingelheim Vetmedica GmbH, hereinafter “WO’295”.
22 Stark, Marcus et al., “Angiotensin II receptor antagonist for the prevention or treatment of systemic diseases in cats”, U.S. Patent No. US 20130190373 A1, published 2013-07-25, assignee BOEHRINGER INGELHEIM VETMEDICA GMBH, hereinafter “US’373”.
23 The full citation for US’683 is Weiler, Cladius, et al., “Liquid pharmaceutical compositions comprising SGLT-2 inhibitors”, U.S. Patent No. US 10709683 B2, published 2019-05-16, priority to EP 15182715, filed 2020-02-17, applicant BOEHRINGER INGELHEIM VETMEDICA GMBH, hereinafter “US’683”.
24 The reference application published as U.S. Patent Publication No. US 20230381101 A1.
25 US’816 as evidenced by References was previously cited in the 102 section.
26 The reference application published as U.S. Patent Publication No. US 20240307628 A1.
27 US’816 as evidenced by References was previously cited in the 102 section.
28 The reference application published as US 20240269105 A1.
29 The reference application published as US 20240390332 A1.
30 US’816 as evidenced by References was previously cited in the 102 section.
31 The reference application published as US 20240307426 A1.
32 US’816 as evidenced by References was previously cited in the 102 section.
33 The reference application published as US 20240050456 A1.
34 US’816 as evidenced by References was previously cited in the 102 section.
35 The reference application published as US 20240398845 A1.
36 US’816 as evidenced by References was previously cited in the 102 section.
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