Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
Per Applicant’s amendment to the claims, submitted on 09/02/2025, claims 12 and 14-19 are amended, claims 12 and 20-25 are canceled, and claims 28-33 are newly added. Currently, claims 12, 14-19, and 26-33 are pending in the instant application.
Claim Rejections - 35 USC § 112 Second Paragraph – Withdrawn
Rejections of claims 12 and 22-24:
In light of Applicant’s amendment to the claims the rejections are hereby withdrawn. The previously indicated indefinite language has been removed from claim 12, and claims 22-24 have been canceled.
Claim Rejections - 35 USC § 112 Second Paragraph – New Grounds of Rejection
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 30-33 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 30 is indefinite for reciting the method of claim 26, wherein the compound “improves the cognitive function of a dog for 8 weeks”, because a person of ordinary skill in the art would not reasonably be able to understand the metes and bounds of the claim. The instant claim is essentially reciting the intended result of carrying out the method of claim 26 without adding further structure (i.e., any positively recited steps) to the previously established method. Accordingly, the instant claim is considered as not further limiting of its parent claim. See MPEP2111.004(I):
“In Hoffer v. Microsoft Corp., 405 F.3d 1326, 1329, 74 USPQ2d 1481, 1483 (Fed. Cir. 2005), the court held that when a "‘whereby’ clause states a condition that is material to patentability, it cannot be ignored in order to change the substance of the invention." Id. However, the court noted that a "‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’" Id. (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003))”
Claim 31 is indefinite for the same reasons as claim 30, as it likewise recites the result of carrying out the method of claim 26 without providing structure to the method.
Claim 32 is indefinite for reciting the method of claim 26 wherein the compound “(a) improves the cognitive function of a dog from severe to moderate, weak, or normal level; or (b) restores near normal cognitive function to a dog”, because a person of ordinary skill in the art would not reasonably be able to understand the metes and bounds of the claim. The instant claim is essentially reciting the intended result of carrying out the method of claim 26 without adding further structure (i.e., any positively recited steps) to the previously established method. Accordingly, the instant claim is considered as not further limiting of its parent claim. See MPEP2111.004(I).
Claim 33 is indefinite for the same reasons as claim 31, as it likewise recites the result of carrying out the method of claim 26 without providing structure to the method.
Claim Rejections - 35 USC § 112 First Paragraph – Withdrawn
Rejections of claims 12, 15, and 17-19:
In light of Applicant’s amendment to the claims the rejections are hereby withdrawn. Claim 12 has been amended to recite a single compound. Applicant’s arguments with regards to claim 15 are persuasive, as safety and efficacy testing was indicated as having been conducted over a representative dosing range. Claims 17-19 have been amended to remove the indicated ranges.
Claim Rejections - 35 USC § 102 - Withdrawn
Rejections of claims 12 and 14-15:
In light of Applicant’s amendment to the claims the rejections are hereby withdrawn. Claim 12 has been amended to a method solely for treating CDS in a companion animal by administering a single compound, which overcomes the 102 rejection over Gwag. However, rejection under 35 USC 103 is necessitated by amendment.
Claim Rejections - 35 USC § 103 – Withdrawn
Rejections of claims 16-19 and 26-27:
In light of Applicant’s amendment to the claims the rejections are hereby withdrawn. The rejections of claims 16-19 and 26-27 were predicated on the rejection of claim 12 under 35 USC 102. As the 102 rejection of claim 12 over Gwag has been overcome by amendment, the rejections of the claims are hereby withdrawn. However, rejection under 35 USC 103 is necessitated by amendment.
Claim Rejections - 35 USC § 103 – Necessitated by Amendment
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.
Claim(s) 12 and 14-15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Gwag (previously referenced) in view of Bosch (previously referenced).
Claim 12 recites a method of treating CDS, comprising administering to a companion animal in need thereof 2-hydroxy-5-[2-(4-trifluoromethyl-phenyl)-ethylamino]-benzoic acid or a pharmaceutically acceptable salt thereof.
Gwag teaches compounds and compositions for treatment of neurodegenerative and neuroinflammatory diseases, such diseases including Alzheimer's disease, Parkinson's disease and Lou Gehrig's disease. One such compound taught by Gwag is 2-hydroxy-5-[2-(4- 10 trifluoromethyl-phenyl)-ethylamino]-benzoic acid (specification page 10, lines 9-10)1. A structural representation is provided below for reference:
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The above compound is identical to 2-hydroxy-5-[2-(4- 10 trifluoromethyl-phenyl)-ethylamino]-benzoic acid of the instant claim. Gwag further indicates that testing was carried out on a double APP/PS1 transgenic dementia mouse model of Alzheimer’s disease. Per Gwag, said mice were dosed at 25 mg/kg/day by food administration. Results of such dosing indicate significantly reduced levels of TNF-a, IL-1B, and IL-6 compared to control (page 46, lines 6-8)2, provision of protecting effects on the brain-blood barrier ( page 46, lines 20-23)3, reduction of amyloid plaque burden ( page 47, lines 3-13)4, and behavior improvements reflected in reduced times in an Elevated plus maze test (page 48, lines 4-6)5. In essence, Gwag teaches the administration of the compound of the instant claim to animals which would be considered as “companion animals” (i.e., mice, see Applicant Specification [0024])6.
While Gwag teaches the administration of a compound of the instant claim to a companion animal, they do not explicitly teach the treatment of CDS. However, it would have been obvious for a person of ordinary skill in the art to utilize the methods of Gwag to treat CDS because:
Gwag teaches the use of APP/PS1 transgenic mice as a model for Alzheimer’s disease
Bosch teaches that CDS in dogs is a natural model for Alzheimer’s disease
As both animals are models for the same disease (AD), a person of ordinary skill in the art would reasonably expect that the treatment taught by Gwag would also be effective for treating CDS in dogs due to shared pathological properties
Bosch provides an overview of CDS pathology in dogs and indicates the condition as being a viable model for Alzheimer’s disease in humans. Bosch indicates that CDS in dogs displays similar pathology to AD, including behavioral changes which correspond to the broad spectrum of behavioral changes in human dementia (page 7)7 and similar AB plaque distributions leading to cognitive decline (page 11)8. Such similar pathology and shared biological markers contribute to Bosch’s conclusion that CDS in dogs is a representative model for AD.
In summary, Gwag teaches the use of APP/PS1 transgenic mice as a model for human AD, and further indicates that administration of 2-hydroxy-5-[2-(4- 10 trifluoromethyl-phenyl)-ethylamino]-benzoic acid ameliorates AD symptoms in such a model, while Bosch teaches that CDS in dogs is a viable model for AD due to similarity of the conditions and pathology. Accordingly, the transgenic mouse model introduced by Gwag, and the canine CDS model introduced by Bosch would share similarities by virtue of being viable animal models for the same disease (AD). A person of ordinary skill in the art would therefore have found it prima facie obvious at the time of invention to apply the methods of Gwag to canines with CDS as there would be a reasonable expectation of success in treating CDS or symptoms of CDS in companion animals.
Claim 14 further limits claim 12 wherein the 2-hydroxy-5-[2-(4- 10 trifluoromethyl-phenyl)-ethylamino]-benzoic acid is orally administered.
Gwag teaches oral dosing of the compound by food administration. Accordingly, the instant claim is rejected for the same obviousness reasons as claim 12.
Claim 15 further limits claim 12 wherein the 2-hydroxy-5-[2-(4- 10 trifluoromethyl-phenyl)-ethylamino]-benzoic acid is administered in a dose from 1 mg/kg body weight to 200 mg/kg body weight.
Gwag teaches administration of the compound at 25 mg/kg. Accordingly, the instant claim is rejected for the same obviousness reasons as claim 12.
Claim(s) 16, is/are rejected under 35 U.S.C. 103 as being unpatentable over Gwag (previously referenced) in view of Bosch, of Gao (previously referenced).
Claim 16 further limits the method of claim 12 wherein the method comprises administering a composition wherein the composition is a capsule further comprising:
60% w/w lactose monohydrate
5% w/w croscarmellose sodium
0.5% magnesium stearate
1% w/w sodium lauryl sulfate
As discussed previously, the combination of the teachings of Gwag and Bosch obviate a method of treating CDS in a companion animal. However, neither Gwag nor Bosch explicitly teach the administration of a composition as recited. However, it would be obvious for a person of ordinary skill in the art to arrive at such a composition because:
Gwag further makes suggestion of multiple dosing forms, including capsules
And Gao teaches each of the recited components as common excipients in capsule formulations
Firstly, and with regards to element (a), Gwag teaches the administration of 2-hydroxy-5-[2-(4- 10 trifluoromethyl-phenyl)-ethylamino]-benzoic acid to mice at a dose of 25 mg/kg/day. Gwag further indicates that compositions of their disclosure may be formulated as solid dosage forms including tablets and capsules, wherein such forms may include diluents, disintegrating agents, and lubricants (page 16, lines 14-20)9.
With regards to element (b), Gao teaches oral capsule formulations comprising celecoxib as an active ingredient along with various pharmaceutically acceptable excipients (paragraph [0059])10. One such exemplary composition is provided in the following Table 1 (paragraph [0349]):
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As can be seen from the above example, the composition comprises: (ii) lactose monohydrate, (iii) croscarmellose sodium, (iv) magnesium stearate, and (v) sodium lauryl sulfate. Gao indicates that each of the aforementioned constituents are considered as excipients. More specifically, that lactose is a diluent (paragraph [0116])11, croscarmellose sodium is a disintegrant (paragraph [0120])12, magnesium stearate is a lubricant (paragraph [0129])13, and sodium lauryl sulfate is a wetting agent (paragraph [0125])14.
While the exact recited percentage amounts are not explicitly taught by Gwag or Gao, these values would be readily elucidated by a person of ordinary skill in the art per routine optimization, as each of the components are commonly used in API capsule formulations per Gao, each of the components has predictable effect as a class of excipient, and there would be a reasonable expectation of success in formulating and administering such a composition. See MPEP 2144.05(II) Routine Optimization:
“Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. ‘[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.’ “
In summary, Gwag teaches the use of 2-hydroxy-5-[2-(4- 10 trifluoromethyl-phenyl)-ethylamino]-benzoic acid to mice at a dose of 25 mg/kg/day, and makes the reasonable suggestion to formulate as a capsule comprising excipients such as diluents, disintegrating agents, and lubricants and Gao teaches the use of lactose monohydrate, croscarmellose sodium, magnesium stearate, and sodium lauryl sulfate as common excipients for capsule formulations which fall squarely within the classes of excipients suggested by Gwag. Given the known properties of each of these excipients, the recited percentage amounts of the composition would constitute a routine optimization of said excipients. Accordingly, a person of ordinary skill in the art would have found it prima facie obvious at the time of invention to be able to combine the aforementioned teachings to develop a method comprising administering a composition of the instant claim as there would have been reasonable expectation that such a composition would be effective in treating CDS in a companion animal.
Claim 17 is rejected under 35 U.S.C. 103 as being unpatentable over Gwag in view of Bosch, and further in view of Sutherland (previously referenced).
Claim 17 further limits the method of claim 12 wherein the method comprises administering a food composition further comprising:
42.7% w/w starch
21.0% w/w crude protein
14% w/w crude fat
1.9% w/w crude fiber
6.10% w/w crude ash
1.4% w/w arginine
0.75% w/w calcium
1.1% w/w lysine
1.18% w/w methionine plus cystine
0.5% w/w phosphorus
As discussed previously, the combination of the teachings of Gwag and Bosch obviate a method of treating CDS in a companion animal. However, neither Gwag nor Bosch explicitly teach the administration of a composition as recited. However, it would be obvious for a person of ordinary skill in the art to arrive at such a composition because:
Gwag teaches feed administration of 2-hydroxy-5-[2-(4- 10 trifluoromethyl-phenyl)-ethylamino]-benzoic acid to mice
Sutherland teaches the use of animal feed compositions as carriers for pharmaceutical actives
With regards to item (a), as previously iterated, Gwag provides an exemplary dosing method wherein mice are dosed by feed administration a composition comprising 2-hydroxy-5-[2-(4- 10 trifluoromethyl-phenyl)-ethylamino]-benzoic acid. While the exemplary dosing scheme of Gwag is drawn to the use of food compositions, they do not explicitly teach a composition matching the recited components. However, this deficiency is ameliorated by the teachings of Sutherland, which provide teachings regarding common excipients for food compositions.
With regards to item (b), Sutherland teaches the administration of probiotic fiber complex to animals for the purpose of conferring various health benefits; such probiotic fiber complexes being incorporated within a feed formulation. Sutherland provides an exemplary feed formulation with the following constituency (paragraph [0193]):
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As can be seen from the table above, the feed composition comprises: (ii) starch, (iii) crude protein, (iv) crude fat, (v) crude fiber, (vi) crude ash, (vii) arginine, (viii) calcium (i.e., dicalcium phosphate), (ix) lysine, (x) methionine + cysteine, and (xi) phosphorous. While the amounts of each constituent are not identical to the recited composition, it would be obvious for a person of ordinary skill in the art to modify the amounts of each constituent per the principle of routine optimization (see MPEP 2144.05(II)). Additionally, there is no indication that the amounts of any of the recited constituents would be critical to the action of the active pharmaceutical ingredient (API). Sutherland’s use of a feed composition is representative of a carrier for the intended active ingredient, wherein the carrier comprises excipients to the active ingredient.
In summary, the combined teachings of Gwag and Bosch obviate a method of treating CDS in companion animals, comprising administering 2-hydroxy-5-[2-(4- 10 trifluoromethyl-phenyl)-ethylamino]-benzoic acid to mice at a dose of 25 mg/kg/day by feed administration and Sutherland teaches feed compositions for administration of actives, wherein the compositions comprise each of the constituents recited in the instant claim. When taken together, it would have been prima facie obvious for one of ordinary skill to combine the teachings of each of the aforementioned to develop a method of the instant claim, as there would have been a reasonable expectation of success in formulating such a composition, and using said composition for the treatment of CDS in a companion animal.
Claim 18 is rejected under 35 U.S.C. 103 as being unpatentable over Gwag in view of Bosch, and further in view of Williams (previously referenced).
Claim 18 further limits the method of claim 12 wherein the method comprises administering a dietary supplement composition further comprising:
12.0% w/w crude protein
1.5% w/w crude fat
0.4% w/w crude fiber
1.5% w/w crude ash
0.02% w/w calcium
0.1% w/w potassium
78.0% w/w water
As discussed previously, the combination of the teachings of Gwag and Bosch obviate a method of treating CDS in a companion animal. However, neither Gwag nor Bosch explicitly teach the administration of a composition as recited. However, it would be obvious for a person of ordinary skill in the art to arrive at such a composition because:
Gwag makes the suggestion of formulating compositions of their invention in liquid form, including a water solution
Williams teaches liquid feed formulations comprising components recited in the instant claim
As previously stated, Gwag teaches the administration of 2-hydroxy-5-[2-(4- 10 trifluoromethyl-phenyl)-ethylamino]-benzoic acid to companion animals (mice), in the form of feed formulations. While the exemplary dosing methods of Gwag are directed to feed, Gwag makes the alternative suggestion to formulate their compositions in the form of a liquid, and more specifically, as a water solution (page 16, lines 14-23)15.
While Gwag does not explicitly teach each of the components recited in the claim, such a deficiency is ameliorated by the teachings of Williams which teaches liquid feed compositions. One such exemplary composition having the following constituency (paragraph [0023], Table 4):
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As can be seen in the above table, the composition comprises: (i) crude protein, (ii) crude fat, (iii) crude fiber, (iv) crude ash, (v) calcium, (vi) potassium, and (vii) water (i.e., moisture). Given the aforementioned teachings of Gwag indicating feed administration of 2-hydroxy-5-[2-(4- 10 trifluoromethyl-phenyl)-ethylamino]-benzoic acid, a person of ordinary skill in the art would have reasonable expectation of success in administering such a compound utilizing an alternative feed formulation such as the one taught by Williams. While the composition of Williams does not explicitly teach the exact recited amounts of the components, it would be obvious for a person of ordinary skill in the art to elucidate such amounts per the principle of routine optimization (see MPEP 2144.05(II)). The feed formulation and components comprising said composition would further be considered as a carrier and excipients to the active formulation.
In summary, the combined teachings of Gwag and Bosch obviate a method of treating CDS in companion animals, comprising administering 2-hydroxy-5-[2-(4- 10 trifluoromethyl-phenyl)-ethylamino]-benzoic acid to mice at a dose of 25 mg/kg/day by feed administration and Williams teaches feed compositions, wherein the compositions comprise each of the constituents recited in the instant claim. When taken together, it would have been prima facie obvious for one of ordinary skill to combine the teachings of each of the aforementioned to develop a method of the instant claim, as there would have been a reasonable expectation of success in formulating such a composition, and using said composition for the treatment of CDS in a companion animal.
Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over Gwag in view of Bosch, and further in view of Nishiguchi (previously referenced).
Claim 19 further limits the method of claim 12 wherein the method comprises administering a chewable tablet composition further comprising:
3% w/w silicon dioxide
0.05% w/w benzoic acid
0.01% w/w sorbic acid
5% w/w magnesium stearate
20% w/w cellulose
40% w/w chicken source
3% w/w dry yeast
19% w/w glucose
As discussed previously, the combination of the teachings of Gwag and Bosch obviate a method of treating CDS in a companion animal. However, neither Gwag nor Bosch explicitly teach the administration of a composition as recited. However, it would be obvious for a person of ordinary skill in the art to arrive at such a composition because:
Gwag makes the suggestion of formulating compositions of their invention in tablet form
Nishiguchi teaches dosage formulations of isoxazoline in the form of chewable tablets, and further teaches the recited components of the instant claim as formulation excipients
As previously stated, Gwag teaches the administration of 2-hydroxy-5-[2-(4- 10 trifluoromethyl-phenyl)-ethylamino]-benzoic acid to companion animals (mice), in the form of feed formulations. While the exemplary dosing methods of Gwag are directed to feed, Gwag makes the alternative suggestion to formulate their compositions in the form of tablets (page 16, lines 14-18)16.
While Gwag does not explicitly teach each of the components recited in the claim, such a deficiency is ameliorated by Nishiguchi which teaches chewable tablet formulations containing isoxazoline as an active pharmaceutical ingredient. Nishiguchi provides exemplary tablets such as the following (page 16, Table 2):
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As can be seen above, the compositions each comprise: (iv) magnesium stearate and (v) cellulose, however do not contain (i) silicon dioxide, (ii) benzoic acid, (iii) sorbic acid, (vi) chicken source, (vii) dry yeast, and (viii) glucose. Each of the constituents (i), (ii), (iii), (vi), (vii), and (viii) would be obvious additions however, because Nishiguchi teaches each of these components as acceptable excipients for use in their tablet compositions. In particular, Nishiguchi teaches: silicon dioxide as a glidant/lubricant which can be used in conjunction with magnesium stearate (paragraph [0103])17; both benzoic acid and sorbic acid as preservatives/stabilizers (paragraph [0108])18; chicken, and yeast as flavoring agents (paragraph [0102])19; and glucose as a diluent (paragraph [0094]-[0095])20. Accordingly, the addition of any of the aforementioned would be obvious as they would be considered common excipients for tablet formulations, and there would be reasonable expectation of success in formulating a tablet using such components. Furthermore, a person of ordinary skill in the art would have found it obvious to formulate at the recited amounts per the principle of routine optimization (see MPEP 2144.05(II)), as each of the excipients are named by Nishiguchi and are designated as excipients (i.e., nonactive ingredients).
In summary, given the combined teachings of Gwag, Bosch, and Nishiguchi, a person of ordinary skill in the art would have had ample motivation and a reasonable expectation of success in formulating a tablet of the instant claim, comprising 2-hydroxy-5-[2-(4- 10 trifluoromethyl-phenyl)-ethylamino]-benzoic acid as an API, and further using such a composition for the treatment of CDS in a companion animal.
Claim(s) 26, is/are rejected under 35 U.S.C. 103 as being unpatentable over Gwag in view of Bosch.
Claim 26 further limits the method of claim 12 wherein the companion animal is a dog.
As previously discussed, the teachings of Bosch are directed towards the pathology of CDS in dogs. Given Bosch’s teachings regarding the shared pathology of canine CDS and human AD and the teachings of Gwag regarding the use of 2-hydroxy-5-[2-(4- 10 trifluoromethyl-phenyl)-ethylamino]-benzoic acid in AD model mice, a person of ordinary skill in the art would have found it obvious to utilize the methods of Gwag in treating CDS in dogs.
Claim(s) 27 is rejected under 35 U.S.C. 103 as being unpatentable over Gwag in view of Bosch, and further in view of Landsberg (previously referenced).
Claim 27 further limits the method of claim 12 wherein the companion animal in need thereof is a cat.
As previously discussed, the combined teachings of Gwag and Bosch obviate a method of claim 12 wherein CDS in a companion animal is treated by administration of 2-hydroxy-5-[2-(4- 10 trifluoromethyl-phenyl)-ethylamino]-benzoic acid. However, neither Gwag nor Bosch explicitly teach the treatment of CDS in a cat. However, it would be obvious to administer such a compound to a cat because Landsberg teaches that CDS is a condition that affects both cats and dogs. Landsberg provides an overview of the effects and treatment of CDS in affected cats and dogs. Landsberg indicates that CDS in cats and dogs demonstrate parallels to the AD in humans, and that CDS in both animals are spontaneous models of AD (page 750)21. While pathologies of CDS in such animals is not identical to human AD, they share key properties, such as AB brain deposition and pre-tangle pathology with increasing age. (page 751)22.
Accordingly, it would have been prima facie obvious for a person of ordinary skill to administer a compound of 2-hydroxy-5-[2-(4- 10 trifluoromethyl-phenyl)-ethylamino]-benzoic acid to a cat suffering from CDS as there would be a reasonable expectation that it would be effective in treating a symptom of CDS.
Claims 28 and 29 are rejected under 35 U.S.C. 103 as being unpatentable over Gwag in view of Bosch.
Claim 28 further limits the method of claim 12 wherein 2-hydroxy-5-[2-(4- 10 trifluoromethyl-phenyl)-ethylamino]-benzoic acid is administered in a dose from about 0.1 mg/kg to about 30 mg/kg of body weight once a day.
As discussed previously, Gwag teaches the dosing of 2-hydroxy-5-[2-(4- 10 trifluoromethyl-phenyl)-ethylamino]-benzoic acid at 25 mg/kg/day.
Claim 29 further limits the method of claim 12 wherein 2-hydroxy-5-[2-(4- 10 trifluoromethyl-phenyl)-ethylamino]-benzoic acid is administered in a dose from about 0.1 mg/kg of body weight to about 10 mg/kg of body weight.
Gwag teaches the administration of 2-hydroxy-5-[2-(4- 10 trifluoromethyl-phenyl)-ethylamino]-benzoic acid to G93A transgenic mice at of 5 mg/kg/day by feed administration. Similarly to 25 mg/kg dose in the APP/PS1 transgenic mice, Gwag found that the 5 mg/kg dose in the G93A mice was capable of effectively reducing inflammatory cytokines TNF-a and IL-1B compared to vehicle control (page 48 lines 22-25, page 49 lines 1-4, and Fig 30)23.
Conclusion
Claims 12, 14-19, and 26-33 are rejected.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/ERIC TRAN/Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
1 “Among the preferable compounds above, 2-hydroxy-5-[2-(4- 10 trifluoromethyl-phenyl)-ethylamino]-benzoic acid (compound 2) and 2-acetoxy-5-[2-(4-trifluoromethyl-phenyl)-ethylamino]- benzoic acid (compound 18) are more preferable as therapeutic agent for treating inflammatory disease than other 2- hydroxybenzoic acid derivatives.”
2 “In result, treatment with compound 2 significantly reduced the levels of TNF-a, IL-Ιβ and IL-6 compared to APP/PS1 mouse fed with general chow only (figure 25).”
3 “In addition, as shown in figure 26, protecting effects on brain-blood vessel barrier were shown in group treated with compound 2 (C and G of figure 26) and group treated with ibuprofen (D and H of figure 26).”
4 “Effect of the 2-hydroxybenzoic acid derivative on dementia was evaluated with Thioflavin-S stain analysis. The treatment 5 with 25 mg/kg/day of compound 2 for 7 months (from 3.5 to 10.5 month-old APP/PS1) caused a significant 53% reduction in amyloid plaque burden compared to APP/PS1 dementia mouse fed with general chow only (figure 27). In addition, the treatment with 25 mg/kg/day of compound 2 for 4 months (from 8.5 to 12.5 month10 old APP/PS1) caused a significant 49.3% reduction in amyloid plaque burden compared to APP/PS1 dementia mouse fed with general chow only.”
5 “In result, the group treated with 25 mg/kg/day of compound 2 for 7 months decreased the time for mouse to stay in the open arm compared to the group provided with chow only (figure 28).”
6 “In some embodiments, the companion animal is selected from a cat, a chinchilla, a dog, a ferret, a gerbil, a guinea pig, a hamster, a hedgehog, a mouse, a rabbit, and a rat. In certain preferred embodiments, the companion animal is a cat or a dog. In some embodiments, the companion animal is a canine or a feline.”
7 “When cognitive dysfunction is not due to a primary cause such as a brain tumor or infarct, its clinical diagnosis as CDS requires the presence of one or more of the following nine behavioral changes… All these symptoms are included in CDS [35], which corresponds to the broad spectrum of behavioral problems equivalent to the definition of human dementia in the Diagnostic Criteria of Mental Disorders [36] stage 4-6 of the Global Deterioration Scale [37].”
8 “Except for some limited reports of Congo red staining plaques, investigators generally agree that canine plaques are formed by Aβ 1-40 and 1-42, and are of the diffuse human type [63-66], rather than the betapleated-sheet-conformation (and so negative for Congo red and thioflavine stainings). As in humans, plaque distribution within the brain is heterogeneous and its abundance increases in parallel to the increase in cognitive decline.”
9 “The pharmaceutical composition of the present invention may be formulated in a solid or liquid form. The solid formulation includes, but is not limited to, a powder, a granule, a tablet, a capsule, a suppository, etc. Also, the solid formulation may further include, but is not limited to, a diluent, a flavoring agent, a binder, a preservative, a disintegrating agent, a lubricant, a filler, etc.”
10 “In yet another embodiment, the novel pharmaceutical compositions of the invention comprise celecoxib together with one or more carrier materials or excipients selected from diluents, disintegrants, binding agents, wetting agents and lubricants. Preferably at least one of the carrier materials is a water soluble diluent or wetting agent. Such a water soluble diluent or wetting agent assists in the dispersion and dissolution of the celecoxib when the pharmaceutical composition is ingested.
11 “The pharmaceutical compositions of the present invention optionally comprise one or more pharmaceutically acceptable diluents as a carrier material. Suitable diluents include, either individually or in combination, lactose USP”
12 “Croscarmellose sodium is a preferred disintegrant for tablet or capsule disintegration”
13 “Magnesium stearate is a preferred lubricant used, for example, to reduce friction between the equipment and granulated mixture during compression of tablet formulations.
14 “Suitable wetting agents include… sodium lauryl sulfate.”
15 “The pharmaceutical composition of the present invention 15 may be formulated in a solid or liquid form… The liquid formulation includes, but is not limited to, a solution such as water solution and propylene glycol solution, a suspension, an emulsion, etc.”
16 “The pharmaceutical composition of the present invention may be formulated in a solid or liquid form. The solid formulation includes, but is not limited to, a powder, a granule, a tablet, a capsule, a suppository, etc. Also, the solid formulation may further include, but is not limited to, a diluent, a flavoring agent, a binder, a preservative, a disintegrating agent, a lubricant, a filler, etc.”
17 “Examples of the glidants and lubricants include hydrous silicon dioxide,… magnesium stearate,… and mixtures of these compounds.”
18 “Examples of the preservatives and stabilizers include… benzoic acid,… sorbic acid,… and mixtures of these compounds.”
19 “Examples of the flavoring substances include… meat powder (for example, a beef meat powder, chicken meat powder, pork meat powder, beef liver powder, chicken liver powder, and pork liver powder),… yeasts such as a bread yeast and beer yeast,… chicken flavor,… and mixtures thereof.”
20 “Examples of the diluents include saccharides,… Examples of the saccharides include monosaccharides such as glucose”
21 “Most mammals show age-related neuropathologic changes. In humans, the most common neurodegenerative disorder is AD, which progressively impairs cognition, behavior, and quality of life. It is increasingly evident that humans, dogs, and cats demonstrate parallels in brain aging associated with cognitive dysfunction. In fact, the aged dog and, to a lesser extent, the aged cat are spontaneous models of AD and therefore can play a valuable role in testing putative AD therapeutics.”
22 “Overall, both dogs and cats show AB brain deposition and pre-tangle pathology with increasing age similar to that seen in AD progression; however, these pathologies do not achieve the severity seen in AD. Nonetheless, brain AB deposition may prove to be relatively early predictive biomarker of CDS consistent with preclinical and/or prodromal stages of AD.”
23 “Lumbar segments of 16 week-old G93A mice fed with general chow only, and 16 week-old G93A mice fed with chow containing 5 mg/kg/day of compound 2 were extracted and their RNA were separated. The mRNA expression degrees of TNF-α and IL-Ιβ, inflammatory cytokines, were evaluated through RT-PCT. In results, administration of compound 2 effectively reduced inflammatory cytokines (Figure 30).”