DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
Claims 2-4, 8-9, 12-13, 20, 23, 26-30 and 37-42 are pending.
Priority
This application, filed on 08/27/2024, is a CON of U.S. application No. 17/538,749, filed on 11/30/2021 (ABN), which is a CON of U.S. application No. 16/126,766, filed on 09/10/2018 (U.S. patent No. 11,213,496), which claims a priority to U.S. provisional application No. 62/555,854, filed on 09/08/2017.
Claim Objections
Claims 23 and 28 are objected to under 37 CFR 1.17(a), because of the recitation of “The method of any one of claim 2”, instead of reciting “The method of claim 2”. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 27-28 is 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 27 recites “an orally dissolving tablet an orally disintegrating tablet”, however, a person skilled in the art cannot reasonably determine the meets and bounds of the limitation in the claim. This is because it is unclear as to whether the recited “an orally dissolving tablet an orally disintegrating tablet”, is referring to one table form or two tablet forms. Appropriated correction is required.
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 28 recites the broad recitation “0.01 mg to 150 mg”, and the claim also recites “0.01mg to 100 mg, 0.01mg to 50 mg, 0.1 mg to 20 mg, 0.1 mg to 10mg, 0.1 mg to 5 mg, 0.1 mg to 3 mg, 2.5mg, 2mg, or 1.5 mg”, 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. Appropriate correction is required.
This lack of clarity makes it impossible to ascertain with reasonable precision when that claim is infringed and when it is not. Lacking such clarity, the skilled artisan would not be reasonably apprised of the metes and bounds of the subject matter for which Applicants seek patent protection. Rather, a subjective interpretation of the claimed language would be required. However, as such is deemed inconsistent with the tenor and express language of 35 U.S.C. § 112, second paragraph, the claims are deemed properly rejected.
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.
Claims 2, 20, 26, 29-30 and 37-38 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Shanler et al (hereinafter “Shanler”, U.S. Pub. No. 20090130027, published 05/21/2009).
Independent claim 2 is directed to a method for treating a condition responsive to epinephrine in a subject in need thereof, comprising administering a therapeutically effective amount of oral dipivefrin or a pharmaceutically acceptable salt thereof, to the subject.
Each of claims 2 and 29-30, does not specify a particular amount for dipivefrin or a pharmaceutically acceptable salt thereof, but it does reads on an amount. Accordingly, for the purpose of examination, an amount of dipivefrin or a pharmaceutically acceptable salt thereof, that is employed in order to elicit the desired biological response, is included in the interpretation of:
i) “a therapeutically effective amount” (claim 2);
ii) “an amount sufficient to provide an epinephrine plasma Cmax of 0.1 to 50.0 ng/mL in the subject” (claim 29); and
iii) “an amount sufficient to provide a pharmacokinetic profile substantially equivalent to the epinephrine pharmacokinetic profile of an US FDA-approved injectable dosage form comprising epinephrine, when the US FDA-approved injectable dosage form is administered either intramuscularly or subcutaneously and the US FDA-approved dosage form comprises 0.3 mg epinephrine and is administered intramuscularly” (claim 30).
Regarding claims 2, 20, 26 and 29-30, Shanler (see claims 1, 4 and 10), teaches a method for treating purpura in a subject comprising administering a therapeutically effective amount of dipivefrin or epinephrine (i.e., purpura is a condition responsive to epinephrine), to the subject. For oral administration, the composition is formulated in the form of aqueous solution, tablet, capsule, liquids, gel, syrup and the like (see ¶ 0073).
Regarding claims 29-30 and 37-38, the recitation of the limitation of the method of claim 2 resulting in: i) providing an epinephrine plasma Cmax of 0.1 to 50 ng/mL in the subject (claim 29); ii) providing the recited epinephrine pharmacokinetic profile (claim 30); iii) providing a therapeutically effective amount of epinephrine within 5-30 minutes of administration (claim 37); and providing a Tmax of epinephrine within 45 minutes of administration (claim 38), is not given any patentable weight because each of the clause is simply expressing the intended result of a process positively recited. Please see Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003). Since Shanler teaches a method of claim 2 (see discussions above), the method of Shanler, must necessarily produce the same outcomes of recited in claims 29-30 and 37-38, because each of the recited outcome is a natural process that flows from the subject and the orally administered dipivefrin. Please see MPEP, 2111.04.
Claims 39-42 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Singh et al (hereinafter “Singh”, U.S. Patent. No. 7,122,198, issued 10/17/2006).
Independent claim 39 is drawn to an orally dissolving tablet comprising dipivefrin or a salt thereof, in a matrix capable of dissolving in oral cavity in 2 minutes or less.
Regarding claims 39-42, Singh (see claim 1) teaches:
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The at least one pharmaceutically active agent or a salt thereof, to be employed for the fast-dissolving tablet according to the invention, can be selected from the group that includes dipivefrin (see column 3, lines 12-18 and column 9, line 32). The tablet of the invention, when orally administered, dissolves or disperses in the mouth within one minute (see column 2, lines 30-36 and column 24, lines 1-6). Suitable at least one mucoadhesive agents include hydroxypropylmethyl cellulose (HPMC) and gelatin (see column 19, lines 36-49).
The Examiner would like to draw the Applicants’ attention to the following:
A reference disclosure can anticipate a claim even if the reference does not describe "the limitations arranged or combined as in the claim, if a person of skill in the art, reading the reference, would ‘at once envisage’ the claimed arrangement or combination." Kennametal, Inc. v. Ingersoll Cutting Tool Co., 780 F.3d 1376, 1381, 114 USPQ2d 1250, 1254 (Fed. Cir. 2015) (quoting In re Petering, 301 F.2d 676, 681(CCPA 1962)).
In the instant case, the instant invention (e.g., claim 39), drawn to an orally dissolving tablet comprising dipivefrin or a salt thereof, in a matrix capable of dissolving in oral cavity in 2 minutes or less. A person skilled in the art reading the Sing reference (see discussions above), would at once envisage the claimed arrangement
Therefore, claims 39-42 are anticipated by Singh.
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.
Claims 2-4, 20, 26-30 and 37-40 are rejected under 35 U.S.C. 103 as being unpatentable over Rawas-Qalaji et al (hereinafter “Rawas-Qalaji”, U.S. Pub. No. 20120322884, published 12/20/2012) in view of: 1) Minatoya et al (hereinafter “Minatoya”, U.S. patent No. 3,904,671, issued 09/09/1975); and 2) Henschler (U.S. patent No. 4,085,270, issued on 04/18/1978).
By way of a background, the Applicant’s invention (see, e.g., ¶ 0001 of the specification), relates to dipivefrin:
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, which is a pivalyl ester of epinephrine:
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, and a method for using dipivefrin as a prodrug for the delivery of epinephrine, in order to treat a condition responsive to epinephrine.
Independent claim 2 is directed to a method for treating a condition responsive to epinephrine in a subject in need thereof, comprising administering a therapeutically effective amount of oral dipivefrin or a pharmaceutically acceptable salt thereof, to the subject.
Each of claims 2 and 29-30, does not specify a particular amount for dipivefrin or a pharmaceutically acceptable salt thereof, but it does reads on an amount. Accordingly, for the purpose of examination, an amount of dipivefrin or a pharmaceutically acceptable salt thereof, that is employed in order to elicit the desired biological response, is included in the interpretation of:
i) “a therapeutically effective amount” (claim 2);
ii) “an amount sufficient to provide an epinephrine plasma Cmax of 0.1 to 50.0 ng/mL in the subject” (claim 29); and
iii) “an amount sufficient to provide a pharmacokinetic profile substantially equivalent to the epinephrine pharmacokinetic profile of an US FDA-approved injectable dosage form comprising epinephrine, when the US FDA-approved injectable dosage form is administered either intramuscularly or subcutaneously and the US FDA-approved dosage form comprises 0.3 mg epinephrine and is administered intramuscularly” (claim 30).
Independent claim 39 is drawn to an orally dissolving tablet comprising dipivefrin or a salt thereof, in a matrix capable of dissolving in oral cavity in 2 minutes or less.
Similar to claims 2 and 39, Rawas-Qalaji (see, e.g., abstract, ¶s 0003, 0013-0017 and reference claims 1, 4-12, 15-17 and 34-40), discloses that the invention provides an oral epinephrine formulation and methods for use of the formulation in the treatment of conditions responsive to epinephrine such as a cardiac event or an allergic reaction, particularly, anaphylaxis. Rawas-Qalaji discloses tablet dissolving or disintegrating in less than about 1 minute (see ¶ 0018).
Although Rawas-Qalaji is not explicit in disclosing an epinephrine prodrug (e.g., dipivefrin), the claimed invention would have been obvious over Rawas-Qalaji. This is because at the time of the instant invention, an epinephrine prodrug (e.g., dipivefrin), was known in the art. For example:
1) Minatoya (see, e.g., column 1 and column 3, line 25), teaches an epinephrine compound of formula I:
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, which is dipivefrin (an epinephrine prodrug), wherein:
i) R = CH3 (an alkyl having 1 carbon atom);
ii) R’ and Y2 = H; and
iii) Y and Y1 = pivalyl (acyl member having 4 carbon atoms).
Minatoya (see, e.g., columns 2 and 8), discloses that the compounds of the invention can be combined with conventional pharmaceutical solid or liquid diluents and carriers in tablets, capsules, syrups, emulsions, solutions, suspensions or the like and administered orally.
Minatoya (see, e.g., abstract and column 8), discloses that compared to the corresponding unesterified compounds, the esters compounds advantageously produce longer duration of bronchodilation and lower cardiovascular stimulating effects.
2) Henschler teaches dipivefrin (1-(3',4'-dipivaloyloxyphenyl)-2-methylamino-ethanol-1) and its HCl salt (see Example 5), formed by masking the masking of the phenolic OH groups in epinephrine (adrenaline), with pivaloyl groups (see column 1). Henschler (see, e.g., column 1, lines 18-31), discloses that the therapeutic efficacy of known orally administered phenolethanolamine class compounds (e.g., adrenaline), are affected by the metabolic oxidation at the phenolic OH groups, which lead rapidly to inactive compounds.
Similar to Minatoya (see discussions above), Henschler discloses that the masking of the phenolic OH groups with for example, acetyl or pivaloyl groups protects the phenolethanolamine compounds against rapid metabolic inactivation, which leads to longer therapeutic effects, when compared to the phenolethanolamine compounds unprotected at the phenolic OH groups. Henschler discloses: i) trimethylacetic acid (pivalic acid) employed in the generation of pivaloyl adrenaline (dipivefrin), as outstandly suitable for masking the phenolic hydroxy groups; and ii) phenolethanolamines masked with pivalic acid as outstandly suitable for achieving long lasting effects. Please see column 1, lines 32-60, column 3, lines 13-28 and the Table on columns 1-2.
Accordingly, at the time of the instant invention, a person skilled in the art would have envisaged a method for treating a condition responsive to epinephrine in a subject in need thereof, with an oral epinephrine prodrug (e.g., oral dipivefrin) or a pharmaceutically acceptable salt thereof, in the disclosures of Rawas-Qalaji, Minatoya and Henschler. This is because at the time of the instant invention, it was known in the art that:
1) oral epinephrine exhibits utility in the treatment of a condition responsive to epinephrine (see discussions above).
2) the therapeutic efficacy of known orally administered phenolethanolamine class compounds (e.g., epinephrine), are affected by the metabolic oxidation at the phenolic OH groups, which lead rapidly to inactive compounds (see discussions above).
3) masking of the phenolic OH groups protect the phenolethanolamine compounds against rapid metabolic inactivation, which leads to longer therapeutic effects, when compared to the phenolethanolamine compounds unprotected at the phenolic OH groups (see discussions above).
4) dipivefrin is an esterified epinephrine formed by masking the masking of the phenolic OH groups in epinephrine with pivaloyl groups (see discussions above).
5) dipivefrin dosage forms include, but not limited to tablets, capsules and oral liquids (see discussions above).
One skilled in the art would have had a reasonable expectation that the administration of oral dipivefrin would lead to longer therapeutic effects, when compared to the administration of epinephrine, which is unprotected at the phenolic OH groups.
Obviousness requires only a reasonable expectation of success, not complete confidence in a given outcome; "at least some degree of predictability" is all that is required. M.P.E.P. § 2143.02.
The prior art can be modified or combined to reject claims as prima facie obvious as long as there is a reasonable expectation of success. See In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986) (see MPEP § 2143.02).
Therefore, claims 2 and 39 are obvious over Rawas-Qalaji, Minatoya and Henschler.
Regarding claims 3-4, Rawas-Qalaji teaches anaphylaxis (see discussions above).
Regarding claim 20, each of Minatoya and Henschler, teaches racemic dipivefrin. Please see discussions above.
Regarding claim 26, Minatoya discloses that compounds of the invention can be combined with conventional pharmaceutical solid or liquid diluents and carriers in tablets, capsules, syrups, emulsions, solutions, suspensions or the like and administered orally (see discussions above). oral liquids (see discussions above).
A person skilled in the art would have found it obvious to combine dipivefrin with conventional pharmaceutical liquid diluents (e.g., water) and carriers in an oral aqueous solution, with a reasonable expectation that the oral aqueous solution would exhibit longer therapeutic effects, when compared to the therapeutic effect of unesterified epinephrine.
Obviousness requires only a reasonable expectation of success, not complete confidence in a given outcome; "at least some degree of predictability" is all that is required. M.P.E.P. § 2143.02.
The prior art can be modified or combined to reject claims as prima facie obvious as long as there is a reasonable expectation of success. See In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986) (see MPEP § 2143.02).
Regarding claim 27, Rawas-Qalaji teaches orally disintegrating tablet (see abstract).
Regarding claim 28, the claimed dipivefrin dosage range of 0.01 to 150 mg, is a result effective variable that would have been routinely determined and optimized in the pharmaceutical art. For example, Minatoya at column 8, lines 58-66, states:
“The individual unit dosage can be varied as desired. For general use it is preferred to incorporate, in a solid vehicle, tablet or capsule, about 0.1 to 100 mg. of the ester (Formula I or Formula II); or in a liquid vehicle, about O. 1 to 100 mg. of the ester (Formula I or Formula II) per teaspoonful or, in an aerosol, 0.02 to 2 mg. per actuation. The effective oral dose for producing bronchodilation is in the approximate range 0.002-2.0 mg/kg.” Emphasis added.
It is noted that no criticality has been demonstrated in the specification with regard to the administration of the claimed dipivefrin dosage range of 0.01 to 150 mg, to any subject of any age, sex or bodyweight, suffering from any a condition responsive to epinephrine.
Furthermore, MPEP § 2144.05(II)(B), states that “after KSR, the presence of a known result-effective variable would be one, but not the only, motivation for a person of ordinary skill in the art to experiment to reach another workable product or process.”
Regarding claims 29-30 and 37-38, the recitation of the limitation of the method of claim 2 resulting in: i) providing an epinephrine plasma Cmax of 0.1 to 50 ng/mL in the subject (claim 29); ii) providing the recited epinephrine pharmacokinetic profile (claim 30); iii) providing a therapeutically effective amount of epinephrine within 5-30 minutes of administration (claim 37); and providing a Tmax of epinephrine within 45 minutes of administration (claim 38, is not given any patentable weight because each of the clause is simply expressing the intended result of a process positively recited. Please see Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003). Since Rawas-Qalaji, Minatoya and Henschler, combine to disclose the method of claim 2 (see discussions above), the method of Rawas-Qalaji, Minatoya and Henschler, must necessarily produce the same outcomes of recited in claims 29-30 and 37-38, because each of the recited outcome is a natural process that flows from the subject and the orally administered dipivefrin. Please see MPEP, 2111.04.
Regarding claim 40 Henschler, teaches dipivefrin HCl (see discussions above).
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a). From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Thus, the claims fail to patentably distinguish over the state of the art as represented by the cited references.
Claims 2-4, 20, 26-30 and 37-40 are rejected under 35 U.S.C. 103 as being unpatentable over Rawas-Qalaji (U.S. Pub. No. 20120322884, published 12/20/2012) in view of: 1) Yuting (CN106109459A, published 11/16/2016, Machine Translation); and 2) Henschler (U.S. patent No. 4,085,270, issued on 04/18/1978).
Similar to claims 2 and 39, Rawas-Qalaji (see, e.g., abstract, ¶s 0003, 0013-0017 and reference claims 1, 4-12, 15-17 and 34-40), disclose that the invention provides an oral epinephrine formulation and methods for use of the formulation in the treatment of conditions responsive to epinephrine such as a cardiac event or an allergic reaction, particularly, anaphylaxis. Rawas-Qalaji discloses tablet dissolving or disintegrating in less than about 1 minute (see ¶ 0018).
Although Rawas-Qalaji is not explicit in disclosing an epinephrine prodrug (e.g., dipivefrin), the claimed invention would have been obvious over Rawas-Qalaji. This is because at the time of the instant invention, an epinephrine prodrug (e.g., dipivefrin), was known in the art. For example:
1) Yuting teaches a pharmaceutical composition comprising dipivefrin HCl and a pharmaceutically acceptable carrier (see abstract and ¶ 0010). Pharmaceutically acceptable carriers include diluents, excipients, fillers, binders, wetting agents, disintegrants, absorption accelerators, surfactants, adsorption carriers or lubricants (see ¶ 0011). Dosage forms include tablets, capsules, oral liquids, buccal agents, granules, granules, pills, powders, ointments, elixirs, suspensions, powders, solutions, injections, suppositories, sprays, drops or patches (see ¶ 0012).
2) Henschler teaches dipivefrin (1-(3',4'-dipivaloyloxyphenyl)-2-methylamino-ethanol-1) and its HCl salt (see Example 5), formed by masking the masking of the phenolic OH groups in epinephrine (adrenaline), with pivaloyl groups (see column 1). Henschler (see, e.g., column 1, lines 18-31), discloses that the therapeutic efficacy of known orally administered phenolethanolamine class compounds (e.g., adrenaline), are affected by the metabolic oxidation at the phenolic OH groups, which lead rapidly to inactive compounds.
Henschler discloses that the masking of the phenolic OH groups with for example, acetyl or pivaloyl groups protects the phenolethanolamine compounds against rapid metabolic inactivation, which leads to longer therapeutic effects, when compared to the phenolethanolamine compounds unprotected at the phenolic OH groups. Henschler discloses: i) trimethylacetic acid (pivalic acid) employed in the generation of pivaloyl adrenaline (dipivefrin), as outstandly suitable for masking the phenolic hydroxy groups; and ii) phenolethanolamines masked with pivalic acid as outstandly suitable for achieving long lasting effects. Please see column 1, lines 32-60, column 3, lines 13-28 and the Table on columns 1-2.
Accordingly, at the time of the instant invention, a person skilled in the art would have envisaged a method for treating a condition responsive to epinephrine in a subject in need thereof, with an oral epinephrine prodrug (e.g., oral dipivefrin) or a pharmaceutically acceptable salt thereof, in the disclosures of Rawas-Qalaji, Yuting and Henschler. This is because at the time of the instant invention, it was known in the art that:
1) oral epinephrine exhibits utility in the treatment of a condition responsive to epinephrine (see discussions above).
2) the therapeutic efficacy of known orally administered phenolethanolamine class compounds (e.g., epinephrine), are affected by the metabolic oxidation at the phenolic OH groups, which lead rapidly to inactive compounds (see discussions above).
3) masking of the phenolic OH groups protect the phenolethanolamine compounds against rapid metabolic inactivation, which leads to longer therapeutic effects, when compared to the phenolethanolamine compounds unprotected at the phenolic OH groups (see discussions above).
4) dipivefrin is an esterified epinephrine formed by masking the masking of the phenolic OH groups in epinephrine with pivaloyl groups see discussions above).
5) dipivefrin dosage forms include, but not limited to tablets, capsules and oral liquids (see discussions above).
One skilled in the art would have had a reasonable expectation that the administration of oral dipivefrin would lead to longer therapeutic effects, when compared to the administration of epinephrine, which is unprotected at the phenolic OH groups.
Obviousness requires only a reasonable expectation of success, not complete confidence in a given outcome; "at least some degree of predictability" is all that is required. M.P.E.P. § 2143.02.
The prior art can be modified or combined to reject claims as prima facie obvious as long as there is a reasonable expectation of success. See In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986) (see MPEP § 2143.02).
Therefore, claims 2 and 39 are obvious over Rawas-Qalaji, Yuting and Henschler.
Regarding claims 3-4, Rawas-Qalaji teaches anaphylaxis (see discussions above).
Regarding claim 20, Henschler teaches racemic dipivefrin. Please see discussions above.
Regarding claim 26, Yuting teaches oral liquids (see discussions above), which necessarily encompass an oral aqueous solution.
Regarding claim 27, Rawas-Qalaji teaches orally disintegrating tablet (see abstract).
Regarding claim 28, the claimed dipivefrin dosage range of 0.01 to 150 mg, is a result effective variable that would have been routinely determined and optimized in the pharmaceutical art. For example, Yuting teaches 80 mg/kg dipivefrin dosage (see ¶ 033).
It is noted that no criticality has been demonstrated in the specification with regard to the administration of the claimed dipivefrin dosage range of 0.01 to 150 mg, to any subject of any age, sex or bodyweight, suffering from any a condition responsive to epinephrine.
Furthermore, MPEP § 2144.05(II)(B), states that “after KSR, the presence of a known result-effective variable would be one, but not the only, motivation for a person of ordinary skill in the art to experiment to reach another workable product or process.”
Regarding claims 29-30 and 37-38, the recitation of the limitation of the method of claim 2 resulting in: i) providing an epinephrine plasma Cmax of 0.1 to 50 ng/mL in the subject (claim 29); ii) providing the recited epinephrine pharmacokinetic profile (claim 30); iii) providing a therapeutically effective amount of epinephrine within 5-30 minutes of administration (claim 37); and providing a Tmax of epinephrine within 45 minutes of administration (claim 38, is not given any patentable weight because each of the clause is simply expressing the intended result of a process positively recited. Please see Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003). Since Rawas-Qalaji, Yuting and Henschler, combine to disclose the method of claim 2 (see discussions above), the method of Rawas-Qalaji, Yuting and Henschler, must necessarily produce the same outcomes of recited in claims 29-30 and 37-38, because each of the recited outcome is a natural process that flows from the subject and the orally administered dipivefrin. Please see MPEP, 2111.04.
Regarding claim 40, each of Yuting and Henschler, teaches dipivefrin HCl. Please see discussions above.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a). From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Thus, the claims fail to patentably distinguish over the state of the art as represented by the cited references.
Claims 2 and 8-9 are rejected under 35 U.S.C. 103 as being unpatentable over Rawas-Qalaji in view of: 1) Minatoya; and 2) Henschler, as applied to claim 2 above and further in view of Gruber et al (hereinafter “Gruber”, U.S. patent No. 5,925,682, issued 07/20/1999).
The limitations of claim 2 as well as the corresponding teachings of Rawas-Qalaji, Minatoya and Henschler, are described above and hereby incorporated into the instant rejections.
Claims 8-9 are similar to claim 2, however, claims 8-9 differ slightly from claim 2 in that claims 8-9 require that the condition responsive to epinephrine is cancer.
Rawas-Qalaji, Minatoya and Henschler, differ from claims 8-9 only insofar as the cited references do not combine to explicitly teach the limitation of claims 8-9.
However, the claim invention would have been obvious over Rawas-Qalaji, Minatoya and Henschler.
This is because, at the time of the instant invention, it was known in the art that cancer is a condition responsive to epinephrine. For example, Gruber teaches cancer as a condition responsive to epinephrine and teaches a method for inhibiting the growth of lymphoma tumor with an effective amount of epinephrine. Please see abstract, columns 4-8, Examples 1-4, Tables 1-3 and reference claims 1-3.
Accordingly, at the time of the instant invention, a person skilled in the art would have found it obvious to modify Rawas-Qalaji, Minatoya and Henschler with Gruber, in order to orally administer dipivefrin to a subject suffering from a condition responsive to epinephrine (e.g., cancer tumor). One skilled in the art would have had a reasonable expectation that the administration of oral dipivefrin would lead to longer therapeutic effects of inhibiting growth of cancer tumor, when compared to the administration of epinephrine, which is unprotected at the phenolic OH groups.
Obviousness requires only a reasonable expectation of success, not complete confidence in a given outcome; "at least some degree of predictability" is all that is required. M.P.E.P. § 2143.02.
The prior art can be modified or combined to reject claims as prima facie obvious as long as there is a reasonable expectation of success. See In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986) (see MPEP § 2143.02).
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a). From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Thus, the claims fail to patentably distinguish over the state of the art as represented by the cited references.
Claims 2 and 8-9 are rejected under 35 U.S.C. 103 as being unpatentable over Rawas-Qalaji in view of: 1) Yuting; and 2) Henschler, as applied to claim 2 above and further in view of Gruber et al (hereinafter “Gruber”, U.S. patent No. 5,925,682, issued 07/20/1999).
The limitations of claim 2 as well as the corresponding teachings of Rawas-Qalaji, Minatoya and Henschler, are described above and hereby incorporated into the instant rejections.
Claims 8-9 are similar to claim 2, however, claims 8-9 differ slightly from claim 2 in that claims 8-9 require that the condition responsive to epinephrine is cancer.
Rawas-Qalaji, Yuting and Henschler, differ from claims 8-9 only insofar as the cited references do not combine to explicitly teach the limitation of claims 8-9.
However, the claim invention would have been obvious over Rawas-Qalaji, Yuting and Henschler.
This is because, at the time of the instant invention, it was known in the art that cancer is a condition responsive to epinephrine. For example, Gruber teaches cancer as a condition responsive to epinephrine and teaches a method for inhibiting the growth of lymphoma tumor with an effective amount of epinephrine. Please see abstract, columns 4-8, Examples 1-4, Tables 1-3 and reference claims 1-3.
Accordingly, at the time of the instant invention, a person skilled in the art would have found it obvious to modify Rawas-Qalaji, Yuting and Henschler with Gruber, in order to orally administer dipivefrin to a subject suffering from a condition responsive to epinephrine (e.g., cancer tumor). One skilled in the art would have had a reasonable expectation that the administration of oral dipivefrin would lead to longer therapeutic effects of inhibiting growth of cancer tumor, when compared to the administration of epinephrine, which is unprotected at the phenolic OH groups.
Obviousness requires only a reasonable expectation of success, not complete confidence in a given outcome; "at least some degree of predictability" is all that is required. M.P.E.P. § 2143.02.
The prior art can be modified or combined to reject claims as prima facie obvious as long as there is a reasonable expectation of success. See In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986) (see MPEP § 2143.02).
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a). From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Thus, the claims fail to patentably distinguish over the state of the art as represented by the cited references.
Claims 2 and 12-13 are rejected under 35 U.S.C. 103 as being unpatentable over Rawas-Qalaji in view of: 1) Minatoya and 2) Henschler, as applied to claim 2 above and further in view of Apan et al (hereinafter “Apan”, J. Clin Anesthesia, 2016, 34, 407-411).
The limitations of claim 2 as well as the corresponding teachings of Rawas-Qalaji, Minatoya and Henschler, are described above and hereby incorporated into the instant rejections.
Claims 12-13 are similar to claim 2, however, claims 12-13 differ slightly from claim 2 in that claims 12-13 require that the condition responsive to epinephrine is a microbial infection.
Rawas-Qalaji, Minatoya and Henschler, differ from claims 12-13 only insofar as the cited references do not combine to explicitly teach the limitation of claims 12-13.
However, the claim invention would have been obvious over Rawas-Qalaji, Minatoya and Henschler.
This is because, at the time of the instant invention, it was known in the art that microbial infection is a condition responsive to epinephrine. For example, Apan teaches a method for the inhibition of bacterial growth with epinephrine. Please see abstract and discussions therein.
Accordingly, at the time of the instant invention, a person skilled in the art would have found it obvious to modify Rawas-Qalaji, Minatoya and Henschler with Apan, in order to orally administer dipivefrin to a subject suffering from a condition responsive to epinephrine (e.g., microbial infection). One skilled in the art would have had a reasonable expectation that the administration of oral dipivefrin would lead to longer therapeutic effects of inhibiting microbial growth, when compared to the therapeutic effects of epinephrine, which is unprotected at the phenolic OH groups.
Obviousness requires only a reasonable expectation of success, not complete confidence in a given outcome; "at least some degree of predictability" is all that is required. M.P.E.P. § 2143.02.
The prior art can be modified or combined to reject claims as prima facie obvious as long as there is a reasonable expectation of success. See In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986) (see MPEP § 2143.02).
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a). From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Thus, the claims fail to patentably distinguish over the state of the art as represented by the cited references.
Claims 2 and 12-13 are rejected under 35 U.S.C. 103 as being unpatentable over Rawas-Qalaji in view of: 1) Yuting and 2) Henschler, as applied to claim 2 above and further in view of Apan et al (hereinafter “Apan”, J. Clin Anesthesia, 2016, 34, 407-411).
The limitations of claim 2 as well as the corresponding teachings of Rawas-Qalaji, Yuting and Henschler, are described above and hereby incorporated into the instant rejections.
Claims 12-13 are similar to claim 2, however, claims 12-13 differ slightly from claim 2 in that claims 12-13 require that the condition responsive to epinephrine is a microbial infection.
Rawas-Qalaji, Yuting and Henschler, differ from claims 12-13 only insofar as the cited references do not combine to explicitly teach the limitation of claims 12-13.
However, the claim invention would have been obvious over Rawas-Qalaji, Minatoya and Henschler.
This is because, at the time of the instant invention, it was known in the art that microbial infection is a condition responsive to epinephrine. For example, Apan teaches a method for the inhibition of bacterial growth with epinephrine. Please see abstract and discussions therein.
Accordingly, at the time of the instant invention, a person skilled in the art would have found it obvious to modify Rawas-Qalaji, Yuting and Henschler with Apan, in order to orally administer dipivefrin to a subject suffering from a condition responsive to epinephrine (e.g., microbial infection). One skilled in the art would have had a reasonable expectation that the administration of oral dipivefrin would lead to longer therapeutic effects of inhibiting microbial growth, when compared to the therapeutic effects of epinephrine, which is unprotected at the phenolic OH groups.
Obviousness requires only a reasonable expectation of success, not complete confidence in a given outcome; "at least some degree of predictability" is all that is required. M.P.E.P. § 2143.02.
The prior art can be modified or combined to reject claims as prima facie obvious as long as there is a reasonable expectation of success. See In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986) (see MPEP § 2143.02).
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a). From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Thus, the claims fail to patentably distinguish over the state of the art as represented by the cited references.
Claims 2-4, 20, 23, 26-30 and 37-42 are rejected under 35 U.S.C. 103 as being unpatentable over Rawas-Qalaji et al (hereinafter “Rawas-Qalaji2007”, U.S. Pub. No. 20070202163, published 08/30/2007) in view of: 1) Minatoya et al (hereinafter “Minatoya”, U.S. patent No. 3,904,671, issued 09/09/1975); and 2) Henschler (U.S. patent No. 4,085,270, issued on 04/18/1978).
Similar to claims 2 and 39, Rawas-Qalaji2007 teaches an orally dissolving tablet comprising epinephrine, or a salt thereof (see abstract and ¶ 0067), in a matrix (see ¶s 0060-0061), capable of dissolving or disintegrating in less than about 1 minute (see ¶ 0050). Epinephrine is the drug of choice for the treatment of anaphylaxis worldwide (see ¶ 0007).
Rawas-Qalaji2007 differs from the claimed invention only insofar as Rawas-Qalaji2007 is not explicit in teaching dipivefrin.
However, the claimed invention would have been obvious over Rawas-Qalaji2007. This is because at the time of the instant invention, dipivefrin was known in the art. For example:
1) Minatoya (see column 1 and column 3, line 25), teaches a compound of formula I:
PNG
media_image4.png
200
400
media_image4.png
Greyscale
, which is dipivefrin, wherein:
i) R = CH3 (an alkyl having 1 carbon atom);
ii) R’ and Y2 = H; and
iii) Y and Y1 = pivalyl (acyl member having 4 carbon atoms).
The compounds of the invention can be combined with conventional pharmaceutical solid or liquid diluents and carriers in tablets, capsules, syrups, emulsions, solutions, suspensions or the like and administered orally. Please see columns 2 and 8.
Minatoya discloses that, compared to the corresponding unesterified compounds, the esters compounds advantageously produce longer duration of bronchodilation and lower cardiovascular stimulating effects. Please see abstract and column 8.
2) Henschler teaches dipivefrin (1-(3',4'-dipivaloyloxyphenyl)-2-methylamino-ethanol-1) and its HCl salt (see Example 5), formed by masking the masking of the phenolic OH groups in epinephrine (adrenaline), with pivaloyl groups (see column 1).
Henschler discloses that the therapeutic efficacy of known orally administered phenolethanolamine class compounds (e.g., adrenaline), are affected by the metabolic oxidation at the phenolic OH groups, which lead rapidly to inactive compounds. Please see column 1, lines 18-31.
Similar to Minatoya (see discussions above), Henschler discloses that the masking of the phenolic OH groups with for example, acetyl or pivaloyl groups protects the phenolethanolamine compounds against rapid metabolic inactivation, which leads to longer therapeutic effects, when compared to the phenolethanolamine compounds unprotected at the phenolic OH groups. Henschler discloses: i) trimethylacetic acid (pivalic acid) employed in the generation of pivaloyl adrenaline (dipivefrin), as outstandly suitable for masking the phenolic hydroxy groups; and ii) phenolethanolamines masked with pivalic acid as outstandly suitable for achieving long lasting effects. Please see column 1, lines 32-60, column 3, lines 13-28 and the Table on columns 1-2.
Accordingly, at the time of the instant invention, a person skilled in the art would have found it obvious to modify Rawas-Qalaji2007 with Minatoya and Henschler in order to orally administer dipivefrin to a subject suffering from a condition responsive to epinephrine.
This is because at the time of the instant invention, it was known in the art that:
1) oral epinephrine can be used to treat a condition responsive to epinephrine. Please see discussions above.
2) the therapeutic efficacy of known orally administered phenolethanolamine class compounds (e.g., epinephrine), are affected by the metabolic oxidation at the phenolic OH groups, which lead rapidly to inactive compounds. Please see discussions above.
3) masking of the phenolic OH groups protect the phenolethanolamine compounds against rapid metabolic inactivation, which leads to longer therapeutic effects, when compared to the phenolethanolamine compounds unprotected at the phenolic OH groups. Please see discussions above.
4) dipivefrin is an esterified epinephrine formed by masking the masking of the phenolic OH groups in epinephrine with pivaloyl groups. Please see discussions above.
5) dipivefrin dosage forms include, but not limited to tablets, capsules and oral liquids. Please see discussions above.
One skilled in the art would have had a reasonable expectation that the administration of oral dipivefrin would lead to longer therapeutic effects, when compared to the administration of epinephrine, which is unprotected at the phenolic OH groups.
Obviousness requires only a reasonable expectation of success, not complete confidence in a given outcome; "at least some degree of predictability" is all that is required. M.P.E.P. § 2143.02.
The prior art can be modified or combined to reject claims as prima facie obvious as long as there is a reasonable expectation of success. See In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986) (see MPEP § 2143.02).
Regarding claims 3-4, Rawas-Qalaji2007 teaches anaphylaxis (see discussions above).
Regarding claim 20, each of Minatoya and Henschler, teaches racemic dipivefrin. Please see discussions above.
Regarding claim 23, Rawas-Qalaji2007 discloses that epinephrine when synthesized, occurs as a racemic mixture comprising 50% as the L-epinephrine isomer and 50% as the D-epinephrine isomer. Only the L-epinephrine is physiologically and pharmacologically active in the mammalian body. Following synthesis of the racemic mixture, the epinephrine is exposed to D-tartaric acid and the L-epinephrine crystallizes out. Please see ¶ 0067.
A person skilled in the art would have found it obvious to employ the method of the prior art (see discussions above), in order to arrive at L-dipivefrin, with a reasonable expectation that the L-dipivefrin would exhibit longer therapeutic efficacy, when compared to the therapeutic efficacy of epinephrine, which is unprotected at the phenolic OH groups.
Regarding claim 26, Minatoya discloses that compounds of the invention can be combined with conventional pharmaceutical solid or liquid diluents and carriers in tablets, capsules, syrups, emulsions, solutions, suspensions or the like and administered orally (see discussions above). oral liquids (see discussions above). A person skilled in the art would have found it obvious to combine dipivefrin with conventional pharmaceutical liquid diluents (e.g., water) and carriers in an oral aqueous solution, with a reasonable expectation that the oral aqueous solution would exhibit longer therapeutic effects, when compared to the therapeutic effect of unesterified epinephrine.
Obviousness requires only a reasonable expectation of success, not complete confidence in a given outcome; "at least some degree of predictability" is all that is required. M.P.E.P. § 2143.02.
The prior art can be modified or combined to reject claims as prima facie obvious as long as there is a reasonable expectation of success. See In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986) (see MPEP § 2143.02).
Regarding claim 27, Rawas-Qalaji2007 teaches orally disintegrating tablet (see discussions above).
Regarding claim 28, the claimed dipivefrin dosage range of 0.01 to 150 mg, is a result effective variable that would have been routinely determined and optimized in the pharmaceutical art. For example:
1) Rawas-Qalaji2007 discloses that the tablet can comprise epinephrine in dosages forms of from about 0.5 mg to about 5 mg, about 5 mg to about 10 mg, about 10 mg to about 25 mg, about 25 mg to about 40 or about 25 mg to about 75 mg (see ¶ 0018).
2) Minatoya at column 8, lines 58-66, states:
“The individual unit dosage can be varied as desired. For general use it is preferred to incorporate, in a solid vehicle, tablet or capsule, about 0.1 to 100 mg. of the ester (Formula I or Formula II); or in a liquid vehicle, about O. 1 to 100 mg. of the ester (Formula I or Formula II) per teaspoonful or, in an aerosol, 0.02 to 2 mg. per actuation. The effective oral dose for producing bronchodilation is in the approximate range 0.002-2.0 mg/kg.” Emphasis added.
It is noted that no criticality has been demonstrated in the specification with regard to the administration of the claimed dipivefrin dosage range of 0.01 to 150 mg, to any subject of any age, sex or bodyweight, suffering from any a condition responsive to epinephrine.
Furthermore, MPEP § 2144.05(II)(B), states that “after KSR, the presence of a known result-effective variable would be one, but not the only, motivation for a person of ordinary skill in the art to experiment to reach another workable product or process.”
Regarding claims 29-30 and 37-38, the recitation of the limitation of the method of claim 2 resulting in: i) providing an epinephrine plasma Cmax of 0.1 to 50 ng/mL in the subject (claim 29); ii) providing the recited epinephrine pharmacokinetic profile (claim 30); iii) providing a therapeutically effective amount of epinephrine within 5-30 minutes of administration (claim 37); and providing a Tmax of epinephrine within 45 minutes of administration (claim 38, is not given any patentable weight because each of the clause is simply expressing the intended result of a process positively recited. Please see Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003). Since Rawas-Qalaji2007, Minatoya, Yuting and Henschler, combine to disclose the method of claim 2 (see discussions above), the method of Rawas-Qalaji2007, Minatoya and Henschler, must necessarily produce the same outcomes of recited in claims 29-30 and 37-38, because each of the recited outcome is a natural process that flows from the subject and the orally administered dipivefrin. Please see MPEP, 2111.04.
Regarding claim 40, Henschler, teaches dipivefrin HCl. Please see discussions above.
Regarding claims 41-42, Rawas-Qalaji2007 discloses that matrix-forming agents include gelatins and sweeteners (see ¶ 0061).
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a). From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Thus, the claims fail to patentably distinguish over the state of the art as represented by the cited references.
Claims 2 and 8-9 are rejected under 35 U.S.C. 103 as being unpatentable over Rawas-Qalaji2007 in view of: 1) Minatoya; and 2) Henschler, as applied to claim 2 above and further in view of Gruber et al (hereinafter “Gruber”, U.S. patent No. 5,925,682, issued 07/20/1999).
The limitations of claim 2 as well as the corresponding teachings of Rawas-Qalaji2007, Minatoya, Yuting and Henschler, are described above and hereby incorporated into the instant rejections.
Claims 8-9 are similar to claim 2, however, claims 8-9 differ slightly from claim 2 in that claims 8-9 require that the condition responsive to epinephrine is cancer.
Rawas-Qalaji2007, Minatoya and Henschler, differ from claims 8-9 only insofar as the cited references do not combine to teach cancer as a condition responsive to epinephrine.
However, the claim invention would have been obvious over Rawas-Qalaji2007, Minatoya and Henschler.
This is because, at the time of the instant invention, it was known in the art that cancer is a condition responsive to epinephrine. For example, Gruber teaches cancer as a condition responsive to epinephrine and teaches a method for inhibiting the growth of lymphoma tumor with an effective amount of epinephrine. Please see abstract, columns 4-8, Examples 1-4, Tables 1-3 and reference claims 1-3.
Accordingly, at the time of the instant invention, a person skilled in the art would have found it obvious to modify Rawas-Qalaji2007, Minatoya and Henschler, with Gruber, in order to orally administer dipivefrin to a subject suffering from a condition responsive to epinephrine (e.g., cancer tumor).
One skilled in the art would have had a reasonable expectation that the administration of oral dipivefrin would lead to longer therapeutic effects of inhibiting growth of cancer tumor, when compared to the administration of epinephrine, which is unprotected at the phenolic OH groups.
Obviousness requires only a reasonable expectation of success, not complete confidence in a given outcome; "at least some degree of predictability" is all that is required. M.P.E.P. § 2143.02.
The prior art can be modified or combined to reject claims as prima facie obvious as long as there is a reasonable expectation of success. See In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986) (see MPEP § 2143.02).
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a). From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Thus, the claims fail to patentably distinguish over the state of the art as represented by the cited references.
Claims 2 and 12-13 are rejected under 35 U.S.C. 103 as being unpatentable over Rawas-Qalaji2007 in view of: 1) Minatoya; and 2) Henschler, as applied to claim 2 above and further in view of Apan et al (hereinafter “Apan”, J. Clin Anesthesia, 2016, 34, 407-411).
The limitations of claim 2 as well as the corresponding teachings of Rawas-Qalaji2007, Minatoya and Henschler, are described above and hereby incorporated into the instant rejections.
Claims 12-13 are similar to claim 2, however, claims 12-13 differ slightly from claim 2 in that claims 12-13 require that the condition responsive to epinephrine is a microbial infection.
Rawas-Qalaji2007, Minatoya and Henschler, differ from claims 8-9 only insofar as the cited references do not combine to teach microbial infection as a condition responsive to epinephrine.
However, the claim invention would have been obvious over Rawas-Qalaji2007, Minatoya and Henschler.
This is because, at the time of the instant invention, it was known in the art that microbial infection is a condition responsive to epinephrine. For example, Apan teaches a method for the inhibition of bacterial growth with epinephrine. Please see abstract and discussions therein.
Accordingly, at the time of the instant invention, a person skilled in the art would have found it obvious to modify Rawas-Qalaji2007, Minatoya and Henschler, with Apan, in order to orally administer dipivefrin to a subject suffering from a condition responsive to epinephrine (e.g., microbial infection).
One skilled in the art would have had a reasonable expectation that the administration of oral dipivefrin would lead to longer therapeutic effects of inhibiting microbial growth, when compared to the administration of epinephrine, which is unprotected at the phenolic OH groups.
Obviousness requires only a reasonable expectation of success, not complete confidence in a given outcome; "at least some degree of predictability" is all that is required. M.P.E.P. § 2143.02.
The prior art can be modified or combined to reject claims as prima facie obvious as long as there is a reasonable expectation of success. See In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986) (see MPEP § 2143.02).
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a). From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Thus, the claims fail to patentably distinguish over the state of the art as represented by the cited references.
Non-Statutory Obviousness-Type 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.
Claims 2-4, 8-9, 12-13, 20, 23, 26-30 and 37-42 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-27 of U.S. patent No.11,213,496 (‘496 patent).
Although the claims at issue are not identical, they are not patentably distinct from each other. The claims of the above cited patent are similarly drawn to the same subject matter, which is an oral dipivefrin and a method for using the oral dipivefrin.
For example, the claims of the instant application are drawn to a method for treating a condition responsive to epinephrine in a subject with an oral dosage form of dipivefrin, whereas, the claims of the ‘496 patent (e.g., claim 2), are directed a method for treating a condition responsive to epinephrine in a human or dog with an oral dosage form of dipivefrin.
Therefore, there is sufficient overlap between the claim scopes to render them obvious over each other. Consequently, the ordinary artisan would have recognized the obvious variation of the instantly claimed subject matter over the reference application subject matter.
Claims 2-4, 8-9, 12-13, 20, 23, 26-30 and 37-42 are rejected on the ground of nonstatutory double patenting as being unpatentable overclaims 1-21 of U.S. patent No.11,213,484 (‘484 patent).
Although the claims at issue are not identical, they are not patentably distinct from each other. The claims of the above cited patent are similarly drawn to the same subject matter, which is an oral dipivefrin and a method for using the oral dipivefrin.
For example, the claims of the instant application are drawn to: i) a method for treating a condition responsive to epinephrine in a subject with an oral dosage form of dipivefrin (e.g., claim 2); and ii) an oral dosage form of dipivefrin (e.g., claim 39), whereas, the claims of the ‘484 patent (e.g., claim 1), are directed a dipivefrin orally disintegrating tablet.
Therefore, there is sufficient overlap between the claim scopes to render them obvious over each other. Consequently, the ordinary artisan would have recognized the obvious variation of the instantly claimed subject matter over the reference application subject matter.
Claims 2-4, 8-9, 12-13, 20, 23, 26-30 and 37-42 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 6-8, 10-11,14, 16-17, 19-22, 25, 27, 31, 33-35 and 37 of U.S. patent application No.19/244,724 (‘724 application).
Although the claims at issue are not identical, they are not patentably distinct from each other. The claims of the above cited patent are similarly drawn to the same subject matter, which is an oral dipivefrin and a method for using the oral dipivefrin.
For example, the claims of the instant application are drawn to: i) a method for treating a condition responsive to epinephrine in a subject with an oral dosage form of dipivefrin (e.g., claim 2); and ii) an oral dosage form of dipivefrin (e.g., claim 39), whereas, the claims of the ‘724 application (e.g., claims 1-3, 21-22), are directed to: i) oral dipivefrin formulation; and ii) a method for treating a condition responsive to epinephrine with an oral dosage form of dipivefrin.
Therefore, there is sufficient overlap between the claim scopes to render them obvious over each other. Consequently, the ordinary artisan would have recognized the obvious variation of the instantly claimed subject matter over the reference application subject matter.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusions
No claim is allowable.
If Applicants should amend the claims, a complete and responsive reply will clearly identify where support can be found in the disclosure for each amendment. Applicants should point to the page and line numbers of the application corresponding to each amendment, and provide any statements that might help to identify support for the claimed invention (e.g., if the amendment is not supported in ipsis verbis, clarification on the record may be helpful). Should the Applicants present new claims, Applicants should clearly identify where support can be found in the disclosure.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to IBRAHIM D BORI whose telephone number is (571)270-7020. The examiner can normally be reached on Monday through Friday 8:00AM-5:00PM(EST).
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, JEFFREY S LUNDGREN can be reached on 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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/IBRAHIM D BORI/
Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
Prosecution Insights