DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Previous Rejections
Applicant’s arguments, filed May 19, 2026, have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Claim Status
Claims 6, 13, and 20 are canceled.
Claims 1-5, 7-12, 14-19, and 21-22 are pending and are examined on the merits in this prosecution.
CLAIM REJECTIONS
Obviousness Rejections
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
1) Claims 1-3 and 7 are rejected under 35 U.S.C. 103(a) as being unpatentable over Bond (WO 2005/034871 A2; cited in IDS dated 8/29/2025).
It is noted that the terms “formulated to treat mucus hypersecretion,” recited in claims 1 and 7-8, and “formulated to treat mucus hypersecretion associated with nicotine withdrawal,” recited in claims 1, 8, 15, and 21 is interpreted by the Examiner as a statement of intended use or purpose since the term does not appear to be a structural limitation of the claimed invention.
As set forth by the Federal Circuit, “It is well established that “[a]n intended use or purpose usually will not limit the scope of the claim because such statements usually do no more than define a context in which the invention operates.” Boehringer Ingelheim Vetmedica, Inc. v. Schering-Plough Corp., 320 F.3d 1339, 1345 (Fed. Cir. 2003).
The term “formulated to treat mucus hypersecretion” is disclosed in the instant Specification in broad terms: “Pharmaceutical compositions according to the present invention can be formulated for administration via a transdermal patch or as chewing gum (see [0042]), and “Depending on the specific conditions being treated, such agents may be formulated and administered systemically or locally. Typically, administration is systemic. Techniques for formulation and administration may be found in Remington's Pharmaceutical Sciences, 18th ed., Mack Publishing Co., Easton, Pa. (1990) (see [0113]).”
It is noted that Bond teaches that “Many diseases and conditions are mediated by beta-adrenergic receptors. In particular, these receptors are involved in many pulmonary airway diseases. Pulmonary airway diseases are characterized by reduced pulmonary function and airway flow. These symptoms are often due to secretion of mucus.” See pg 2, [0004].
As such, Bond teaches the limitation of claim 1.
The claim term “a therapeutically effective quantity of a beta-adrenergic inverse agonist” is defined in the instant disclosure ([0108]) as follows:
with nadolol administered orally, treatment can begin with 1 mg dosages, then progress through 3 mg, 5 mg, 10 mg, 15 mg, and then to higher maintenance dosages such as 25 mg, 30 mg, 50 mg, 75 mg, 100 mg, 150 mg or higher as deemed necessary, depending on the particular condition to be treated, the severity, and the response of the condition to the treatment. One particularly preferred dosage regimen begins at 10 mg, then progresses through 25, 50, 75, 100 and 150 mg based on defined dose escalation criteria determined by lung function, symptoms, heart rate, and blood pressure, as detailed further below. When the beta-adrenergic inverse agonist is administered to treat or prevent mucus hypersecretion in a subject attempting smoking cessation, criteria related to the effect of the beta-adrenergic inverse agonist treatment on the physiological state, mood, behavior, or craving of the subject for nicotine can also be included in the dose escalation calculation.
Regarding claim 1, Bond teaches a pharmaceutical composition comprising: (1) nadolol, a beta-adrenergic inverse agonist; and (2) a pharmaceutically acceptable carrier (pg 6, [0022]).
Regarding the claim term therapeutically effective quantity of a beta-adrenergic inverse agonist,” the term is defined in the instant disclosure ([0108]) as an amount of 1 mg, 3 mg, 5 mg, 10 mg, 15 mg, 25 mg, 30 mg, 50 mg, 75 mg, 100 mg, 150 mg or higher as deemed necessary (pgs 37-38, [0108]), Bond teaches a therapeutically effective amount of the beta-adrenergic inverse agonist nadolol as 1 mg, 3 mg, 5, mg, 10 mg, 15 mg, 30 mg, and 50 mg (pg 6, [0022]), amounts disclosed by the instant disclosure as therapeutically effective. In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art”, a prima facie case of obviousness exists. MPEP 2144.05 (I). This teaching also reads on claims 2 and 3.
For the recitation of claim 1 of “at least one pharmaceutically acceptable carrier suitable for administration of the composition for treating mucus hypersecretion,” Bond teaches the following regarding carriers (pg 26, [0096]):
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The instant specification discloses the following regarding a pharmaceutically acceptable carrier suitable for administration of the composition for treating mucus hypersecretion (pg 29, [0087]):
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As such, it is clear that the description of the carrier(s) utilized for a composition formulated for mucus hypersecretion is identical to that taught by Bond since the instant disclosure is identical to that taught by Bond.
Therefore, for claim 1, Bond teaches a therapeutically effective of nadolol as the beta-adrenergic inverse agonist, as discussed above. Bond teaches the beta-adrenergic inverse agonist is present in a composition comprising a pharmaceutically acceptable carrier (pg 6, [0022]).
As discussed above, the limitation of the “pharmaceutical composition is formulated to treat mucus hypersecretion” is considered an expression of intended use and is not afforded patentable weight since it does not limit the structure of the formulation.
For claim 7, Bond teaches administration of the b-adrenergic inverse agonists together with corticosteroids such as methylprednisolone and prednisolone (pg 43, [0137]).
The examiner acknowledges that some picking and choosing was used to arrive at the instantly claimed methods in view of Bond. However, the claimed combination of components, including the therapeutically effective amount of nadolol, is taught as known and used for administration to a subject with a pulmonary airway disease such as asthma, bronchiectasis, bronchitis, chronic obstructive pulmonary disease, Churg-Strauss syndrome, pulmonary sequelae of cystic fibrosis, emphysema, allergic rhinitis, and pneumonia (pgs 75-76, claim 18). Further, Bond teaches administration with the same excipients (pg 26, [0096] as disclosed in the instant specification ([0087]).
It would have therefore been prima facie obvious to a person having ordinary skill in the art to formulate the pharmaceutical composition comprising the claimed combination of ingredients, including nadolol, with a reasonable expectation of success that the treatment would be efficacious for the treatment of a pulmonary airway disease, as taught by Bond.
2) Claim 4 is rejected under 35 U.S.C. 103(a) as being unpatentable over Bond (cited above), in view of Gale (US 5,635,203; cited in IDS dated 8/29/2025).
Claim 4 is directed to the composition of claim 1 in the form of a transdermal patch.
The teachings of Bond are discussed above.
While Bond teaches delivery of the composition by transdermal means (pg 38, [0123]), Bond does not teach a transdermal patch as a form of delivery.
Gale teaches the missing element of Bond.
Gale teaches a transdermal patch for administration of a drug (Abstract). Gale teaches nadolol as a drug that may be administered by the patch (col 6: 61). Regarding the recitation “wherein the administration via the transdermal patch results in continuous levels of the nadolol in the bloodstream of the subject,” Gale teaches the transdermal patch is designed to “effectively deliver drug for an extended period of time from several hours up to seven days or longer. Seven days is generally the maximum time limit for application of a single device because the adverse effect of inclusion of a skin site increases with time” (col 5: 67 to col 6:4).
It would have been obvious for a person of ordinary skill in the art, before the effective filing date of the claimed invention, to administer the composition of Bond as a transdermal patch. A person of ordinary skill would have been motivated to administer the composition of Bond as a transdermal patch because Gale Franklin teaches a transdermal patch formulation comprising nadolol has the advantage of providing the nadolol continuously over the period of a week, providing controlled release of the drug over an extended time period.
3) Claim 5 is rejected under 35 U.S.C. 103(a) as being unpatentable over Bond (cited above), in view of McCarty (US 2007/0071806 A1).
The teachings of Bond are discussed above.
While Bond teaches delivery of the composition by oral means, including buccal tablets, (pg 27, [0098]), Bond does not teach chewing gum as a form of delivery.
McCarty teaches the missing element of Bond.
McCarty teaches chewing gum for administration of a drug (pg 6, [0051]). McCarty teaches nadolol, as well as expectorants, bronchodilators, mucolytics, anti-inflammatory agents, and antibiotics as drugs that may be administered by the patch (pgs 3-4, [0026]; pg 7, [0063]).
It would have been obvious for a person of ordinary skill in the art, before the effective filing date of the claimed invention, to administer the composition of Bond as a chewing gum. A person of ordinary skill would have been motivated to administer the composition of Bond as a chewing gum because McCarty teaches a chewing gum formulation comprising nadolol and an additional drug such as an expectorant, bronchodilator, mucolytic, anti-inflammatory agent, and antibiotic has the advantage of providing the nadolol and the second drug in a controlled release formulation (pg 7, [0059]).
4) Claims 8-10, 14-17, and 21-22 are rejected under 35 U.S.C. 103(a) as being unpatentable over Bond (cited above), in view of Apgar (“Use of Bupropion as an Aid in Smoking Cessation,” Am Fam Physician, 1998, 57(7): 1641-1646).
The teachings of Bond are discussed above.
Bond does not teach the addition of a compound to promote smoking cessation.
Apgar teaches the missing element of Bond.
Apgar teaches bupropion hydrochloride is approved as an effective smoking cessation aid and is effective for alleviation of some of the withdrawal effects from smoking cessation (pgs 1-2).
It is noted that claim 20 is considered an expression of intended use of the composition of claim 15
The person of ordinary skill would have had a reasonable expectation of success in adding Apgar's bupropion to the composition of Bond since Bond teaches nadolol, a beta-adrenergic receptor agonist, is useful in treating many pulmonary airway diseases characterized by reduced pulmonary function and airway flow, and bupropion is taught by Apgar for smoking cessation, a known causative for pulmonary disease. The skilled artisan would have been motivated to select Apgar's bupropion as an active agent in Bond’s composition because Apgar teaches that bupropion is effective in reducing smoking and reduction of smoking is a key element in treating pulmonary disease.
5) Claim 11 is rejected under 35 U.S.C. 103(a) as being unpatentable over Bond (cited above), in view of Apgar (cited above) and Gale (cited above).
Claim 11 is directed to the composition of claim 8 in the form of a transdermal patch.
The teachings of Bond, Apgar, and Gale are discussed above. Gale further teaches the transdermal patch is effective as a delivery device for antimicrobial agents (col 6: 27).
It would have been obvious for a person of ordinary skill in the art, before the effective filing date of the claimed invention, to administer the composition of Bond and Apgar, comprising bupropion and nadolol, in the form of a transdermal patch. A person of ordinary skill would have been motivated to administer the composition of Bond and Apgar as a transdermal patch because Gale teaches a transdermal patch formulation has the advantage of providing the nadolol continuously over the period of a week, providing controlled release of the drug over an extended time period.
6) Claims 12 and 19 are rejected under 35 U.S.C. 103(a) as being unpatentable over Bond (cited above), in view of Apgar (cited above) and McCarty (cited above).
The teachings of Bond, Apgar, and McCarty are discussed above. Briefly, Bond teaches diseases and conditions that are mediated by beta-adrenergic receptors such as nadolol, in particular, pulmonary airway diseases. Apgar teaches bupropion for smoking cessation and McCarty teaches a chewing gum composition that may comprise agents for smoking cessation, bronchodilators, anti-infectives, antifungals, antivirals, bupropion, and nadolol (pg 7, [0063]).
It would have been obvious for a person of ordinary skill in the art, before the effective filing date of the claimed invention, to administer the composition of Bond and Apgar, comprising bupropion and nadolol, in the form of a chewing gum. A person of ordinary skill would have been motivated to administer the composition of Bond and Apgar as a chewing gum because McCarty teaches a chewing gum formulation is a formulation that is useful for administering a broad range of pharmaceuticals including bupropion and nadolol, as well as agents for smoking cessation, bronchodilators, anti-infectives, antifungals, antivirals, bupropion, and nadolol.
7) Claim 18 is rejected under 35 U.S.C. 103(a) as being unpatentable over Bond (cited above), in view of Apgar (cited above) and Gale (cited above) and Suffin (US 2005/0096311 A1).
The teachings of Bond, Apgar, and Gale are discussed above. Briefly, Bond teaches diseases and conditions that are mediated by beta-adrenergic receptors such as nadolol, in particular, pulmonary airway diseases; Apgar teaches bupropion for smoking cessation; and Gale teaches a transdermal patch formulation is effective as a delivery device for antimicrobial agents.
The combination of Bond, Apgar, and Gale does not teach a transdermal patch comprising bupropion.
Suffin teaches the missing element of the combination of Bond, Apgar, and Gale.
Suffin teaches bupropion, as well as nadolol, may be formulated as a transdermal patch composition (pg 1, [0007]; pg 10, [0051]).
It would have been obvious for a person of ordinary skill in the art, before the effective filing date of the claimed invention, to add bupropion to the composition of Bond, Apgar, and Gale, comprising nadolol and an antimicrobial agent, to comprise a dosage in the form of a chewing gum. A person of ordinary skill would have been motivated to administer the composition of Bond, Apgar, Gale, and Suffin as a chewing gum because Gale and Suffin teach a chewing gum formulation useful for administering a broad range of pharmaceuticals including bupropion, nadolol, and bupropion as well as agents for smoking cessation, bronchodilators, anti-infectives, antifungals, and antivirals.
Examiner’s Reply to Attorney Arguments dated 5/14/2026
It is noted by the Examiner that the method closely associated with claim 1 of the instant application has been previously issued as US 9,993,444. Claim 1 of the ‘444 patent reads:
A method of preventing or controlling mucus hypersecretion in the respiratory tract comprising administering a therapeutically effective quantity of a β-adrenergic inverse agonist to a subject with mucus hypersecretion for a period required to increase the likelihood of the subject quitting smoking, wherein the mucus hypersecretion is associated with smoking cessation and the subject is attempting smoking cessation, wherein the method increases the likelihood of the subject quitting smoking and prevents or reduces at least one of the anatomical or physiological changes causing symptoms associated with smoking cessation, and wherein the β-adrenergic inverse agonist is a β2-selective inverse agonist selected from the group consisting of nadolol, carvedilol, and ICI-118,551, wherein the prevention or control of mucus hypersecretion increases the likelihood of the subject quitting smoking and wherein a chronic administration of a β-adrenergic inverse agonist has the effect of upregulating the population of active β-adrenergic receptors.
It is further noted that the parent application (16/002,665) of the present application, reciting a nearly identical independent claim (claim 17) that had been rejected by Examiner, was previously appealed to the Patent Trial and Appeal Board (Appeal 2024-000653) and the rejections over Bond (WO 2005/034871 A2) were affirmed by the Board. For reference, claim 17 of the ‘665 application recites the following:
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1. Rejection of claims 1-3 and 6-7 under 35 U.S.C. § 103(a) over Bond ‘871
The applicant argues on page 25 of the Applicant’s response (hereinafter referred to as “Remarks”) that: “Although Bond '871 does disclose the use of nadolol to treat a number of diseases and conditions, it does not disclose or suggest the use of nadolol as a single agent or in combination with other agents to treat mucus hypersecretion associated with attempts to quit smoking.” The applicant argues that “Bond '871 provides no guidance in the reference with respect to this issue for any specific condition, such as, but not limited to, mucus hypersecretion in patients attempting smoking cessation, that can affect the dosage in terms of any of the starting dosage, the rate of dosage change, or the maximum dosage.”
The applicant concludes (page 28 of the Remarks) that “Bond '871 actually teaches away from the present invention.”
The Examiner acknowledges the arguments presented, but does not consider them persuasive. First, it is noted that the claims are not drawn to a method of smoking cessation, but rather a composition comprising nadolol, an additional compound to treat mucus hypersecretion, and a carrier. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
It is the position of the Examiner that the terms "formulated to treat mucus hypersecretion" and “formulated t treat mucus hypersecretion associated with nicotine withdrawal for promoting smoking cessation are statements of intended use or purpose, and the applicant has provided no evidence that the terms impose a further structural limitation on the claimed pharmaceutical composition. As discussed above, Bond teaches the claimed formulation with regard to dose, carriers, formulations, and additional pharmaceutical agents that may be added.
It is noted that the same reasoning given above was used by the Patent Trial and Appeal Board for the appeal cited above. See pages 3-4 of the decision.
The applicant argues that the decision in Boehrinqer Ingelheim Vetmedica regarding the recitation in a preamble should not apply to this case. The applicant argues:
The Federal Circuit, in determining whether these terms were to be given weight as a claim limitation, stated that a preamble simply stating the intended use or purpose of the invention would usually not limit the scope of the claim, unless the preamble would function to provide antecedents for ensuing claim terms and limits the claim accordingly, citing C.R. Bard, Inc. v. M3 Sys., Inc.,
The Examiner acknowledges the arguments presented, but does not consider them persuasive. The quote from Boehrinqer cited in the rejection clearly supports the Examiner’s position regarding the fact that claim language reciting an intended use or purpose does not limit the scope of a claim, but merely defines the “context in which the invention operates."
The applicant argues on page 36 of the Remarks that:
With respect to claims 2 and 3, the statement in the Office Action that in the case where the claimed ranges overlap or lie inside ranges disclosed by the prior art, a prima facie case of obviousness exists, citing MPEP 2144.05(1), does not support the rejection. The issue of "range" logically would only come into play when the reference in question actually teaches the claimed method and the only issue is the range of a variable such as the dosage of a therapeutically active compound (as here) or variables such as temperature or pressure in a chemical reaction.
[Emphasis by the Examiner]
The Examiner acknowledges the arguments presented, but does not consider them persuasive. As discussed above, the instant claims are drawn to a composition, not to a “claimed method.” Since Bond teaches compositions comprising the amounts claimed in claims 2 and 3, the claims are properly rejected.
2. Rejection of claim 4 under 35 U.S.C. § 103(a) over Bond '871 and Gale
The applicant argues on pages 46-48 of the Remarks that Gale does not address or remedy the alleged deficiencies of Bond ‘871:
Although Gale et al. '203 does disclose use of a specific alternative for a transdermal patch, it does not remedy the deficiencies of Bond '871 with respect to the guidance required for the use of nadolol to treat mucus hypersecretion associated with attempts to quit smoking. There is no reference in Gale et al. '203 that specifically refers to the use of nadolol in a pharmaceutical composition that could be used for that purpose.
The applicant also argues that Gale is not sufficiently specific in that the reference lists many general categories and individual compounds as deliverable in a transdermal patch.
The Examiner acknowledges the arguments presented, but does not consider them persuasive. It is reiterated that the position of the Examiner is that the claims are drawn to a composition, not to a method, and that the claimed composition is identical or nearly identical to the composition described by Bond ‘871, and that claim 1 is properly rejected.
As acknowledged by the applicant, Bond ‘871 teaches the transdermal route of administration (pg 38, [0123]) and Gale discloses the use of nadolol in the form of a transdermal patch. As set forth in MPEP 2143.03, “when a claim requires selection of an element from a list of alternatives, the prior art teaches the element if one of the alternatives is taught by the prior art.” Since nadolol is specifically taught by Gale, the selection of nadolol as an alternative is proper. As stated by the Board on page 10 of the ‘653 appeal decision,
In an obviousness determination, a reference may be relied on for all that it would have reasonably suggested to one having ordinary skill in the art. The fact that Gale teaches numerous drugs that are suitable for transdermal administration, does not render any of the disclosed drugs less obvious. Merck & Co. v. Biocraft Labs., 874 F.2d 804, 807 (Fed. Cir. 1989) ("That the [prior art] patent discloses a multitude of effective combinations does not render any particular formulation less obvious.")
As such, it would be prima facie obvious to administer the claimed composition in the form of a transdermal patch, even though Gale teaches a number of drugs administered by transdermal patch.
3. Rejection of claim 5 Over Bond '871 and McCarty
The applicant argues on pages 54-55 of the Remarks that McCarty does not address or remedy the alleged deficiencies of Bond ‘871:
In particular, McCarty '806 does not address or remedy the deficiencies of Bond '871 as stated above with respect to the rejections of claims 1 -3 and 6-7 for obviousness over Bond '871 .
Although McCarty '806 does disclose use of a specific alternative for a delivery system involving the use of chewing gum, it does not remedy the deficiencies of Bond '871 with respect to the guidance required for the use of nadolol to treat mucus hypersecretion associated with attempts to quit smoking. There is no reference in McCarty '806 that specifically refers to the use of nadolol in a pharmaceutical composition that could be used for that purpose….
The applicant argues that McCarty is not sufficiently specific in that the reference lists many general categories and individual compounds as deliverable in a chewing gum composition. The applicant also argues that nadolol is not charged at physiological pH.
The Examiner acknowledges the arguments presented, but does not consider them persuasive. It is reiterated that the claims are drawn to a composition, not to a method, that the claimed composition is identical or nearly identical to the composition described by Bond ‘871, and that claim 1 is properly rejected over Bond ‘871.
Bond ‘871 teaches an oral route of administration (pg 38, [0123]) and McCarty discloses the use of nadolol in the form of a chewing gum.
MPEP 2143.03 is cited for the question of specificity. This section of the MPEP states: “when a claim requires selection of an element from a list of alternatives, the prior art teaches the element if one of the alternatives is taught by the prior art.” Since nadolol is taught by McCarty in a chewing gum formulation, the selection of nadolol as an alternative is proper.
Regarding the argument that nadolol is not ionic, nadolol (structure shown below), possesses a secondary amine that is protonatable.
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As such, it would be prima facie obvious to administer the claimed composition in the form of a transdermal patch, even though Gale teaches a number of drugs administered by transdermal patch.
4. Rejection of claims 8-10, 13-16, and 20-22 under 35 U.S.C. 103(a) over Bond '871 and Apqar.
The applicant argues on page 61 of the Remarks that McCarty does not address or remedy the alleged deficiencies of Bond ‘871. The applicant argues “One of ordinary skill in the art would not automatically combine two or more drugs into a pharmaceutical composition without clear guidance from the art to do so.” The applicant argues that the combination of Bond ‘871 and Apgar does not explicitly teach the combination of bupropion and nadolol, and that the rejection of the claims is a product of impermissible hindsight.
The Examiner acknowledges the arguments presented, but does not consider them persuasive. It is reiterated that the claims are drawn to a composition, not to a method, that the claimed composition is identical or nearly identical to the composition described by Bond ‘871, and that claim 1 is properly rejected over Bond ‘871.
As set forth in MPEP 2144, “The reason or motivation to modify the reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant.” In the instant case, the Examiner has provided a motivation for modifying Bond ‘871.
The applicant argues that “there must be clear guidance for adding the second drug to the pharmaceutical composition.” The Examiner disagrees; the legal standard is a reasonable expectation of success. Since nadolol, a non-selective beta blocker, and bupropion, a norepinephrine-dopamine reuptake inhibitor, possess different pharmacological mechanisms, one of ordinary skill would not a priori predict the drugs to be incompatible.
The applicant argues on pages 61-62 of the Remarks:
The drugs might interact negatively so that, for example, the presence of a second drug might interfere with the binding of the first drug to its intended molecular target, the presence of a second drug might affect the metabolism of the first drug such as, for example, increasing the expression of a catabolic enzyme such as a cytochrome P450 enzyme so that a therapeutically sufficient quantity of the first drug is not maintained in the bloodstream or the tissue or organ to be treated, or the presence of the second drug may induce side effects that would require a reduction in dosage or the discontinuation of the first drug. Additionally, the presence of the second drug may be physically incompatible with the first drug in the pharmaceutical composition, for example by causing precipitation of the first drug. Moreover, even if these effects do not occur, the drugs may bind to the same molecular target so that there is no benefit in adding the second drug if the first drug saturates the molecular target.
However, the applicant has provided no factual support for these statements. As such, the statements are considered attorney opinion, unsupported by factual evidence, and therefore possess no probative value. See MPEP 2145(I).
5. Rejection of claim 11 under 35 U.S.C. 103(a) over Bond '871, Apgar, and Gale.
The applicant argues on page 64 of the Remarks that neither Apgar nor Gale remedy the alleged deficiencies of Bond ‘871.
The applicant argues Apgar discloses the use of bupropion to promote smoking cessation, but does not disclose or suggest the use of nadolol to suppress mucus hypersecretion in order to aid smoking cessation. The applicant further argues Gale discloses the use of a transdermal patch, and does disclose the delivery of nadolol by transdermal patch, but does not disclose any specific use of nadolol or details regarding the instantly recited method of use.
The Examiner acknowledges the arguments presented, but does not consider them persuasive. It is reiterated that the claims are drawn to a composition, not to a method, that the claimed composition is identical or nearly identical to the composition described by Bond ‘871, and that claim 1 is properly rejected over Bond ‘871. Since the claims are drawn to a composition, the utility of the composition is considered an intended use or purpose and applicant has presented no factual evidence of structural differences between the claimed composition and that of Bond ‘871.
6. Rejection of Claims 12 and 19 under 35 U.S.C. 103(a) over Bond '871, Apqar, and McCarty.
The applicant argues on page 68 of the Remarks that neither Apgar nor McCarty remedy the alleged deficiencies of Bond ‘871. The applicant argues that neither Apgar nor McCarty teach nadolol for smoking cessation. The applicant argues that nadolol is not ionizable (page 69 of the Remarks).
The Examiner acknowledges the arguments presented, but does not consider them persuasive. As previously stated by the Examiner, the instant claims are drawn to a composition, not to a method, that the claimed composition is identical or nearly identical to the composition described by Bond ‘871, and that claim 1 is properly rejected over Bond ‘871. Regarding the argument that neither Apgar nor McCarty teach nadolol for smoking cessation, the recitation of ‘promoting smoking cessation” in claims 8 and 15, upon which claims 12 and 19 are, respectively dependent, is considered a statement of intended use or purpose, and in no way changes the structure of the claimed composition.
The Examiner disagrees with applicant's argument that nadolol is not ionizable since, at physiological pH 7.4, the amine group of nadolol is substantially protonated.
7. Rejection of claim 18 under 35 U.S.C. 103(a) over Bond '871, Apqar, Gale, and Suffin
The applicant argues the following: “The deficiencies of Bond '871 with respect to the failure of the reference to provide sufficient guidance for one of ordinary skill in the art to use nadolol to promote smoking cessation by suppressing mucus hypersecretion.”
The Examiner acknowledges the argument presented, but does not consider it persuasive. As previously stated by the Examiner, the instant claims are drawn to a composition, not to a method, that the claimed composition is identical or nearly identical to the composition described by Bond ‘871, and that claim 1 is properly rejected over Bond ‘871.
The applicant argues the following: “Although Suffin et al. '311 does disclose combination therapies including bupropion as one element of the combination, there is no disclosure or suggestion in the reference of the use of a combination of bupropion and nadolol to treat mucus hypersecretion associated with attempts to quit smoking.”
The Examiner acknowledges the argument presented, but does not consider it persuasive. As set forth in MPEP 2144, “The reason or motivation to modify the reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant.” As such, Suffin teaches the claimed elements of bupropion and nadolol, and provides motivation for the combination. Since the combination is taught in the prior art, and the claimed intended use of treating mucus hypersecretion associated with attempts to quit smoking is considered an intended use without patentable weight, the rejection is proper and therefore maintained.
The applicant argues the following: “even though Suffin et al. '311 does disclose the use of a transdermal patch to deliver bupropion, the reference does not disclose or suggest the use of a transdermal patch to deliver a pharmaceutical composition including both nadolol and bupropion.”
The Examiner acknowledges the argument presented, but does not consider it persuasive. As discussed in the rejection above, Gale teaches a transdermal patch for administration nadolol. It is well within the skill of practitioner of the pharmaceutical arts to combine two pharmaceutically active compounds on a single patch.
CONCLUSION
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHAEL P COHEN whose telephone number is (571)270-7402. The examiner can normally be reached on M-Th 8:30-5:30; F 9-4.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sahana Kaup, can be reached on (571)272-0580. The phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MICHAEL P COHEN/Primary Examiner, Art Unit 1612
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