DETAILED ACTION
The receipt is acknowledged of applicant’s IDS filed 07/31/2025; and amendment filed 11/14/2025.
Claims 1, 4-7, 10-27, 31-55, 58 are pending.
Claims 7, 13, 14, 16-23, 25-27, 31, 33-39, 41, 44-55 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions and species. Election was made without traverse in the reply filed on 12/02/2020.
Claims 1, 4-6, 10-12, 15, 24, 32, 40, 42, 43, 58 are subject of this office action.
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. under 35 U.S.C. 120 as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Applications No. 16/578,064, 16/130,325, 15/818,056 and 14/32,561, fail to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application.
There is not adequate support for some limitation recited in the instant claims in the previously filed applications. For example, application No. 14/32,561 does not disclose “epinephrine”, “nasal delivery” or “two inhalable doses, first administered nasally and second administered by oral inhalation”, and further “third administered sublingually, as instantly claimed by the present application (claim 1). Applications 15/818056 and 16/130,325 do not disclose “nasal delivery” or “two inhalable doses, first administered nasally and second administered by oral inhalation”, and do not disclose “third sublingual dose”. Application 16/578,604 does not disclose “two inhalable doses, first administered nasally and second administered by oral inhalation”, and does not disclose “third dose administered sublingually”. Applicant first disclosed “inhalation of two doses, first administered nasally and second administered by oral inhalation, and third dose administered sublingually”, in the present application.
Thus, Applicant does not have sufficient support in the parent applications to earn the priority date of the instantly claimed “first nasal inhalation dose, second oral inhalation dose, and third sublingual dose”.
Accordingly, the filing date of the present application, which is 11/08/2019, will be considered for examining instant claimed method in terms of the delivery of “first nasal inhalation dose, second oral inhalation dose, and third sublingual dose”.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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 1, 4-6, 10-12, 15, 24, 32, 40, 42, 43, 58 are rejected under 35 U.S.C. 103 as being unpatentable over Fleming (US 2015/0005356) in view of any of the article by Ergometrine (from “Indian Medical Gazette”), the article by Dahlof et al. (Systemic adsorption of adrenaline after aerosol, eye-drop and subcutaneous administration to healthy volunteers), or the article by Lecks et al. (Drug Therapy of Asthma), and the above combination further in view of Hill (US 2007/0293582) Potta et al. (US 2017/0079907), and the article by Bakke et al. (Oral spray immunization may be an alternative to intranasal vaccine delivery to induce systemic antibodies but not nasal mucosal cellular immunity), all references are of record.
Applicant Claims
Claim 1 is directed to a method of elevating plasma epinephrine levels, the method comprising: administering a first dosage of an inhalable l-epinephrine formulation to a subject by dispensing from a dispensing container
the first dosage into or past at least one of said subject’s nostrils delivery to the subject nasal mucosa, followed by
administering a second dosage of the inhalable 1-epinephrine formulation from the dispensing container into or past said subject’s mouth for delivery to the subject’s lungs by oral inhalation, wherein the second dosage is provided at least five minutes after the first dosage, and followed by
administering a third dosage of inhalable 1-epinephrine, from the dispensing container sublingually and/or buccally inside said subject’s mouth for delivery to the subject’s oral mucosa;
wherein the inhalable l-epinephrine formulation is adapted for transmucosal absorption, has a pH of about 3 to about 4.5, and comprises:
epinephrine present at about 0.6% w/w to about 6% w/w;
a IN solution of hydrochloric acid present at about 24% w/w to about 36% w/w;
sodium metabisulfite present at about 0.25% w/w to about 0.5% w/w;
absolute ethanol or dehydrated alcohol present at about 32% w/w to 48% w/w;
propylene glycol present at about 4% w/w to 6% w/w; and
the balance water, and
at least one of blood pressure, pulse, and breathing is maintained or substantially stabilized or normalized in the subject, experiencing or anticipating at least one of severe allergy, anaphylaxis, anaphylactic shock, sepsis, septic shock, respiratory difficulty, and cardiac difficulty.
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
Fleming teaches methods of treating a subject in acute severe anaphylaxis by administering a pharmaceutical composition of epinephrine intranasally to the nasal mucosa (abstract; ¶ 0017). The reference teaches treatment of anaphylaxis, bronchospasm or cardiac arrest in subjects or for increasing mean arterial pressure in subjects outside ER or situations in battlefield or hypotensive shock. The reference teaches a fast onset time of epinephrine compositions that are suitable for intranasal use and have a capacity for providing high blood plasma epinephrine concentrations rapidly after administration (¶¶ 0026, 0030, 0095). The composition is administered to mucosal surfaces of the nasal cavities using inhaler or spray devices comprising a reservoir and means for expelling the pharmaceutical dose in the form of a spray, wherein a quantity of the pharmaceutical composition is contained within the reservoir/container. The device can expel a single or multiple doses. The device can be programmed to dispense one or more pharmaceutical dose. The nasal spray is designed for discharge of multiple spray doses, e.g., 1 to 10 or more. It may be designed to administer the intended dose with multiple sprays, e.g., two sprays, e.g., one in each nostril, or as a single spray, e.g., in one nostril, or to vary the dose in accordance with the body weight or maturity of the patient. The dose is adjusted so that patient can receive the exact optimal dose (¶¶ 0023-0025, 0027, 0078, 0088, 0089, 0092). The composition may be also delivered to the lung by direct inhalation in case of bronchospasms using known devices, e.g. nebulizer (¶ 0077). Epinephrine is present in the composition in amounts ranging from 0.05 mg to 10 mg, preferably from 0.05 mg to 0.75 mg or 0.75 mg to 1.5 mg or 1.5 mg to 3.0 mg or 3.0 to 4.5 mg or 4.5 to 6.0 mg or 6.0 to 7.5 mg or 7.5 to 9.0 mg or 9.0 to 10.0 mg. The epinephrine dose may be adjusted according to the weight of the patient at an increment of at least 0.01 mg/kg, or one wherein the dose may be repeated a number of times if the patient is refractory or experiences rebound anaphylaxis. The intranasal epinephrine composition provides an initial rise in epinephrine plasma levels which is at least 2-fold, preferably 3 to 10-fold more than baseline levels, within 20, 15, 10, 5 and 3 minutes (Tmax), followed by a sustained therapeutic efficacy of the drug for at least 60, 50, 40, 30 minutes after administration (¶ 0018). The dose has volume up to 200 µl when administered from inhaler (¶ 0024), which is equivalent to 0.2 mL. The reference teaches composition of epinephrine in the form of liquid or suspension of particles comprising pharmaceutically acceptable excipients (¶¶ 0022, 0074). The reference teaches the use of multiple dose device for multiple doses, or single use device, one for each dose (¶¶ 0023, 0089). The reference teaches the intranasal composition having pH from 3-6, and can have pH 3.5-5.0 adjusted by hydrochloric acid (¶¶ 0076, 0099). The composition further comprises metabisulfite, ethanol, propylene glycol and water (¶¶ 0047, 0053, 0056, 0072, 0085, 0116, 0120). Doses can be repeated (¶ 0018; claim 20).
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.012)
While Fleming teaches multiple doses administered from inhaler or sprayer, and while teaches intranasal administration to the nasal mucosa that would inevitably permits oral inhalation and mucosal delivery that may spread to sublingual area, and further suggest delivery to the lung by inhalation, the reference does not explicitly teach second dose of epinephrine is administered to the oral mucosa for oral inhalation or administering third dose sublingually or buccally as claimed by claim 1.
While Fleming teaches intranasal composition having pH of 3.5-5, and comprising the claimed ingredients of hydrochloric acid, metabisulfite, ethanol, propylene glycol and water, the reference however the reference does not teach the amount of each of the claimed ingredient as claimed by claims 1 and 58.
While Fleming teaches repeated doses of epinephrine, the reference does not explicitly teach period of 5 minutes before first and second dose as claimed by claim 2.
Ergometrine teaches administering adrenaline (epinephrine) solution by vaporizer provides uniform and successful oral inhalation of adrenaline solution without discomfort and side effects of hypodermic injection of adrenaline (see the provided article).
Dahlof teaches both repeated nasal inhalation and repeated oral inhalation of adrenaline to treat upper airway hyper-reactive conditions, and teaches nasal inhalation of adrenaline is similar to oral inhalation but long lasting (see the entire document, and in particular abstract).
Lecks teaches oral inhalation as suitable route for administering epinephrine (table at page 127).
Hill teaches treating anaphylaxis using different dosage forms so that if first and second dosage forms are ineffective or not tolerated, ephedrine is continued to be administered via alternate route of administration (¶ 0007). The reference teaches the first and second dose are injection, and the following doses are sublingual (0017). Epinephrine dose can be repeated every 3-10 minutes (¶¶ 0005, 0029, 0076, 0083, 0111, 0120, 0130-0132, 0140, 0151, claims 46-47).
Potta teaches treating anaphylaxis by administering sublingual epinephrine spray formulation. The sublingual epinephrine spray formulation is rapidly absorbed via blood vessels under the tongue, and therefore bypass hepatic first pass metabolic processes which provides improved bioavailability. Sublingual spray formulation has more rapid onset of action, and more storage stability (abstract; ¶¶ 0006, 0007, 0016, 0017). The formulation has pH from 2.0 to 5.0. The formulation comprises 1-50% hydrochloric acid, 0.001-2% sodium metabisulfite, 1-50% ethanol, 0.5-5 propylene glycol, and water (¶¶ 0043-0050).
Bakke teaches using the same formulation from a spray bottle for intranasal spray delivery and mouth spray delivery to the oral mucosa and lung (see the entire document, and in particular abstract, page 224).
Finding of Prima Facie Obviousness Rational and Motivation
(MPEP §2142-2143)
Therefore, it would have been obvious to one having ordinary skill in the art before the effective filing date of the present invention to elevate plasma epinephrine level to treat anaphylaxis in subject in need thereof by administering multiple doses of epinephrine from an inhaler or spay devices to the nasal mucosa and down to the airway as taught by Fleming, and further administer epinephrine to the lung by inhalation in case of bronchospasm, and use the inhaler or the spray devices to deliver this second dose of epinephrine to the oral cavity to provide oral inhalation as taught by any of Ergometrine, Dahlof, or Lecks. One would have been motivated to do so because Ergometrine teaches administering epinephrine by solution by oral inhalation provides uniform and successful delivery of epinephrine without discomfort and side effects of hypodermic injection, and because Dahlof teaches repeated oral inhalation is similar to repeated nasal inhalation, and because Lecks teaches oral inhalation as suitable rout for administering epinephrine. One would reasonably expect elevating plasma epinephrine level to treat anaphylaxis including bronchospasm by administering multiple doses of epinephrine from an inhaler or spray devices that deliver the epinephrine by intranasal inhalation and further deliver epinephrine by oral inhalation to ensure successful uniform delivery of stable epinephrine formulation from the different routes of administration to prolong the time of action of epinephrine without the discomfort and side effects of injection.
Further, it would have been obvious to one having ordinary skill in the art before the effective filing date of the present invention to elevate plasma epinephrine level to treat anaphylaxis in subject in need thereof by administering multiple doses of epinephrine from an inhaler or spay devices to the nasal mucosa and down to the airway and further administer epinephrine to the lung by oral inhalation in case of bronchospasm as taught by Fleming combined with any of Ergometrine, Dahlof, or Lecks, and use alternate route to administer a subsequent third dose, other than routes used to administer the first dose and second dose, such as sublingual dose as taught by Hill. One would have been motivated to do so because Hill teaches that using different dosage forms such as sublingual following the first compensates for if first dosage form are ineffective or not tolerated, so epinephrine is continued to be administered via alternate route of administration. One would reasonably expect treat anaphylaxis using one or two liquid intranasal doses of epinephrine followed by oral inhalation and sublingual dosage administration wherein epinephrine administration is continued and tolerated.
Furthermore, one having ordinary skill in the art would have been motivated to deliver the subsequent third dose of inhalable epinephrine taught by combination of the references above by sublingual route using formulation taught by Potta because Potta teaches administering sublingual epinephrine spray formulation treats anaphylaxis because sublingual epinephrine spray formulation is rapidly absorbed via blood vessels under the tongue, and therefore bypass hepatic first pass metabolic processes which provides improved bioavailability, more rapid onset of action, and more storage stability.
One having ordinary skill in the art would have modified the intranasal formulation of Fleming that has pH of 3.5-5, and comprises hydrochloric acid, sodium metabisulfite, ethanol, propylene glycol and water, to adjust the amounts to that taught by Potta because Potta teaches suitability of the combination of such ingredients in the taught amounts for transmucosal delivery.
One having ordinary skill in the art would have used combination of nasal inhalable oral inhalable formulations, and sublingual formulation taught by combination of the above references to administer subsequent doses to the nasal mucosa, oral mucosa, and buccal delivery by sublingual application because Bakke teaches the same spray bottle used for nasal inhalable dose can be used to oral inhalation and mucosal oral delivery. One would have been motivated to do so because the inhalable spray bottle is readily available for oral inhalation and for delivery to the oral/buccal mucosa for convenience and time saving in emergency situation. It is obvious to administer the first dose to the first anatomical convenient site of the body, i.e. nose, that inevitably will provide oral inhalation also, then followed by sublingual administration because reaching the sublingual mucosa will take few more seconds than the nasal spraying.
Combination of the cited references suggests multiple spray inhalable doses administered intranasally, as well as orally and sublingually to the oral mucosa as claimed by claim 1.
The claimed formulation claimed by claims 1 and 58 including the claimed pH and ingredients and amounts are taught by Potta. Potta teaches pH and amount of the ingredients either embrace or overlap with the claimed pH and amounts. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05 [R-5].
Regarding claim 1 that the first dosage and the second dosage are provided at least five minutes apart, Hill teaches epinephrine doses may be repeated every 3-10 minute. Further one having ordinary skill in the art would have determined when to administer the second dose based on individual patient needs.
Regarding claim 1 that the subject is experiencing or anticipating at least one of severe allergy, anaphylaxis, anaphylactic shock, sepsis, septic shock, respiratory difficulty, and cardiac difficulty, these conditions are taught at least by Fleming.
Regarding claim 4 that the method is performed when an at least one injection of an injectable liquid I-epinephrine formulation is not available or is not possible, Fleming teaches that epinephrine can be administered intranasally outside the ER wherein epinephrine injections, and injections in general, are not available.
Regarding claim 5 that the method is performed at least until emergency medical services arrives to treat or transport said subject, this is an expected common practice performed by personnel in or outside the medical field in emergency situation to initiate any possible treatment when available till medical service arrives.
Regarding claim 6 that the subject is a soldier on a battlefield, this is taught by Fleming.
Regarding the dosages of epinephrine of 0.1-50 mg, 1-15 mg, and 2-8 mg as claimed by claims 10, 11 and 12, respectively, Fleming teaches from 0.05 mg to 10 mg, preferably from 0.05 mg to 0.75 mg or 0.75 mg to 1.5 mg or 1.5 mg to 3.0 mg or 3.0 to 4.5 mg or 4.5 to 6.0 mg or 6.0 to 7.5 mg or 7.5 to 9.0 mg or 9.0 to 10.0 mg, that embrace all the claimed ranges. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05 [R-5].
Regarding the dosage volume of 0.05-0.35 mL as claimed by claim 15, Fleming teaches up to 200 µl, which is equivalent to up to 0.2 mL that falls within the claimed range. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05 [R-5].
Regarding the elected device of administration as claimed by claim 24 of inhaler adapted for both nasal and oral inhalation this is taught by Young.
Regarding the elected liquid formulation as claimed by claim 32, it is taught by Fleming.
Regarding claim 40 that the second dosage include the same amount of epinephrine as the first dosage, Fleming teaches repeating the dose, which implies the same dose. In any event, one having ordinary skill in the art would have determined the amount of each dose based on the individual patient needs.
Regarding adjustable dosage as claimed by claim 42, Fleming teaches the dose is adjusted so that patient can receive the exact optimal dose and teaches the dose varies in accordance with the body weight or maturity of the patient.
Regarding the composition comprising excipients claimed by claim 43, this is taught by Fleming.
Absent any evidence to the contrary, and based upon the teachings of the prior art, there would have been a reasonable expectation of success in practicing the instantly claimed invention. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the present invention.
Response to Arguments
Applicant's arguments filed 11/24/2025 have been fully considered but they are not persuasive.
Priority
The Examiner acknowledges Applicant statement that “Applicant does not acquiescence to or agree with the Examiner’s position, but applicant responds to the Examiner’s rejections in order to advance prosecution of the present application”.
Rejections under 35 U.S.C. § 103
Applicant argues that independent claim 1 recites a method comprising three distinct administration steps in which an inhalable 1-epinephrine formulation is administered via three different routes directed to three different mucosal surfaces in a prescribed sequence. Applicant maintains that the PTO has failed to provide evidence that the specific sequence of administration steps required by claim 1 are obvious in view of the cited art.
In response to this argument, applicant’s attentions to the scope of the present claims that are directed to method of elevating plasma 1-epinephrine,….the method comprising administering first dosage,… second dosage…. and third dosage….to distinct mucosal surfaces, and the combination of the cited references teaches administering epinephrine to the claimed three mucosal surfaces: nasal mucosa, oral mucosa, and bronchial mucosa. Administration to the nasal mucosa is taught by Fleming that teaches multiple doses administered from inhaler or sprayer intranasally to the nasal mucosa that would inevitably permits spread of the inhaled drug to the oral mucosa that may spread to sublingual area, and Fleming further suggest delivery to the lung by inhalation. This teaching suggests delivery to the oral mucosa during the passage of the epinephrine delivered to the nasal mucosa to be inhaled that cannot be avoided. The reference is relied upon for all it suggests to one skilled in the art, and conclusion of obviousness does not require absolute predictability, rather reasonable expectation of success. One having ordinary skill in the art would have used combination of nasal inhalable, oral inhalable formulations, and sublingual formulation taught by combination of the above references to administer subsequent doses to the nasal mucosa, oral mucosa, and buccal delivery by sublingual application because Bakke teaches the same spray bottle used for nasal inhalable dose can be used to oral inhalation and mucosal oral delivery. One would have been motivated to do so because the inhalable spray bottle is readily available for oral inhalation and for delivery to the oral/buccal mucosa for convenience and time saving in emergency situation. It is obvious to administer the first dose to the first anatomical convenient site of the body, i.e. nose, that inevitably will provide oral inhalation also, then followed by sublingual administration because reaching the sublingual mucosa will take few more seconds than the nasal spraying.
Applicant argues that the PTO has cited multiple documents, some of which teach plural dosing of epinephrine. However, none of these references teaches or suggests the regimen required by the claims.
In response to this argument, it is argued that the present claims also require plural dosing of epinephrine as claimed, and combination of the cited references suggests the claimed regimen as set forth in this office action.
Applicant argues that the cited references describe various dosing regimens motivated by rationales that are particular to the specific problem discussed in each. Applicant maintains, however, that the PTO has failed to articulate a rationale by which these disparate teachings should lead a skilled person to the specific steps and sequence set forth in claim 1. The PTO alleges that the distinct administration routes recited in claim 1 are equivalent or identical. The PTO even seems to suggest that a dosing by a single route should be counted as providing more than one administration step. However, these assertions are in direct contradiction to the express language of claim 1, which clearly recites three distinct administration steps. The PTO further alleges that “the language of the claims permits any order of the claimed steps.” Again, this assertion is in direct contradiction to the express language of claim 1 (“followed by”) which dictates a specific sequence of the recited administration steps. Applicant maintains that the cited art, alone or in combination, does not reasonably lead the skilled artisan to Applicant’s method comprising the claimed steps, let alone the claimed order of those steps.
In response to this arguments, it is argued that, in considering the disclosure of the reference, it is proper to take into account not only the specific teachings of the reference but also the inferences which one skilled in the art would reasonably be expected to draw therefrom. In re Preda, 401 F.2d 825, 826, 159 USPQ 342, 344 (CCPA 1968). The rational to modify or to combine the prior art does not have to be expressly stated in the prior art; the rational may be expressly or impliedly contained in the prior art or it may be reasoned from knowledge generally available to one of ordinary skill in the art. The reason or motivation to modify the reference may often suggest what the inventor has done, but for a different purpose or to solve different problem. It is not necessary that the prior art suggest the combination or modification to achieve the same advantage or result discovered by applicant. In re Linter, 458 F.2d 1013, 173 USPQ 560 (CCPA 1972). In the instant case, the combination of the cited references teaches the claimed 3 method of administration of epinephrine, and also suggested repeated administration. One having ordinary skill in the art would have drawn from the teachings of the references that nasal administration is inevitably followed by oral mucosa administration and inhalational administration. Similarly, spray administration to the oral mucosa would inevitably be followed by spread to the respiratory tract leading to inhalation. All the cited references are analogous art and reasonably pertinent to the particular problem with which the inventor was concerned, which is treating anaphylaxis using epinephrine administered to the mucosal surfaces, nasal, oral, and pulmonary. Therefore it is reasonable to be relied upon as a basis for rejection of the claimed invention. It has been held that a prior art reference must either be in the field of the inventor’s endeavor or, if not, then reasonably concerned with the problem with which applicant is concerned in order to be relied upon. See In re Oetiker, 977 F.2d 1443, 24 USPQ2d 1443 (Fed. Cir. 1992). It has been held that it is obvious to combine prior art elements according to known methods to yield predictable results. A finding that the prior art included each element claimed, although not necessarily in a single prior art reference, with the only difference between the claimed invention and the prior art being the lack of actual combination of the elements in a single prior art reference, was held obvious by the court.
It has been held that it is obvious to combine prior art elements according to known methods to yield predictable results. A finding that the prior art included each element claimed, although not necessarily in a single prior art reference, with the only difference between the claimed invention and the prior art being the lack of actual combination of the elements in a single prior art reference, was held obvious by the court. Further, it has been held that reversing of order of the prior art process is prima facie obvious absence superior and unexpected results, see Ex parte Rubin, 128 USPQ 440 (Bd. App. 1959). Selection of any order of performing process steps is prima facie obvious in absence of new unexpected results, see In re Burhans, 154 F.2d 690, 69 USPQ 330 (CCPA 1946). Any order of mixing ingredients is prima facie obvious, see In re Gibson 39 F.2d 975, 5USPQ 330 (CCPA 1930).
It is further noted the claimed first, second and third doses are not more that repeating the first step, and duplication, reversal or rearrangement of parts or steps was held to be an obvious expedient. In re Gazda, 219 F.2d 449, 104 USPQ 400 (CCPA 1955); In re Japikse, 181 F.2d 1019, 86 USPQ 70 (CCPA 1950); In re Kuhle, 526 F.2d 553, 188 USPQ 7 (CCPA 1975).
The obviousness does not require absolute predictability of success all that is required is a reasonable expectation of success. See In re Kubin, 561 F.3d at 1360. The Court has held that "the test of obviousness is not express suggestion of the claimed invention in any or all of the references but rather what the references taken collectively would suggest to those of ordinary skill in the art presumed to be familiar with them." See In re Rosselet, 146 USPQ 183, 186 (CCPA 1965). "There is no requirement (under 35 USC 103(a)) that the prior art contain an express suggestion to combine known elements to achieve the claimed invention. Rather, the suggestion to combine may come from the prior art, as filtered through the knowledge of one skilled in the art." Motorola, Inc. v. Interdigital Tech. Corp., 43 USPQ2d 1481, 1489 (Fed. Cir.1997). An obviousness determination is not the result of a rigid formula disassociated from the consideration of the facts of a case. Indeed, the common sense of those skilled in the art demonstrates why some combinations would have been obvious where others would not. See KSR Int'l Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007) ("The combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.").
It is obvious to administer the first dose to the first anatomical convenient site of the body, i.e. nose, that inevitably will provide oral inhalation also, then followed by sublingual administration because reaching the sublingual mucosa will take few more seconds than the nasal spraying. All the claimed steps are suggested by the cited references. It has been held that it is prima facie obvious to reverse the order of the prior art process steps, Ex parte Rubin , 128 USPQ 440 (Bd. App. 1959). See also In re Burhans, 154 F.2d 690, 69 USPQ 330 (CCPA 1946), selection of any order of performing process steps is prima facie obvious in the absence of new or unexpected results; In re Gibson, 39 F.2d 975, 5 USPQ 230 (CCPA 1930), selection of any order of mixing ingredients is prima facie obvious. Applicants failed to show superior and unexpected results obtained from of the claimed step order and riming because the prior art achieved the same ultimate results of treating anaphylaxis.
The reference will not lead one skilled in the art in a different direction from treating anaphylaxis using repeated doses of epinephrine applied to the oral mucosa, either nasal, oral, or pulmonary. "A reference may be said to teach away when a person of ordinary skill, upon reading the reference, would be discouraged from following the path set out in the reference, or would be led in a direction divergent from the path that was taken by the applicant. The degree of teaching away will of course depend on the particular facts; in general, a reference will teach away if it suggests that the line of development flowing from the reference's disclosure is unlikely to be productive of the result sought by the applicant." In re Gurley, 27 F.3d 551,553 (Fed. Cir. 1994).
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.
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/ISIS A GHALI/Primary Examiner, Art Unit 1611 /I.G./