ucsDETAILED 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
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Election/Restrictions
Applicant’s election without traverse of Group II and a species of sarcoidosis in the reply filed on 8/1/25 is acknowledged.
Claim Status
Claims 1-16 are cancelled. Claims 17-36 are pending. Claims 17-30 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claim 34 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 8/1/25.
Claims 31-33 and 35-36 are currently under consideration for patentability under 37 CFR 1.104.
Information Disclosure Statement
The information disclosure statement filed on 8/1/25 has been considered. A signed copy is enclosed.
Notably, the disclosure statement filed lists a Search Report. The listing of the references cited in a Search Report itself is not considered to be an information disclosure statement (IDS) complying with 37 CFR 1.98. 37 CFR 1.98(a)(2) requires a legible copy of: (1) each foreign patent; (2) each publication or that portion which caused it to be listed; (3) for each cited pending U.S. application, the application specification including claims, and any drawing of the application, or that portion of the application which caused it to be listed including any claims directed to that portion, unless the cited pending U.S. application is stored in the Image File Wrapper (IFW) system; and (4) all other information, or that portion which caused it to be listed. In addition, each IDS must include a list of all patents, publications, applications, or other information submitted for consideration by the Office (see 37 CFR 1.98(a)(1) and (b)), and MPEP § 609.04(a), subsection I. states, "the list ... must be submitted on a separate paper." Therefore, the references cited in the Search Report have not been considered. Applicant is advised that the date of submission of any item of information or any missing element(s) will be the date of submission for purposes of determining compliance with the requirements based on the time of filing the IDS, including all "statement" requirements of 37 CFR 1.97(e). See MPEP § 609.05(a).
Note: If copies of the individual references cited on the Search Report are also cited separately on the IDS (and these references have not been lined-through) they have been considered.
Claim Objections
Claim 31 is objected to because of the following informalities: the claim depends from a non-elected invention. Applicant should amend the claim to incorporate the limitations from claim 17 to overcome the objection. Appropriate correction is required.
Claim 32 is objected to because of the following informalities: the claim recites several genera of diseases without adding proper punctuation to appropriately separate the genera. For example, semi-colons should be used between groupings that also have specific species separated by commas, for example “inflammations of the lower airways due to a bacterial, viral, fungal, or parasitic infection” should be followed with a semi-colon. The other lists within lists that are present in the claim should be treated similarly. All sub-genera should be specifically set apart with a semi-colon, with commas used to separate individual species within the sub-genera. Appropriate correction is required.
Claim 32 is objected to because of the following informalities: the phrase “and/or necrotic conditions of lower respiratory tract” should be amended to read “and/or necrotic conditions of the lower respiratory tract”. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 31-33 and 35-36 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 31 recites “a method of treating an anti-inflammatory pulmonary disease”. The term “anti-inflammatory pulmonary disease” renders the claim indefinite. The diseases listed in the specification are all described as “inflammatory” (see e.g. page 1), and the peptide treatments are listed as “anti-inflammatory peptides”. It is therefore unclear what diseases constitute “anti-inflammatory diseases” and how those “anti-inflammatory diseases” would be treated by “anti-inflammatory peptides”.
Claim 31 recites “wherein the aerosol has a fine particle mass of at least 50% and wherein the liquid droplets have a median mass aerodynamic diameter in a range from about 2.8 to 6.0 μm.” The term “fine particle mass of at least 50%” is defined in the instant specification as “percentage of the particles in the generated aerosol with a diameter in the range of 1 pm to 5 pm” (see e.g. page 38, instant specification). However, the claim requires a diameter range that is different from the specification definition. Therefore, it is unclear if the particles must be within both ranges, or if only one range is required.
Claim 32-33 and 35 recites the limitation "the inflammatory pulmonary disease". There is insufficient antecedent basis for this limitation in the claim. The rejected claims all depend from claim 31, which recites “an anti-inflammatory pulmonary disease”.
The term “chronic lower respiratory diseases” in claim 32 is a relative term which renders the claim indefinite. The term “chronic” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
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 32 recites the broad recitation “lung diseases due to an external agent”, and the claim also recites “inflammations of the lower airways due to a bacterial, viral, fungal, or parasitic infection” 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.
The term “principally affecting” in claim 32 is a relative term which renders the claim indefinite. The term “principally affecting” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
The phrase “respiratory diseases principally affecting the interstitium, suppurative and/or necrotic conditions of lower respiratory tract” renders claim 32 indefinite. It is unclear what alternatives are represented by the phrase, and if the diseases are both identified by the location and necrosis, or if the necrosis is alternative to the disease location.
The term “postprocedural” in claim 32 is a relative term which renders the claim indefinite. The term “postprocedural” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
The term “or related” in claim 32 is a relative term which renders the claim indefinite. The term “or related” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
The term “specific to the perinatal period” in claim 32 is a relative term which renders the claim indefinite. The term “specific to the perinatal period” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. In particular, it is unclear what criteria such as length of time must be met for the perinatal period.
Claim 32 recites “trauma an injuries of the lower respiratory tract and/or the thorax”, which renders the claim indefinite. The instant specification defines “trauma” to “refer to injuries of different size and scope in the affected pulmonary tissue”. Therefore the term “trauma” and “injuries” appear to be identical in scope, which renders the use of both terms in the claim indefinite.
Claim 33 recites “adult respiratory distress syndrome”. This disease name is not recognized in the art, and the instant specification uses the acronym “ARDS” to refer to both “adult respiratory distress syndrome” and “acute respiratory distress syndrome”. It is therefore unclear what is encompassed by the term “adult respiratory distress syndrome”.
Claim Interpretation
Claim 31 recites “an anti-inflammatory disease”, however, the dependent claims and the specification only list inflammatory pulmonary diseases. Therefore, the claims will be interpreted to encompass the inflammatory diseases listed in the dependent claims and specification.
The term “fine particle mass of at least 50%” is defined as “percentage of the particles in the generated aerosol with a diameter in the range of 1 pm to 5 pm” (see e.g. page 38, instant specification). This conflicts with the range in instant claim 17. Therefore, the examined claims will be interpreted to read on a method of administering a therapeutically effective amount of an aviptadil aerosol comprising at least 50% particles in the generated aerosol with a diameter of 2.8-6.0 μm.
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 (i.e., changing from AIA to pre-AIA ) 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
1. Claim(s) 31-33 and 35-36 is/are rejected under 35 U.S.C. 103 as being unpatentable over Prasse et al (Am J Respir Crit Care Med Vol 182. pp 540–548, 2010) in view of Muller-Quernheim (EP 3 583 933 A1; filed 6/20/18; published 12/25/19).
The instant claims are directed to a method of treating an anti-inflammatory pulmonary disease, comprising administering a therapeutically effective amount of the aerosol of claim 17 to a subject in need thereof. The aerosol comprises liquid droplets comprising aviptadil, wherein the aerosol has a fine particle mass of at least 50%, and wherein the liquid droplets have a median mass aerodynamic diameter in a range from about 2.8 μm to about 6.0 μm. The pulmonary disease can be sarcoidosis, which the instant specification indicates is a chronic lower respiratory disease (see instant specification page 21). The aerosol can be administered by inhalation.
Prasse teaches treatment of patients with sarcoidosis, that are nebulized with vasoactive intestinal peptide (VIP) (see e.g. Prasse abstract). The sarcoidosis was an inflammatory disorder of the lung (see e.g. Prasse page 547, right column). The vasoactive intestinal peptide was Aviptadil (see e.g. Prasse page 541, left column). The treatment was an inhalation treatment (see e.g. Prasse abstract, and Prasse page 541, left column, top paragraph).
Prasse does not teach the fine particle mass of at least 50%, and wherein the liquid droplets have a median mass aerodynamic diameter in a range from about 2.8 μm to about 6.0 μm.
Muller-Quernheim teaches an aviptadil aerosol comprising droplets having a particle size small enough to be easily inhaled for use in the treatment of Chronic Beryllium Disease, where the droplets can have a diameter of 2.8 to 4.5 μm (see e.g. Muller-Quernheim claims 1 and 4). Muller-Quernheim teaches that at least 80% of the droplets have a diameter between 2.0 and 6.0 μm (see e.g. Muller-Quernheim claim 3), which overlaps with the required fine particle mass of the instant claims. Notably, the aerosol can be produced by an M-neb dose+ 300/8 nebulizer (see e.g. Muller-Quernheim claim 9), which is one type of nebulizer indicated by the instant specification as being suitable to produce the required aerosol particles (see e.g. instant specification page 34 and 36, and instant Example 14). Muller-Quernheim teaches MMAD of less 1-10 μm (see e.g. Muller-Quernheim paragraph [0007]). Furthermore Muller-Quernheim teaches the exact same drug concentrations for Aviptadil dissolved in 0.9% saline (see Muller-Quernheim Example 2 in paragraph [0066]), which is identical to the Aviptadil solutions used in the instant examples (see e.g. instant specification Example 14, page 62).
It would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to use the aerosol formulation of Muller-Quernheim to treat the sarcoidosis of Prasse, because Muller-Quernheim teaches that the aerosols produced by Muller-Quernheim can be applied by a nebulizer at a particle size small enough to be easily inhaled into the lower respiratory tract to reach deep alveolar deposition (see Muller-Quernheim paragraph [0005]). Considering that the instant specification characterizes sarcoidosis as a “chronic lower respiratory disease” (se e.g. instant specification page 21), it would be advantageous to use a formulation that is specifically designed to reach the lower respiratory tract. It would be expected, absent evidence to the contrary, that use of the formulation of Muller-Quernheim with the same drug as Prasse, which is known to treat sarcoidosis, would produce the desired disease treatment. The advantages of using a formulation known to treat lower respiratory disease provides the motivation to make the aforementioned modification of the method of Prasse, based on the teachings of an effective formulation as taught by Muller-Quernheim, with a reasonable expectation of success.
Furthermore, the use of the formulation of Muller-Quernheim would be a known variation in the art that could be reasonably applied to the method of Prasse by one of skill in the art. The Supreme Court set forth in KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), that if the scope and content of the prior art included a similar or analogous product, with differences between the claimed invention and prior art that were encompassed in known variation or in a principle known in the art, and one of ordinary skill in the art could have combined the elements as claimed by known methods, the claimed variation would have been predictable in to one of ordinary skill in the art. The formulation of Muller-Quernheim is specifically designed to treat lower respiratory diseases, and because Prasse recognizes the potential treatment effect of aviptadil for sarcoidosis, applying the formulation of Muller-Quernheim to the patients of Prasse would be encompassed in a known variation or principle in the art. Thus, the combination of prior art references as combined provided a prima facie case of obviousness, absent convincing evidence to the contrary.
Regarding the specific range of the median mass aerodynamic diameter, Muller-Quernheim teaches a range that overlaps with the instant claims. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990) (see e.g. MPEP 2144.05).
Furthermore, Applicant’s attention is drawn to MPEP 2144.05(II)(A), Routine Optimization - Optimization Within Prior Art Conditions or Through Routine Experimentation:
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree “will not sustain a patent”); In re Williams, 36 F.2d 436, 438 (CCPA 1929) (“It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.”). See also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007) (identifying “the need for caution in granting a patent based on the combination of elements found in the prior art.”).
Although this passage does not specifically point to, for example, MMAD, this passage points to numerous variables that affect the function of inventions, such as concentration of reagents and temperature ranges. Furthermore this passage indicates that the optimization of such variables is often obvious activity for one of ordinary skill in the art. It is submitted that the claimed MMAD is akin to the variables discussed in the cited MPEP passage, because said MMAD is an optimizable variable that would affect at least the toxicity and/or efficacy, i.e., function, of the claimed invention. Given the “normal desire of scientists or artisans to improve upon what is already generally known,” it would have been prima facie obvious to one of ordinary skill in the art to optimize the claimed MMAD, because such optimization would produce a more effective invention.
2. Claim(s) 31-33 and 35-36 is/are rejected under 35 U.S.C. 103 as being unpatentable over Prasse et al (Am J Respir Crit Care Med Vol 182. pp 540–548, 2010) in view of Laube et al (Eur Respir J 2011; 37: 1308–1331).
The instant claims are directed to a method of treating an anti-inflammatory pulmonary disease, comprising administering a therapeutically effective amount of the aerosol of claim 17 to a subject in need thereof. The aerosol comprises liquid droplets comprising aviptadil, wherein the aerosol has a fine particle mass of at least 50%, and wherein the liquid droplets have a median mass aerodynamic diameter in a range from about 2.8 μm to about 6.0 μm. The pulmonary disease can be sarcoidosis, which the instant specification indicates is a chronic lower respiratory disease (see instant specification page 21). The aerosol can be administered by inhalation.
Prasse teaches treatment of patients with sarcoidosis, that are nebulized with vasoactive intestinal peptide (VIP) (see e.g. Prasse abstract). The sarcoidosis was an inflammatory disorder of the lung (see e.g. Prasse page 547, right column). The vasoactive intestinal peptide was Aviptadil (see e.g. Prasse page 541, left column). The treatment was an inhalation treatment (see e.g. Prasse abstract, and Prasse page 541, left column, top paragraph).
Prasse does not teach the fine particle mass of at least 50%, and wherein the liquid droplets have a median mass aerodynamic diameter in a range from about 2.8 μm to about 6.0 μm.
Laube et al teach that particles that are <5 μm have the greatest potential for deposition in the lungs (see e.g. Laube page 1310, right column). The proportion of particles within an aerosol that are <5 μm mm is often referred to as the fine-particle fraction (FPF), or the fine-particle dose (FPD) if expressed in absolute mass of drug in particles <5 μm (see e.g. Laube table 1). Aerosols with high FPFs have a high probability of penetrating beyond the upper airways and depositing in the lungs (see e.g. Laube page 1310, right column). Thus, it is not surprising that current devices generate aerosols with a significant proportion of their particles in the 1–5 μm range (see e.g. Laube page 1310, right column).
It would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to formulate an aerosol formulation using the guidance of Laube to treat the sarcoidosis of Prasse, because Laube teaches that particle size can enhance the ability of the particles to be absorbed into the lung for treatment of disease. Considering that the instant specification characterizes sarcoidosis as a “chronic lower respiratory disease” (se e.g. instant specification page 21), it would be advantageous to use a formulation that is specifically designed to reach the area of disease. It would be expected, absent evidence to the contrary, that use of the formulation of Prasse, formulated according to the guidance in Laube, would reasonably produce the desired disease treatment. The advantages of optimizing a formulation known to treat sarcoidosis to achieve maximum efficacy provides the motivation to make the aforementioned modification of the method of Prasse, based on the teachings of an effective formulation as taught by Laube, with a reasonable expectation of success.
Furthermore, the use of the formulation guidelines of Laube would be a known variation in the art that could be reasonably applied to the method of Prasse by one of skill in the art. The Supreme Court set forth in KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), that if the scope and content of the prior art included a similar or analogous product, with differences between the claimed invention and prior art that were encompassed in known variation or in a principle known in the art, and one of ordinary skill in the art could have combined the elements as claimed by known methods, the claimed variation would have been predictable in to one of ordinary skill in the art. The formulation of Laube is designed to maximize efficacy based on the specific particle size, and because Prasse recognizes the potential treatment effect of aviptadil for sarcoidosis, applying the guidelines of Laube to adjust particle size be encompassed in a known variation or principle in the art. Thus, the combination of prior art references as combined provided a prima facie case of obviousness, absent convincing evidence to the contrary.
Furthermore, Applicant’s attention is drawn to MPEP 2144.05(II)(A), Routine Optimization - Optimization Within Prior Art Conditions or Through Routine Experimentation:
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree “will not sustain a patent”); In re Williams, 36 F.2d 436, 438 (CCPA 1929) (“It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.”). See also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007) (identifying “the need for caution in granting a patent based on the combination of elements found in the prior art.”).
Although this passage does not specifically point to, for example, MMAD, this passage points to numerous variables that affect the function of inventions, such as concentration of reagents and temperature ranges. Furthermore this passage indicates that the optimization of such variables is often obvious activity for one of ordinary skill in the art. It is submitted that the claimed MMAD is akin to the variables discussed in the cited MPEP passage, because said MMAD is an optimizable variable that would affect at least the toxicity and/or efficacy, i.e., function, of the claimed invention. Given the “normal desire of scientists or artisans to improve upon what is already generally known,” it would have been prima facie obvious to one of ordinary skill in the art to optimize the claimed MMAD, because such optimization would produce a more effective invention.
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.
1. Claims 31-33 and 35-36 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. 7,951,778 in view of Muller-Quernheim (EP 3 583 933 A1; filed 6/20/18; published 12/25/19).
Although the claims at issue are not identical, they are not patentably distinct from each other.
The instant claims are directed to a method of treating an anti-inflammatory pulmonary disease, comprising administering a therapeutically effective amount of the aerosol of claim 17 to a subject in need thereof. The aerosol comprises liquid droplets comprising aviptadil, wherein the aerosol has a fine particle mass of at least 50%, and wherein the liquid droplets have a median mass aerodynamic diameter in a range from about 2.8 μm to about 6.0 μm. The pulmonary disease can be sarcoidosis, which the instant specification indicates is a chronic lower respiratory disease (see instant specification page 21). The aerosol can be administered by inhalation.
The reference patent teaches treatment of patients with sarcoidosis, with vasoactive intestinal peptide (VIP) (see e.g. reference claim 1). The vasoactive intestinal peptide has the same sequence as Aviptadil (see e.g. reference claim 1). The treatment was an inhalation treatment (see e.g. reference claim 3).
The reference patent does not teach the fine particle mass of at least 50%, and wherein the liquid droplets have a median mass aerodynamic diameter in a range from about 2.8 μm to about 6.0 μm.
Muller-Quernheim teaches an aviptadil aerosol comprising droplets having a particle size small enough to be easily inhaled for use in the treatment of Chronic Beryllium Disease, where the droplets can have a diameter of 2.8 to 4.5 μm (see e.g. Muller-Quernheim claims 1 and 4). Muller-Quernheim teaches that at least 80% of the droplets have a diameter between 2.0 and 6.0 μm (see e.g. Muller-Quernheim claim 3), which overlaps with the required fine particle mass of the instant claims. Notably, the aerosol can be produced by an M-neb dose+ 300/8 nebulizer (see e.g. Muller-Quernheim claim 9), which is one type of nebulizer indicated by the instant specification as being suitable to produce the required aerosol particles (see e.g. instant specification page 34 and 36, and instant Example 14). Muller-Quernheim teaches MMAD of less 1-10 μm (see e.g. Muller-Quernheim paragraph [0007]). Furthermore Muller-Quernheim teaches the exact same drug concentrations for Aviptadil dissolved in 0.9% saline (see Muller-Quernheim Example 2 in paragraph [0066]), which is identical to the Aviptadil solutions used in the instant examples (see e.g. instant specification Example 14, page 62).
It would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to use the aerosol formulation of Muller-Quernheim to treat the sarcoidosis of the reference patent because Muller-Quernheim teaches that the aerosols produced by Muller-Quernheim can be applied by a nebulizer at a particle size small enough to be easily inhaled into the lower respiratory tract to reach deep alveolar deposition (see Muller-Quernheim paragraph [0005]). Considering that the instant specification characterizes sarcoidosis as a “chronic lower respiratory disease” (se e.g. instant specification page 21), it would be advantageous to use a formulation that is specifically designed to reach the lower respiratory tract. It would be expected, absent evidence to the contrary, that use of the formulation of Muller-Quernheim, which uses the same drug as the reference patent, and which is known to treat sarcoidosis, would produce the desired disease treatment. The advantages of using a formulation known to treat lower respiratory disease provides the motivation to make the aforementioned modification of the method of the reference patent, based on the teachings of an effective formulation as taught by Muller-Quernheim, with a reasonable expectation of success.
Furthermore, the use of the formulation of Muller-Quernheim would be a known variation in the art that could be reasonably applied to the method of the reference patent by one of skill in the art. The Supreme Court set forth in KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), that if the scope and content of the prior art included a similar or analogous product, with differences between the claimed invention and prior art that were encompassed in known variation or in a principle known in the art, and one of ordinary skill in the art could have combined the elements as claimed by known methods, the claimed variation would have been predictable in to one of ordinary skill in the art. The formulation of Muller-Quernheim is specifically designed to treat lower respiratory diseases, and because the reference patent recognizes the potential treatment effect of aviptadil for sarcoidosis, applying the formulation of Muller-Quernheim to the patients of the reference patent would be encompassed in a known variation or principle in the art. Thus, the combination of prior art references as combined provided a prima facie case of obviousness, absent convincing evidence to the contrary.
Regarding the specific range of the median mass aerodynamic diameter, Muller-Quernheim teaches a range that overlaps with the instant claims. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990) (see e.g. MPEP 2144.05).
Furthermore, Applicant’s attention is drawn to MPEP 2144.05(II)(A), Routine Optimization - Optimization Within Prior Art Conditions or Through Routine Experimentation:
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree “will not sustain a patent”); In re Williams, 36 F.2d 436, 438 (CCPA 1929) (“It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.”). See also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007) (identifying “the need for caution in granting a patent based on the combination of elements found in the prior art.”).
Although this passage does not specifically point to, for example, MMAD, this passage points to numerous variables that affect the function of inventions, such as concentration of reagents and temperature ranges. Furthermore this passage indicates that the optimization of such variables is often obvious activity for one of ordinary skill in the art. It is submitted that the claimed MMAD is akin to the variables discussed in the cited MPEP passage, because said MMAD is an optimizable variable that would affect at least the toxicity and/or efficacy, i.e., function, of the claimed invention. Given the “normal desire of scientists or artisans to improve upon what is already generally known,” it would have been prima facie obvious to one of ordinary skill in the art to optimize the claimed MMAD, because such optimization would produce a more effective invention.
2. Claims 31-33 and 35-36 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. 7,951,778 in view of Laube et al (Eur Respir J 2011; 37: 1308–1331).
The instant claims are directed to a method of treating an anti-inflammatory pulmonary disease, comprising administering a therapeutically effective amount of the aerosol of claim 17 to a subject in need thereof. The aerosol comprises liquid droplets comprising aviptadil, wherein the aerosol has a fine particle mass of at least 50%, and wherein the liquid droplets have a median mass aerodynamic diameter in a range from about 2.8 μm to about 6.0 μm. The pulmonary disease can be sarcoidosis, which the instant specification indicates is a chronic lower respiratory disease (see instant specification page 21). The aerosol can be administered by inhalation.
The reference patent teaches treatment of patients with sarcoidosis, with vasoactive intestinal peptide (VIP) (see e.g. reference claim 1). The vasoactive intestinal peptide has the same sequence as Aviptadil (see e.g. reference claim 1). The treatment was an inhalation treatment (see e.g. reference claim 3).
The reference patent does not teach the fine particle mass of at least 50%, and wherein the liquid droplets have a median mass aerodynamic diameter in a range from about 2.8 μm to about 6.0 μm.
Laube et al teach that particles that are <5 μm have the greatest potential for deposition in the lungs (see e.g. Laube page 1310, right column). The proportion of particles within an aerosol that are <5 μm mm is often referred to as the fine-particle fraction (FPF), or the fine-particle dose (FPD) if expressed in absolute mass of drug in particles <5 μm (see e.g. Laube table 1). Aerosols with high FPFs have a high probability of penetrating beyond the upper airways and depositing in the lungs (see e.g. Laube page 1310, right column). Thus, it is not surprising that current devices generate aerosols with a significant proportion of their particles in the 1–5 μm range (see e.g. Laube page 1310, right column).
It would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to formulate an aerosol formulation using the guidance of Laube to treat the sarcoidosis of the reference patent, because Laube teaches that particle size can enhance the ability of the particles to be absorbed into the lung for treatment of disease. Considering that the instant specification characterizes sarcoidosis as a “chronic lower respiratory disease” (se e.g. instant specification page 21), it would advantageous to use a formulation that is specifically designed to reach the area of disease. It would be expected, absent evidence to the contrary, that use of the formulation of the reference patent, according to the guidance in Laube, would reasonably produce the desired disease treatment. The advantages of optimizing a formulation known to treat sarcoidosis to achieve maximum efficacy provides the motivation to make the aforementioned modification of the method of the reference patent, based on the teachings of an effective formulation as taught by Laube, with a reasonable expectation of success.
Furthermore, the use of the formulation guidelines of Laube would be a known variation in the art that could be reasonably applied to the method of the reference patent by one of skill in the art. The Supreme Court set forth in KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), that if the scope and content of the prior art included a similar or analogous product, with differences between the claimed invention and prior art that were encompassed in known variation or in a principle known in the art, and one of ordinary skill in the art could have combined the elements as claimed by known methods, the claimed variation would have been predictable in to one of ordinary skill in the art. The formulation of Laube is designed to maximize efficacy based on the specific particle size, and because the reference patent recognizes the potential treatment effect of aviptadil for sarcoidosis, applying the guidelines of Laube to adjust particle size would be encompassed in a known variation or principle in the art. Thus, the combination of prior art references as combined provided a prima facie case of obviousness, absent convincing evidence to the contrary.
Furthermore, Applicant’s attention is drawn to MPEP 2144.05(II)(A), Routine Optimization - Optimization Within Prior Art Conditions or Through Routine Experimentation:
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree “will not sustain a patent”); In re Williams, 36 F.2d 436, 438 (CCPA 1929) (“It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.”). See also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007) (identifying “the need for caution in granting a patent based on the combination of elements found in the prior art.”).
Although this passage does not specifically point to, for example, MMAD, this passage points to numerous variables that affect the function of inventions, such as concentration of reagents and temperature ranges. Furthermore this passage indicates that the optimization of such variables is often obvious activity for one of ordinary skill in the art. It is submitted that the claimed MMAD is akin to the variables discussed in the cited MPEP passage, because said MMAD is an optimizable variable that would affect at least the toxicity and/or efficacy, i.e., function, of the claimed invention. Given the “normal desire of scientists or artisans to improve upon what is already generally known,” it would have been prima facie obvious to one of ordinary skill in the art to optimize the claimed MMAD, because such optimization would produce a more effective invention.
3. Claim 31-33 and 35-36 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 12-13 of copending Application No. 18/556,073 (reference application) in view of Muller-Quernheim (EP 3 583 933 A1; filed 6/20/18; published 12/25/19).
Although the claims at issue are not identical, they are not patentably distinct from each other.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The instant claims are directed to a method of treating an anti-inflammatory pulmonary disease, comprising administering a therapeutically effective amount of the aerosol of claim 17 to a subject in need thereof. The aerosol comprises liquid droplets comprising aviptadil, wherein the aerosol has a fine particle mass of at least 50%, and wherein the liquid droplets have a median mass aerodynamic diameter in a range from about 2.8 μm to about 6.0 μm. The pulmonary disease can be sarcoidosis, which the instant specification indicates is a chronic lower respiratory disease (see instant specification page 21). The aerosol can be administered by inhalation.
The reference claims teach a method of treating sarcoidosis in a subject in need thereof, comprising administering an effective amount of aviptadil to the subject by inhalation (see e.g. reference claim 12 and 13).
The reference application does not teach the fine particle mass of at least 50%, and wherein the liquid droplets have a median mass aerodynamic diameter in a range from about 2.8 μm to about 6.0 μm.
Muller-Quernheim teaches an aviptadil aerosol comprising droplets having a particle size small enough to be easily inhaled for use in the treatment of Chronic Beryllium Disease, where the droplets can have a diameter of 2.8 to 4.5 μm (see e.g. Muller-Quernheim claims 1 and 4). Muller-Quernheim teaches that at least 80% of the droplets have a diameter between 2.0 and 6.0 μm (see e.g. Muller-Quernheim claim 3), which overlaps with the required fine particle mass of the instant claims. Notably, the aerosol can be produced by an M-neb dose+ 300/8 nebulizer (see e.g. Muller-Quernheim claim 9), which is one type of nebulizer indicated by the instant specification as being suitable to produce the required aerosol particles (see e.g. instant specification page 34 and 36, and instant Example 14). Muller-Quernheim teaches MMAD of less 1-10 μm (see e.g. Muller-Quernheim paragraph [0007]). Furthermore Muller-Quernheim teaches the exact same drug concentrations for Aviptadil dissolved in 0.9% saline (see Muller-Quernheim Example 2 in paragraph [0066]), which is identical to the Aviptadil solutions used in the instant examples (see e.g. instant specification Example 14, page 62).
It would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to use the aerosol formulation of Muller-Quernheim to treat the sarcoidosis of the reference application, because Muller-Quernheim teaches that the aerosols produced by Muller-Quernheim can be applied by a nebulizer at a particle size small enough to be easily inhaled into the lower respiratory tract to reach deep alveolar deposition (see Muller-Quernheim paragraph [0005]). Considering that the instant specification characterizes sarcoidosis as a “chronic lower respiratory disease” (se e.g. instant specification page 21), it would advantageous to use a formulation that is specifically designed to reach the lower respiratory tract. It would be expected, absent evidence to the contrary, that use of the formulation of Muller-Quernheim, which encompasses the same drug in the method of the reference application, and which is known to treat sarcoidosis, would produce the desired disease treatment. The advantages of using a formulation known to treat lower respiratory disease provides the motivation to make the aforementioned modification of the method of the reference application, based on the teachings of an effective formulation as taught by Muller-Quernheim, with a reasonable expectation of success.
Furthermore, the use of the formulation of Muller-Quernheim would be a known variation in the art that could be reasonably applied to the method of the reference application by one of skill in the art. The Supreme Court set forth in KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), that if the scope and content of the prior art included a similar or analogous product, with differences between the claimed invention and prior art that were encompassed in known variation or in a principle known in the art, and one of ordinary skill in the art could have combined the elements as claimed by known methods, the claimed variation would have been predictable in to one of ordinary skill in the art. The formulation of Muller-Quernheim is specifically designed to treat lower respiratory diseases, and because the reference application recognizes the potential treatment effect of aviptadil for sarcoidosis, applying the formulation of Muller-Quernheim to the patients of the reference application would be encompassed in a known variation or principle in the art. Thus, the combination of prior art references as combined provided a prima facie case of obviousness, absent convincing evidence to the contrary.
Regarding the specific range of the median mass aerodynamic diameter, Muller-Quernheim teaches a range that overlaps with the instant claims. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990) (see e.g. MPEP 2144.05).
Furthermore, Applicant’s attention is drawn to MPEP 2144.05(II)(A), Routine Optimization - Optimization Within Prior Art Conditions or Through Routine Experimentation:
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree “will not sustain a patent”); In re Williams, 36 F.2d 436, 438 (CCPA 1929) (“It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.”). See also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007) (identifying “the need for caution in granting a patent based on the combination of elements found in the prior art.”).
Although this passage does not specifically point to, for example, MMAD, this passage points to numerous variables that affect the function of inventions, such as concentration of reagents and temperature ranges. Furthermore this passage indicates that the optimization of such variables is often obvious activity for one of ordinary skill in the art. It is submitted that the claimed MMAD is akin to the variables discussed in the cited MPEP passage, because said MMAD is an optimizable variable that would affect at least the toxicity and/or efficacy, i.e., function, of the claimed invention. Given the “normal desire of scientists or artisans to improve upon what is already generally known,” it would have been prima facie obvious to one of ordinary skill in the art to optimize the claimed MMAD, because such optimization would produce a more effective invention.
4. Claim 31-33 and 35-36 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 12-13 of copending Application No. 18/556,073 (reference application) in view of Laube et al (Eur Respir J 2011; 37: 1308–1331).
Although the claims at issue are not identical, they are not patentably distinct from each other.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The instant claims are directed to a method of treating an anti-inflammatory pulmonary disease, comprising administering a therapeutically effective amount of the aerosol of claim 17 to a subject in need thereof. The aerosol comprises liquid droplets comprising aviptadil, wherein the aerosol has a fine particle mass of at least 50%, and wherein the liquid droplets have a median mass aerodynamic diameter in a range from about 2.8 μm to about 6.0 μm. The pulmonary disease can be sarcoidosis, which the instant specification indicates is a chronic lower respiratory disease (see instant specification page 21). The aerosol can be administered by inhalation.
The reference claims teach a method of treating sarcoidosis in a subject in need thereof, comprising administering an effective amount of aviptadil to the subject by inhalation (see e.g. reference claim 12 and 13).
The reference application does not teach the fine particle mass of at least 50%, and wherein the liquid droplets have a median mass aerodynamic diameter in a range from about 2.8 μm to about 6.0 μm.
Laube et al teach that particles that are <5 μm have the greatest potential for deposition in the lungs (see e.g. Laube page 1310, right column). The proportion of particles within an aerosol that are <5 μm mm is often referred to as the fine-particle fraction (FPF), or the fine-particle dose (FPD) if expressed in absolute mass of drug in particles <5 μm (see e.g. Laube table 1). Aerosols with high FPFs have a high probability of penetrating beyond the upper airways and depositing in the lungs (see e.g. Laube page 1310, right column). Thus, it is not surprising that current devices generate aerosols with a significant proportion of their particles in the 1–5 μm range (see e.g. Laube page 1310, right column).
It would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to formulate an aerosol formulation using the guidance of Laube to treat the sarcoidosis of the reference claims, because Laube teaches that particle size can enhance the ability of the particles to be absorbed into the lung for treatment of disease. Considering that the instant specification characterizes sarcoidosis as a “chronic lower respiratory disease” (se e.g. instant specification page 21), it would advantageous to use a formulation that is specifically designed to reach the area of disease. It would be expected, absent evidence to the contrary, that the treatment of the reference claims could be formulated according to the guidance in Laube to reasonably produce the desired disease effect. The advantages of optimizing a formulation known to treat sarcoidosis to achieve maximum efficacy provides the motivation to make the aforementioned modification of the method of the reference claims, based on the teachings of an effective formulation as taught by Laube, with a reasonable expectation of success.
Furthermore, the use of the formulation guidelines of Laube would be a known variation in the art that could be reasonably applied to the method of the reference claims by one of skill in the art. The Supreme Court set forth in KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), that if the scope and content of the prior art included a similar or analogous product, with differences between the claimed invention and prior art that were encompassed in known variation or in a principle known in the art, and one of ordinary skill in the art could have combined the elements as claimed by known methods, the claimed variation would have been predictable in to one of ordinary skill in the art. The formulation of Laube is designed to maximize efficacy based on the specific particle size, and because the reference claims recognizes the potential treatment effect of aviptadil for sarcoidosis, applying the guidelines of Laube to adjust particle size be encompassed in a known variation or principle in the art. Thus, the combination of prior art references as combined provided a prima facie case of obviousness, absent convincing evidence to the contrary.
Furthermore, Applicant’s attention is drawn to MPEP 2144.05(II)(A), Routine Optimization - Optimization Within Prior Art Conditions or Through Routine Experimentation:
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree “will not sustain a patent”); In re Williams, 36 F.2d 436, 438 (CCPA 1929) (“It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.”). See also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007) (identifying “the need for caution in granting a patent based on the combination of elements found in the prior art.”).
Although this passage does not specifically point to, for example, MMAD, this passage points to numerous variables that affect the function of inventions, such as concentration of reagents and temperature ranges. Furthermore this passage indicates that the optimization of such variables is often obvious activity for one of ordinary skill in the art. It is submitted that the claimed MMAD is akin to the variables discussed in the cited MPEP passage, because said MMAD is an optimizable variable that would affect at least the toxicity and/or efficacy, i.e., function, of the claimed invention. Given the “normal desire of scientists or artisans to improve upon what is already generally known,” it would have been prima facie obvious to one of ordinary skill in the art to optimize the claimed MMAD, because such optimization would produce a more effective invention.
5. Claim 31-33 and 36 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 24-26, 31-37 of copending Application No. 17/595,025 (reference application) in view of Muller-Quernheim (EP 3 583 933 A1; filed 6/20/18; published 12/25/19).
Although the claims at issue are not identical, they are not patentably distinct from each other.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The instant claims are directed to a method of treating an anti-inflammatory pulmonary disease, comprising administering a therapeutically effective amount of the aerosol of claim 17 to a subject in need thereof. The aerosol comprises liquid droplets comprising aviptadil, wherein the aerosol has a fine particle mass of at least 50%, and wherein the liquid droplets have a median mass aerodynamic diameter in a range from about 2.8 μm to about 6.0 μm. The pulmonary disease can be sarcoidosis, which the instant specification indicates is a chronic lower respiratory disease (see instant specification page 21). The aerosol can be administered by inhalation.
The reference claims teach a method of treating pneumonitis in a subject in need thereof, comprising administering an effective amount of vasoactive intestinal peptide to the subject by inhalation (see e.g. reference claim 24-25). Aviptadil is a synthetic formulation of human vasoactive intestinal peptide (see instant specification pages 3-4). The reference patent specifically teaches treatment that increases regulatory T-cells in the subjects lower respiratory system (see e.g. reference claim 36).
The reference application does not teach the fine particle mass of at least 50%, and wherein the liquid droplets have a median mass aerodynamic diameter in a range from about 2.8 μm to about 6.0 μm.
Muller-Quernheim teaches an aviptadil aerosol comprising droplets having a particle size small enough to be easily inhaled for use in the treatment of Chronic Beryllium Disease, where the droplets can have a diameter of 2.8 to 4.5 μm (see e.g. Muller-Quernheim claims 1 and 4). Muller-Quernheim teaches that at least 80% of the droplets have a diameter between 2.0 and 6.0 μm (see e.g. Muller-Quernheim claim 3), which overlaps with the required fine particle mass of the instant claims. Notably, the aerosol can be produced by an M-neb dose+ 300/8 nebulizer (see e.g. Muller-Quernheim claim 9), which is one type of nebulizer indicated by the instant specification as being suitable to produce the required aerosol particles (see e.g. instant specification page 34 and 36, and instant Example 14). Muller-Quernheim teaches MMAD of less 1-10 μm (see e.g. Muller-Quernheim paragraph [0007]). Furthermore Muller-Quernheim teaches the exact same drug concentrations for Aviptadil dissolved in 0.9% saline (see Muller-Quernheim Example 2 in paragraph [0066]), which is identical to the Aviptadil solutions used in the instant examples (see e.g. instant specification Example 14, page 62).
It would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to use the aerosol formulation of Muller-Quernheim to treat the lower respiratory disease of the reference application, because Muller-Quernheim teaches that the aerosols produced by Muller-Quernheim can be applied by a nebulizer at a particle size small enough to be easily inhaled into the lower respiratory tract to reach deep alveolar deposition (see Muller-Quernheim paragraph [0005]). It would be expected, absent evidence to the contrary, that use of the formulation of Muller-Quernheim would apply the same treatment in the method of the reference application, which is known to treat lung disease. The advantages of using a formulation known to treat lower respiratory disease provides the motivation to make the aforementioned modification of the method of the reference application, based on the teachings of an effective formulation as taught by Muller-Quernheim, with a reasonable expectation of success.
Furthermore, the use of the formulation of Muller-Quernheim would be a known variation in the art that could be reasonably applied to the method of the reference application by one of skill in the art. The Supreme Court set forth in KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), that if the scope and content of the prior art included a similar or analogous product, with differences between the claimed invention and prior art that were encompassed in known variation or in a principle known in the art, and one of ordinary skill in the art could have combined the elements as claimed by known methods, the claimed variation would have been predictable in to one of ordinary skill in the art. The formulation of Muller-Quernheim is specifically designed to treat lower respiratory diseases, and because the reference application recognizes the potential treatment effect of aviptadil for lower respiratory disease, applying the formulation of Muller-Quernheim to the patients of the reference application would be encompassed in a known variation or principle in the art. Thus, the combination of prior art references as combined provided a prima facie case of obviousness, absent convincing evidence to the contrary.
Regarding the specific range of the median mass aerodynamic diameter, Muller-Quernheim teaches a range that overlaps with the instant claims. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990) (see e.g. MPEP 2144.05).
Furthermore, Applicant’s attention is drawn to MPEP 2144.05(II)(A), Routine Optimization - Optimization Within Prior Art Conditions or Through Routine Experimentation:
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree “will not sustain a patent”); In re Williams, 36 F.2d 436, 438 (CCPA 1929) (“It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.”). See also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007) (identifying “the need for caution in granting a patent based on the combination of elements found in the prior art.”).
Although this passage does not specifically point to, for example, MMAD, this passage points to numerous variables that affect the function of inventions, such as concentration of reagents and temperature ranges. Furthermore this passage indicates that the optimization of such variables is often obvious activity for one of ordinary skill in the art. It is submitted that the claimed MMAD is akin to the variables discussed in the cited MPEP passage, because said MMAD is an optimizable variable that would affect at least the toxicity and/or efficacy, i.e., function, of the claimed invention. Given the “normal desire of scientists or artisans to improve upon what is already generally known,” it would have been prima facie obvious to one of ordinary skill in the art to optimize the claimed MMAD, because such optimization would produce a more effective invention.
6. Claim 31-33 and 36 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 24-26, 31-37 of copending Application No. 17/595,025 (reference application) in view of Laube et al (Eur Respir J 2011; 37: 1308–1331).
Although the claims at issue are not identical, they are not patentably distinct from each other.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The instant claims are directed to a method of treating an anti-inflammatory pulmonary disease, comprising administering a therapeutically effective amount of the aerosol of claim 17 to a subject in need thereof. The aerosol comprises liquid droplets comprising aviptadil, wherein the aerosol has a fine particle mass of at least 50%, and wherein the liquid droplets have a median mass aerodynamic diameter in a range from about 2.8 μm to about 6.0 μm. The pulmonary disease can be sarcoidosis, which the instant specification indicates is a chronic lower respiratory disease (see instant specification page 21). The aerosol can be administered by inhalation.
The reference claims teach a method of treating pneumonitis in a subject in need thereof, comprising administering an effective amount of vasoactive intestinal peptide to the subject by inhalation (see e.g. reference claim 24-25). Aviptadil is a synthetic formulation of human vasoactive intestinal peptide (see instant specification pages 3-4). The reference patent specifically teaches treatment that increases regulatory T-cells in the subjects lower respiratory system (see e.g. reference claim 36).
The reference application does not teach the fine particle mass of at least 50%, and wherein the liquid droplets have a median mass aerodynamic diameter in a range from about 2.8 μm to about 6.0 μm.
Laube et al teach that particles that are <5 μm have the greatest potential for deposition in the lungs (see e.g. Laube page 1310, right column). The proportion of particles within an aerosol that are <5 μm mm is often referred to as the fine-particle fraction (FPF), or the fine-particle dose (FPD) if expressed in absolute mass of drug in particles <5 μm (see e.g. Laube table 1). Aerosols with high FPFs have a high probability of penetrating beyond the upper airways and depositing in the lungs (see e.g. Laube page 1310, right column). Thus, it is not surprising that current devices generate aerosols with a significant proportion of their particles in the 1–5 μm range (see e.g. Laube page 1310, right column).
It would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to formulate an aerosol formulation using the guidance of Laube to treat the lower respiratory disease of the reference claims, because Laube teaches that particle size can enhance the ability of the particles to be absorbed into the lung for treatment of disease. It would be expected, absent evidence to the contrary, that use of the formulation of the reference claims could be applied according to the guidance in Laube to reasonably produce the desired disease treatment. The advantages of optimizing a formulation known to treat lung disease to achieve maximum efficacy provides the motivation to make the aforementioned modification of the method of the reference claims, based on the teachings of an effective formulation as taught by Laube, with a reasonable expectation of success.
Furthermore, the use of the formulation guidelines of Laube would be a known variation in the art that could be reasonably applied to the method of the reference claims by one of skill in the art. The Supreme Court set forth in KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), that if the scope and content of the prior art included a similar or analogous product, with differences between the claimed invention and prior art that were encompassed in known variation or in a principle known in the art, and one of ordinary skill in the art could have combined the elements as claimed by known methods, the claimed variation would have been predictable in to one of ordinary skill in the art. The formulation of Laube is designed to maximize efficacy based on the specific particle size, and because the reference claims recognizes the potential treatment effect of aviptadil for lung disease, applying the guidelines of Laube to adjust particle size be encompassed in a known variation or principle in the art. Thus, the combination of prior art references as combined provided a prima facie case of obviousness, absent convincing evidence to the contrary.
Furthermore, Applicant’s attention is drawn to MPEP 2144.05(II)(A), Routine Optimization - Optimization Within Prior Art Conditions or Through Routine Experimentation:
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree “will not sustain a patent”); In re Williams, 36 F.2d 436, 438 (CCPA 1929) (“It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.”). See also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007) (identifying “the need for caution in granting a patent based on the combination of elements found in the prior art.”).
Although this passage does not specifically point to, for example, MMAD, this passage points to numerous variables that affect the function of inventions, such as concentration of reagents and temperature ranges. Furthermore this passage indicates that the optimization of such variables is often obvious activity for one of ordinary skill in the art. It is submitted that the claimed MMAD is akin to the variables discussed in the cited MPEP passage, because said MMAD is an optimizable variable that would affect at least the toxicity and/or efficacy, i.e., function, of the claimed invention. Given the “normal desire of scientists or artisans to improve upon what is already generally known,” it would have been prima facie obvious to one of ordinary skill in the art to optimize the claimed MMAD, because such optimization would produce a more effective invention.
Conclusion
No claim is allowed.
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/ANDREA K MCCOLLUM/Examiner, Art Unit 1674