DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Status
Claims 1-97 are cancelled. Claims 98-116 are new and pending. Claims 111-116 are withdrawn. Claims 98-110 are under examination.
Priority
This application is a continuation-in-part of PCT/US2021/047774 filed on 8/26/2021 which claims priority from US provisional application 63/070,718 filed on 8/26/2020.
Information Disclosure Statements
The information disclosure statement filed on 10/02/2023 has been considered by the examiner.
The information disclosure statement filed 3/5/2025 fails to comply with the provisions of 37 CFR 1.98(a)(4) because it lacks the appropriate size fee assertion. It has been placed in the application file, but the information referred to therein has not been considered as to the merits.
Election/Restriction
Applicant’s election without traverse of Group I (claims 98-110) and the species of first mucolytic agent – 2-mercaptoethane sulfonate and second mucolytic agent - DNase in the reply filed on 10/27/2025 is acknowledged. Claims 111-116 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention and species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10/27/2025. The election is treated as without traverse as applicant did not traverse the requirement in the response.
Claim Rejections - 35 USC § 112(a) – Written Description “Derivatives”
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 100-110 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. Note that N and C only refer to the N and C-terminus of the amino acid without defining a structure or modification thereto. N-derivative or C-derivative of cysteine is not provided a definition of what the derivative groups would be and the application only provides for the species of N-acetylcysteine, N-butylcysteine and dipeptide of cysteine and glutamic acid. There is no description on how the entire genus of such derivatives would be made and there are not enough species of varying derivatives to give full support for the genus of C- and N- derivatives of cysteine. Therefore, although applicant has a few species (N-acetylcysteine, N-butylcysteine and dipeptide of cysteine and glutamic acid) in the specification and claims, they do not have full written support for the genus of N- and C- derivatives of cysteine.
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 100-110 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 100 is indefinite for the recitation of “N-derivatives and C-derivatives of amino acid cysteine” as the specification does not define what the N and C-derivatives may be and only offers limited amount of derivatives such as N-acetylcysteine, N-butylcysteine and dipeptide of cysteine and glutamic acid. Note that N and C only refer to the N and C-terminus of the amino acid without defining a structure or modification thereto. This does not make clear what the meets and bounds of these derivatives are for considering the prior art. Note there would be many proteins and peptides that contain cysteine and it would be unclear if all of these would also be considered cysteine derivatives. For the purpose of compact prosecution, if a compound contains a cysteine moiety and any group on either the N or C-terminus of the cysteine, it will be considered an N- or C- derivative of cysteine.
Claims 101-110 are rejected for being directly or indirectly dependent on an indefinite claim.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 98-105 and 110 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Underwood US 20220117893 (Has additional inventor, filed on 2-21-2020, effective filing date of 2-22-2019).
“Target location of the airways of a subject” is read broadly as a portion of the airways where drug release from the particles mainly occurs. In the specification, this targeting is determined by particle size (e.g. MMAD) (i.e. size important for how far particles travel into the airways) and formulation agents/excipients such as the liposome lipids.
“Predominant absorption” at a target site will be read as the most absorption of the drug takes place at the target site, however, lesser amounts of absorption may occur elsewhere.
“Predetermined delay” is read as a delay in drug release based on formulation/structure of the particle(s) that provides for extended release over the time for immediate release. If the prior art provides for extended, sustained, delayed or controlled release for its formulations, it will be read to have a predetermined delay that offers extended release.
Underwood teaches therapeutic agent as first and second inhalable particles with first and second mucolytic contained in biodegradable encapsulate (abstract and claim 1 of Underwood). Underwood teaches first and second mucolytic can be selected from a group that contains 2-mercaptoethane sulfonate and DNase (claim 2 of Underwood). Underwood teaches the first encapsulation being a liposomal formulation (claim 3 of Underwood). Underwood teaches “wherein said first particles are sized to be from about 5 microns to about 50 microns, said second particles are sized to be from about 0.01 microns to about 6 microns, whereby said first particles are configured for predominant absorption at a first target location of said airways and said second particle are configured for predominant absorption at a second target location of said airways” (claim 4 of Underwood). Underwood teaches particles stored in solution form or dry powder form (claim 9 of Underwood). Underwood teaches “said first biodegradable encapsulation is configured to release said first mucolytic immediately upon inhalation of said therapeutic agent by said subject, said second biodegradable encapsulation is configured to release said second mucolytic with a predetermined delay, whereby providing an extended time release mucolytic therapy to said subject” (claim 7 of Underwood). Underwood teaches antibiotic, antiviral and antifungal (paragraphs 50-51 of Underwood). Underwood teaches ciprofloxacin, aminoglycosides, tobramycin and other antibiotics (paragraph 51). Underwood teaches polyene antifungals, amphotericin B, Nystatin, ketoconazole, ciclopirox and other antifungals (paragraph 51). Underwood teaches “At least one of such inhalable particles may include a mucolytic within a biodegradable encapsulation, such as a liposomal formulation, microsphere, nanoparticles or engineered spray particles” (paragraph 22). Underwood teaches using the invention for various conditions that are lung and respiratory airway diseases (paragraphs 60-74).
Claim 98 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Cipolla US 20120282328.
“Target location of the airways of a subject” will be read broadly as any portion of the airways the prior art teaches.
Cipolla teaches “A formulation, comprising:a pharmaceutically acceptable excipient; and liposome-encapsulated ciprofloxacin wherein the liposomes are unilamellar, and comprise cholesterol and hydrogenated soy phosphatidyl-choline (HSPC) at a ratio such that the liposomes maintain integrity when aerosolized, and provide a ciprofloxacin release rate from the liposomes of 0.5% to 20% per hour” (claim 26 of Cipolla). Cipolla teaches “additional drug is an anti-inflammatory chosen from corticosteroids, leukotriene receptor antagonists, leukotriene synthesis inhibitors, and cyclooxygenase inhibitors” (claim 32 of Cipolla). Cipolla teaches DNase and other mucolytic agents (paragraphs 21, 80 and 95). Cipolla provides liposomes of the invention used with DNase, a mucolytic agent (paragraph 95). Cipolla teaches “20 nm to 1 micron as a size of liposome for pulmonary delivery (paragraph 53). Cipolla teaches 0.5 microns to 12 microns for droplets or particles (paragraphs 56 and 59). Cipolla teaches liposomes provided as dry powder that can be inhaled (paragraph 61). Cipolla teaches formulation of dry powder or suspended or dissolved in a liquid (paragraph 38). Cipolla provides for treating airways (paragraph 97). Cipolla teaches the encapsulation with liposomes makes them biocompatible and biodegradable (paragraph 43).
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.
Claim 106-108 are rejected under 35 U.S.C. 103 as being unpatentable over Underwood US 20220117893 (Has additional inventor, filed on 2-21-2020, effective filing date of 2-22-2019) and Cipolla US 20120282328.
Underwood teaches the claims as discussed above.
Underwood does not teach the limitations of claims 106-108 although it allows for a formulation to be used as a dry powder inhaler to target the airways.
Cipolla teaches “A formulation, comprising:a pharmaceutically acceptable excipient; and liposome-encapsulated ciprofloxacin wherein the liposomes are unilamellar, and comprise cholesterol and hydrogenated soy phosphatidyl-choline (HSPC) at a ratio such that the liposomes maintain integrity when aerosolized, and provide a ciprofloxacin release rate from the liposomes of 0.5% to 20% per hour” (claim 26 of Cipolla). Cipolla teaches “additional drug is an anti-inflammatory chosen from corticosteroids, leukotriene receptor antagonists, leukotriene synthesis inhibitors, and cyclooxygenase inhibitors” (claim 32 of Cipolla). Cipolla teaches DNase and other mucolytic agents (paragraphs 21, 80 and 95). Cipolla provides liposomes of the invention used with DNase, a mucolytic agent (paragraph 95). Cipolla teaches “20 nm to 1 micron as a size of liposome for pulmonary delivery (paragraph 53). Cipolla teaches 0.5 microns to 12 microns for droplets or particles (paragraphs 56 and 59). Cipolla teaches liposomes provided as dry powder that can be inhaled (paragraph 61). Cipolla teaches formulation of dry powder or suspended or dissolved in a liquid (paragraph 38). Cipolla provides for treating airways (paragraph 97). Cipolla teaches “anti-infective refers to agents that act against infections, such as bacterial, viral, fungal, mycobacterial, or protozoal infections” (paragraph 34). Cipolla teaches ciprofloxacin, tobramycin, penicillins and others (paragraph 35). Cipolla teaches polymixins, amphotericin B, ciclopirox, ketoconazole, and others (paragraph 35). Cipolla teaches “corticosteroids (such as beclometasone, budesonide, ciclesonide, fluticasone, etiprednol, mometasone, and the like)” (paragraph 37). Cipolla teaches “β2-adrenergic receptor agonists (such as albuterol, bambuterol, salbutamol, salmeterol, formoterol, arformoterol, levosalbutamol, procaterol, indacaterol, carmoterol, milveterol, procaterol, terbutaline, and the like), and antimuscarinics (such as trospium, ipratropium, glycopyrronium, aclidinium, and the like). Combinations of drugs may be used” (paragraph 36). Paragraphs 15-17 provide for liposomes.
One of ordinary skill in the art before the time of filing would have included the other active compounds as provided by Cipolla into a formulation for reaching the airways to treat diseases/infections as provided by Underwood as they would be expected to provide their beneficial effects (anti-infective, bronchodilation, anti-inflammatory) to the subject in need. Both references are to treating conditions of the airways with a particulate/powder formulation that can be administered via the airways (MPEP 2144.06). Thus, there was a reasonable expectation of success in combining the teachings of the prior art and producing multifunctional formulations to treat the airways/lungs of a subject in need.
Claim 106, 107, 108 and 109 is rejected under 35 U.S.C. 103 as being unpatentable over Underwood US 20220117893 (Has additional inventor, filed on 2-21-2020, effective filing date of 2-22-2019) and Longest US 20150107589.
Underwood teaches the claims as discussed above.
Underwood does not provide for species of agents of claims 106-109.
Longest teaches dry powder inhalers (abstract). Longest teaches “Other examples include bronchodilators including albuterol, terbutaline, isoprenaline and levalbuterol, and racemic epinephrine and salts thereof; anti-cholinergics including atropine, ipratropium bromide, tiatropium and salts thereof; expectorants including dornase alpha (pulmozyme) (used in the management of cystic fibrosis; corticosteroids such as budesonide, triamcinolone, fluticasone” (paragraph 54). Longest teaches the antiviral agent ribavirin (paragraph 54) as well as the antivirals, including aciclovir, ganciclovir, birivudin, valaciclovir, zidovudine, didanosin, thiacytidin, stavudin, lamivudin, zalcitabin, ribavirin, nevirapirin, delaviridin, trifluridin, ritonavir, saquinavir, indinavir, foscarnet, amantadin, podophyllotoxin, vidarabine, tromantadine, and proteinase inhibitors (paragraph 57). Longest teaches the use of various medicaments (paragraph 53).
One of ordinary skill before the time of filing would have included antivirals, bronchodilators, anti-cholinergic agents and corticosteroids such as those listed in Longest in formulations motivated by the prior art as they are seen as effective agents to be used for dry powder inhalers for delivery to the lungs/airways to treat viral infections. One of ordinary skill in the art would have had a reasonable expectation of success in adding such antiviral agents and obtaining successful antiviral treatment in addition to mucolytic treatment through the combination of the prior art.
Claims 99-108 and 110 in addition to claim 98 are rejected under 35 U.S.C. 103 as being unpatentable over Cipolla US 20120282328, Eichel US3663690 and Rosenblatt US 20190046488.
“Target location of the airways of a subject” is read broadly as a portion of the airways where drug release and absorption from the particles mainly occurs. In the specification, this targeting is determined by particle size (e.g. MMAD) (i.e. size important for how far particles travel into the airways) and formulation agents/excipients such as the liposome lipids that aid to extend/delay release.
“Predominant absorption” at a target site will be read as the most absorption of the drug takes place at the target site, however, lesser amounts of absorption may occur elsewhere.
“Predetermined delay” is read as a delay in drug release based on formulation/structure of the particle(s) that provides for extended release compared to the time for immediate release. If the prior art provides for extended, sustained, delayed or controlled release for its formulations, it will be read to have a predetermined delay that offers extended release.
Cipolla teaches “A formulation, comprising:a pharmaceutically acceptable excipient; and liposome-encapsulated ciprofloxacin wherein the liposomes are unilamellar, and comprise cholesterol and hydrogenated soy phosphatidyl-choline (HSPC) at a ratio such that the liposomes maintain integrity when aerosolized, and provide a ciprofloxacin release rate from the liposomes of 0.5% to 20% per hour” (claim 26 of Cipolla). Cipolla teaches “additional drug is an anti-inflammatory chosen from corticosteroids, leukotriene receptor antagonists, leukotriene synthesis inhibitors, and cyclooxygenase inhibitors” (claim 32 of Cipolla). Cipolla teaches DNase and other mucolytic agents (paragraphs 21, 80 and 95). Cipolla provides liposomes of the invention used with DNase, a mucolytic agent (paragraph 95). Cipolla teaches “20 nm to 1 micron as a size of liposome for pulmonary delivery (paragraph 53). Cipolla teaches 0.5 microns to 12 microns for droplets or particles (paragraphs 56 and 59). Cipolla teaches liposomes provided as dry powder that can be inhaled (paragraph 61). Cipolla teaches formulation of dry powder or suspended or dissolved in a liquid (paragraph 38). Cipolla provides for treating airways (paragraph 97). Cipolla teaches “anti-infective refers to agents that act against infections, such as bacterial, viral, fungal, mycobacterial, or protozoal infections” (paragraph 34). Cipolla teaches ciprofloxacin, tobramycin, penicillins and others (paragraph 35). Cipolla teaches polymixins, amphotericin B, ciclopirox, ketoconazole, and others (paragraph 35). Cipolla teaches “corticosteroids (such as beclometasone, budesonide, ciclesonide, fluticasone, etiprednol, mometasone, and the like)” (paragraph 37). Cipolla teaches “β2-adrenergic receptor agonists (such as albuterol, bambuterol, salbutamol, salmeterol, formoterol, arformoterol, levosalbutamol, procaterol, indacaterol, carmoterol, milveterol, procaterol, terbutaline, and the like), and antimuscarinics (such as trospium, ipratropium, glycopyrronium, aclidinium, and the like). Combinations of drugs may be used” (paragraph 36). Paragraphs 15-17 provide for liposomes. Cipolla provides for sustained release a site of infection and that liposomal encapsulation allows for sustained drug release (extended) (paragraphs 16-17). Cipolla teaches different treatments and means of administration can be used to treat a single patient (paragraph 62). Cipolla teaches combination therapies with the liposome formulations (paragraph 95). Cipolla teaches “At least one therapeutic agent in addition to the free and liposome-encapsulated anti-infective may also be included in the composition. That therapeutic agent may be free drug or encapsulated drug present with a pharmaceutically acceptable carrier useful for direct inhalation into human lungs. The other drugs may include enzymes to reduce the viscoelasticity of the mucus such as DNase or other mucolytic agents” (paragraph 21). Cipolla provides for both immediate and sustained release profiles for its formulations (abstract).
Although Cipolla allows for other mucolytic agents besides DNase and the ability to have other active agents encapsulated in liposomes (liposomal carriers), it does not provide for 2-mercaptoethane sulfonate as elected by the applicant or that both actives should be mucolytic agents.
Eichel teaches treatment for broncho-pulmonary disorders that involve mucolytic agents (abstract). Eichel teaches the combination of two mucolytics a DNase and UMA which is a mercapto compound (columns 2 and 3). Eichel teaches there is a viscosity lowering effect of the combination on mucous (column 3). Eichel also teaches the use of N-acetylcysteine with DNase (column 4).
Rosenblatt teaches antimicrobial compositions to treat infection (abstract). Rosenblatt teaches inhaling of the compositions by the subject (paragraph 25). Rosenblatt teaches the form of particles (paragraph 22). Rosenblatt teaches chelators such as mercaptoethane sulfonate as additional antimicrobial agents (claims 22 and 28 of Rosenblatt). Rosenblatt teaches mucolytic medications (paragraph 100).
One of ordinary skill in the art before the time of filing would have seen the use of combinations of multiple mucolytic agents along with anti-infectives and other useful agents for treating the pulmonary system as useful for treating diseases such as pulmonary/airway diseases with a combination of agents using liposome encapsulation by the combined teachings of the prior art where Cipolla allows for liposomal formulations of multiple drugs that can be made as liposomal encapsulates with DNase as an exemplified mucolytic agent while Eichel motivates the combination of two mucolytics and Rosenblatt provides for the use of mercaptoethane sulfonate in treating infections with additional teachings of inhalation delivery. Therefore, there was a reasonable expectation of success in combining the teachings of the references and arriving at such compositions with the ability to act as mucolytics as well as have other functionalities that can successfully target the airways and pulmonary system for treatment. Cipolla provides for size ranges of liposomes/particulates including smaller and larger that would allow one of ordinary skill in the art to make formulations that can reach different depths of the airways based on particle size, and thus, target different locations.
Claim 109 in addition to claim 98-108 and 110 is rejected under 35 U.S.C. 103 as being unpatentable over Cipolla US 20120282328, Eichel US3663690, Rosenblatt US 20190046488 and Longest US 20150107589.
Cipolla, Eichel and Rosenblatt teach the claims as provided above. Cipolla does teach antivirals as antiinfectives (see above, act against…viral..infections).
Cipolla, Eichel and Rosenblatt do not teach antiviral species of claim 109, although Cipolla allows for antivirals.
Longest provides for dry powder inhalers and drugs therefor (abstract). Longest teaches the antiviral agent ribavirin (paragraph 54) as well as the antivirals, including aciclovir, ganciclovir, birivudin, valaciclovir, zidovudine, didanosin, thiacytidin, stavudin, lamivudin, zalcitabin, ribavirin, nevirapirin, delaviridin, trifluridin, ritonavir, saquinavir, indinavir, foscarnet, amantadin, podophyllotoxin, vidarabine, tromantadine, and proteinase inhibitors (paragraph 57).
One of ordinary skill before the time of filing would have included antivirals such as those listed in Longest in formulations motivated by the prior art as they are seen as effective agents to be used for dry powder inhalers for delivery to the lungs/airways to treat viral infections. One of ordinary skill in the art would have had a reasonable expectation of success in adding such antiviral agents and obtaining successful antiviral treatment in addition to mucolytic treatment through the combination of the prior art.
Non-Statutory Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 98-110 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, 3-7, 9-12 of copending Application No. 17/433,220 (reference application) in view of Cipolla US 20120282328 and Longest US 20150107589. Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets provide for lipid encapsulates of first and second mucolytic agents and use of antifungal agents for inhalation delivery and controlled release.
‘220 does not teach the elected species of DNase as another mucolytic agent nor teach some of the additional agents besides antifungal agents for its formulations.
Cipolla teaches “A formulation, comprising:a pharmaceutically acceptable excipient; and liposome-encapsulated ciprofloxacin wherein the liposomes are unilamellar, and comprise cholesterol and hydrogenated soy phosphatidyl-choline (HSPC) at a ratio such that the liposomes maintain integrity when aerosolized, and provide a ciprofloxacin release rate from the liposomes of 0.5% to 20% per hour” (claim 26 of Cipolla). Cipolla teaches “additional drug is an anti-inflammatory chosen from corticosteroids, leukotriene receptor antagonists, leukotriene synthesis inhibitors, and cyclooxygenase inhibitors” (claim 32 of Cipolla). Cipolla teaches DNase and other mucolytic agents (paragraphs 21, 80 and 95). Cipolla provides liposomes of the invention used with DNase, a mucolytic agent (paragraph 95). Cipolla teaches “20 nm to 1 micron as a size of liposome for pulmonary delivery (paragraph 53). Cipolla teaches 0.5 microns to 12 microns for droplets or particles (paragraphs 56 and 59). Cipolla teaches liposomes provided as dry powder that can be inhaled (paragraph 61). Cipolla teaches formulation of dry powder or suspended or dissolved in a liquid (paragraph 38). Cipolla provides for treating airways (paragraph 97). Cipolla teaches “anti-infective refers to agents that act against infections, such as bacterial, viral, fungal, mycobacterial, or protozoal infections” (paragraph 34). Cipolla teaches ciprofloxacin, tobramycin, penicillins and others (paragraph 35). Cipolla teaches polymixins, amphotericin B, ciclopirox, ketoconazole, and others (paragraph 35). Cipolla teaches “corticosteroids (such as beclometasone, budesonide, ciclesonide, fluticasone, etiprednol, mometasone, and the like)” (paragraph 37). Cipolla teaches “β2-adrenergic receptor agonists (such as albuterol, bambuterol, salbutamol, salmeterol, formoterol, arformoterol, levosalbutamol, procaterol, indacaterol, carmoterol, milveterol, procaterol, terbutaline, and the like), and antimuscarinics (such as trospium, ipratropium, glycopyrronium, aclidinium, and the like). Combinations of drugs may be used” (paragraph 36). Paragraphs 15-17 provide for liposomes. Cipolla provides for sustained release a site of infection and that liposomal encapsulation allows for sustained drug release (extended) (paragraphs 16-17). Cipolla teaches different treatments and means of administration can be used to treat a single patient (paragraph 62). Cipolla teaches combination therapies with the liposome formulations (paragraph 95). Cipolla teaches “At least one therapeutic agent in addition to the free and liposome-encapsulated anti-infective may also be included in the composition. That therapeutic agent may be free drug or encapsulated drug present with a pharmaceutically acceptable carrier useful for direct inhalation into human lungs. The other drugs may include enzymes to reduce the viscoelasticity of the mucus such as DNase or other mucolytic agents” (paragraph 21). Cipolla provides for both immediate and sustained release profiles for its formulations (abstract).
Longest provides for dry powder inhalers (abstract). Longest teaches the antiviral agent ribavirin (paragraph 54) as well as the antivirals, including aciclovir, ganciclovir, birivudin, valaciclovir, zidovudine, didanosin, thiacytidin, stavudin, lamivudin, zalcitabin, ribavirin, nevirapirin, delaviridin, trifluridin, ritonavir, saquinavir, indinavir, foscarnet, amantadin, podophyllotoxin, vidarabine, tromantadine, and proteinase inhibitors (paragraph 57).
One of ordinary skill in the art would have selected DNase as an additional mucolytic agent and other active agents of the prior art in making new formulations for inhalation treatment of infections and other diseases of the pulmonary system based on claims of ‘220 combined with the teachings of Cipolla and Longest and had a reasonable expectation of success in producing formulations that could better treat pulmonary diseases/conditions. Cipolla connects the use of other therapeutic agents with mucolytic agent.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 98-100 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, 8, 9, 13-15 of copending Application No. 18/939,439 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets provide for lipid encapsulates/delivery vehicle that would have sodium 2-mercaptoethane sulfonate and DNase as agents (claims 1 and 8 of ‘439). ‘439 also provides for a size range of 1-5 microns, which is in the range of applicant’s claims. ‘439 also provides for dry powder that can be administered via dry powder inhaler. ‘439 also provides for spray dried nanoparticle form.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARK V STEVENS whose telephone number is (571)270-7080. The examiner can normally be reached M-F 9:00 am to 6:00 pm EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Brian-Yong Kwon can be reached on (571)272-0581. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/MARK V STEVENS/Primary Examiner, Art Unit 1613