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 .
Receipt is acknowledged of Amendments, Remarks and a Declaration filed on 08/13/26. Claims 1, 5, 6, 14 and 20 have been amended.no claims have been added or cancelled. Accordingly, claims 1-20 remain pending and under examination on the merits.
Rejections and/or objections not reiterated from the previous Office Action are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set of rejections and/or objections presently being applied to the instant application.
Claim Interpretation
Claim 1 is directed to a composition in the form of a dry powder for inhalation administration comprising a glycylcycline and lactose. The recitation of “for inhalation” is an intended use limitation which does not materially affect the scope of the claimed composition and as such not given patentable weight.
The recitation of X90 in claims 1, 5, 11 and 20 is also known in the art as D90 or DV90 which means, at least 90% by weight of the active particles in a dry powder formulation have an aerodynamic diameter of not more than 10 μm.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-9, 11 and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Mocnik et al (WO2014032956) in view of Morton (US 20110236492).
Mocnik et al teach a composition comprising tigecycline and lactose (See abstract).
Regrading claims 1-2, 8-9 and 11 in part, Mocnik et al teach a lyophilized powder, wherein said powder is prepared by the lyophilization of an aqueous solution having a pH of 7.2-7.7 comprising tigecycline as the active ingredient, and lactose as the only excipient (See Page 2, lines 35-39).
Further regrading claims 1-2 and 8-9, Mocnik et al also teach a bulk solution comprising 25 mg/mL of tigecycline and 50 mg/mL of lactose monohydrate lyophilized in 10 mL vials (See page 4, lines 16-19).
Thus, a powder formulation comprising 25 mg of tigecycline and 50 mg of lactose results in a composition comprising 33% of tigecycline and 66% of lactose, meeting claims 1 and 8-9. This composition also has a ratio of 1:2 (tigecycline:lactose), meeting claim 2.
Regarding claims 11, 13, Mocnik et al teach a bulk solution comprising 25 mg/mL of tigecycline and 50 mg/mL of lactose monohydrate lyophilized in 10 mL vials. The pH of the formulation was adjusted using diluted hydrochloric acid to the target value as specified for the bulk solutions prior to lyophilization (See page 4, lines 16-19).
Mocnik et al’s teachings differ from the examined claims in that they lack a specific disclosure on the particle size distribution, particle size and the addition of leucine. These are known in the art as taught by Morton.
Morton teaches refinement of the processing of particles that are to form a dry powder formulation which is to be administered to the lung using a dry powder inhaler (DPI) device, the said particles comprising an active material and a carrier material in the presence of additive material to provide a powder composition which exhibits excellent powder properties and which is economical to produce (See abstract). One class of recommended active agents is antibiotics (See [0060], 28).
Regarding claims 3-4 in part, Morton discloses that it is particularly advantageous for the additive to comprise an amino acid, including leucine or isoleucine (See [0053]).
Regarding claims 3-4 and 6-7 in part, Morton discloses the process of making a formulation as mixing a composition comprising 15 g of micronised apomorphine and 0.75 g leucine, mixing a second composition comprising 19 g of Sorbolac 400 lactose and 1 g leucine and then mixing 4.2 g of the apomorphine-based material and 15.8 g of the Sorbolac-based material in a high shear mixer for 5 minutes. Morton discloses that “An FPF of over 50% was obtained with MMAD 1.5 microns, illustrating this system gave a very good dispersion” (See [0119]-[0121]). (Examiner has calculated the total amount of leucine in this mixed powder to be 5.20%, meeting claims 3-4).
Regrading claims 5, 6 and 11 in part, Morton teach for delivery to the lower respiratory tract or deep lung, the MMAD of the active particles is not more than 5 μm, and preferably not more than 3 μm, and at least 90% (i.e X90) by weight of the active particles in a dry powder formulation should have an aerodynamic diameter of not more than 10 μm, preferably not more than 5 μm (See [0015]-[0016]).
Also, regarding claim 7 in part, Morton teaches that the said dry powder formulations have an FPF of 66 to about 75% (See [0105]).
It would have been prima facie obvious to a person of ordinary skilled in the art at the time the invention was made to have combined the teachings of Morton with Mocnik et al to arrive at the instant invention. It would have been obvious to do so because Mocnik et al teach a powder composition comprising tigecycline as the active ingredient, and lactose for treating subjects in need of antibiotic treatment. While Mocnik et al are silent regarding administering the said powder formulation for inhalation, one of ordinary skill in the art would have been motivated to have incorporated the teachings of Morton on a suitable powder composition for inhalation and prepare the powder formulation of Mocnik et al at the appropriate particle size distribution for efficient delivery of the said powders with a reasonable expectation of success.
In other words, the claims would have been obvious because a person of ordinary skill has good reasons to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Mocnik et al (WO2014032956) in view of Morton (US 20110236492) as applied to claim 11, and in further view of Caponetti et al (US 20160081925).
Mocnik et al’s teachings are delineated above and incorporated herein.
Specifically, Mocnik et al teach a composition comprising tigecycline and lactose (See abstract). Regarding claim 11 in part, disclosed is a bulk solution comprising 25 mg/mL of tigecycline and 50 mg/mL of lactose monohydrate, wherein the aqueous solution has a pH of 7.2-7.7, lyophilized in 10 mL vials (See Page 2, lines 35-39 and page 4, lines 16-19).
Mocnik et al lack a specific disclosure on the powder’s particle size range or it being formed by spray drying. These are known in the art as taught by Morton and Caponetti et al.
Morton’s teachings are delineated above and incorporated herein.
Regarding claim 11, Morton et al teach the proper particle size range for inhalation into the pulmonary system.
Caponetti et al teach drug formulations in dry powder form for administration by inhalation and indicated for the treatment of obstructive airway syndromes including lung infections comprising one or more active agents, leucine and lactose (See Abstract and claim 1).
Regarding claim 12, Caponetti et al teach that the preferred production process for the said powder is spray drying, starting from a solution of leucine, a sugar and a surfactant in which the drug is dissolved or dispersed (See [0079] and [0084]–[0088]).
It would have been prima facie obvious to a person of ordinary skilled in the art at the time the invention was made to have combined the teachings of Morton and Caponetti et al with Mocnik et al to arrive at the instant invention. Regarding the combination of Morton and Mocnik et al, as stated above, it would have been obvious to do so because Mocnik et al teach a powder composition comprising tigecycline as the active ingredient, and lactose for treating subjects in need of antibiotic treatment. While Mocnik et al are silent regarding administering the said powder formulation for inhalation, one of ordinary skill in the art would have been motivated to have incorporated the teachings of Morton on a suitable powder composition for inhalation and prepare the powder formulation of Mocnik et al ate the appropriate particle size distribution for efficient delivery of the said powders with a reasonable expectation of success.
In other words, the claims would have been obvious because a person of ordinary skill has good reasons to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.
Further, it would have been obvious to have incorporated the teachings of Caponetti et al on the method of spray drying the solution into powder because it is known and disclosed that spray drying is an advantageous method of drying which results in chemical stability, low-density particles and low humidity content of the said inhalable powders.
Thus, the claims would have been obvious because the technique for improving a particular formulation was part of the ordinary capabilities of a person of ordinary skill in the art, in view of the teaching of the technique for improvement in other situations.
Claims 14-17 are rejected under 35 U.S.C. 103 as being unpatentable over Mocnik et al (WO2014032956) in view of Morton (US 20110236492) and Wallace Jr. et al (Comparison of the in vitro activity of the glycylcycline tigecycline with those of tetracycline, minocycline, and doxycycline against isolates of nontuberculous mycobacteria).
Mocnik et al teach a composition comprising tigecycline and lactose (See abstract).
Regrading claims 14-17 in part, Mocnik et al teach a lyophilized powder, wherein said powder is prepared by the lyophilization of an aqueous solution having a pH of 7.2-7.7 comprising tigecycline as the active ingredient, and lactose as the only excipient (See Page 2, lines 35-39).
Further regrading claims 14-17, Mocnik et al teach a bulk solution comprising 25 mg/mL of tigecycline and 50 mg/mL of lactose monohydrate lyophilized in 10 mL vials (See page 4, lines 16-19).
Thus, a powder formulation comprising 25 mg of tigecycline and 50 mg of lactose results in a composition comprising 33% of tigecycline and 66% of lactose, meeting claim 14 in part.
Additionally, regarding claims 14-17, Mocnik et al teach tigecycline has antibacterial activity and is useful in the prevention and treatment of bacterial infections, such as infections caused by e.g. S. pneumoniae and L. pneumophila. (See page 1, lines 9-20).
Morton’s teachings are delineated above and incorporated herein. Morton teaches particles comprising an active agent for inhalation wherein the X90 of said particles is less than 10 microns and preferably less than 5 microns.
Mocnik et al and Morton’s teachings differ from the examined claims in that they lack a specific disclosure on the said composition in a method of treating a mycobacterial infection. This is known in the art as taught by Wallace et al.
Wallace et al teach a comparison of the in vitro activity of the glycylcycline tigecycline (formerly GAR-936) with those of tetracycline, doxycycline, and minocycline by broth microdilution against 76 isolates belonging to seven species of rapidly growing mycobacteria (RGM) and 45 isolates belonging to five species of slowly growing nontuberculous mycobacteria (NTM). This new antimicrobial offers exciting therapeutic potential for the RGM, especially for isolates of the M. chelonae-M. abscessus group, against which the activities of the currently available drugs are limited (See Abstract).
Wallace et al disclose results for the clinical isolates of the common pathogenic species of the RGM showing that the MICs of tigecycline for all isolates were very low, with comparable values for tetracycline-susceptible and tetracycline-resistant strains (See page 3165, 1st col., Results).
The activity of tigecycline could be highly useful clinically, especially against RGM species causing serious diseases (See page 3166).
It would have been prima facie obvious to a person of ordinary skilled in the art at the time the invention was made to have combined the teachings of Wallace et al with that of Mocnik et al and Morton to arrive at the instant invention. It would have been obvious to do so because Mocnik et al teach a powder composition comprising tigecycline as the active ingredient, and lactose for treating subjects in need of antibiotic treatment. Morton provides guidance on suitable inhalation features of a dry powder composition including the particle size and particle size distribution. While Mocnik et al and Morton are silent regarding administering the said powder formulation for treating mycobacterial infections, one of ordinary skill in the art would have been motivated to have incorporated the teachings of Wallace et al on a composition comprising the glycylcycline tigecycline as showing clinical activity against mycobacteria including RGM. That is while Mocnik et al and Morton generally discloses treating infections with a powder composition comprising tigecycline, Wallace et al show the specific pathogens and diseases treated and eradicated by the said tigecycline.
In other words, the claims would have been obvious because a person of ordinary skill has good reasons to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.
Claims 1-20 are rejected under 35 U.S.C. 103 as being unpatentable over Caponetti et al (US 20160081925) in view of van Ingen (WO 2020239696 or US 20220233555, below recitations are from the US document), Morton (US 20110236492) and Mocnik et al (WO2014032956).
Caponetti et al teach drug formulations in dry powder form for administration by inhalation and indicated for the treatment of obstructive airway syndromes including lung infections comprising one or more active agents, leucine and lactose (See Abstract and claim 1).
Regarding claims 1-4, 9, 11 and 18-19, in part, Caponetti et al teach a pharmaceutical composition for inhalation comprising: a) a first powder comprising budesonide in amounts greater than 5% by weight of said first powder, leucine in amount from 5 to 70% by weight of said first powder, lactose in amount from 20 to 90% by weight of said first powder; b) a second powder comprising formoterol or a in an amount greater than 1% by weight of said second powder, leucine in amount from 5 to 70% by weight of said second powder, lactose in amount from 20 to 90% by weight of said second powder; c) a third powder comprising leucine in amount from 5 to 70% by weight of said third powder and lactose in amount from 20 to 90% by weight of said third powder. Thus, the powder has greater than 6% of active agents, from about 15% of leucine and from 60% of lactose (See claim 1 and [0058]).
Caponetti et al teach that preferred particle size of said powder includes at least 50% of the particle size distribution (X50) should be below 5 μm, and preferably below 3 μm, to optimize the drug's deposition in the lower lung.
Regarding claim 6, in part, Caponetti et al teach particles with an aerodynamic diameter of less than 5 μm and show that the MMAD of the tested formulations is about 2 μm (See [0155] and Tables 7-8).
Regarding claim 7, in part, Caponetti et al teach that the said composition has a fine particle fraction (FPF) greater than 60% and a delivered fraction (DF) greater than 90% (See abstract, [0058] and claim 1).
Regarding claims 11-12, in part, Caponetti et al teach that the preferred production process for the said powder is spray drying, starting from a solution of leucine, a sugar and a surfactant in which the drug is dissolved or dispersed. As for the preferred particle size of said powder, at least 50% of the particle size distribution (X50) should be below 5 μm, and preferably below 3 μm (See [0079]-[0080] and [0084]–[0088]).
Caponetti et al do not teach the said powder formulation comprising a glycylcycline, it’s amorphous form, the particle size distribution or a method of treating mycobacterial infection. These are known in the art and would have been obvious to incorporate as taught by van Ingen, Morton and Mocnik et al.
van Ingen teach a method of treating a subject infected with gram positive bacteria, the method comprising the step of administering glycylcycline to the subject via inhalation. Inhalation of these antibiotics was found to potently treat infection by Mycobacterium microbes such as Mycobacterium abscessus (See abstract and claim 1).
Regarding claim 1, van Ingen teach an inhalable formulation comprising glycylcycline microparticles having a volume diameter lower than 10 μm, preferably formulated for nebulisation or for dry powder inhalation, wherein the inhalable formulation comprises at least 1 wt.-%, preferably at least 10 wt. %, more preferably at least 80 wt.-% of glycylcycline (See [0010] and [0045]).
Regarding claim 10, van Ingen teach that the said microparticles may be crystalline or amorphous. The percentage of amorphicity, expressed as weight percent with respect to the total weight of the microparticles, may be at least 90% (See [0049]).
Regarding claims 14-16, van Ingen teach treating a subject that is infected with mycobacteria, preferably with nontuberculous mycobacteria (NTM). The subjects are infected with a mycobacterium including M. abscessus, M. fortuitum, M. mucogenicum, etc, (i.e. RGM), as evidenced by Wallace et al and Specification (e.g. [0113] of the published Spec) (See [0010]).
Mocnik et al and Morton’s teachings are delineated above and incorporated herein.
It would have been prima facie obvious to a person of ordinary skilled in the art at the time the invention was made to have combined the teachings of van Ingen, Morton and Mocnik et al with Caponetti et al to arrive at the instant invention. It would have been obvious to do so because Caponetti et al teach dry powder compositions comprising one or more pharmaceutically active agents, lactose and leucine for inhalation. It is disclosed that leucine facilitates the disaggregation of the particles. Caponetti et al further teach a method of spray drying the solution into powder because it is known and disclosed that spray drying is an advantageous method of drying which results in chemical stability, low-density particles and low humidity content of the said inhalable powders. van Ingen teach a dry powder composition comprising glycylcycline microparticles having a volume diameter lower than 10 μm, for dry powder inhalation, comprising at least 10 wt. % of glycylcycline. van Ingen further teach that the said microparticles may be amorphous with at least 90% amorphicity. The said dry powder compositions comprising glycylcycline are said to be effective in treating mycobacteria, preferably with nontuberculous mycobacteria (NTM), including M. abscessus, etc, (i.e. RGM). Morton teaches dry powder compoistions for inhalation comprising an active agent and excipients and wherein the particle size distribution, X90 may be less than 10 microns and preferably less than 5 microns. Mocnik et al teach a powder composition comprising tigecycline as the active ingredient, and lactose for treating subjects in need of antibiotic treatment. The said powder formulation may comprise about 33% of tigecycline.
Thus, the combination of references teaches each and every element of the claimed invention. It would have been obvious to combine them because all references teach a dry powder composition comprising an active agent and suitable excipients/carriers/additive. Caponetti et al teach the advantage of incorporating lactose and leucine, van Ingen teach a stearate and Mocnik et al teach lactose. Also, Caponetti et al teach various active agents including bronchodilators and steroids, however van Ingen and Mocnik et al teach dry powders comprising a glycylcycline for treating infections including mycobacterial infections caused by NTM including RGM. That is substituting one active agent for another in a composition is obvious. The claims would have been obvious because the substitution of one known element for another would have yielded predictable results to one of ordinary skill in the art at the time of the invention. Morton teaches suitable features of a dry powder composition for effective delivery of an active agent including particle size distributions.
In other words, the claims would have been obvious because a person of ordinary skill has good reasons to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.
From the combined teaching of the cited references, one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention, as a whole, would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made.
Response to Arguments
Applicant's arguments filed 08/13/26 have been fully considered but they are not persuasive.
Applicant’s amendments to the claims have necessitated modified grounds of rejections. Applicant’s arguments so far as they pertain to the maintained references and rejections are discussed below.
First relevant argument is regarding the rejection of claims under obviousness over Mocnik et al in view of Morton. Applicant argues that “there is nothing in the combination of Mocnik et al. and Morton which can make Claims 1-9, 11, and 13 obvious. In support of this assertion, Applicants direct the Examiner's attention to the duly executed Declaration under 37 C.F.R. $ of Dr. Giovani Caponetti ("the Declaration of Caponetti") filed herewith. As noted in paragraph no. 5 of the Declaration of Caponetti, he is an expert in the fields of biopharmaceaties and pharmacokinetics and in particular the design and use of pharmaceutical formulations to be administered by inhalation for the treatment of diseases and conditions such as a mycobacterial infection. As explained in paragraph no. 10 of the Declaration of Caponetti, Mocnik et al. is directed to stabilized tigecycline/lactose formulations, including lyophilized powders or cakes intended to be reconstituted but does not disclose any dry powder formulation engineered for inhalation, nor any particle-size distribution or X₉₀ value” (See Remarks, page 8).
The arguments have been given full consideration and found not persuasive. Mocnik et al teach a dry powder composition comprising a glycylcycline, i.e. tigecycline as the active ingredient and lactose as the excipient. While Mocnik et al teach this powder for reconstitution, the said powder is not materially different than the claimed powder. That is, it has the same component and form. Regarding the argument of “for inhalation, as stated above, this is an intended use limitation and does not materially affect the scope of the claim. Regarding the particle size distribution, clearly the powers of Mocnik have a particle size, but Mocnik et al do not expressly disclose this feature. However, it would have been obvious to one of ordinary skill in the art to incorporate Morton’s teachings on this feature as particle size and particle size distributions influence the delivery of the said powder. Morton teaches that for inhalation of a dry powder composition and to achieve an effective delivery of an active agent, the particles have a particle size of less than 10 microns (i.e. MMAD) and a particle size distribution, X90 of less than 10 and preferably less than 5 microns. Thus, it would have been obvious to one of ordinary skill in the art t have combined the references to prepare and use the powders of Mocnik et al for inhalation.
Applicant also argues that “Morton is cited in the Office Action to supply the missing inhalation-related particle-size teaching, its disclosure does not make obtaining the presently claimed X₉₀ value routine or predictable. Thus, while Morton states that, ideally, at least 90% of the active particles in a dry powder formulation should have an aerodynamic diameter of not more than 10 µm, the immediately following passages explain that achieving a suitable and narrow particle-size distribution is technically difficult” (See Remarks, page 8).
This argument is similarly unpersuasive. It is noted that the courts have held that "[i]t is impermissible within the framework of section 103 to pick and choose from any one reference only so much of it as will support a given position, to the exclusion of the other parts necessary to the full appreciation of what such reference fairly suggests to one of ordinary skill in the art." In re Wesslau, 353 F.2d 238, 241 (C.C.P.A. 1965); see also Bausch & Lomb, Inc. v. Barnes-Hind/Hydrocurve, Inc., 796 F.2d 443,448-49 (Fed. Cir. 1986). Morton teaches that by using conventional processes to produce powders may result in variations in particle size. See below:
When dry powders are produced using conventional processes, the active particles will vary in size, and often this variation can be considerable. This can make it difficult to ensure that a high enough proportion of the active particles are of the appropriate size for administration to the correct site. It is therefore desirable to have a dry powder formulation wherein the size distribution of the active particles is as narrow as possible. For example, the geometric standard deviation of the active particle aerodynamic or volumetric size distribution (σg), is preferably not more than 2, more preferably not more than 1.8, not more than 1.6, not more than 1.5, not more than 1.4, or even not more than 1.2. This will improve dose efficiency and reproducibility. (See [0017]).
However, Morton also teaches how to effectively prepare powder formulation with effective particle size distribution. See below:
In order to improve the properties of powder formulations, and in particular to improve the flowability and dispersibility of the formulation, dry powder formulations often include additive materials which are intended to reduce the cohesion between the fine particles in the dry powder formulation. It is thought that the additive material interferes with the weak bonding forces between the small particles, helping to keep the particles separated and reducing the adhesion of such particles to one another, to other particles in the formulation if present and to the internal surfaces of the inhaler device. (See [0026]).
Morton clearly teaches that the particles for effective delivery to the lungs should have a particle size distribution of less than 10 and preferably less than 5 microns (See [0013]-[0016]).
Applicant also argues that “As also noted in paragraph no. 11 of the Declaration of Caponetti, while in subsequent paragraphs, Morton may discuss certain possible approaches to solve these problems, the suggested approaches are not understood to be applicable to powder pharmaceutical compositions in general, let alone the specific compositions claimed in the above-identified application” (See Remarks, page 9).
The examiner cannot find a basis for the above argument. Morton clearly is teaching dry powders for inhalation (See Title, abstract, claims and the entire disclosure). The dry powder compositions of Morton may have any active agents including antibiotics and excipients including lactose and leucine. The suitable features of a dry powder formulation for inhalation including particle size, particle size distribution, FPF, FPD, etc, are all disclosed and explained. While Morton does not name tigecycline, they do disclose antibiotics and other active agents and that one of ordinary skill in the art would be more than motivated to incorporate Morton’s disclosure to any active agent suitable for inhalation (See [0060]).
Next argument is that “As also noted in paragraph no. 13 of the Declaration of Caponetti,, Morton is concerned with tailored particle engineering methods, such as co-milling and surface modification of active and carrier particles with additives, which are technically remote from the simple lyophilized tigecycline/lactose product of Mocnik et al. Accordingly, the combination of these references requires hindsight. Starting from Mocnik et al., the skilled person would have had no specific motivation to modify the lyophilized tigecycline/lactose composition to obtain the presently claimed particle-size distribution, and Morton does not provide a reasonable expectation that this could be achieved while preserving the required composition and suitability for inhalation” (See Remarks, pages 9-10).
This argument is not found persuasive either. Applicant appears to assign a very narrow skill set to one skilled in the art. Regarding an ordinary artisan MPEP 2141 states that ““A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton.” KSR, 550 U.S. at 421, 82 USPQ2d at 1397. “[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle.” Id. at 420, 82 USPQ2d at 1397. Office personnel may also take into account “the inferences and creative steps that a person of ordinary skill in the art would employ.” Id. at 418, 82 USPQ2d at 1396; and 2) MPEP 716.07: “It is to be presumed also that skilled workers would as a matter of course, if they do not immediately obtain desired results, make certain experiments and adaptations, within the skill of the competent worker.” In the instant case, Mocnik et al teach a powder composition comprising tigecycline and lactose. Morton teaches suitable particle size and particle size distribution for inhalable powder formulations. One of ordinary skill in the art would have been motivated to have incorporated features disclosed by Morton into the powder formulation of Mocnik et al to prepare a dry powder formulation for inhalation.
It is further noted that the courts have held that “the test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981).
Regarding the rejection of claims over Caponetti et al in view of Mocnik et al and Morton, Applicant argues that “as noted in paragraph no. 15 of the Declaration of Caponetti, submit that there is nothing in Caponetti et al. which can cure the deficiencies of the combination of Mocnik et al. and Morton. In particular, Caponetti et al. is not even concerned with glycylcyclines, let alone to tigecycline, but to inhalable dry powder formulations comprising budesonide and formoterol for the treatment of asthma and COPD. Thus, although Caponetti et al. generally discloses spray-dried inhalable powders comprising lactose and leucine, its teaching is tied to a very different therapeutic and formulation context, involving corticosteroid/LABA combinations and, in preferred embodiments, the presence of a surfactant. Accordingly, this reference does not provide any motivation to apply spray drying to a tigecycline/lactose system as disclosed in Mocnik et al particularly in view of the known stability issues of tigecycline” (See Remarks, page 10).
The above argument is also not found convincing. Obviousness is established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so. See MPEP § 2143.01 and KSR International Co. v. Teleflex Inc., 550 U.S. 398, 82 USPQ2d 1385, 1395-97 (2007).
As Applicant is well aware, if one reference taught all the claimed limitations, it would be applied as an anticipatory reference. The rejections of record are under obviousness, where there is a modification to the teachings of the primary reference. Caponetti et al teach dry powder formulations comprising active agents and excipients for inhalation and disclose some features of a dry powder formulation for inhalation. Mocnik et al is relied upon for the active agent, i.e. the glycylcyclines, tigecycline.
Applicant then argues that “As further noted in paragraph no. 16 of the Declaration of Caponetti, while Mocnik et al. may disclose tigecycline/lactose lyophilized formulations, it does not disclose inhalable dry powders having the presently claimed particle-size distribution, nor does it provide any teaching that its lyophilized product could be converted into a respirable dry powder having an X₉₀ lower than 10.0 µm” (See Remarks, page 11).
The above argument was responded to earlier and found unpersuasive. That is, Mocnik et al teach the dry powder composition comprising tigecycline and lactose. The only missing element is the particle size range. Morton et al teach this feature of a dry powder composition for inhalation.
Also argued is that “In addition, as explained in paragraph no. 17 of the Declaration of Caponetti, Morton merely identifies a technical target and the associated difficulties and does not provide any teaching that any lyophilized tigecycline/lactose powder, such as that of Mocnik et al., could be straightforwardly converted into a respirable powder having the claimed X₉₀ with a reasonable expectation of success. Thus, even considering the three references together, there is no clear teaching or motivation that would have led the skilled person to select a glycylcycline, reduce its content below 50 wt.%, formulate it with lactose in an amount equal to or greater than the drug, and further obtain a dry powder having the specific X90 as required by presently amended Claim 1. Therefore, the combination of these references appears to require multiple selections from unrelated or divergent teachings, without providing any reasonable expectation of success” (See Remarks, page 11).
This argument is neither convincing nor sufficient to overcome the rejection. Assuming that Applicant’s above argument is referring to the rejection of claims over Caponetti et al in view of van Ingen and Mocnik et al, the argument of “reducing the content to below 50%” is referring to van Ingen’s teachings. The argument is not persuasive because van Ingen prefers higher active agent loading but also teaches that the formulation can have from 1%, from 10% and higher concentrations of the active agent. A reference is relied upon for all that is disclosed and not the preferred embodiments. See In re Boe, 355, F.2d 961, 148 USPQ 510, 510 (CCPA 1966).
Applicant also points to the statement made in the first Office action regarding the relationship between X50 and X90. Applicant included a graph showing that X90 does not always fall below 10 microns, when X50 is below 10 microns (See Remarks, pages 11-12).
While Applicant’s statement is correct, as the graph shows, it would be expected that the X90 can also be less than 10 microns. Additionally, Morton is relied upon for an X90 of less than 7 microns.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to the Declaration under Rule 132
Dr. Giovani Caponetti provided a Declaration under Rule 132 that is dated 08/13/26. The Declaration meets the formal requirements. In the most relevant part, the Declaration details the reasons why the combination of references would not have motivated one of ordinary skill in the art to arrive at the claimed invention.
A Declaration is due full consideration and weight for all that it discloses. Declarations are reviewed for the following considerations: 1) whether the Declaration presents a nexus such as a side-by-side or single-variable comparison (In re Huang, 40 USPQ2d 1685, 1689 (Fed. Cir. 1996)), 2) whether the Declaration presents a comparison to the closest art, 3) whether the Declaration is commensurate in scope with the scope of the claims (In re Kulling, 14 USPQ2d 1056, 1058 (Fed. Cir. 1990)), 4) whether the Declaration shows a difference in kind rather than merely a difference in degree (In re Waymouth, 182 USPQ 290, 293 (C.C.P.A. 1974)), and 5) whether the prima facie case is sufficiently strong that allegedly superior results are insufficient to overcome the case for obviousness (Pfizer Inc. v. Apotex, Inc., 82 USPQ2d 1321, 1339 (Fed. Cir. 2007)).
The relevant criterion here are Nos. 4 and 5, whether the Declaration is whether the Declaration shows a difference in kind rather than merely a difference in degree and whether the prima facie case is sufficiently strong that allegedly superior results are insufficient to overcome the case for obviousness.
The examiner has carefully reviewed the Declaration and found it insufficient to overcome the rejections of record or to place the claims on a condition of allowance. As the Remarks and the arguments recited in the Declaration were very similar, the response to the Declaration is the same as those stated above. In short, The Declaration does not show a material difference between the claimed invention and that of taught by the combined references. Also, the prima facie case is sufficiently strong that allegedly superior results are insufficient to overcome the case for obviousness.
Claims 1-20 are rejected.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Mina Haghighatian whose telephone number is (571)272-0615. The examiner can normally be reached M-F, 7-5 EST.
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/Mina Haghighatian/
Mina Haghighatian
Primary Examiner
Art Unit 1616
