DETAILED ACTION
Status of the Application
Receipt is acknowledged of Applicants’ claimed invention, filed 12 January 2024, in the matter of Application N° 18/411,292. Said documents have been entered on the record. The Examiner further acknowledges the following:
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
The claims which are instantly filed are the originally filed claims of this application and have not been amended in any way (i.e., additions, cancellations, or amendments). The claims as filed are also noted as being an exact match to those which were filed on 17 March 2022, in parent application 17/697,298.
No new matter has been added.
Thus, claims 1-20 represent all claims currently under consideration.
Information Disclosure Statement
One Information Disclosure Statement (IDS) filed 12 January 2024 is acknowledged and has been considered. Those references listed on the IDS which do not appear in the instant application have been verified as being present in the parent applications and considered in accordance with MPEP §609.02(I).
Specification
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
Claim Objections
Claim 3 is objected to because of the word “nasopharynx” is misspelled as “nasophaiynx.” Appropriate correction is required.
Claim Rejections - 35 USC §112
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 1-20 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 claims contain 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 pre-AIA the inventors, at the time the application was filed, had possession of the claimed invention.
Claims 1 and 12 respectively recite the following:
1. A composition comprising an antiviral therapeutic agent wherein said antiviral therapeutic agent comprises pleconaril, wherein said pleconaril is optimized for therapeutic efficacy, wherein said composition consists of pleconaril in an inclusion complex, or wherein the pleconaril is incorporated into micelles, and wherein the pleconaril particles in the inclusion complex or in the micelles are in the size range of 1-50, 5-40, [or] 10-35 microns.
12. A method of treating viral infections and diseases associated with Picornaviridae, Coronaviridae, Orthomyxoviridae, Paramyxoviridae, Reoviridae, and Adenoviridae, comprising administering a composition comprising an antiviral therapeutic agent wherein said antiviral therapeutic agent comprises pleconaril, wherein said pleconaril is optimized for therapeutic efficacy, wherein said composition consists of pleconaril in an inclusion complex, or wherein the pleconaril is incorporated into micelles, and wherein the pleconaril particles in the inclusion complex or in the micelles are in the size range of 1-50, 5-40, [or] 10-35 microns, and wherein administration of the pleconaril reduces symptoms associated with the viral infection.
In each instance, the Examiner notes that pleconaril is recited as being in an inclusion complex or in a micelle and that the inclusion complex or micelle is further recited as having a size within the range of 1-50, 5-40, or 10-35 microns.
Thorough review of the instant specification by the Examiner reveals no support for this claimed structure with relation to the recited size ranges.
To be clear, the Examiner acknowledges that the specification supports containment of pleconaril within micelles (see pg. 15, lines 3-5; only reference to micelles) and within inclusion complexes (see pg. 14, line 19 to pg. 15, line 2).
Regarding the recited size ranges, the specification states the following (pg. 13, lines 4-13):
“In one aspect, the inventors have enabled site specific delivery of pleconaril, controlled by size of particles delivered (potentially bi- or tri-modal distribution of pleconaril particle from sub-micron range approximately 1-50, 5-40, 10-35 and 30+ micron) or use of a novel delivery device to deliver to the nasopharynx and anterior internal nares, the locations where infection has the highest likelihood in resulting in an acute respiratory infection or cold. The present invention discloses drug delivery advantages for enhanced therapeutic activity including a significantly reduced size of pleconaril particles wherein 90% of the particles are less than 1 micron constituting nanosuspensions with enhanced dissolution properties, increased therapeutic activity and reduced drug dose but formulated in a manner that prevents these particles from lung delivery.”
Thus, the Examiner also acknowledges that the specification presents support for particles within the recited size ranges which seemingly have a lower limit in the sub-micron range. The disconnect between the recited limitations and the requisite support is that the specification presents no discussion connecting either micelles or inclusion complexes to any of these ranges.
The Examiner supports this position by looking to that which is empirically known and understood by the state of the art regarding both of the recited structures.
Regarding micellar dimensions, the art recognizes that micelles are formed using detergents (aka surfactants) and that they are volumetrically defined in terms of Ångstroms (tenth of a nanometer) (see e.g., Oliver et al.; PLOS ONE; May 2013; Figure 1; pg. 3; IDS reference). Ångstroms are four orders of magnitude smaller than the recited size ranges.
Regarding inclusion complexes, the instant specification defines these as being formed from cyclodextrins (see Spec. pg. 14, line 24). The Examiner acknowledges that the specification says that “[i]nclusion complexes include [aka comprise] cyclodextrins.” The broadest reasonable interpretation of this is that while inclusion complexes might contain other compounds (e.g., active ingredient guest), they fundamentally are formed using cyclodextrin. Here again, the state of the art presents the skilled artisan with that which is long-known about cyclodextrin and inclusion complexes. Del Valle (Process Biochemistry; 2003; IDS reference), for instance, published a review of cyclodextrin, their properties, and their uses. Of particular note is that the reference directly ties them to being used to form inclusion complexes (see e.g., Abstract; Figure 2). Of particular interest is characterizing data presented in Table 1 which defines the three most prominent forms of cyclodextrin: α-, β-, and γ-CD. Like the micelles discussed above, cyclodextrins are very clearly well within the sub-nano dimensional realm (i.e., Ångstroms). Applicants’ attention is directed to the “Outer diameter” and “Height of torus” parameters.
Thus, the aforementioned limitations of claims 1 and 12 are considered lack written description in the instant specification.
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 1-20 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 pre-AIA the applicant regards as the invention.
As instantly recited, claim 1 recites the following:
A composition comprising an antiviral therapeutic agent wherein said antiviral therapeutic agent comprises pleconaril, wherein said pleconaril is optimized for therapeutic efficacy, wherein said composition consists of pleconaril in an inclusion complex, or wherein the pleconaril is incorporated into micelles, and wherein the pleconaril particles in the inclusion complex or in the micelles are in the size range of 1-50, 5-40, [or] 10-35 microns.
Claim 12 recites the following:
A method of treating viral infections and diseases associated with Picornaviridae, Coronaviridae, Orthomyxoviridae, Paramyxoviridae, Reoviridae, and Adenoviridae, comprising administering a composition comprising an antiviral therapeutic agent wherein said antiviral therapeutic agent comprises pleconaril, wherein said pleconaril is optimized for therapeutic efficacy, wherein said composition consists of pleconaril in an inclusion complex, or wherein the pleconaril is incorporated into micelles, and wherein the pleconaril particles in the inclusion complex or in the micelles are in the size range of 1-50, 5-40, [or] 10-35 microns, and wherein administration of the pleconaril reduces symptoms associated with the viral infection.
Both of the independent claims are considered to be rendered indefinite by the above emphasized claim language. That is, Applicants’ recited pairing of “the composition” with the two different transitional phrases makes it unclear as to the scope of the claimed or administered composition. On one hand the composition consists of an inclusion complex or micelles containing pleconaril. On the other hand, the composition is recited as comprising inclusion complexes or micelles of pleconaril. Clarification of the claimed inventions is respectfully requested.
Claim Rejections - 35 USC §102
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.
Claims 1-6, 10, and 11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Reisdorph et al. (Virology; 2003; IDS reference).
The limitations recited in claim 1 are discussed at length above. One interpretation of the claimed subject matter, in view of the written description rejection, is that the invention be considered to be a composition comprising pleconaril wherein said composition consists of an inclusion complex or micelle of the antiviral therapeutic agent pleconaril. That is, one interpretation of the recited composition is that it is an inclusion complex containing pleconaril within. Of course, with respect to the position taken within the written description rejection, it is established that neither inclusion complexes nor micelles have a size within the micron range. Thus, for the purposes of consideration on the merits, the Examiner will consider the claimed composition to be anticipated where the structural limitations have been met.
Reisdorph is considered to disclose the claimed structural merits (see e.g., Figure 4D; pg. 38) which expressly teach pleconaril with cyclodextrin. This teaching is considered to additionally teach the limitations recited in claims 2-6, 10, and 11, each of which are considered to recite properties which result from the composition which is recited in claim 1. See MPEP §2111.01(IV) and §2112.01(I) and (II). With regard to said limitations recited in claims 2-4 and 6, until some material difference in the properties of the composition are demonstrated, said the instant limitations are considered by the Examiner to be directed toward the composition, which is instantly claimed.
Thus, the reference is considered to anticipate each of the recited limitations.
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 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. Applicants are 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.
Claims 1-20 are rejected under 35 U.S.C. 103 as being unpatentable over Pilgaonkar et al. (US Pre-Grant Publication Nº 2012/0093738 A1; IDS reference) in view of Reisdorph et al. (Virology; 2003; IDS reference).
The limitations of independent claims 1 and 12 are discussed above at length. In order to address the remaining limitations recited in the dependent claims, notably those which recite additional components present in the pharmaceutical composition, the Examiner broadly and reasonably interprets the composition of claim 1 as comprising pleconaril, encapsulated in either the inclusion complex or micelle. However, here the Examiner interprets the claimed composition as not consisting of the encapsulated pleconaril, but comprising it. Otherwise, a claim which seeks to further limit such a composition would be considered to be improperly dependent.
Pilgaonkar teaches a taste-masked pharmaceutical formulation for oral administration comprising: a) at least one influenza antiviral; b) at least one taste-masking agent; and at least one pharmaceutically acceptable excipient (claim 1). Pleconaril is taught and suggested as being one of many different types of influenza antiviral compounds which may embody the genus disclosed in claim 1 (see e.g., claim 23 or ¶[0086]). The taste-masking agent of claim 1 is further defined in claim 5 as being selected from such compounds as “a cyclodextrin.” Claim 14 and ¶[0037] and ¶[0038] further define the cyclodextrin compounds which may be used. Of particular note is that ¶[0038] teaches that the bitter taste of the influenza antiviral is masked by complexation with cyclodextrins which are further fundamentally defined as being α, β, or γ cyclodextrins, respectively possessing six, seven, or eight α-(1,4)-linked D-glucopyranose units. Cyclodextrins are explicitly taught as forming inclusion complexes with the influenza antiviral molecule be acting as a hydrophobic host cavity. The paragraph further teaches that the formed inclusion complex is employed in the composition of the present invention (i.e., with an excipient in the downstream taste-masking composition) and that in the alternative, the influenza antiviral of choice and cyclodextrin may exists apart in the composition.
With respect to the composition recited in claim 1, the Examiner acknowledges two deficiencies.
First, Pilgaonkar fails to teach that the practiced inclusion complexes have a size within the range as claimed. This, limitation with respect to the recited modes of active entrapment are discussed above as raising the issue of new matter. To that end, the Examiner respectfully advances that no art appears to be available which discloses inclusion complexes having micron-ranged sizes. As such, the claim will be considered met by any compositional showing in the art of cyclodextrin inclusion complexes containing pleconaril.
Second, the Pilgaonkar does not expressly combine pleconaril and cyclodextrin. Further with respect to the recited method of treatment in claim 12, the Examiner acknowledges that Pilgaonkar does not expressly teach treating a viral infection or disease rooted in any of the recited viral strains (e.g., Picornaviridae).
Reisdorph is considered to remedy the second of these perceived shortcomings.
Reisdorph, as discussed above, directly teaches combining pleconaril with cyclodextrins to form inclusion complexes (e.g., Figure 4D). Pilgaonkar discloses that the practiced compositions are administered to patients to abate the symptoms of or even prevent viral infections (see e.g., ¶[0005]). Reisdorph provides the skilled artisan with motivation to specifically select pleconaril (aka picovir; Abstract) and combine it with cyclodextrin teaching that the former stabilizes the “capsid” or overall composition (Abstract). Furthermore, Reisdorph expressly teaches that pleconaril is useful in combatting picornaviruses, even styling the composition as the “Achilles’ heel” to such viruses (see e.g., Discussion, pg. 40).
Thus, in view of the combined teachings of Pilgaonkar and Reisdorph, the Examiner respectfully advances the position that a person of ordinary skill in the art at the time the instant invention was filed would have had clear motivation to modify the compositions practiced by Pilgaonkar and have more than a reasonable expectation of producing a composition (claim 1) which is administered to patients to reduce the symptoms of infection or disease cause by such pathogens as Picornaviridae (claim 12).
The recited “optimized” limitations of claims 1-3 are broadly and reasonably interpreted as reciting the structural limitations recited by claim 1. Therein, where pleconaril is “optimized for ease of delivery, for dosing, for stability and reduced toxicity,” the Examiner considers this to be met with the above showing that pleconaril is formed into an inclusion complex with cyclodextrin. It is considered to be further met with the showing that is combined with one or more excipients (see Pilgaonkar; e.g., Abstract and claim 1).
The properties recited in claims 3 and 4 are considered to be met for the same reason.
Regarding the limitations recited in claims 13 and 14, the Examiner broadly and reasonably considers the composition being optimized as being drawn to product-by-process limitations rather than the composition itself. Notably as the composition which is administered in claim 12 has been shown to be orally administered in the art and for the same reasons as are instantly claimed. As it is orally administered, the ordinarily skilled artisan will immediately recognized that the composition will be first exposed to the nasopharynx part of the upper respiratory system on consumption.
The limitations recited in claim 5 are expressly met as discussed above as the inclusion complex is disclosed as being formed using cyclodextrins.
The limitations recited in claims 6 and 18 drawn to the administered composition being biocompatible, biodegradable, and/or bioadhesive are considered to be inherently met by the teaching of Pilgaonkar as evidenced by the fact that the prepared compositions contain an active and are orally administered in order to deliver (and release) the active to the intended recipient.
The limitations of claims 7 and 16 are considered to be met by Pilgaonkar. The Abstract and claim 1 expressly teach the presence of a pharmaceutically acceptable excipient. Fatty acids are also taught as being used in the compositions and are defined by the reference as encompassing pharmaceutically acceptable oils. See e.g., ¶[0028]-[0031].
The limitations of claims 8 and 19 recite that the composition is “suitable for administration from a pressurized metered dose inhaler device.” The Examiner, again, considers the claim to be drawn to the composition recited in claim 7 and not its recited intended use. That it is suitable to be administered from an MDI device is not considered to further limit the recited composition.
The limitations of claims 10 and 17 are considered to be expressly met by Pilgaonkar (e.g., claim 1).
The limitations recited in claims 9 and 20 require that the administered composition further comprise ester mixtures of saturated fatty acids.
In defining the excipients which may be used in forming its orally-administered taste-masking dosage forms, Pilgaonkar teaches that the pharmaceutically acceptable excipients which are suitable will include fats, oils, fatty acids, fatty acid esters, and combinations thereof. See ¶[0028]. Fatty acid esters are discussed further in the reference in ¶[0049] as including such compounds as polyethylene sorbitan fatty acid ester and sorbitan fatty acid esters (aka Tween). Thus, the reference is considered to teach and suggest the recited limitations to a person of ordinary skill in the art.
Lastly, claim 15 recites the different symptoms which are associated with the viral infection which is treated by the method of claim 12. As an initial point, the combined teachings of Pilgaonkar and Reisdorph are considered to meet the limitations of claim 12 and as such, treatment of symptoms associated with infections or diseases caused by strains such as Picornaviridae are considered to be met. However, the Examiner notes that ¶[0002] of Pilgaonkar defines influenza as being a viral infection characterized by such symptoms as fever, muscle aches, sore throat, headache, nonproductive cough, and rhinitis. Thus, in treating influenza virus with the practiced composition, the ordinarily skilled artisan (i.e., anyone who has ever had the flu) would reasonably expect to treat any one of the recited symptoms set forth in claim 15.
Based on the foregoing combined teachings of the references, it is immediately apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed composition and using it to treat the recited infections or diseases. 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 filed, absent a clear showing of evidence to the contrary.
All claims have been rejected; no claims are allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Jeffrey T. Palenik whose telephone number is (571) 270-1966. The Examiner can normally be reached on 9:30 am - 7:00 pm; M-F (EST).
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s supervisor, Robert A. Wax can be reached on (571) 272-0623. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Jeffrey T. Palenik/
Primary Examiner, Art Unit 1615
Prosecution Insights