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 .
DETAILED ACTION
Claim Status
Claims 1-23 are currently pending in this application.
Election/Restrictions
Applicant’s election with traverse of Group I, claims 1-12, in the reply filed Jul. April 3, 2026 is acknowledged. Claims 13-23 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected subject matter, there being no allowable generic or linking claim. Claims 1-12 have been considered on the merits.
Priority
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. US 63/390,040; 63/431,946; 63/444,451; 63/447,371; 63/458,471; 63/459,762; 63/472,674; 63/523,970; 63/526,786; and 18/22,784, each fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for any of the instant claims due to the pharmaceutically acceptable excipient, such as a propellant. Therefore the earliest effective filing date of the instant claims is Feb. 22, 2024.
Status of Rejections
The previous claim rejections under 35 USC §§ 101, 112(a), 112(b), 112(d), and non-statutory double patenting are withdrawn in view of the claim amendments except as maintained below or as specifically modified in light of current claim amendments.
Claim Interpretation
In the claims, the term “porosome” is interpreted in view of the application lacking any formal definition as ordinarily understood as a lipoprotein organelle comprising about 30-40 unique proteins (e.g., with many repeated in a symmetrical pattern) as well as non-protein components (e.g., cytoskeletal anchors, cholesterol, ceramide, phosphatidic acid, diacylglycerol, and phosphatidylinositol phosphates), and which may include sizes of 15-180 nm depending on its source cell type (e.g., masses far greater than 650-10,000 kDa) (see Kovari 2014 at Fig. 1, 5; instant FIG. 1-3, [0002]-[0004], FIG. 10). Porosomes naturally occur in most mammalian cell types and are membrane-based organelles with dynamic/transient structures, such as due to the physical binding by associated regulatory proteins (e.g., as in instant FIG. 4) and docking of secretory vesicles; however there is a consistent core comprising SNARE complexes comprising, e.g., comprising SNAP-23/SNAP-25 (Jena, Discoveries 2: e24 (2014) at Fig. 3; Jena, J Mol Struct 1073: 187-95 (2014) at pg. 5-7, Fig. 6). However in view of the instant specification, the term “porosome” encompasses a soluble proteinaceous core/subpart of the porosome organelle of a cell ([0010], [0220], [0289]), such as lacking bulk lipids and/or obtained by immunoprecipitation affinity targeting a core protein of the porosome complex (e.g., a SNAP) to isolate “porosomes,” often in the presence of a detergent for solubilization (e.g., Triton, Tween, etc.) (see instant [0220], [0289]; Jena, supra, J Mol Struct 1073 at Table 1-2). Additionally, a functional porosome or isolated porosome (e.g., the simplified soluble core or central plug) may be placed within an artificial lipid membrane or reconstituted within a cell (see instant [0004], [0026], [0034], FIG. 15-18, 20; [0211]). Further, a porosome can be “artificial” ([0018]), which is encompassed by the term “porosome” of claims 1-2 and 6-12, unless artificial porosomes are isolated from modified cells according to claims 3-5 (e.g., due to forced expression of an exogenous/endogenous component incorporated therein by transgenic manipulation (FIG. 6-7)).
In claim 1, the term “functional” with regard to a CFTR protein is interpreted as encompassing a CFTR protein family member (e.g., by sequence homology) capable of any CFTR function, e.g., including one or more of folding, trafficking to the plasma membrane via a secretory pathway, inserting on a cell surface as part of CFTR protein complex, ion conductance (e.g., Cl- export and/or bicarbonate), ENaC modulation, fluid/mucus regulation in a lumen, luminal pH regulation, respiratory epithelial function, pancreatic function, and neurological function (see Ramananda et al., Int J Mol Sci 25: 3384 (2024) at pg. 5-7, Fig. 2). The CFTR protein family is large, including proteins in various vertebrate species and within humans alone there are over 130 variants, some of which are partial loss of function alleles (e.g., 5T) or merely polymorphisms like S912L (see e.g., Kerem and Kerem, Eur J Hum Genet 4: 65-73 (1996) at Table 1; www.omim.org/entry/602421, last visited May 11, 2026; Bombieri et al., Hum Genet 106: 172-8 (2000)).
Claims 1-5 are each interpreted as a product-by-process encompassing any porosome, whether isolated or obtained by another process. Note for patentability over the prior art purposes, product-by-process claims are treated outrightly as products, while for patent infringement purposes, product-by-process claims are treated exclusively as process claims. See Abbott v. Sandoz, 566 F.3d 1282 (Fed. Cir. 2009). While the recited process used in making the claimed product comprises isolating porosomes from specifically recited cell types, there is no unrecited structural feature(s) clearly implied in these claims beyond the presence of human derived porosome structures for claims 4 and 5 as porosome components can be exogenously expressed in heterologous cells via recombinant transgenes (Perniss et al., Sci Rep 7: 3517 (2017); Price et al., J Biol Chem 271: 25184-91 (1996); Stutts et al., J Biol Chem 272: 14037-40 (1997), at abstracts). A chemical composition and its properties are inseparable (see MPEP 2112.01). Further, “[w]hen the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990) (MPEP 2112(V)).
Claim Rejections - 35 USC § 101 (maintained)
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-10 and 12 are rejected under 35 U.S.C. 101 because the claimed invention is not directed to patent eligible subject matter. Based upon an analysis with respect to the claim as a whole, claims do not recite something significantly different than a judicial exception. The rationale for this determination is explained below.
The claims are directed to:
A composition comprising:
(i) one or more porosomes comprising a CFTR protein; and
(ii) at least one pharmaceutically acceptable excipient;
wherein the composition is suitable for inhalation by a subject as a mist.
In claim 1, the modifier “nebulizer” in view of the instant specification may impose an implied claim limitation on the composition as being a mist or suitable for being formed into a mist during administration to a subject, such as via a nebulizer device (see instant [0085], [0129]). Thus, claim 1 is directed to the combination of either (1) a nature-based product (porosome) and a synthetic component (excipient(s)); or (2) multiple nature-based products when the excipient(s) are also nature-based, e.g., water, water comprising sodium chloride, serum albumin, etc.
This nature-based product comprising at least one product of nature (porosome) is analyzed to determine whether it has markedly different characteristics from any naturally occurring counterpart(s) in their natural state. The structural/functional limitations of claim 1 are present in naturally occurring human porosomes, namely a porosome comprising a “functional” human CFTR protein, such a naturally occurring wild-type variant thereof of human lung/bronchial epithelial cell origin (i.e., a human, wild-type CFTR protein). The structural/functional limitations from (1) the excipient and (2) formulated for delivery to a subject by inhalation as a mist requires nothing more than an aqueous composition that can be nebulized into a mist, such as a human wild-type porosome in physiologic saline (see e.g., claim 9, mentioning water and sodium chloride).
Thus, claim 1 encompass porosome compositions consisting only of multiple nature-based products. Claim 6 requires the porosome to comprise SNAP-23 and IQGAP1, whereas claim 10 limits the porosome size to specifically recited median diameter ranges; however all of these structural limitations are present in at least a subset of naturally occurring porosomes as set forth in another section herein.
Therefore, all the claims encompass multi-molecular structures (porosomes) having no difference in characteristics to naturally occurring counterparts as claimed. The only difference is these structures may be purified away from their natural environment (isolated) and combined with an excipient(s), such as another naturally occurring component that was purified (e.g., sterile saline). However, there is no evidence that merely bringing an isolated porosome and generic excipient such as sterile water together results in any markedly different characteristic, and thus the claims are directed to a “product of nature” exception. In re Roslin Institute (Edinburgh), 750 F.3d 1333, 1338-39 (Fed. Cir. 2014). The mere combination of two or more nature-based but isolated products that do not naturally occur together does not automatically confer patent subject matter eligibility to the combination. For example, see the USPTO Subject Matter Eligibility Guidance, Example 3. Purified amazonic acid (claim 1 versus claim 5); Example 28. Vaccines (claim 3 versus claim 4).
Because the claimed invention of claims 1-10 and 12 does not include any additional features that could add significantly more to the exception, the claimed culture does not qualify as eligible subject matter, and should be rejected under 35 U.S.C. § 101 as explained below. The claimed porosome has the same structure and function as its closest natural counterparts functions in nature without marked modification, e.g., as wild-type CFTR porosomes in human airway epithelial cells. Although the at least two components may form a non-natural complex, e.g., between the excipient and porosome, none of the claims require such a structure is formed.
Thus, an examination of Step 2A prong 2, the answer is no because the claimed invention does not integrate the judicial exception, in the instant case a system, into a practical application. It is only the recited limitations in the claims that are examined under 101 and not aspects such as what the system is used for. It is emphasized that the claimed invention is a product and not a process of using or making a product.
An examination of Step 2B, the answer is no with respect to the claimed invention. There are no other additional elements recited in the instant claims that would amount to significantly more than the judicial exceptions. Each of the two molecules as claimed are indistinguishable from those that exist in nature and there are no limitations that add any additional elements to the claimed compositions. Combining a naturally occurring product with an excipient generally does not appear to change an isolated porosome function/structure in any significant or meaningful way to amount to more than the judicial exception.
Response to Arguments
Applicant’s arguments in the response of 8/17/26 (at pg. 7-8) regarding the 101 subject matter eligibility rejections are not found wholly persuasive.
As indicated above, claim 11 is directed to a patent eligible subject. Claim 11 requiring a certain particle or droplet size is considered to both be an additional feature adding significantly more to the exception and integrating the judicial exception into a patent eligible practical application by conferring a markedly different characteristic to the composition in view of the natural counterparts. Claim 11 aligns with applicant arguments that a markedly different structure is present useful for delivery of a porosome to a subject, such as a therapeutic porosome dose(s) for amelioration of secretory defects caused by aberrant CFTR in cystic fibrosis patients.
Applicant traverses the rejection by arguing all claims are directed to a humanmade therapeutic pharmaceutical composition by its formulation and intended use: a nebulizer porosome composition suitable for inhalation by a subject, comprising an isolated porosome together with a pharmaceutically acceptable excipient, where the use is for reconstituting a porosome complex comprising functional CFTR protein into a respiratory epithelial cell. However as noted above the phrases “formulated for reconstituting a porosome complex” into a respiratory epithelial cell and “suitable for inhalation by a subject” encompass porosome solutions lacking any markedly different characteristic from the natural counterpart, despite being suitable for nebulization and inhalation administration.
The response argues that formulated in a manner suitable for being formed into a mist during administration to a subject provides an important distinction. However, under a broadest reasonable interpretation, this encompasses most aqueous solutions comprising such a porosome as recited. Similarly, the response also argues that a pharmaceutical nebulizer composition “configured” for inhaled administration is somehow limiting the subject matter to something markedly different from natural porosomes. However, reading of the instant specification does not support this conclusion. In view of the specification, this “configuration” or “suitability” is not considered to be so limiting because it encompasses aqueous solutions like buffered saline commonly used in research. As noted in the response, non-limiting examples include a wide range of compositions, such as liquids, suspensions, dispersions, dry powders, and importantly droplet or particle sizes capable of penetrating the bronchial tubes (see instant [0099]). Further, non-limiting examples of excipient components include diluents, stabilizers, propellants, surfactants, and preservatives (see instant [0101]).
While claim limitations truly limiting the composition to a practical application involving inhaled delivery or nebulization would overcome section 101, the current claim language is not considered accomplishing this when it encompasses, e.g., a natural porosome in a saline solution. But see claim 11. There is no evidence merely placing an extracted/isolated porosome complex in a buffered saline changes the native biological structure in meaningful, to the contrary the goal seems to be to preserve porosome structure/function for delivery to a cell to produce a functional reconstituted porosome (e.g., to provide improved CFTR function and mucus secretion). The claims fail to recite a limitation to any markedly different characteristic, instead using vague functional language that broadly reads on natural porosomes.
As detailed above, it is only the limitations in the claims limiting the claimed product that are examined under 101 and no other aspects such as an intended use or how the product is made.
Claim Rejections - 35 USC § 112(a), Written Description (maintained)
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 1-5 and 7-12 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 and under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter. 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.
The claimed invention as a whole is not adequately described if the claims require essential or critical elements that are not adequately described in the specification and that is not conventional in the art as of applicant’s effective filing date. Possession may be shown by actual reduction to practice, clear depiction of the invention in a detailed drawing, or by describing the invention with sufficient relevant identifying characteristics such that a person skilled in the art would recognize that the inventor had possession of the claimed invention. Pfaff v. Wells Electronics, Inc., 48 USPQ2d 1641,1646 (1998).
In making a determination of whether the application complies with the written description requirement under 35 U.S.C. 112(a) or 35 U.S.C. 112, first paragraph, it is necessary to understand what Applicant is claiming and what Applicant has possession of. Claim 1 recites a product, a porosome composition comprising a porosome from a human airway epithelial cell and comprising a normal human CFTR protein and a pharmaceutically acceptable excipient wherein the product is suitable for being nebulized into a mist for administration to a subject in the intended use of reconstitution a porosome complex in a respiratory epithelial cell of the subject.
As claim 6 requires the porosome to comprise SNAP-23 and IQGAP1, the scope of claim 1 (as well as claims 2-5 and 7-12) encompasses wherein the porosome lacks one or both of SNAP-23 and IQGAP1. Thus, claims 1-5 and 7-12 are also broad in that the porosome of the claims may lack one or both of SNAP-23 and IQGAP1.
The specification is silent as to any species of porosome lacking SNAP-23, instead only disclosing that SNAP-23 levels are reduced in certain human cells homozygous for the CFTR point mutation deletion F509 (ΔF508) while teaching porosomes of other human cells inherently have SNAP-23 (e.g., CFBE41o-6.2) ([0071], FIG. 22, 26, Table 3, [0289]). The instant specification does describe a single species of porosome lacking IQGAP1, ones isolated from cells homozygous for the CFTR point mutation deletion F509 (ΔF508), at least in certain human bronchial epithelial cell lines (e.g., CFBE41o) (see instant [0155], [0291], Table 3), but this is not a representative species as there is no description of how this can satisfy the limitation of being a “functional” CFTR protein.
Therefore, the scope of claims 1-5 and 7-12 directed to porosomes lacking IQGAP1 or SNAP-23 are limited to those known in the prior art, e.g., isolated from an IQGAP1 or SNAP-23 knockout cell line. The prior art teaches CFTR proteins perform functions in nature, including folding, trafficking to the plasma membrane via a secretory pathway, inserting on a cell surface as part of CFTR protein complex, ion conductance (e.g., Cl- export and/or bicarbonate), ENaC modulation, fluid/mucus regulation in a lumen, luminal pH regulation, respiratory epithelial function, pancreatic function, and neurological function, such as due to functions of distinct substructures, such as transmembrane domains, channel pore, regulatory domain (Ramananda et al., Int J Mol Sci 25: 3384 (2024) at pg. 5-7, Fig. 2; Hwang et al., J Gen Physiol 150: 539-70 (2018) at Fig. 1, 3-4). The prior art does not show or predict a porosome lacking IQGAP1 or SNAP-23 and having a functional CFTR protein. However applicant is invited to furnish evidence to the contrary.
Thus, the skilled artisan could not rely upon the disclosure in the specification such that the specification would sufficiently describe that Applicant was in possession of the entire scope of porosomes of claims 1-5 and 7-12 implied by the principle of claim differentiation in view of dependent claim 6, i.e., a porosome composition for reconstituting a porosome complex in a subject after inhalation of the porosome composition.
Response to Remarks
Applicant’s remarks in the response (at pg. 7) are not found relevant nor persuasive. Applicant simply states the claim amendments render this issue moot, but as set forth above, all these issues are maintained, except for one in light of the amendment to claim 2. There is unpredictability in the existence of porosome structures excluded by claim 6 yet satisfying the limitations of claim 1.
Claim Rejections - 35 USC § 112(b) (maintained)
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 1-12 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 1 recites a “human WT-CFTR” protein, which is a term neither defined in the claim nor the instant specification (the same for “WT-CFTR”), thus it is not clear how “WT-” limits the CFTR protein. If this is an abbreviation, then the abbreviation needs to be spelled out at least at its first occurrence in the claim set. Claims 3-12 are included in this rejection for depending from indefinite claim 1.
Claim 2 recites the term “isolated” regarding a porosome(s) in a composition also comprising an excipient(s) and optional other components. Thus, it is incoherent as to how any porosome in such a composition having other stuff is “isolated” under the ordinary meaning of the term. As noted by the instant specification, the term “comprising” is open ended ([0077]). If the applicant acts as her own lexicographer to redefine a term of a claim contrary to its ordinary meaning, the written description must clearly define the claim term and set forth the uncommon definition so as to put one reasonably skilled in the art on notice that the applicant intended to so redefine that claim term. Process Control Corp. v. HydReclaim Corp., 190 F.3d 1350, 1357, 52 USPQ2d 1029, 1033 (Fed. Cir. 1999). In the instant case, there is no such clear redefinition of “isolated” regarding a porosome, and, thus, the term “isolated” as used in these claims is indefinite.
Claim 11 recites the term “the particle or droplet,” which lack sufficient antecedent basis in the claim and in claim 1.
Response to Remarks
Applicant’s remarks in the response (at pg. 7) are not found relevant nor persuasive. Applicant simply states the claim amendments render this issue moot, but as set forth above, all these issues are maintained at least for some the claims.
Claim Rejections - 35 USC § 102 (modified)
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 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 1-6 and 10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hou (Hou et al., Journal of Proteomics 96: 82-91 (2014); IDS ref.), with claim 6 specifically as evidenced by Loureiro (Loureiro et al., Front Pharmacol 10: 619 (2019)).
The claims are interpreted as provided in a previous section.
Regarding claim 1, Hou discloses a composition comprising isolated porosome complexes and a pharmaceutically acceptable excipient (PBS) wherein the complexes comprise CFTR protein (pg. 84, left col., last para, to right col., 1st para.; Fig. 3; pg. 87, left col., 3rd para., to end of pg.; Table 1). The PBS qualifies as a pharmaceutically acceptable excipient and the composition qualifies as a suitable formulation for an intended use in a nebulizer for inhalation by a subject and reconstitution of porosome complex into a respiratory epithelial cell, i.e., capable of being made into a mist.
Regarding claims 2 and 5, Hou discloses wherein the CFTR porosomes complexes are from the human bronchial epithelial cell line (Calu-3) having normal/wild-type CFTR protein (pg. 83, right col., last para.).
Regarding claims 3-4, these product-by-process limitations do not imply any structural limitation to the claimed product not already recited in claim 1. Thus, claims 3-4 are anticipated by virtue of Hou anticipated claim 1, as set forth above. A composition of claim 1 made by different processes is considered indistinguishable regardless of whether made by A/G magnetic agarose or A/G agarose affinity column techniques absent evidence to the contrary. Similarly, a composition of claim 1 made by different processes is considered indistinguishable regardless of whether made precisely with an elution pH of 3.0 etc. absent evidence to the contrary. Thus without more, claim 3 or 4 prima facie fails to further limit the subject matter of a claim 1 as a product-by-process claim for applying art. Note, product-by-process claims are not limited to the manipulations of the recited steps, only the structure implied by the steps (MPEP 2113), and no unrecited structure is clearly implied for claim 3 or 4 that is not in an isolated porosome absence evidence to the contrary (e.g., shown with side-by-side comparative data ensuring a difference caused by the method of making).
Regarding claim 6, Hou discloses wherein the complex comprise the ubiquitously expressed SNAP-23 (Fig. 3D), and as evidenced by Loureiro, IQGAP1 is a ubiquitously expressed protein physically associating with CFTR in human cells (Table 3). To the extent either of these structures are argued to be absent from these prior art porosomes as laid out above, note the 112(a) written description rejection above.
Regarding claim 10, Hou discloses wherein the porosomes have a diameter of approximately 100 nm (pg. 83, right col., 2nd para.; Fig. 1-2; pg. 87, left col., para. 1-2; Abstract). Note, “[w]hen the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990) (MPEP 2112(V)). Thus, Hou anticipates the claimed invention.
Response to Arguments
Applicant’s arguments in the response of 8/17/26 (pg. 10) are not found persuasive. Applicant traverses by arguing Hou does not disclose all elements of the amended claims, such as claim 1, within its four corners and “arranged as in the claim.” This is not found persuasive as set forth fully above in the instant rejection modified from the previous rejection.
Claim Rejections - 35 USC § 103 (maintained)
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.
Claims 1-5 and 7-12 are rejected under 35 U.S.C. 103 as being unpatentable over Hou (Hou et al., Journal of Proteomics 96: 82-91 (2014); IDS ref.) in view of Ramjeesingh (Ramjeesingh et al., Hum Gene Ther 9: 521-8 (1998)) and Schwarz (Schwarz et al., Int J Mol Sci 23: 9597 (2022)).
As set forth above, claims 1-6 and 10 are anticipated by Hou, and thus the subject matter of claims 1-6 and 10 are render obvious in view of Hou. The claims are interpreted as provided in a previous section.
Hou teaches compositions comprising immuno-isolated porosome complexes and a pharmaceutically acceptable excipient (PBS) wherein the complexes comprise wild-type CFTR as isolated from Calu-3 cells (pg. 84, left col., last para, to right col., 1st para.; Fig. 3; pg. 87, left col., 3rd para., to end of pg.; Table 1).
Regarding claims 7-9, Hou does not expressly teach wherein the composition is a suspension or aerosol suitable form suitable for inhalation by a subject, such as representing a liquid nebulizer composition comprising water and sodium chloride.
However Ramjeesingh teaches CFTR protein replacement therapy for treating mammalian subjects with cystic fibrosis wherein isolated wild-type CFTR protein is administered in vivo to a subject in need (CFTR defective mouse) (pg. 522, right col., last para., to pg. 524, 1st para.).
Schwarz teaches using various nebulizer systems to deliver therapeutics to lung tissues of subjects with cystic fibrosis via an aerosol-producing device that transforms an aqueous water composition comprising saline (sodium chloride) into aerosol particles, e.g., Zirela, eFlow rapid, LC Plus, and/or AAD (Table 2, pg. 8, 4.1). Further, Schwarz teaches most drugs indicated for the treatment of cystic fibrosis are formulated as liquid solutions or suspensions and are administered using nebulizers, such as vibrating (VM) or jet nebulizers (pg. 2, e.g., as in Table 2).
It would have been prima facie obvious to one of ordinary skill in the art before the effective time of filing to prepare a liquid composition for a nebulizer comprising wild-type CFTR-containing porosomes as taught by Hou in an aqueous liquid comprising a pharmaceutically acceptable excipient such as saline as taught by Schwarz as a CFTR nebulizer delivery system for use in treating cystic fibrosis. One of ordinary skill in the art would be motivated to do so with a reasonable expectation of success because the nebulizer field was well-established with various nebulizer systems as taught by Schwarz and Ramjeesingh teaching WT-CFTR protein-treated animals incorporating the protein into airway epithelial cells resulting in improved ion conductance via electrophysiology for some subjects (Abstract; Fig. 1, 3-5).
Regarding claim 11, Hou does not teach wherein the nebulizer/aerosol droplet size is 0.5-5 µm.
However Schwarz teaches how to optimize aerosol particle size and results for sizes between 3.5-5 µm (mass mean aerodynamic diameter (MMAD)) (Table 1). Note, a prima facie case of obviousness exists where claimed ranges overlap ranges disclosed in the prior art (MPEP 2144.05).
Regarding claim 12, Hou does not teach wherein the nebulizer is made to contain a minimum amount of porosomes at least 1 x 1015.
However Schwarz teaches emitted doses of at least 90 mg therapeutic per nebulizer use (Table 1), which is equivalent to at least 8 x 1016 porosomes by weight, given a core porosome molecular mass of 650 kDa (see Lee et al., J Proteomics 75: 3952-62 (2012) at Fig. 5). Thus, it would have been prima facie obvious to one of ordinary skill in the art before the effective time of filing to prepare a similar minimum amount or optimize the system for such porosome amounts over 1 x 1015.
Therefore, the claimed invention as a whole is prima facie obvious prior to the earliest effective filing date in the absence of evidence to the contrary.
Response to Arguments
Applicant’s arguments in the response of 8/17/26 (at pg. 10-14) are not found persuasive. Applicant traverses arguing that the porosome composition of Hou is not formulated for a liquid nebulizer composition for inhaled administration by a subject. However as noted above this functional language is not interpreted to exclude a PBS solution comprising extracted porosomes from bronchial/lung epithelial cells Calu-3, such as indicated in dependent claim 2. Applicant also traverses arguing the CFTR-porosomes isolated by methods of Hou are not suitable for administration to a subject but does not present any evidence to support this. As noted above, it is the opinion of this office action that the functional language of suitable for inhalation and formulated for nebulizer use are met merely by a buffered aqueous solution comprising extracted porosomes as recited.
Applicant is recommended to recite in the claims what structure(s) define/distinguish a “nebulizer” composition product over a non-nebulizer composition beyond, e.g., capable of being made into a mist. Use of a nebulizer to deliver a composition by inhalation are well-known in the prior art for treating cystic fibrosis with other drugs. Ramjeesingh and Schwarz are used to support this general proposition of known prior art delivery method with a validated prior art use as delivery system to airway epithelia. Furthermore, the claims are directed to a product and are not limited by any intended use unless an unrecited limitation is clearly implied by such language.
There is no requirement that an “express, written motivation to combine must appear in prior art references before a finding of obviousness.” See Ruiz v. A.B. Chance Co., 357 F.3d 1270, 1276, 69 USPQ2d 1686, 1690 (Fed. Cir. 2004). It must be recognized that any judgement on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time of the claimed invention was made, and does not include knowledge gleaned only from the applicant’s disclosure, such a reconstruction is proper. See in re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). Furthermore, obviousness may be 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 found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See in re Fine 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007).
Applicant traverses by arguing impermissible hindsight bias in reconstructing the prior art teachings; however, this is a specific legal term of art not properly invoked. It must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). It was within the level of ordinary skill at the time the claimed invention was made to combine a buffered aqueous composition with a nebulizer delivery system for inhalation.
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-10 and 12 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of copending Application No. 19/265,874 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because claim 1 of the reference application teaches each of instant claims 7 and 8. Thus, reference claim 1 teaches a species of instant claim 1 wherein the composition is formulated for inhaled or nasal administration. Instant claims 2-10 are taught by reference claims 2-7. This is a provisional nonstatutory double patenting rejection because the reference application claims have not in fact been patented.
Claims 1-12 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of copending Application No. 19/265,874 (reference application) as applied above, and further in view of Schwarz (Schwarz et al., Int J Mol Sci 23: 9597 (2022)).
Although the reference claims do not teach wherein the nebulizer/aerosol droplet size is 0.5-5 µm, reference claims 6-7 teach wherein the composition is an aerosol formulation suitable for inhalation delivery via a nebulizer and reference claims 8 and 10 teach administering the composition to the airway cells of a subject, such as subject with cystic fibrosis (i.e., homozygous for ΔF508). Further, Schwarz teaches how to optimize aerosol particle size for delivery of cystic fibrosis therapeutic via inhalation and shows effective drug delivery for droplet sizes between 3.5-5 µm (mass mean aerodynamic diameter (MMAD)) (Table 1). It would have been prima facie obvious to one of ordinary skill in the art to design a nebulizer aerosol composition comprising droplets of sizes 3.5-5 µm for inhalation by a cystic fibrosis subject as taught by Schwarz to achieve nebulizer delivery to airway epithelial cells as taught by the reference claims. Note, a prima facie case of obviousness exists where claimed ranges overlap ranges disclosed in the prior art (MPEP 2144.05).
Claims 1-2, 5, and 7-9 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 18-21 and 30-33 of copending Application No. 18/446,111 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because reference claims 30-32 teaches a porosome composition for inhalation comprising extracted functional porosomes for nebulizer administration to a subject, such as prepared from Calu-3 cells comprising mucin secreting porosome complexes comprising human WT-CFTR. While instant claim 1 and 9 differs in that the composition must comprise a pharmaceutically acceptable excipient and be suitable for inhalation to administer a porosome complex to respiratory epithelial cell, water can be categorized as such an excipient and could function as a diluent and/or carrier for nebulizer inhalation delivery, such as taught by reference claim 31. Instant claims 2 and 5 are taught by reference claim 30 teaching the Calu-3 human bronchial epithelial cell line. Instant claims 7-8 are taught by reference claim 31. This is a provisional nonstatutory double patenting rejection because the reference application claims have not in fact been patented.
Response to Remarks
Applicant’s remarks in the response (at pg. 14) are not found relevant nor persuasive. Applicant simply states deferring this issue to a later date. However the double-patenting rejections will not be held in abeyance. See 37 C.F.R. 1.111(b), which allows that some objections or “requirements as to form” may be held in abeyance but includes no provision for holding rejections in abeyance. Section 1.111(b) also requires applicants to respond to each rejection with “arguments pointing out the specific distinctions believed to render the claims, including any newly presented claims, patentable over any applied references.” For each rejection, for example, applicants might provide a proper terminal disclaimer (or at least indicate a willingness to submit one when double patenting is the only remaining issue); explain why the rejection is overcome by amendments; provide convincing arguments that the rejection was made in error; and/or explain why amendments or claim cancellations in the copending applications have rendered the rejection moot. If any of the conflicting pending application matures to a patent, modifying the rejection to account for claim-number changes will not constitute a new ground of rejection.
Conclusion
No claim is allowed.
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 ERIC J ROGERS whose telephone number is (571)272-8338. The examiner can normally be reached Monday - Friday 9:00-6:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Tracy Vivlemore can be reached on (571) 272-2914. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ERIC J ROGERS/Examiner, Art Unit 1638
/JAMES D SCHULTZ/Supervisory Patent Examiner, Art Unit 1631
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