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 18-33 are currently pending in this application and are considered on the merits.
Election/Restriction
Election was made without traverse of Group V, claims 18 and 20, in the reply filed Jul. 17, 2026 to a process comprising an extracted functional porosome reconstituted in a human cell. During a telephone conversation with Joseph Romagnano on Sept. 11, 2026 a provisional election was made with traverse to the species of source of a lung epithelial cell. Claims 21 and 24-29 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention. Affirmation of this election must be made by applicant in replying to this Office action, the basis of which is below.
Species Election
This application contains claims directed to the following patentably distinct species of porosome source for extracting, e.g., from those recited in claims 19-21, 24, 30, or 32, such as a source that is a liposome, organoid, artificial lipid bilayer membrane, or organism/cell that is human, pig or other nonhuman mammal and cell-type (e.g., Calu-3) that is a stem, epithelial, connective tissue, hormone secreting, nerve, skeletal muscle, blood cell, or immune system cell, and/or cell type having comprising exocrine pancreatice porosomes, insulin-secreting porosomes, mucin-secreting porosomes, and/or porosomew ith CFTR-associated seceretory porosome complexes, such as extracted from any animal cell, including of an arthropod, worm, marine invertebrate, fish, insect, amphibian, reptile, bird, primate, rabbit, equine, bovine, porcine, canine, feline, or rodent (see e.g., instant [0169]).
The species are independent or distinct and there is a search and/or examination burden for the patentably distinct species as set forth above because at least the following reason(s) apply. The disclosure provides no indication that all such extracted porosomes recited in the claims share a common relationship. These varied porosomes have considerable variation amongst themselves and between each other, both in structure and function. For example, regarding functional reconstituion in a human cell, the functions of insulin regulation, insulin secretion, glucose response, mucin secretion, CFTR structure/presence, bicarbonate secretion, zymogen granule response, and/or amylase, lipase, trypsinogen, and nuclease secretion. In addition, these species are not obvious variants of each other based on the current record. Applicant is required under 35 U.S.C. 121 to elect a single disclosed species, or a single grouping of patentably indistinct species, for prosecution on the merits to which the claims shall be restricted if no generic claim is finally held to be allowable. Currently, claims 18, 23, and 31 are generic. Claims 18-20, 22-23, and 30-33 are considered on the merits.
Priority
Acknowledgement is made of applicant’s claim for the benefit of the prior-filed applications US 63/396,040, 63/431,946, and 63/444,451 under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c). 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 prior-filed application 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 one or more claims of this application. Entitlement to priority to Aug. 8, 2022 and Dec. 12, 2022 does not apply to the subject matter of claims 18-33, therefore the earliest effective filing date of the instant claims is Feb. 22, 2023 based on US 63/447,371.
Objections to the Disclosure
Paragraphs [0076], [0082], [0123], [0138], [0140] and [0146] in the specification each refers to colors (e.g., blue, yellow, red, green) in the drawings (FIGs. 1, 3-4, 12-13, 17); however, color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection will not be held in abeyance.
Claim Objections
Claim 29 recites the term “release” regarding insulin, which appears to be used synonmyously with “secretion” or “secreting” respectively in claims 27 and 24. Appropriate correction is requested for consistency within the claim set.
Claim Interpretation
In claim 18, the term “the human cell” comprising the reconstituted extracted porosome previous is implied to have exhibited a secretory defect resulting from a malfunctioning porosome protein(s) prior to the reconstituting step.
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 et al., Micron. 56: 37-43 (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 complexe comprising, e.g., 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 ([0004], [0152]), 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.), such as an isolating a porosome simplified soluble core or central plug (see instant [0075]-[0076]; Jena, supra, J Mol Struct 1073 at Table 1-2). Further, a porosome can be considered “artificial” ([0015]).
In claim 1, the term “functional” with regard to a porosome complex is interpreted as encompassing porosomes capable of any porosome complex function, e.g., secretion across a lipid membrane of, e.g., an enzyme, hormone, or neurotransmitter and/or altering neurotransmission, mucus secretion or insulin secretion ([0004]). Thus, certain secretory defects caused by porosome malfunction are related to such function(s), including defects observed with cystic fibrosis, diabetes, Alzheimer's, Down Syndrome, schizophrenia, digestive, and immune disorders, among others ([0004]).
In claims 20, 21, and 30, no claim limitation expressly or implicitly limits the extracted porosomes of claim 18, e.g., as claim 30 does not require porosome complexes to have been extracted from Calu-3 cells.
In the claims, the terms “TREK-1,” “Gi3,” “Syntaxin-1A,” and “SNAP-25 immunoreactivity” are interpreted as refering to a specific type of protein, not any polynucleotide containing molecule.
In claim 32, the term “CFTR-associated secretory porosome complex” is interpreted as meaning a secretory porosome complex physically associated with CFTR (e.g., comprising) instead of a secretory porosome complex abstractly associated with CFTR, such as complex known to be capable of associating with CFTR.
Claim Rejections - 35 USC § 112(a), Written Description
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 18-20, 22-23, and 30-32 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
When the claims are analyzed in light of the specification and instant claim 33, the instant invention of claim 18 encompasses methods wherein an additional step is necessary to ensure correction insertion and orientation of the porosome into the human cell. Thus, dependent claims 19-20, 22-23, and 30-32 encompass such methods as well.
M.P.E.P. §2163 states “To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116.”
M.P.E.P. § 2163 also recites, “An applicant shows possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention… one must define a compound by ‘whatever characteristics sufficiently distinguish it' . A lack of adequate written description issue also arises if the knowledge and level of skill in the art would not permit one skilled in the art to immediately envisage the product claimed from the disclosed process.”
Claim 18 requires the method result that a secretory defect is ameliorated or corrected, which implies the reconstituted extracted porosomes insert and orient correctly to compensate for such defective function in the human cell. However depedent claim 33 narrows claim 18 to wherein no additional step is necessary. Thus, by the principle of claim differention, claim 18 must encompass methods wherein additional steps are necessary to achiver correct insertion and/or orientation, which both are a prequisute for achieving ameliorating or correcting of a secretory defent resulting from a malfunction of one or more porosome proteins in the human cell absent evidence to the contrary.
There is no general knowledge in the prior art regarding reconsituting porosomes in a human cell beyond using instead a mouse cell and by a process lacking any additional step for insertion/orientation (see Naik et al., Endocrinology 157: 54-60 (2016); IDS ref.; describing spontaneous insertion and proper orientation, at least stochastically). The instant written description lacks any description of such a step intended as additional to the method of claim 1 and intended to promote/enhance insertion or orinetation, not to mention ensure it. The skilled artisan could not rely upon the insant disclosure such that the specification would sufficiently describe that Applicant was in possession of methods having additionl steps that promote correct insertion and/or orientation of an extracted lung epithelial porosome into any human cell.
In conclusion, this limited disclosure in view of the prior art is not deemed sufficient to reasonably convey to one skilled in the art that applicant is in possession of the full scope 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 applicants effective filing date. Nothing in dependent claims 19-20, 22-23, and 30-32 alter this analysis. Thus, a person of ordinary skill in the art would understand claims 18-20, 22-23, and 30-32 omit an essential matter, namely requisite additional steps merely aluded to by claim 33 but not described in the instant description, claims or the prior art.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(B) CONCLUSION. —The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 20-22, 25-27, and 31 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.
Claim 20 recites the step of reconstituting “isolated porosomes” into organoids, artificial lipid bilayer or liposome, which is ambiguous and incoherent as to how this step relates to any step of independent claim 18 from which it depends, such as whether the porosomes reconstituted into organoids, artificial lipid bilayer membrane or liposome is “the source” therein or if there is any relationship between the extracted porosomes and the isolated porosomes at any stage in the process. Claims 21-22 is included in the rejection for depending from indefinite claim 20.
Claim 21 recites isolated complexes reconstituted in liposomes, which is incoherent as to how a complex can be both isolated and reconstituted in an additional composition of matter comprising liposomes.
Claims 25-27 each recites a relative term in “enriched” or “increased” or “elevated.” As no reference point, standard or means for determining a boundary for enriched, increased or elevated as to the contrary are recited in the claim or implied in the claim by the instant specification, the skilled artisan is not notified of the metes and bounds of this relative limitation. Claims 28-29 are included in the rejection for depending from indefinite claim 27.
Claim 27 recites “the glucose-stimulated insulin secretion,” which lacks sufficient antecedent basis in the claim or in claim 24 from which it depends, and thus, should be preceded by an indefinite article instead of the definite article ‘the.’ Claims 28-29 are included in the rejection for depending from indefinite claim 27.
Claim 31 recites the step of “preparing” a suspension of extracted porosome complexes, which is ambiguous and incoherent as to how this steps relates to any step of claim 18 and/or 30 from which it depends, such as whether the prepared porosomes are “the source” or if there is any relationship between the extracted porosomes of claim 18 and the prepared extracted porosomes at any stage in the claimed process, such as administering via a nebulizer extracted porosomes to the human cell.
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.
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 18-19, 23, and 30 are rejected under 35 U.S.C. 103 as being unpatentable over Naik (Naik et al., Endocrinology 157: 54-60 (2016); IDS ref.) in view of Jena (Jena, Discoveries 2: e24 (2014)).
Regarding claim 18, Naik teaches a method of reconstituting extracted porosomes from a source into a cell to form functional porosome complexes (Abstract, pg. 59-60). (This concept was noted as in prior art at [0003] in each of US 63/444,451 and US 63/447,371 but without a specific reference.)
Naik does not teach wherein the cell is a human cell, instead using mouse cells. Naik also does not teach wherein the recipient cell exhibits any amelioration or correction of a secretory defect resulting from malfunction of a porosome protein, instead reconstituting exogenous porosomes from mouse cells back into the outer plasma membrane of the same type of mouse cells resulting in increased insulin secretion in response to glucose due to increasing the total number of functional porosome complexes.
However Jena teaches cystic fibrosis is caused by malfunction of the CFTR, a chloride channel transporter in airway epithelia as well as in Calu-3 cells in culture (abstract).
Naik teaches human mucin-secreting cells of the airway epithelia have porosomes and methods of isolating them (pg. 57) and thus the method of reconstitution for mouse cells would be obvious to apply to an extracted human mucin-secreting cell porosome to show rescue of a porosome defect in the recipient human cell, such as an abnormal/diseased human mucin-secreting cell due to a heritable porosome mutation. As noted in the 112(a) section, no additional step is necessary for reconstitution by the method taught by Naik and thus achieving functional porosome complexes in the recipient cell would have a reasonable expectation of success based on the mouse cell model. One of ordinary skill in the art would be motivated to show proof of concept by assaying amelioration or correction of a secretory defect in a malfunctioning human cell to translate the in vitro mouse cell data to an in vitro human cell system and to study mechanisms of porosome mediated secretion in diseased human cells (see Jena at pg. 8 last para.; Fig. 6). Thus, a method encompassed by claim 18 is obvious prior to the effective filing date of the instantly claimed invention, such as wherein the source is a human airway epithelial cell regarding claim 19.
Regarding claim 23, Jenna teaches these airway epithelial cell porosomes comprise chloride channels (abstract).
Regarding claim 30, Jenna teaches human Calu-3 airway epithelial cells are a suitable source for extracting such porosomes from cell cultured cells, such as via immunoisolation (Fig. 3; pg. 1-6).
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 18-19, 23, and 30-32 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 claims 1-2 and 8-10 of the reference application teaches a method of administering to a subject (e.g., a human) a porosome composition formulated for inhaled administration comprising a functional porosome comprising a functional CFTR proteins, such as wherein the porosome complex was isolated from a human bronchial/lung epithelial cell and increases mucin and/or chloride secretion in human airway epithelial cells (i.e., relieves a porosome defect) in the subject. Thus, reference claim 1 teaches a species of instant claim 1 wherein the composition is formulated for inhaled or nasal administration. Instant claims 19, 23, and 30-32 are taught by reference claims 2, 10, 2, 7 and 1, respectively. This is a provisional nonstatutory double patenting rejection because the reference application claims have not in fact been patented.
Claims 18-19, 23, and 30-33 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of copending Application No. 18/584,830 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because claims 14-17, 19-20 and 23 of the reference application teaches a method of reconstituting an isolated functional porosome complex into the human cell of a patient (e.g., via a contacting) to treat a porosome defect of cystic fibrosis and/or a CFTR mutation or improve a CFTR function, such as wherein the isolated porosome comprises WT CFTR and is provided via inhalation (claims 15 and 17).
Instant claim 19 differs in that the source of the porosome is specifically human epithelial cells; however reference claim 2 teaches a nebulizer composition comprising a functional human WT-CFTR protein extracted from human bronchial epithelial cells. Regarding instant claim 23, porosomes containing functional CFTR inherently comprise chloride channels and CFTR-associated secretory porosome complex, i.e., to treat cystic fibrosis or CFTR mutation in the patient. Regarding instant claim 30, reference claim 5 teaches extracting the porosomes from Calu-3 cells. Regarding instant claim 31, reference claims 7 and 13 teach administering a porosome suspension composition via nebulizer. Regarding instant claim 33, the reference claims are silent as to any step necessary to ensure correct insertion or orientation of a porosome complex.
This is a provisional nonstatutory double patenting rejection because the reference application claims have not in fact been patented.
Conclusion
No claim is allowed.
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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/ERIC J ROGERS/
Examiner, Art Unit 1638
/JAMES D SCHULTZ/Supervisory Patent Examiner, Art Unit 1631
Prosecution Insights