DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1-20, of record 7/01/2024, are pending. Prosecution on the merits commences for claims 1-20.
PRIORITY
When reviewing the priority claims for the instant application, the Examiner noted that the Filing Receipt for the instant application, mailed 7/16/2024, is not consistent with the data provided in the Application Data Sheet, of record 7/01/2024.
The Filing Receipt acknowledges priority of the instant application as a DIVISIONAL of US Application No. 18/079,749, filed 12/12/2022. However, the Application Data Sheet, of record 7/01/2024, indicates the instant application is a DIVISIONAL of US Application No. 18/079,749, filed 12/12/2022, which is a CONTINUATION of US Patent No. 11,554,148, filed 7/19/2021, which is a CIP of PCT/US21/37137, filed 6/12/2021, which claims priority to US Provisional Application No. 63/087,781 filed 10/05/2020 and US Provisional Application No. 63/038,810 filed 6/03/2020.
The Filing Receipt is controlling with regard to an application’s priority claim and date (MPEP 503). Should Applicant wish to claim priority back to 6/03/2020, Applicant must request a corrected filing receipt (MPEP 211.02(a)). The Examiner is unable to assist with the request/correction of the filing receipt. Applicant should contact the Office of Patent Application Processing (OPAP) for further assistance.
Currently, the pending application has priority to US Application No. 18/079,749, filed 12/12/2022.
FILING RECEIPT
MPEP 503:
OPAP mails a filing receipt to the attorney or agent, if any, otherwise to the applicant, at the correspondence address of record for each application filed which meets the minimum requirements to receive a filing date. The filing receipt includes the application number, filing date, a confirmation number, and, if available, the number of an art unit where the application is likely to be examined. The filing receipt also includes other information about the application as applicable, such as continuing data, national stage data, foreign priority data, foreign filing license data, entity status information, and the date the Office anticipates publishing the application under 35 U.S.C. 122(b). The filing receipt represents the official assignment by the USPTO of a specific application number and confirmation number to a particular application. See 37 CFR 1.54(b). The application number officially assigned to an application on the filing receipt may differ from the application number identified on a postcard receipt submitted with such application, and, as between inconsistent filing receipts and postcard receipts, the application number on the filing receipt is controlling.
Applicants are encouraged to check their filing receipts for accuracy with particular attention to the inventor’s and applicant’s names, benefit and priority claims, and whether or not a nonpublication request, if submitted, was recognized.
MPEP 211.02(a) Correcting or Adding a Benefit Claim After Filing
I. CORRECTED FILING RECEIPT
If applicant receives a filing receipt with missing or incorrect benefit claim information, applicant may request a corrected filing receipt. The Office will not grant a request for a corrected filing receipt to include a benefit claim unless the proper reference to the prior application is included (i) in an ADS (for applications filed on or after September 16, 2012) or (ii) in the first sentence(s) of the specification or an ADS (for applications filed prior to September 16, 2012) within the time period required by 37 CFR 1.78 with a few exceptions. See MPEP § 211.03. If the proper reference was previously submitted in an application filed on or after September 16, 2012, the request for a corrected filing receipt should indicate that the reference was properly and timely made in the ADS. If the proper reference was previously submitted in an application filed prior to September 16, 2012, the request for a corrected filing receipt should indicate that the reference was properly and timely made and where such reference is located (i.e., the specification, an amendment to the specification, or an ADS). The Office may notify applicants on or with the filing receipt that a benefit claim may not have been recognized because the benefit claim was improper but applicants are advised that only the benefit claims that are listed on the filing receipt have been recognized by the Office. Therefore, applicants should carefully and promptly review their filing receipts in order to avoid the need for a petition (37 CFR 1.78 ) and the petition fee.
CLAIMS
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Independent claim 1 is broadly drawn to a composition comprising a plasmid encoding a BMI1 protein formulated with a carrier suitable for use in the eye, and independent claim 13 is broadly drawn to a method of intraocular administration of a nucleic acid encoding a BMI1 protein to treat a retinopathy.
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Paragraph [0191] of the published specification discloses pharmaceutically acceptable carriers “suitable for administration to the eye”:
In one embodiment, the recombinant AAV (rAAV) containing the desired transgene and cell-specific promoter for use in the target ocular cells as detailed above is optionally assessed for contamination by conventional methods and then formulated into a pharmaceutical composition intended for subretinal or intravitreal injection. Such formulation involves the use of a pharmaceutically and/or physiologically acceptable vehicle or carrier, particularly one suitable for administration to the eye, e.g., by subretinal injection, such as buffered saline or other buffers, e.g., HEPES, to maintain pH at appropriate physiological levels, and, optionally, other medicinal agents, pharmaceutical agents, stabilizing agents, buffers, carriers, adjuvants, diluents, etc. For injection, the carrier will typically be a liquid. Exemplary physiologically acceptable carriers include sterile, pyrogen-free water and sterile, pyrogen-free, phosphate buffered saline. A variety of such known carriers are provided in U.S. Pat. Publication No. 7,629,322, incorporated herein by reference. In one embodiment, the carrier is an isotonic sodium chloride solution. In another embodiment, the carrier is balanced salt solution. In one embodiment, the carrier includes tween. Emphasis added.
Claim Objections
Claims 10, 11, 12, and 16-20 are objected to because of the following informalities:
Claim 10 recites “scape loading” instead of “scrape loading” in line 2.
Claim 11 is objected to for the use of periods “.” within the body of the claim. While there is no set statutory form for claims, the present Office practice is to insist that each claim begin with a capital letter and end with a period. Periods may not be used elsewhere in the claims except for abbreviations. See Fressola v. Manbeck, 36 USPQ2d 1211 (D.D.C. 1995). See M.P.E.P. § 608.01(m).
Claim 12 should be amended to recite, “wherein the acceptable carrier is selected from the group consisting of pyrogen-free water…. [[or]] and sterile, pyrogen-free[[,]] phosphate buffered saline.”
Claim 16 should be amended to recite “the therapeutically effective amount of the [[a]] pharmaceutical composition…”
Claim 17 should be amended to recite “administered to the [[a]] patient” in line 1.
Claim 18 should be amended to recite “administered to the [[a]] patient” in line 1.
Claim 19 should be amended to recite “a bird, a cow,
Claim 20 should be amended to recite “wherein the pharmaceutical composition [[is]] further comprises a polymersome, a polyplex, a dendrimer, an inorganic nanoparticle, a polynucleotide-liposome complex or a cell-penetrating peptide” or similar language.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites the limitation "the eye” in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim 3 recites the limitation "the DNA or RNA” plasmid in line 1. There is insufficient antecedent basis for this limitation in the claim.
Claim 3, drawn to a composition, requires wherein the plasmid “is purified from about 80% to 90% pure” which is confusing. It is unclear whether the claim requires a step of purification, or if the claim is defining the purity of the plasmid?
If the claim is requiring wherein the plasmid is actively purified in the claim, the presence of an active step within a composition claim creates indefiniteness. A single claim which claims both an apparatus and the method steps of using the apparatus is indefinite under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph. See In re Katz Interactive Call Processing Patent Litigation, 639 F.3d 1303, 1318, 97 USPQ2d 1737, 1748-49 (Fed. Cir. 2011). The presence of a method step within a composition claim creates confusion as to whether infringement occurs when one creates the composition or whether infringement occurs when the one actually uses the composition. See MPEP 2173.05 (p).
If the claim is attempting to define the purity of the plasmid, is the purity with regard to the plasmid within the carrier? Similar to the percentage of the plasmid in the carrier (i.e., wherein the composition comprises 80-90% plasmid and 20-10% carrier)? Or is the purity relating to a previous source of the plasmid prior to the addition to the carrier?
Claim 4 is directed to “A method of transfecting a cell in the eye with the pharmaceutical composition of claim 2, wherein following transfection, the transfected cell expresses a BMI1 protein.” The claim is confusing for several reasons. Initially, the “method” claim comprises no active step. Attempts to claim a process without setting forth any steps involved in the process generally raises an issue of indefiniteness under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph. MPEP 2173.05(q). The Examiner notes that 2173.05(q) relates to “use” claims. The Examiner is not alleging the claim recites “use” verbatim. Rather, the rejection is based on a similar fact pattern where indefiniteness arises because there are no active steps delimiting how the process is practiced. Although a claim should be interpreted in light of the specification disclosure, it is generally considered improper to read limitations contained in the specification into the claims. See In re Prater, 415 F.2d 1393, 162 USPQ 541 (CCPA 1969) and In re Winkhaus, 527 F.2d 637, 188 USPQ 129 (CCPA 1975), which discuss the premise that one cannot rely on the specification to impart limitations to the claim that are not recited in the claim.
In addition, it is noted that the recitation of “the eye” in line 1 of claim 4 lacks proper antecedent basis. While claim 1 recites a pharmaceutical composition comprising a plasmid and pharmaceutically acceptable carrier suitable for use in “the eye”, claim 1 does not actually require an eye. Thus, there is no physical eye in claims 4, 2 or 1 in which “the eye” can refer back to.
Line 2 of claim 4, requires wherein following transfection, the transfected cell expresses “a BMI1 protein” which is unclear. Is the “a BMI1 protein” expressed really “the BMI1 protein” that is encoded on the plasmid of claim 1? Or is the “a BMI1 protein” a different BMI1 protein, such as an endogenous BMI1 protein upregulated in response to expressing the BMI1 protein encoded on the plasmid?
Claim 6, which is drawn to a method of transfecting a cell in an eye with the pharmaceutical composition comprising a plasmid encoding a BMI1 protein and a carrier (dependent upon claims 4, 2 and 1) recites “wherein the DNA or RNA plasmid is purified to at least about 90% pure, at least about 95% pure, at least about 98% or at least about 99% pure” which is unclear.
It is unclear how or what active steps are encompassed by the recited “is purified” within the confines and structures recited in the claim. If the claim is attempting to define the purity of the plasmid, is the purity with regard to the plasmid within the carrier? Similar to the percentage of the plasmid in the carrier (i.e., wherein the composition comprises 80-90% plasmid and 20-10% carrier)? Or is the purity relating to a previous source of the plasmid prior to the addition to the carrier?
Claim 8 requires wherein “the DNA or RNA plasmid is episomally expressed” which is confusing. Is plasmid itself being expressed? Or is the gene encoding the BMI protein being expressed? Is the claim drawn to wherein the DNA or RNA plasmid is an episomal plasmid? Or is the gene encoding the BMI protein episomally expressed from the plasmid?
Claim 11 recites the limitation "the chemical complex” in line 1. There is insufficient antecedent basis for this limitation in the claim.
Claim 11 recites “wherein the chemical complex comprises the steps of: a. calcium or strontinium co-precipitation; b. complexation with lipid; and c. complexation with ligand” which is confusing, even if the claim was dependent upon claim 9. Claim 9 which requires wherein the plasmid is transfected into the cell through…cellular uptake as a chemical complex.” Thus, claim 9 merely requires the plasmid is transfected via “cellular uptake as a chemical complex” thus the “a chemical complex” is referring to a composition. Is claim 11 attempting to provide the steps required in forming the chemical complex? Forming the chemical complex with the plasmid? Where in claim 11 is the plasmid? Or is “the chemical complex” of claim 11 attempting to use complex as a verb? A skilled artisan would not know the metes and bounds of the claimed invention.
Claim 12 is directed to embodiments which define the pharmaceutically acceptable carrier of the composition, and recites one acceptable carrier as “tween” or “Tween 20.” “Tween” is a trademark, and the claim is using the trademark to identify a particular material or product, and thus renders the claim indefinite.
MPEP 2173.05(u):
The presence of a trademark or trade name in a claim is not, per se, improper under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph, but the claim should be carefully analyzed to determine how the mark or name is used in the claim. It is important to recognize that a trademark or trade name is used to identify a source of goods, and is not the name of the goods themselves. Thus a trademark or trade name does not define or describe the goods associated with the trademark or trade name. See definitions of trademark and trade name in MPEP § 608.01(v).
If the trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of the 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph. Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). See also Eli Lilly & Co. v. Apotex, Inc., 837 Fed. Appx. 780, 784-85, 2020 USPQ2d 11531 (Fed. Cir. 2020) …. The claim scope is uncertain since the trademark or trade name cannot be used properly to describe any particular material or product. In fact, the value of a trademark would be lost to the extent that it became the generic name of a product, rather than used as an identification of a source or origin of a product. Thus, the use of a trademark or trade name in a claim to describe a material or product would not only render a claim indefinite, but would also constitute an improper use of the trademark or trade name. If the applicant responds to such a rejection by replacing the trademark or trade name with a generic term, the examiner should determine whether there is sufficient support in the application for use of a generic term. See MPEP § 2163, subsection II.A.3(b).
Claims 14, 15, 16, 17, 18 and 19 are all directed to “The method of claim 12.” However, claim 12 is drawn to a composition (Claim 12: “The composition of claim 1, wherein the acceptable carrier is….”). Thus the recitation of “The method of claim 12” in line 1 in each of claims 14-19 lacks proper antecedent basis in the claims.
The Examiner assumes that claims 14-19 were meant to be dependent upon method claim 13. Thus, the Examiner will interpret claims 14-19 as being dependent upon method claim 13 in order to advance prosecution.
To the extent that claims 14-19 depend upon claim 13:
Claim 16 recites “the therapeutically effective amount” in line 1. There is insufficient antecedent basis for this limitation in the claim.
Claim 17 requires wherein the composition is administered to a patient suffering from “a retinopathy or a glaucoma” once daily .… once every few days or once weekly.”
Initially, the recitation of administering the composition “once every few days” in claim 17 is a relative term which renders the claim indefinite. The term “every few days” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
In addition, claim 13 (upon which claim 17 should depend) is directed to a method….to treat a retinopathy in a patient.” And claim 14 presents glaucoma as a type of retinopathy. Thus, it is unclear how to differentiate “a glaucoma” from the broader encompassing “a retinopathy” in claim 17. MPEP 2173.05(c).
Claim 18 is similarly rejected for requiring administration to a patient suffering from “a retinopathy or a glaucoma” in line 2.
Claims 2, 5, 7, 9-10, 13 and 20 are included in the rejection because they depend from a rejected claim.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-2, 12 and 20 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by US Patent Application Publication No. 2005/0130302 to Nakauchi.
With regard to claim 1, Nakauchi discloses pharmaceutical compositions comprising gene therapy vectors encoding nucleic acids encoding BMI-1 peptides for the treatment of a disease or disorder (paragraphs [0023], [0028], [0041], [0045]-[0046], [0048], [0116], [0164], [0216]-[0217], [0271], [0274], [0293]-[0298]). Nakauchi discloses a vector encoding the BMI-1 peptides includes recombinant DNA plasmids (paragraphs [0217]-[0218]). Nakauchi discloses the disease or disorders that can be treated with the BMI-1 encoding nucleotides include retinal degeneration (paragraph [0283]). Nakauchi discloses the pharmaceutical compositions comprising nucleic acids encoding BMI-1 further comprising pharmaceutically acceptable carriers (paragraphs [0310]-[0336]). The pharmaceutically acceptable carriers disclosed in Nakauchi read on a “pharmaceutically acceptable carrier for the eye” absent evidence to the contrary.
Thus, Nakauchi anticipates claim 1.
With regard to claim 2, Nakauchi discloses the vector includes a recombinant DNA plasmid (paragraphs [0217]-[0218]).
With regard to claims 12 and 20, Nakauchi discloses the pharmaceutically acceptable carriers include buffered saline ([0313]), tween (paragraph [0312]), sterile water (paragraph [0334]), hydrophilic polymers, polyethylene glycol, cellulose, liposomes, and microparticles (paragraphs [0312], [0327]-[0329], [0338]).
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 4-11 and 13-19 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of treating a retinopathy in a patient suffering from macular degeneration, the method comprising; administering to the patient by intravitreal, subretinal, suprachoroidal and/or sub-internal limiting membrane injection an effective amount of an adeno-associated virus (AAV) encoding a heterologous BMI1 protein into an eye of the patient, wherein the AAV is selected from one of serotypes 2, 5, 7, 8, 9 or rhl0, wherein said administration results in transduction of a retinal pigment epithelium (RPE) cell by the AAV encoding the heterologous BMI1 protein, and wherein said transduction results in expression of the therapeutically effective amount of the heterologous BMI1 protein in the transduced RPE cell; and wherein the expression of the heterologous BMI1 protein in the RPE cell results in a reduction in macular degeneration in the patient suffering from macular degeneration, does not reasonably provide enablement for “A method of transfecting a cell in the eye with the pharmaceutical composition of claim 2, wherein following transfection, the transfected cell expresses a BMI1 protein” according to claim 4 or “A method of treatment, comprising administering a DNA or RNA plasmid that encodes a BMI1 protein, and a pharmaceutically acceptable carrier by intraocular injection into the eye to treat a retinopathy in a patient” according to claim 13. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims. The factors to be considered in determining whether undue experimentation is required are summarized in In re Wands, 858 F.2d 731, 737, 8 U.S.P.Q.2d 1400, 1404 (Fed. Cir. 1988) (a) the breadth of the claims; (b) the nature of the invention; (c) the state of the prior art; (d) the level of one of ordinary skill; (e) the level of predictability in the art; (f) the amount of direction provided by the inventor; (g) the existence of working examples; and (h) the quantity of experimentation needed to make or use the invention based on the content of the disclosure. While all of these factors are considered, a sufficient number are discussed below so as to create a prima facie case.
the breadth of the claims; the nature of the invention
The claims encompass broad methods of delivering a plasmid encoding BMI1 to an eye such that 1) BMI1 is expressed (claim 4) or 2) by intraocular injection into the eye to treat a retinopathy in a patient (claim 13). Claim 4 provides no specific methodology, and claim 13 does not require the injected plasmid express the BMI protein, although the methodology treats a retinopathy. The claims do not require any specific plasmid, any specific promoters/enhancers, any specific methodology of administration (for claim 4) other than “intraocular injection” for claim 13.
The claims encompass methods of delivering plasmid DNA or RNA in vivo (to the eye) sufficiently to express BMI1 in the eye. Thus, the claims as written are broad.
the amount of direction provided by the inventor; the existence of working examples
The instant specification provides generic information regarding DNA or RNA delivery via transfection to “cells,” including physical administration, or cellular uptake as a chemical complex (calcium phosphate DNA co-precipitation, strontium phosphate DNA co-precipitation), microinjection, electroporation, scrape loading, and microparticle bombardment (paragraphs [0169]-[0170]). However, these sections of non-viral delivery to “cells” are not directed to the delivery of plasmids encoding BMI1 to an eye, in vivo, as required by the claims.
The working examples directed to in vivo methods (prophetic or on animal models) use AAV vectors. The working examples that are in vitro utilize cell lines (and are thus not “transfecting a cell in the eye”) also utilize AAV vectors. Thus, there is no disclosure in the specification or working examples as how to successfully practice the claimed invention.
the art is unpredictable
Non-viral gene delivery to the eyes at the time of the invention was unpredictable. Amato states, “Though some preclinical gene therapy studies have successfully used non-viral DNA systems, these agents are hard to export to an in vivo clinical setting, mainly because of transiency of gene expression, ultimately resulting in a relatively inefficient delivery” (internal citations omitted. page 3, in Amato Gene Therapy in Inherited Retinal Diseases: An Update on Current State of the Art. Frontiers in Medicine, 2021. 8: :750586.doi: 10.3389/fmed.2021.750586). and Bordet states, “Although transduction of retinal cells and some therapeutic benefits have been demonstrated in animal models, DNA nanoparticles (NPs) have not yet been evaluated in ocular gene therapy clinical trials, mainly because of low and/or short term transduction” (page 1688, Bordet et al. Ocular gene therapies in clinical practice: viral vectors and nonviral alternatives. Drug Discovery Today, 2019. 24(8). 1685-1693).
Koirala teaches that ocular gene therapy most often uses viral delivery because “non-viral alternatives have been plagued by low transfection efficiency, short-term expression and low expression levels” (Abstract, Koirala et al. A Review of Therapeutic Prospects of Non-viral Gene Therapy In the Retinal Pigment Epithelium. Biomaterials, 2013. 34:7158-7167). Koirala acknowledges that there have been advancements in non-viral delivery to the eye, and their potential use is promising but still has challenges. “Topical and intravitreal delivery of liposomes to the eye has been tried, however these delivery methods have yielded very low transfection efficiency for the retina and RPE” and “but liposome-mediated gene delivery is not currently a highly active area for RPE therapeutic research” (page 7160).
Discussing polymer delivery carriers, Koirala acknowledges data from in vivo use is lacking, inefficient and toxic. “PEI-based gene delivery has been tested in the eye. In common with other delivery vectors, intravitreal delivery was not very successful, however, results from topical treatment (for example for corneal conditions) has been more positive. Its ability to transfect RPE cells has been mostly studied in vitro, and the ability of these polymers to generate panretinal transfection and rescue of RPE disease models has not been established” (internal citations omitted, page 7160).
“Chitosan-based gene delivery has been tested in several animal models of genetic diseases. It has been shown to transfect the cornea, retina, lungs and other cells and tissues as well, although therapeutic rescue after ocular delivery has yet to be demonstrated. Chitosan particles have been tested for RPE transfection in vitro, and studies demonstrated efficient transfection, biocompatibility, and cell viability after treatment portending positive outcomes in future in vivo studies if toxicity issues can be resolved” (internal citations omitted, page 7160).
Koirala also acknowledges naked DNA transfection into the eye is inefficient and results in low gene expression. “[I]n general, delivery of DNA without compaction or another physical method (such as electroporation) is unlikely to be a clinically viable gene transfer method, even in the RPE” (Page 7161).
Koirala also discloses local delivery to the eye, such as topical delivery has low efficiency, and using electroporation is nascent and can cause injury (page 7164). “Electroporation increases the permeability of the plasma membrane by an externally applied electrical field to allow nucleic acids to enter the cell. Though this is a routine process for transforming bacterial cells, yeast cells and human cells in vitro, its use in live animals requires a great deal of caution. In the eye, recent advancements in electrotransfer have allowed transfection of the retina and the RPE by supra-choroidal electrotransfer without detaching the retina. If this approach is mechanically feasible in larger animals such as non-human primates and humans without causing retinal tear or injuries to the eye, this may be a significant upgrade compared to subretinal injections for ocular gene transfer” (internal citations omitted, page 7164).
Thus, at the time of the invention, non-viral delivery of DNA encoding genes to an eye, wherein delivery would predictably result in transgene expression, let alone therapeutically effective transgene expression, would not have been considered predictable.
The quantity of experimentation needed to make or use the invention based on the disclosure
The instant disclosure makes no advancements on non-viral gene delivery to the eye, nor reduces the methods to practice. A skilled artisan would require an undue amount of experimentation in order to practice the claimed invention, based on the instant disclosure.
Conclusion
Given the sparse nature with regard to the full scope of the instant claims, and the unpredictability in the art, one of skill in the art would not conclude that the specification was enabled for the full scope of the pending claims. Claims 5-11 and 14-19 are included in the rejection because they do not aid in overcoming the scope of the pending claims.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KIMBERLY A ARON whose telephone number is (571)272-2789. The examiner can normally be reached Monday-Friday 9AM-5PM.
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KAA
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633
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