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 .
Applicant’s amendments to the claims dated 10/24/22 are acknowledged. Claims 1-19 are pending. Claims 1, 3-10, 12-13, and 16 are modified. Claim 19 is new. Prosecution on the merits commences for claims 1-19.
PRIORITY
The instant application, filed 10/24/2022, is a 371 National Stage Application of PCT/EP2021/060647, filed 04/23/2021, which claims priority to EP20305407.7, filed 04/27/2020 and EP20315217.8, filed 04/24/2020. Certified copies of EP20305407.7 and EP20315217.8 have been filed in the instant application. Thus, the earliest possible priority for the instant application is 04/24/2020.
Specification - Abstract
The abstract of the disclosure is objected to because it contains a typographical error. The abstract recites “immunodulation” instead of “immunomodulation” at line 8 A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Specification
The disclosure is objected to because of the following informalities:
The Section labeled “FIGURES:” on page 26 of the specification filed 10/24/2022 should be relabeled “BRIEF DESCRIPTION OF THE FIGURES” or similar (MPEP 608.01(f)).
The Brief Description of the Figures section on pages 26-27 is objected to because the brief description does not reference the multiple figure views of the figure of record and/or does not label the multiple views properly. If a Figure 1 has views 1A, 1B and 1C, then the Brief Description of the Figures must reference each view; AND each view must be labeled with “FIG.” in front of the specific view (MPEP 608.01(f), 37 CFR 1.84(u)(1)). Thus, the Brief Description of the Figures on page 26, at lines 9-20 must be amended to insert “FIG. 1A”, “FIG. 1B” and “FIG. 1C” as appropriate. The Brief Description of the Figures on page 27, at lines 1-10 must be amended to insert “FIG. 3A”, and “FIG. 3B” as appropriate.
Line 18 on page 9 of the specification filed 10/24/2022 has typographical errors. The line recites “(AAV-7), and AAV type 8 (AAV-8).) and AAV type 9 (AAV9).” Thus, there is an extraneous “and” in front of “AAV type 8” as well as an extraneous “.)”. Deletion to recite “(AAV-7), .
Appropriate correction is required.
Nucleotide and/or Amino Acid Sequence Disclosures
The application is objected because the specification filed 10/24/2022 at page 28, lines 20-23, discloses amino acid sequences that are required to be included in a separate Sequence Listing. All sequences longer than 10 unbranched nucleotides or four unbranched amino acid sequences referenced in the specification must include a SEQ ID NO and must be included in a Sequence Listing (see, 37 CFR §§ 1.821 through 1.825; MPEP 2421.01-2421.02).
However, the disclosed sequences are not associated with a sequence identifier and are not included in a Sequence Listing. There is no Sequence Listing and no Computer Readable Form (CRF) of the Sequence Listing in the present application.
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
1) Specific deficiency – Nucleotide and/or amino acid sequences appearing in the specification are not identified by sequence identifiers in accordance with 37 CFR 1.821(d).
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
2) Specific deficiency - This application fails to comply with the requirements of 37 CFR 1.821 - 1.825 because it does not contain a "Sequence Listing" as a separate part of the disclosure or a CRF of the “Sequence Listing.”.
Required response - Applicant must provide:
A "Sequence Listing" part of the disclosure; together with
An amendment specifically directing its entry into the application in accordance with 37 CFR 1.825(a)(2);
A statement that the "Sequence Listing" includes no new matter as required by 37 CFR 1.821(a)(4); and
A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(a)(3).
If the "Sequence Listing" part of the disclosure is submitted according to item 1) a) or b) above, Applicant must also provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
If the "Sequence Listing" part of the disclosure is submitted according to item 1) c) or d) above, applicant must also provide:
A CRF in accordance with 37 CFR 1.821(e)(1) or 1.821(e)(2) as required by 1.825(a)(5); and
A statement according to item 2) a) or b) above.
Drawings
The drawings are objected to because they are not in compliance with 37 CFR 1.84. 37 CFR 1.84(u)(1) requires a figure with multiple views (i.e. Figure 1 with views A, B and C), then each view must be labeled “FIG. 1A”, “FIG. 1B” and “FIG. 1C.” (37 CFR 1.84(u)(1)). Thus, Figures 1 and 3 are objected to and require revision.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. 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 to the drawings will not be held in abeyance.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 10/24/2022 has been considered by the examiner and an initialed copy of the IDS is included with the mailing of this office action.
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
CLAIMS
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Independent claims 1, 3 and 4 are broadly directed to methods of co-administering a gene therapy composition AND a peptide encoded by the gene therapy composition to a subject. The claims of 10/24/22 are presented below, showing insertions only. Claim 1 recites the peptides first, and then recites the gene therapy composition, whereas claims 3 and 4 recite the gene therapy composition (vector) first and then the peptides. Thus, the aligned claims show the portions relating to the peptides are in shaded cels, and the portions relating to the gene therapy composition are in bolded text.
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Claim 18 is directed to a pharmaceutical composition comprising (at least) a vector containing a transgene of interest and a peptide encoded by the transgene or the vector.
CLAIM INTERPRETATION
Claim 1 as written, requires
A) [preamble] the subject has previously received ocular gene therapy with a vector encoding “a transgene”; and
B) [active steps] administering
1) at least one peptide that derives from “a transgene product” or “the vector”; and
2) “gene therapy;” and
C) [functional result] results in the prevention of immune responses to the transduced cells expressing the transgene product.
The at least one peptide “that derives from a transgene product” administered in the active step is not required to be derived from the “vector containing a transgene” of the preamble; however, the at least one peptide “that derives from … the vector” in the active step is required to be derived from the vector of the preamble.
The published specification defines “derived” at paragraph [0020]:
As used herein, the term "derived from" refers to a process whereby a first component ( e.g., a first polypeptide), or information from that first component, is used to isolate, derive or make a different second component (e.g., a second polypeptide that is different from the first one).
The published specification defines “gene therapy” at paragraph [0018]:
As used herein, the term "gene therapy" refers to the introduction of a polynucleotide into a cell's genome that restores, corrects, or modifies the gene and/or expression of the gene. Thus the term "ocular gene therapy" refers to a gene therapy that is applied to the ocular sphere, in particular
for expressing a transgene product in a retinal cell.
Thus, the “gene therapy” administered in the active step of claim 1 does not require the vector encoding the transgene that was previously administered to the patient in the preamble. Thus, the “gene therapy” administered may comprise wholly different compositions, such as a different vector, or a different transgene.
The methods of claims 3 and 4, directed to “expressing a transgene of interest in the retina of a patient” and “treating a retinal disease in a patient in need thereof” respectively, do not recite any specific functional result within the body of the claim. The preambles serve to localize the expression of the transgene (claim 3) or define the patient population (claim 4). As such, prior art which meets the limitations of the preamble, and/or anticipate and/or render obvious the active steps of the claims would be relevant/read on the pending claims.
Claim Objections
Claims 1-2, 6, 10-15, and 17 are objected to because of the following informalities:
Claims 1 and 2 are objected to for syntax errors. Claim 1 recites “immune responses” in line 5, whereas claim 2 recites “the immune response is” in line 1. The syntax between the claims is incorrect. Applicant should amend claim 1 to “an immune response” OR amend claim 2 to “the immune responses comprise [[is]]”. Applicant need only amend claim 1 OR claim 2.
Claim 6 is objected to for reciting the same retinal disease in multiple locations in the claim. Claim 6 repeats:
“retinitis pigmentosa” at line 2 and then again at lines 6-7.
“ Leber’s congenital amaurosis” at line 3 and then again at line 5.
Claim 6 also recites, “age related macular degeneration, atrophic age related macular degeneration (AMD)” at lines 7-8. The abbreviation “(AMD)” should be moved to the first recitation of “age related macular degeneration” in the claim, unless Applicant intends for AMD to represent “atrophic age related macular degeneration.” Amendment to “age related macular degeneration (AMD), atrophic AMD
Claim 10 recites, “wherein the vector is an adenoviral vector (AVV)” which comprises typographical errors. The claim should be amended to recite “wherein the viral vector is an adeno-associated viral vector (AAV)
Claim 11 is missing a comma after “of claim 10” in line 1, and should be amended to recite “of claim 10, wherein”.
Claim 12 recites “wherein the peptide.” However, claim 1 recites “at least one peptide.” Applicant should amend claim 12 to reflect the verbiage used in earlier claims.
Claim 13 is missing a comma after “of claim 12” in line 1.
Claim 14 is missing a comma after “of claim 13” in line 1.
Claim 15 is missing a comma after “of claim 12” in line 1.
Claim 17 is missing a comma after “of claim 12” in line 1.
Appropriate correction is required.
Claim Rejections - 35 USC § 112 – new matter
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 5-6 and 19 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 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. This is a new matter rejection.
Claim 5 is directed to wherein the patient suffers from a retinal acquired disease that is macular degeneration or diabetic retinopathies.
Claim 6 is directed to wherein the patient suffers from an inherited retinal disease selected from the group consisting of retinitis pigmentosa, Leber's congenital amaurosis, X-linked retinoschisis, autosomal recessive severe early- onset retinal degeneration, congenital achromatopsia, Stargardt's disease, Best's disease, Doyne's disease, cone dystrophy, Usher's syndrome, age related macular degeneration (AMD), atrophic AMD, neovascular AMD, diabetic maculopathy, proliferative diabetic retinopathy (PDR), cystoid macular oedema, central serous retinopathy, retinal detachment, intra-ocular inflammation, glaucoma, posterior uveitis, choroideremia, and Leber hereditary optic neuropathy.
The claims are rejected because although there is support for all of these retinal diseases within the specification and priority documents, there does not appear to be support that all of the listed retinal diseases in the claims are necessarily “acquired” or “inherited” retinal diseases. Disclosures relating the retinal diseases that can be treated by the invention, and the status of the disease as acquired or inherited, are found at paragraphs [0015] and [0046]-[0048] of the published specification. Nearly Identical disclosures can be found in earliest priority document EP20315217.8, filed 04/24/2020.
[0015] As used herein the term "retinal disease" refers to a broad class of diseases wherein the functioning of the retina is affected for example due to a damage or degeneration of the photoreceptors; ganglia or optic nerve; or even neovascularization. One skilled in the art can distinguish inherited retinal diseases and acquired retinal diseases. Representative examples of retinal acquired diseases include but are not limited to macular degeneration such as age related macular degeneration, and diabetic retinopathies. Examples of inherited retinal diseases include but are not limited to retinitis pigmentosa, Leber's congenital Amaurosis, X-linked Retinoschisis. Thus non-limiting examples of retinal diseases include: autosomal recessive severe early-onset retinal degeneration (Leber's Congenital Amaurosis), congenital achromatopsia, Stargardt's disease, Best's disease, Doyne's disease, cone dystrophy, retinitis pigmentosa, X-linked retinoschisis, Usher's syndrome, age related macular degeneration, atrophic age related macular degeneration, neovascular AMD, diabetic maculopathy, proliferative diabetic retinopathy (PDR), cystoid macular oedema, central serous retinopathy, retinal detachment, intra-ocular inflammation, glaucoma, posterior uve1t1s, choroideremia, and Leber hereditary optic neuropathy.
[0047] For example, the method of the invention is performed in order to treat or prevent macular degeneration. Briefly, the leading cause of visual loss in the elderly is macular degeneration (MD), which has an increasingly important social and economic impact in the United States. As the size of the elderly population increases in this country, age related macular degeneration (AMD) will become a more prevalent cause of blindness than both diabetic retinopathy and glaucoma combined. Although laser treatment has been shown to reduce the risk of extensive macular scarring from the "wet" or neovascular form of the disease, there are currently no effective treatments for the vast majority of patients with MD.
[0048] The method of the invention may also be performed in order to treat or prevent an inherited retinal degeneration. One of the most common inherited retinal degenerations is retinitis pigmentosa (RP), which results in the degeneration of photoreceptor cells, and the RPE. Other inherited conditions include Bardet-Biedl syndrome (autosomal recessive); Bassen-Kornzweig syndrome, Best disease, choroidema, gyrate atrophy, Leber congenital amaurosis, Refsun syndrome, Stargardt disease; Cone or cone-rod dystrophy (autosomal dominant and X-linked forms); Congenital stationary night blindness (autosomal dominant, autosomal recessive and X-linked forms); Macular degeneration (autosomal dominant and autosomal recessive forms); Optic atrophy, autosomal dominant and X-linked forms); Retinitis pigmentosa (autosomal dominant, autosomal recessive and X-linked forms); Syndromic or systemic retinopathy (autosomal dominant, autosomal recessive and X-linked forms); and Usher syndrome (autosomal recessive).
Applicant should review the specification and priority documents, and delete any recited retinal disease in either claim 5 or claim 6 that is not clearly indicated as an acquired retinal disease or inherited retinal disease; or, provide page and line number for the support that the claimed retinal diseases have been disclosed as an “acquired” or “inherited” retinal diseases.
Any retinal disease that is not clearly identified as an acquired or inherited retinal disease could be encompassed in a new dependent claim directed to patients suffering from “a retinal disease” selected from the group consisting of… – wherein the status of acquired or inherited is not claimed.
Claim 19 is included in the rejection because it depends from rejected claim 5.
Claim Rejections - 35 USC § 112 - indefinite
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 1-19 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. With regard to claim 1, the claim recites,
“A method for preventing a secondary vision loss in a patient who received an ocular gene therapy with a vector containing a transgene comprising
administering to the patient
a therapeutically effective dose of at least one peptide that derives from a transgene product or the vector,
simultaneously with gene therapy,
thereby preventing induction of immune responses to the transduced cells expressing the transgene product.”
On a high level, claim 1 encompasses a method of co-administering peptides and nucleic acids to a patient who has already had gene therapy with a vector containing a transgene. However, the minimal structural requirements of the claim are not defined and their relationships to each other are not defined which results in indefiniteness of the claim. For example:
Presumably the vector encoding a transgene recited in the preamble continues to express a transgene product in vivo before the administration step of the claim, although this limitation is not positively recited.
In the administration step, one of two populations of peptides are administered (for the sake of argument, “Peptide A” encompasses peptides derived from “a transgene product” and “Peptide B” encompasses peptides derived from “the vector.”
Presumably the “gene therapy” composition administered to the patient in the active step of the claim also comprises at least a transgene -- although not positively recited-- in light of the specification’s disclosure relating to “gene therapy” at paragraph [0018] (see Claim Interpretation Section above). Thus, is it assumed the “gene therapy” composition comprising a presumable transgene would therefore express a transgene product in a transduced cell.
As a result of the administration step, it is assumed the administered peptides (“Peptide A” or “Peptide B” noted above) would be located systemically/extracellularly, and the “gene therapy” composition would transform a cell (presumably in cells already comprising the “a vector encoding a transgene” of the preamble, and express a transgene product, although these results are not positively recited.
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A non-limiting visualization of the minimal structural requirements of the claimed method can be visualized below:
The claim is indefinite because:
1) It is not clear how the administered “at least one peptide that derives from a transgene product or the vector” relates to the vector previously administered “a vector containing a transgene recited in the preamble.”
Is the “a peptide that derives from a transgene product” derived from the same transgene encoded on the vector? So, if the vector comprises a transgene encoding peptide “X”, is the “a transgene product” administered to the patient peptide X (or variant thereof)? Is “Peptide A” supposed to be “Peptide X” that is encoded on the vector?
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Or, is the “a peptide that derives from a transgene product” derived from a different transgene? If the vector comprises a transgene encoding peptide “X”, is the “a transgene product” administered to the patient a wholly different peptide, such as a “Peptide Y”? Is “Peptide A” supposed to be “Peptide Y”?
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2) It is not clear how the administered peptides derived from “the vector” relate to the vector of the preamble. The “a vector encoding a transgene” of the preamble necessarily encodes “a transgene.” Thus, do the administered peptides derived from “the vector” exclude a peptide encoded by the transgene of the vector? In which case, Peptide B cannot be Peptide X?
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Or, do the administered peptides derived from “the vector” include a peptide encoded by the transgene of the vector? In which case, Peptide B can be Peptide X?
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, the claim recites the broad recitation a peptide that derives from the vector, wherein the vector comprises a transgene, and the claim also recites a peptide that derives from a transgene, which encompasses the transgene of the vector, and is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
3) It is not clear how the administered “gene therapy” relates to the vector previously administered “a vector containing a transgene recited in the preamble. If the transgene encoded on the vector of the preamble encodes transgene X, does the “gene therapy” composition, presumably encoding a transgene, encode the same transgene X of the “vector encoding a transgene” of the preamble (or variant thereof)? In such a case, a transduced cell will express a transgene product Peptide X from the
vector of the preamble as well as a transgene product Peptide X from the gene therapy composition.
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Or, if the transgene encoded on the vector of the preamble encodes a Transgene X, does the “gene therapy” composition, presumably encoding a transgene, encode a different transgene (a Transgene Z)? In such a case, a cell transduced with both the vector encoding a Transgene X of the preamble and the gene therapy composition encoding a Transgene Z, will express a transgene product Peptide X and a transgene product Peptide Z.
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4) It is also not clear how the administered “at least one peptide that derives from a transgene product or the vector” relates to the administered “gene therapy” composition? As noted above, the “gene therapy” composition, presumably encodes a transgene. Does the gene therapy composition comprise a transgene A or a transgene B that encodes the Peptide A or Peptide B administered? If so, in such a case, a patient who is administered Peptide A, will have a cell transduced with the gene therapy composition encoding transgene A, and will produce Peptide A.
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And, a patient who is administered Peptide B, will have a cell transduced with the gene therapy composition encoding transgene B.
Or, does the gene therapy composition comprise a transgene that does not encode a peptide that is administered in the method? Thus, if Peptide A or Peptide B are administered the gene therapy composition encodes a transgene W, and will produce Peptide W, wherein transgene W does not encode either Peptide A or Peptide B.
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The analysis of pending claim 1 is assuming the “gene therapy” composition comprising a transgene transduces the same cells as previously transduced with the “a vector containing a transgene” of the preamble. However, the methodology also reasonably includes wherein the “gene therapy” composition comprising a transgene transduces cells that have not previously been transduced with the “a vector containing a transgene” of the preamble, and represent a distinct population of transduced cells.
As such, claim 1 encompasses embodiments wherein there may be one transduced cell expressing one transgene product, one transduced cell expressing two different transgene products, two different transduced cells expressing the same transgene product, or two different transduced cells expressing two different transgene products. In light of the ambiguity of the claim and the lack of structural relationships between the claimed “a vector encoding a transgene”, the “at least one peptide that derives from a transgene product or the vector”, and the “gene therapy” composition, and “the transduced cell” a skilled artisan would not know the metes and bounds of the claimed invention.
Also, because the methodology encompasses embodiments wherein there may be one transduced cell expressing one transgene product, one transduced cell expressing two different transgene products, or two different transduced cells expressing the same transgene product, or two different transduced cells expressing two different transgene products, the functional limitation of thereby preventing induction of immune responses to “the transduced cells expressing the transgene product” is indefinite. It is not clear which population of transduced cells and what transgene product is being referred to. This is an antecedent basis rejection. MPEP 2173.05(e).
Claim 3 is directed to a method for expressing a transgene of interest in the retina of a patient comprising injecting into a subretinal space of the patient a therapeutically effective amount of a vector containing a transgene of interest in combination with a therapeutically effective amount of at least one peptide that derives from a product of the transgene or the vector.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, the claim recites the broad recitation a peptide that derives from the vector, wherein the vector comprises a transgene, and the claim also recites a peptide that derives from the transgene encoded on the vector, and is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 4 is directed to A method of treating a retinal disease in a patient in need thereof, comprising injecting into the subretinal space of the patient an amount of a vector containing a transgene of interest in combination with a therapeutically effective amount of at least one peptide that derives from a product of the transgene or the vector.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, the claim recites the broad recitation a peptide that derives from the vector, wherein the vector comprises a transgene, and the claim also recites a peptide that derives from the transgene encoded on the vector, and is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 7, dependent upon claim 1, recites, “wherein the transgene product” is a polypeptide that enhances the function of a retinal cell. Because claim 1 is indefinite with respect to “the transgene product,” the recitation of “the transgene product” in this claim also lacks proper antecedent basis, and is indefinite for the same reasons – as it is unclear which transduced cells and what transgene product is being referred back to.
Claim 8, dependent upon claim 1, recites, “wherein the transgene product” is a polypeptide that an endonuclease that provides site-specific knock-down of gene function. Because claim 1 is indefinite with respect to “the transgene product,” the recitation of “the transgene product” in this claim also lacks proper antecedent basis, and is indefinite for the same reasons – as it is unclear which transduced cells and what transgene product is being referred back to.
Claim 12, dependent upon claim 1, requires the one or more peptides is an immunodominant peptide “that derives from the transgene product” or the vector. Because claim 1 is indefinite with respect to “the transgene product,” the recitation of “the transgene product” in this claim also lacks proper antecedent basis, and is indefinite for the same reasons – as it is unclear which transduced cells and what transgene product is being referred back to.
Claim 15, dependent upon claim 12, requires the at least one peptide is an immunodominant peptide “that derives from the transgene product”. Because claim 12 is dependent upon claim 1, and claim 1 is indefinite with respect to “the transgene product,” the recitation of “the transgene product” in this claim also lacks proper antecedent basis, and is indefinite for the same reasons – as it is unclear which transduced cells and what transgene product is being referred back to.
Claim 16 requires “wherein the vector is injected in the subretinal space simultaneously with 2-6, or 8-10 immunodominant peptides” is indefinite. Claim 1 refers to “a vector” only with regard to “a patient who received an ocular gene therapy with a vector containing a transgene” in the preamble. Thus, it is not clear whether this claim is attempting to further define the methodology that was used in the ocular gene therapy of the preamble? Or if this is attempting to define the active step of claim 1, relating to administering “at least one peptide” simultaneously with the “gene therapy” composition and “one or more peptides”?
Claim 17, requires wherein the method of claim 12 wherein the vector is injected with at least one immunodominant peptide comprising a MHC-class I restricted epitope and/or at least one immunodominant peptide comprising a MHC-class II restricted epitope, which is indefinite. Both claim 12, which is dependent upon claim 1, and claim 1, refer to “a vector” only with regard to “a patient who received an ocular gene therapy with a vector containing a transgene” in the preamble. Thus, it is not clear whether this claim is attempting to further define the methodology that was used in the ocular gene therapy of the preamble? Or if this is attempting to define the active step of claim 1, relating to administering “at least one peptide” simultaneously with the “gene therapy” composition and “one or more peptides”?
Claim 18 recites, at least, a pharmaceutical composition comprising “a vector containing the transgene of interest, at least one peptide that derives from the transgene product or vector” which is indefinite.
The recitation of “the transgene of interest” in lines 1-2 lacks proper antecedent basis in the claim (MPEP 2173.05(e)).
The recitation of “the transgene product” in line 2 lacks proper antecedent basis in the claim (MPEP 2173.05(e)).
In addition, the claimed vector necessarily comprises a transgene, and as such “at least one peptide that derives from the transgene product or vector” is indefinite because it is not clear whether a peptide that derives from the vector includes a peptide from the transgene encoded on the vector, i.e. the transgene product? A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim recites the broad recitation a peptide that derives from the vector comprising a transgene, and the claim also recites a peptide that derives from a transgene, which encompasses the transgene of the vector, and is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claims 2, 5-6, 9-11, 13-14, and 19 are included in the rejection because they depend from a rejected claim.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(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, 3-16, and 18-19 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by US Patent Application Publication No. 2019/0142975 to Keravala.
With regard to claims 1, 3, 4, and 18, Keravala discloses methods of ocular gene therapy comprising administering to the eye a vector encoding a therapeutic transgene, wherein the patient comprises neutralizing antibodies to the vector, and the vector is administered in a dosage sufficient to evade the neutralizing antibodies (Abstract, paragraphs [0004]-[0017], [0166]-[0167] examples). The vector includes both non-viral and viral vectors, such as AAV, wherein the patient comprises neutralizing antibodies to the proteins of the vector, including the AAV capsid (paragraphs [0077]-[0081]). The viral vector comprises a genome that encodes the capsid proteins that are targeted by the neutralizing antibodies. The vector encoding the therapeutic transgene is formulated as a pharmaceutical composition comprising a pharmaceutically acceptable carrier (paragraphs [0189]-[0192], [0211]-[0214]). Keravala discloses the vectors encoding therapeutic transgene are administered to the subretinal space in therapeutically effective doses to treat the disease (paragraphs [0015], [0165], [0064], [0223] Examples).
By administering the vectors encoding the therapeutic transgenes in dosages sufficient to evade the neutralizing antibodies in the patient, the methods prevent the neutralizing antibodies from inhibiting the therapeutic effect of the gene therapy (paragraphs [0064]-[0066], [0162]-[0167]). Thus, Keravala anticipates claims 1, 3, 4, and 18.
With regard to claims 5-6, and 19 Keravala discloses the patient suffers from age-related macular degeneration, diabetic retinopathy, Leber’s Congenital Amaurosis, and retinitis pigmentosis (paragraphs [0010], [0144], [0157]).
With regard to claims 7-8, Keravala discloses the transgene produced enhances the function of a retinal cell, or encodes an endonuclease to knock-down gene function (paragraphs [0141], [0145]-[0158]).
With regard to claims 9-11, Keravala discloses the vector is an AAV vector, including an AAV8 viral vector (paragraph [0134]—[0136], [0079]-[0080]).
With regard to claims 12-16, Keravala discloses the neutralizing antibodies “specifically bind” antigens on the AAV, which reads on wherein the bind the capsid proteins of the AAV, wherein the genome of the virus encodes transgenes, including transgenes encoding structural/capsid proteins from other viruses in VP1 (paragraphs [0004], [0025]-[0030], [0059], [0066], [0079]-[0137], [0163]-[0165], [0173]-[0174], [0202]). Keravala discloses the methodology includes administering assembled viruses in sufficient quantities to evade the immune system, wherein the patient already has neutralizing antibodies (paragraphs [0165], [0171]) or to a patient in a first dose, wherein the patient does not have neutralizing antibodies, and then a second dose, allowing for the ability to increase the dose following the generation of neutralizing antibodies to the virus, wherein the dosages range from 1 x1011 – 1 x 1015 vector genomes (paragraphs [0169], [0174], [0190], [0199]-[0203]). See also, paragraphs [0020]-[0021] and FIGs. 1-2).
Claims 1-19 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by US Patent Application Publication No. 2014/0336245 to Mingozzi.
With regard to claims 1, 3, 4, and 18, Mingozzi discloses methods of ocular gene therapy comprising administering to the eye a vector encoding a therapeutic transgene, with the concomitant administration of empty vectors capsids, administered in a dosage mitigate virus neutralization and avoid anti-AAV immune responses (Abstract, paragraphs [0003]-[0017], [0052]-[0054], [0087]). The empty AAV capsids are administered concomitantly as vectors encoding the transgene and act as a decoy, binding neutralization antibodies and/or preventing and/or inhibiting an immune response to the capsid (paragraphs [0010]-[0015], [0036]-[0081]). The vector encoding the therapeutic transgene and the empty capsids are formulated as a pharmaceutical composition comprising a pharmaceutically acceptable carrier (paragraphs [0015]-[0016], [0038], [0088]-[0091]). Mingozzi discloses the vectors encoding therapeutic transgene are administered ocularly, to transduce and be expressed in retinal cells, which reads on administration “to a subretinal space” in therapeutically effective doses to treat retinal disease (paragraphs [0052], [0093], [0054]). Thus, Mingozzi anticipates claims 1, 3, 4, and 18.
With regard to claims 2 and 17, Mingozzi discloses the administration of the capsid proteins prevents cytotoxic immune responses to the viral capsids, which include MHC I epitopes (paragraph [0007], [0082], [0214]).
With regard to claims 5-6, and 19 Mingozzi discloses the patient suffers from age-related macular degeneration, glaucoma and retinitis pigmentosis (paragraphs [0053], [0058]).
With regard to claims 7-8, Mingozzi discloses the transgene produced enhances the function of a retinal cell, or encodes an endonuclease to knock-down gene function (paragraphs [0052]-[0054], [0093]).
With regard to claims 9-11, Mingozzi discloses the vector is an AAV vector, including an AAV8 viral vector (paragraphs [0013], [0016], [0034]-[0046]).
With regard to claims 12-16, Mingozzi discloses the neutralizing antibodies are generated from, and bind, the VP1-VP3 capsid proteins of the AAV in specific dosages/ratios in order to inhibit the immune response (paragraphs [0009], [0036]-[0046], [0091], [0096] Example 3).
Conclusion
No claims are allowed.
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KAA
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633