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 .
Claim Status
Claims 1-30 are pending and examined herein.
Priority
This application is a CON of 17/127,001 (filed 12/18/2020; Patent No. 11491243), which is a CON of 16/399,979 (filed 04/30/2019; Patent No. 10874750), which has PRO 62/744,068 (filed 10/10/2018), PRO 62/688,640 (filed 06/22/2018), and PRO 62/664,741 (filed 04/30/2018). Therefore, the earliest priority date is 04/30/2018.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, 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 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 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”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 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 statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - The incorporation by reference paragraph required by 37 CFR 1.834(c)(1), 1.835(a)(2), or 1.835(b)(2) is missing.
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 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.
Specific deficiency - Sequences appearing in the Figure 3 of drawings are not identified by sequence identifiers in accordance with 37 CFR 1.831(c). Sequence identifiers for sequences (i.e., “SEQ ID NO:X” or the like) must appear either in the drawings or in the Brief Description of the Drawings.
Required response – Applicant must provide:
Amended drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required sequence identifiers (i.e., “SEQ ID NO:X” or the like) into the Brief Description of the Drawings, 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.
Claim Objections
Claim 27 is objected to because of the following informalities: claim 27 recites the limitation “wherein the vIGF2 at the N-terminus of the polypeptide”. Such recitation makes the limitation incomplete. Claim 27 should recite, “wherein the vIGF2 is at the N-terminus of the polypeptide”. 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 1-30 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.
The term "high affinity" in claim 1 is a relative term which renders the claim indefinite. The term "high affinity" 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. It is unclear with how much affinity the peptide has to bind to the M6P receptor to be considered “high affinity”. Accordingly, the term “high affinity renders the claims indefinite.
Claims 7 and 8, which depend from claim 1, recite the limitation "the vIGF2 peptide" in line 1. There is insufficient antecedent basis for this limitation in the claim.
Claims 27 and 28, which depend from claim 1, recite the limitation "the vIGF2" in line 1. There is insufficient antecedent basis for this limitation in the claim.
Those claims identified in the statement of rejection but not explicitly referenced in the rejection are also rejected for depending from a rejected claim but failing to remedy the indefiniteness therein.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-22, 27-28, and 30 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.
Claims 1-22, 27-28, and 30 are drawn to a genus of peptides that bind to the CI-MPR with high affinity, including variants of IGF2 at least 90% identical to SEQ ID NO: 1, and to a genus of enzymatically active fragments of therapeutic proteins. As indicated in MPEP § 2163, the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show that Applicant was in possession of the claimed genus. In addition, MPEP § 2163 states that a representative number of species means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
In the instant case, the claims encompass a genus of peptides that bind to the CI-MPR with high affinity, including variants of IGF2 at least 90% identical to SEQ ID NO: 1, and to a genus of enzymatically active fragments of therapeutic proteins. Therefore, the variants of IGF2 having at least 90% identical to SEQ ID NO: 1 have not been defined in terms of structure.
The instant specification at pages 4-5 and 8 teaches that the peptide that binds to CI-MPR is a vIGF2, which includes those with variant amino acids at positions 6, 26, 27, 43, 48, 49, 50, 54, 55, or 65 (E6R, F26S, Y27L, V43L, F48T, R49S, S50I, A54R, L55R, and K65R) compared to WT IGF2 and, in Table 3 on pages 52-53, provides 14 specific examples of variant IGF2 (SEQ ID NOs: 2-11, 30, 31, 34, and 35). The instant specification in Example 1 teaches vIGF2 sequence differs from wt IGF2 in that it lacks residues 1-4 and contains the following mutations: E6R, Y27L, and K65R and has the amino sequence of SEQ ID NO: 31, also has an N-terminal linker of SEQ ID NO: 18, and with a combined sequence of SEQ ID NO: 43. The instant specification in Example 2 teaches vIGF2 peptide (SEQ ID NO: 31) with an N-terminal linker (SEQ ID NO: 18) chemically coupled to alglucosidase-alfa, designated here as vIGF2- alglucosidase-alfa, to determine whether the vIGF2 peptide could improve affinity for CI-MPR. The instant specification in Example 4 teaches that the vIGF2 having the sequence set forth in SEQ ID NO: 31, a nucleic acid encoding a 2GS linker (SEQ ID NO:18) followed by a nucleic acid encoding a recombinant human GAA with the N- terminal 60 amino acids removed (SEQ ID NO:46) to prevent premature processing and removal of the vIGF2.
Aoyagi-Scharber (cited in IDS filed 2/9/2023) teaches IGF2 variants (“IGF-II”) having a deletion or replacement of amino acid residues corresponding to positions selected from the group consisting of 30-40, 31-40, 32-40, 33-40, 34-40, 30-39, 31-39, 32-39, 34-37, 33-39, 34-39, 35-39, 36-39, 37-40 of mature human IGF-II, and combinations thereof. Aoyagi-Scharber further teaches various embodiments of IGF-II having a deletion or a replacement of amino acids corresponding to positions 2-7 of mature human IGF-II, a deletion or a replacement of amino acids corresponding to positions 1-7 of mature human IGF-II, a deletion or a replacement of amino acids corresponding to positions 62-67 of mature human IGF-II, an amino acid substitution at a position corresponding to Tyr27, Leu43, or Ser26 of mature human IGF-II. In various embodiments, at least an amino acid substitution selected from the group consisting of Tyr27Leu, Leu43Val, Ser26Phe and combinations thereof, amino acids corresponding to positions 48-55 of mature human IGF-II, at least three amino acids selected from the group consisting of amino acids corresponding to positions 8, 48, 49, 50, 54, and 55 of mature human IGF-II, at positions corresponding to positions 54 and 55 of mature human IGF-II, amino acids each of which is uncharged or negatively charged at pH 7.4, and IGF2 Δ8-67 R37A (i.e., amino acids 8-67 of mature human IGF-II with the Arg at position 37 of mature human IGF-II substituted by Ala).
The instant specification does not show any other peptides that bind to the CI-MPR with high affinity; including any other variants of IGF2 at least 90% identical to SEQ ID NO: 1, nor does it provide any information regarding the structure of any other variant that results in high affinity binding to CI-MPR. The specification also fails to show any enzymatically active fragment of any of the therapeutic proteins. The specification fails to describe any additional species by any relevant, identifying characteristics or properties other than by functionality (high affinity to CI-MPR or enzymatically active).
The claims encompass a large genus of peptides that bind to the CI-MPR with high affinity, including variants of IGF2 at least 90% identical to SEQ ID NO: 1, and to a genus of enzymatically active fragments of therapeutic proteins, which are structurally/functionally unrelated. A sufficient written description of a genus of peptides that bind to the CI-MPR with high affinity, including variants of IGF2 at least 90% identical to SEQ ID NO: 1, and to a genus of enzymatically active fragments of therapeutic proteins may be achieved by a recitation of a representative number of variants and amino acid substitutions, or a recitation of structural features common to members of the genus, which features constitute a substantial portion of the genus. However, in the instant case, there is no structural feature which is representative of all the members of the genus of peptides that bind to the CI-MPR with high affinity, including variants of IGF2 at least 90% identical to SEQ ID NO: 1, and to a genus of enzymatically active fragments of therapeutic proteins recited in the claims, and there is no information as to a correlation between structure and function.
Because the specification only discloses 14 specific variants of IGF2, and no examples of enzymatically active fragments of the genus, and the lack of description of any additional species by any relevant, identifying characteristics or properties, one of skill in the art would not recognize from the disclosure that Applicant was in possession of the claimed invention.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-21 and 27-30 is/are rejected under 35 U.S.C. 103 as being unpatentable over Aoyagi-Scharber et al. (WO2014085621A1, published 6/5/2014; cited in IDS filed 2/9/2023) in view of Puzzo et al. (Rescue of Pompe disease in mice by AAV-mediated liver delivery of secretable acid -glucosidase; Science Translational Medicine, 9 (418), pp. 1-12, published 11/29/2017; cited in IDS filed 2/9/2023).
Aoyagi-Scharber et al. is directed to delivery of alpha-glucosidase for the treatment of lysosomal diseases and describes a nucleic acid encoding (nucleic acids encoding the therapeutic fusion protein; paragraph [0029]) a polypeptide comprising: (a) a therapeutic protein (lysosomal enzyme, paragraph [0006]); (b) a peptide that binds to the cation-independent mannose 6-phosphate (M6P) receptor (CI-MPR) with high affinity (IGF-II; paragraph [0006]); and (c) a linker between the therapeutic protein and the peptide that binds CI-MPR (spacer peptides; paragraph [0006]) (claim 1), wherein the peptide is a variant IGF2 (vIGF2) peptide (IGF-II mutein; paragraph [0012]) (claim 2), wherein the vIGF2 peptide comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 1 (SEQ ID NO: 5 of Aoyagi-Scharber et al. is 100% identical to SEQ ID NO: 1 of the instant application) and having at least one substitution at one or more positions selected from the group consisting of positions 26, 27, 43, 48, 49, 50, 54 and 55 (amino acid substitution corresponding to Tyr27, Leu43, or Ser26. Amino acids corresponding to positions 8, 48, 49, 50, 54 and 55; paragraph [0019]) of SEQ ID NO: 1, wherein the vIGF2 peptide comprises an N-terminal deletion at positions 1-4 of SEQ ID NO: 1 (deletion of amino acids corresponding to positions 1-7 of mature human IGF-II; paragraph [0019]) (claim 3), wherein the at least one substitution is selected from the group consisting of F26S, Y27L, V43L of SEQ ID NO:1 (at least an amino acid substitution selected from the group consisting of Tyr27Leu, Leu43Val, or Ser26Phe; paragraph [0019]) (claim 4), wherein the vIGF2 peptide comprises at least two substitutions at two or more positions selected from the group consisting of positions 26, 27, 43, 48, 49, 50, 54, 55 of SEQ ID NO: 1 (at least an amino acid substitution selected from the group consisting of Tyr27Leu, Leu43Val, or Ser26Phe. At least three amino acids selected from the group consisting of amino acids corresponding to positions 8, 48, 49, 50, 54 and 55; paragraph [0019]) (claim 5), wherein the at least two substitutions are selected from the group consisting of F26S, Y27L, V43L of SEQ ID NO: 1 (at least an amino acid substitution selected from the group consisting of Tyr27Leu, Leu43Val, or Ser26Phe; paragraph [0019]) (claim 6), wherein the vIGF2 peptide comprises an N-terminal deletion at positions 1-4 of SEQ ID NO: 1 (deletion of amino acids corresponding to positions 1-7 of mature human IGF-II; paragraph [0019]) (claim 7), wherein the vIGF2 peptide has decreased affinity for insulin receptor and IGF1R as compared to native IGF2 peptide (reduced or diminished affinity for the IGF-I receptor and/or reduced or diminished affinity for the insulin receptor; paragraph [0006]) (claim 8), wherein the vIGF2 peptide is capable of facilitating uptake of the therapeutic protein into a cell (see table 2 showing increased uptake of the therapeutic protein fused to a linker and vIGF2) (claim 9), wherein the vIGF2 peptide is capable of facilitating uptake of the therapeutic protein into a lysosome (improved uptake into lysosomes; paragraph [0006]) (claim 10), wherein the therapeutic protein is capable of replacing a defective or deficient protein associated with a genetic disorder in a subject having the genetic disorder (enzyme that is capable of reducing accumulated materials in mammalian lysosomes or that can rescue or ameliorate on or more lysosomal storage disease symptoms; paragraph [0080]) (claim 11), wherein the genetic disorder is a lysosomal storage disorder (enzyme that is capable of reducing accumulated materials in mammalian lysosomes or that can rescue or ameliorate on or more lysosomal storage disease symptoms; paragraph [0080]) (claim 12), wherein the genetic disorder is Pompe disease (Pompe Disease, table 1) (claims 13 and 14), wherein the genetic disorder is Batten disease/CLN1 (Batten Disease - Juvenile Neuronal Ceroid Lipofuscinosis; Infantile Neuronal Ceroid; paragraph [0080]; table 1) (claims 13 and 15), wherein the therapeutic protein comprises a soluble lysosomal enzyme or an enzymatically active fragment thereof (lysosomal enzyme; paragraph [0080]) (claim 16), wherein the therapeutic protein is alpha-glucosidase (acid-1,4-Glucosidase; table 1) (claims 17 and 18), wherein the therapeutic protein is palmitoyl protein thioesterase (Palmitoyl-Protein Thioesterase; table 1) (claims 17 and 19); wherein the nucleic acid construct further comprises a translation initiation sequence (nucleic acid of the invention that permit expression of the targeted therapeutic fusion protein; paragraph [0031]) (claim 20), wherein the polypeptide further comprises a signal peptide wherein the signal peptide is capable of increasing secretion of the therapeutic protein as compared to the therapeutic protein without the signal peptide (BM-40 extracellular matrix protein signal peptide sequence; paragraph [0164]) (claim 21), wherein the vIGF2 at the N-terminus of the polypeptide (the peptide tag is attached to the N-terminus or C-terminus of the lysosomal enzyme; paragraph [0020]) (claim 27), wherein the vIGF2 is at the C-terminus of the polypeptide (the peptide tag is attached to the N-terminus or C-terminus of the lysosomal enzyme; paragraph [0020]) (claim 28), wherein the linker peptide comprises SEQ ID NO: 18-20 (SEQ ID NOs: 12 and 26 comprise one of SEQ ID NOs: 18-20 of the instant application (claim 29).
However, Aoyagi-Scharber et al. lack the vector wherein the vector is a gene therapy vector (claim 1), wherein the gene therapy vector is a virus vector selected from the group consisting of an adenovirus vector, an adeno-associated virus (AAV) vector, a retrovirus vector, a lentivirus vector, a pox virus vector, a vaccinia virus vector, an adenovirus vector, and a herpes virus vector (claim 30).
Puzzo et al. is directed to delivery of alpha-glucosidase for the treatment of lysosomal diseases and describes a gene therapy vector (adeno-associated virus (AAV) vectors optimized for hepatic expression to deliver the GAA transgenes; abstract) (claim 1), wherein the gene therapy vector is an adeno-associated virus (AAV) vector (adeno-associated virus (AAV) vectors optimized for hepatic expression to deliver the GAA transgenes; abstract) (claim 30). Puzzo et al. further describe that secretable GAA showed improved therapeutic efficiency and lower immunogenicity (abstract).
Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have modified the nucleic acid construct described by Aoyagi-Scharber et al. by introducing it in a gene therapy vector as described by Puzzo et al. A person of ordinary skill in the art would have been motivated to do so in order to have improved therapeutic efficiency and lower immunogenicity when administering GAA (Puzzo et al., abstract). Given the teachings of the prior art and the level of the ordinary skilled artisan before the effective filing date of the claimed invention, it must be considered, absent evidence to the contrary, that said skilled artisan would have had a reasonable expectation of success in practicing the claimed invention.
Accordingly, Aoyagi-Scharber et al. in view of Puzzo et al. render obvious claims 1-21 and 27-30.
Claim 23 is rejected under 35 U.S.C. 103 as being unpatentable over Aoyagi-Scharber et al. (cited in IDS filed 2/9/2023) in view of Puzzo et al. (cited in IDS filed 2/9/2023) as applied to claims 1-21 and 27-30 above, and further in view of Do (WO2014143734A2, published September 18, 2014; cited in IDS filed 2/9/2023).
Aoyagi-Scharber et al. in view of Puzzo et al. is directed to delivery of alpha-glucosidase for the treatment of lysosomal diseases and renders obvious claims 1-21 and 27-30 as applied above.
Aoyagi-Scharber et al. in view of Puzzo et al. lack the vector wherein the vIGF2 peptide comprises the sequence of SEQ ID NO: 31 (claim 23).
Do is directed to delivery of alpha-glucosidase for the treatment of lysosomal diseases and describes a vIGF2 peptide comprises the sequence of SEQ ID NO: 31 (SEQ ID NO: 2 of Do is 100% identical to SEQ ID NO: 31 of the instant application (claim 23). Do further describes that said vIGF2, in addition to have reduced binding to IGF-I receptor and insulin receptor, also has reduced binding to serum IGF binding proteins and prevents chemical modification (page 8, third paragraph).
Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the nucleic acid construct described by Aoyagi-Scharber et al. in view of Puzzo et al. and have the vIGF2 of SEQ ID NO: 31 as described by Do. A person of ordinary skill in the art would have been motivated to do so in order to reduced binding to serum IGF binding proteins and prevent chemical modification of vIGF2 (page 8, third paragraph). (Puzzo et al., abstract). Given the teachings of the prior art and the level of the ordinary skilled artisan before the effective filing date of the claimed invention, it must be considered, absent evidence to the contrary, that said skilled artisan would have had a reasonable expectation of success in practicing the claimed invention.
Accordingly, Aoyagi-Scharber et al. in view of Puzzo et al. and further in view of Do render obvious claim 23.
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 filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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/apply/applying-online/eterminal-disclaimer.
Claims 1-30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. US11491243B2. Although the claims at issue are not identical, they are not patentably distinct from each other because there is significant overlap in the claims.
Claims 1-18 of the ‘234 patent teach a method for treating a genetic disorder, administering to a subject in need thereof a gene therapy vector or a pharmaceutical composition comprising the gene therapy vector, wherein the gene therapy vector comprises a nucleic acid construct encoding a polypeptide comprising: (a) a therapeutic protein, wherein the therapeutic protein is a lysosomal enzyme; (b) a peptide that binds to the cation-independent mannose 6-phosphate (M6P) receptor (CI-MPR), wherein the peptide is a variant (vIGF2) peptide comprising the sequence of SEQ ID NO: 31; (c) a linker between the therapeutic protein and the peptide that binds CI-MPR; and (d) a signal peptide selected from a binding immunoglobulin protein (BiP) signal peptide and a Gaussia signal peptide; wherein the genetic disorder is a lysosomal storage disorder. Claims 1-18 of the ‘234 patent encompass the genetic disorder is selected from the group consisting of aspartylglucosaminuria, Batten disease, cystinosis, Fabry disease, Gaucher disease type I, Gaucher disease type II, Gaucher disease type III, Pompe disease, Tay Sachs disease, Sandhoff disease, metachromatic leukodystrophy, mucolipidosis type I, mucolipidosis type II, mucolipidosis type III, mucolipidosis type IV, Hurler disease, Hunter disease, Sanfilippo disease type A, Sanfilippo disease type B, Sanfilippo disease type C, Sanfilippo disease type D, Morquio disease type A, Morquio disease type B, Maroteau-Lamy disease, Sly disease, Niemann-Pick disease type A, Niemann-Pick disease type B, Niemann-Pick disease type C1, Niemann-Pick disease type C2, Schindler disease type I, Schindler disease type II, adenosine deaminase severe combined immunodeficiency (ADA-SCID), chronic granulomatous disease (CGD), and neuronal ceroid lipofuscinosis. Claims 1-18 of the ‘234 patent encompass the therapeutic proteins alpha-galactosidase A, beta.-glucocerebrosidase, glucocerebrosidase, lysosomal acid lipase, glycosaminoglycan alpha-L-iduronohydrolase, iduronate-2-sulfatase, N-acetylgalactosamine-6-sulfatase, glycosaminoglycan N-acetylgalactosamine 4-sulfatase, palmitoyl protein thioesterase-1, and alpha-glucosidase, the nucleic acid construct further comprises a translation initiation sequence, the SEQ ID NOs: 18-21, 23, 31, 33, 36 and 38, the vIGF2 peptide is at the N-terminus of the polypeptide, vIGF2 peptide is at the C-terminus of the polypeptide, and the gene therapy vector is a virus vector selected from the group consisting of an adenovirus vector, an adeno-associated virus (AAV) vector, a retrovirus vector, a lentivirus vector, a pox virus vector, a vaccinia virus vector, an adenovirus vector, and a herpes virus vector.
Claims 1-30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 10874750B2. Although the claims at issue are not identical, they are not patentably distinct from each other because other because there is significant overlap in the claims. Claims 1-19 of the ‘750 patent teach a gene therapy vector, wherein the gene therapy vector comprises a nucleic acid construct encoding a polypeptide comprising: (a) a therapeutic protein, wherein the therapeutic protein is a lysosomal enzyme; (b) a peptide that binds to the cation-independent mannose 6-phosphate (M6P) receptor (CI-MPR), wherein the peptide is a variant (vIGF2) peptide comprising the sequence of SEQ ID NO: 31; (c) a linker between the therapeutic protein and the peptide that binds CI-MPR; and (d) a signal peptide selected from a binding immunoglobulin protein (BiP) signal peptide and a Gaussia signal peptide; wherein the genetic disorder is a lysosomal storage disorder. Claims 1-19 of the ‘750 patent encompass the genetic disorder is selected from the group consisting of aspartylglucosaminuria, Batten disease, cystinosis, Fabry disease, Gaucher disease type I, Gaucher disease type II, Gaucher disease type III, Pompe disease, Tay Sachs disease, Sandhoff disease, metachomatic leukodystrophy, mucolipidosis type I, mucolipidosis type II, mucolipidosis type III, mucolipidosis type IV, Hurler disease, Hunter disease, Sanfilippo disease type A, Sanfilippo disease type B, Sanfilippo disease type C, Sanfilippo disease type D, Morquio disease type A, Morquio disease type B, Maroteau-Lamy disease, Sly disease, Niemann-Pick disease type A, Niemann-Pick disease type B, Niemann-Pick disease type C1, Niemann-Pick disease type C2, Schindler disease type I, Schindler disease type II, adenosine deaminase severe combined immunodeficiency (ADA-SCID), chronic granulomatous disease (CGD), and neuronal ceroid lipofuscinosis. Claims 1-19 of the ‘750 patent encompass the therapeutic proteins alpha-galactosidase A, beta.-glucocerebrosidase, glucocerebrosidase, lysosomal acid lipase, glycosaminoglycan alpha-L-iduronohydrolase, iduronate-2-sulfatase, N-acetylgalactosamine-6-sulfatase, glycosaminoglycan N-acetylgalactosamine 4-sulfatase, palmitoyl protein thioesterase-1, and alpha-glucosidase, the nucleic acid construct further comprises a translation initiation sequence, the SEQ ID NOs: 18-21, 23, 31, 33, 36 and 38, the vIGF2 peptide is at the N-terminus of the polypeptide, vIGF2 peptide is at the C-terminus of the polypeptide, and the gene therapy vector is a virus vector selected from the group consisting of an adenovirus vector, an adeno-associated virus (AAV) vector, a retrovirus vector, a lentivirus vector, a pox virus vector, a vaccinia virus vector, an adenovirus vector, and a herpes virus vector.
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Claims 1-24 and 26-30 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims of copending Application No. US20240091321A1 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because there is significant overlap in the claims.
Claims 1-29 of the ‘321 application teach a gene therapy vector comprising a nucleic acid construct encoding (a) a nucleic acid sequence encoding a therapeutic protein, and (b) a nucleic acid sequence encoding a variant IGF2 (vIGF2) peptide that is at least 95% identical to at least one sequence selected from SEQ ID NO: 90-103, comprising an N-terminal deletion at positions 1-4 of Applicant’s SEQ ID NO: 1. Claims 1-29 of the ‘321 application teach the genetic disorder is a lysosomal storage disorder, the genetic disorder is aspartylglucosaminuria, neuronal ceroid lipofuscinosis, CLN1/PPT1 disease, CLN2/PPT1 disease, cystinosis, Fabry disease, Gaucher disease type I, Gaucher disease type II, Gaucher disease type III, Pompe disease, Tay Sachs disease, Sandhoff disease, metachomatic leukodystrophy, mucolipidosis type I, mucolipidosis type II, mucolipidosis type III, mucolipidosis type IV, Hurler disease, Hunter disease, Sanfilippo disease type A, Sanfilippo disease type B, Sanfilippo disease type C, Sanfilippo disease type D, Morquio disease type A, Morquio disease type B, Maroteau-Lamy disease, Sly disease, Niemann-Pick disease type A, Niemann-Pick disease type B, Niemann-Pick disease type C1, Niemann-Pick disease type C2, Schindler disease type I, Schindler disease type II, adenosine deaminase severe combined immunodeficiency (ADA-SCID), and neuronal ceroid lipofuscinosis, alpha-galactosidase (A or B), β-galactosidase, β-hexosaminidase (A or B), galactosylceramidase, arylsulfatase (A or B), β-glucocerebrosidase, glucocerebrosidase, lysosomal acid lipase, lysosomal enzyme acid sphingomyelinase, formylglycine-generating enzyme, iduronidase (e.g., alpha-L), acetyl-CoA:alpha-glucosaminide N-acetyltransferase, glycosaminoglycan alpha-L-iduronohydrolase, heparan N-sulfatase, N-acetyl-α-D-glucosaminidase (NAGLU), iduronate-2-sulfatase, galactosamine-6-sulfate sulfatase, N-acetylgalactosamine-6-sulfatase, N-sulfoglucosamine sulfohydrolase, glycosaminoglycan N—acetylgalactosamine 4-sulfatase, β-glucuronidase, hyaluronidase, alpha-N-acetyl neuraminidase (sialidase), gangliosidesialidase, phosphotransferase, alpha-glucosidase, alpha-D-mannosidase, beta-D-mannosidase, aspartylglucosaminidase, alpha-L-fucosidase, battenin, PPT1, TPP1, and other Batten-related proteins (e.g., ceroid-lipofuscinosis neuronal protein 6), or an enzymatically active fragment thereof, gene therapy vector is a virus vector and is an adenovirus vector, an adeno-associated virus (AAV) vector, a retrovirus vector, a lentivirus vector, a pox virus vector, a vaccinia virus vector, an adenovirus vector, or a herpes virus vector. Claims 1-29 of the ‘321 application teach SEQ ID NO: 80 with 100% sequence identity to instant SEQ ID NO: 31, SEQ ID NO: 133 with 100% sequence identity to instant SEQ ID NO: 36 and linkers comprising SEQ ID NOs: 181-188 with 100% sequence identity to Applicant’s the SEQ ID NOs: 18-21 and 33.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claim is allowed.
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/KHALEDA B HASAN/Examiner, Art Unit 1636
/NEIL P HAMMELL/Supervisory Patent Examiner, Art Unit 1636