Office Action 1: Notice of Allowance (2025-02-05)

CLAIMS:
What is claimed is:
1\. A fusion protein comprising: i) an adhesion molecule-1 (ICAM-1) targeting segment; ii) an enzyme segment that is catalytically activated at a lysosomal pH; iii) a first protease cleavage sequence segment between i) and ii), and optionally, one or more of: iv) a protein purification tag; and v) a second protease cleavage sequence.
2\. The fusion protein of claim 1, wherein the ICAM-1 targeting segment is repeated at least 2 times in the fusion protein.
3\. The fusion protein of claim 2, wherein the repeated ICAM-1 targeting segments are separated from one another by an amino acid linker sequence.
4\. The fusion protein of claim 2, wherein the ICAM-1 targeting segment comprises SEQ ID NO:1 (NNQKIVNIKEKVAQIEA (2γ3), NNQKIVNLKEKVAQLEA (SEQ ID NO: 26), NNQKLVNIKEKVAQIEA(SEQ ID NO: 27), YPASYQR (SEQ ID NO: 28), YQATPLP (SEQ ID NO: 29), GSLLSAA (SEQ ID NO: 30), FSPHSRT (SEQ ID NO: 31), YPFLPTA (SEQ ID NO: 32), GCKLCAQ (SEQ ID NO: 33), and a combination thereof.
5\. The fusion protein of claim 4, wherein the ICAM-1 targeting segment is repeated 2-10 times.
6\. The fusion protein of claim 5, wherein the first protease cleavage sequence comprises a cathepsin L or cathepsin B protease cleavage site.
7\. The fusion protein of claim 6, wherein the first protease cleavage sequence comprises a cathepsin B cleavage site.
8\. The fusion protein of claim 7, wherein the fusion protein is within a eukaryotic cell.
9\. A method comprising introducing the fusion protein of claim 1 into a eukaryotic cell.
10\. The method of claim 9, wherein the ICAM-1 targeting segment is repeated at least 2 times in the fusion protein.
11\. The method of claim 10, wherein the repeated ICAM-1 targeting segments are separated from one another by an amino acid linker sequence.
12\. The method of claim 10, wherein the ICAM-1 targeting segment comprises an amino acid sequence selected from the group of amino acid sequences consisting of: SEQ ID NO:1 (NNQKIVNIKEKVAQIEA (23), NNQKIVNLKEKVAQLEA (SEQ ID NO: 26), NNQKLVNIKEKVAQIEA(SEQ ID NO: 27), YPASYQR (SEQ ID NO: 28), YQATPLP (SEQ ID NO: 29), GSLLSAA (SEQ ID NO: 30), FSPHSRT (SEQ ID NO: 31), YPFLPTA (SEQ ID NO: 32), GCKLCAQ (SEQ ID NO: 33), and a combination thereof.
13\. The method of claim 12, wherein the ICAM-1 targeting segment is repeated 2-10 times.
14\. The method of claim 13, wherein the first protease cleavage sequence comprises a cathepsin L cleavage site or a cathepsin B protease cleavage site.
15\. The method of claim 14, wherein the fusion protein is cleaved at the first protease cleavage sequence such that the enzyme segment is separated from the fusion protein within a lysosome of the eukaryotic cell, and wherein the protease cleavage site comprises a cathepsin B protease cleavage site.
16\. The method of claim 15, wherein the eukaryotic cell is present in an individual who has been diagnosed with a lysosomal storage disease.
17\. An expression vector encoding the fusion protein of claim 1.
18\. The expression vector of claim 17, wherein the ICAM-1 targeting segment is repeated at least 2 times in the fusion protein.
19\. The expression vector of claim 1i, wherein the ICAM-1 targeting segment comprises an amino acid sequence selected from the group of amino acid sequences consisting of: SEQ ID NO:1 (NNQKIVNIKEKVAQIEA (2γ3), NNQKIVNLKEKVAQLEA (SEQ ID NO: 26), NNQKLVNIKEKVAQIEA(SEQ ID NO: 27), YPASYQR (SEQ ID NO: 28), YQATPLP (SEQ ID NO: 29), GSLLSAA (SEQ ID NO: 30), FSPHSRT (SEQ ID NO: 31), YPFLPTA (SEQ ID NO: 32), GCKLCAQ (SEQ ID NO: 33).
20\. A cell comprising the expression vector of claim 17.

OFFICE 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 .
EXAMINER’S COMMENT
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 01/18/2024 is acknowledged.  The submission is in compliance with the provisions of 37 CFR 1.97.  Accordingly, the information disclosure statement has been considered by the examiner.
Restrictions
Restriction to one of the following inventions is required under 35 U.S.C. 121:
This application contains claims directed to the following patentably distinct species: SEQ ID NO:1 (NNQKIVNIKEKVAQIEA (2y3), NNQKIVNLKEKVAQLEA (SEQ ID NO: 26), NNQKLVNIKEKVAQIEA(SEQ ID NO: 27), YPASYQR (SEQ ID NO: 28), YQATPLP (SEQ ID NO: 29), GSLLSAA (SEQ ID NO: 30), FSPHSRT (SEQ ID NO: 31), YPFLPTA (SEQ ID NO: 32), and GCKLCAQ (SEQ ID NO: 33).  The species are independent or distinct because each of the ICAM targeting segments as set forth in abovementioned SEQ ID NOs are structurally and functionally distinct.
Applicant is required under 35 U.S.C. 121 to elect a single disclosed species for prosecution on the merits to which the claims shall be restricted if no generic claim is finally held to be allowable.  Currently, claims 1-20 are generic.
Applicant is advised that a reply to this requirement must include an identification of the species that is elected consonant with this requirement, and a listing of all claims readable thereon, including any claims subsequently added.  An argument that a claim is allowable or that all claims are generic is considered nonresponsive unless accompanied by an election.
Upon the allowance of a generic claim, applicant will be entitled to consideration of claims to additional species which depend from or otherwise require all the limitations of an allowable generic claim as provided by 37 CFR 1.141. If claims are added after the election, applicant must indicate which are readable upon the elected species. MPEP § 809.02(a).
Election
The attorney of record, John Lopinski, telephonically elected SEQ ID NO: 26 on 01/10/2025.  Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).  SEQ ID NO:1 (NNQKIVNIKEKVAQIEA (2γ3), NNQKIVNLKEKVAQLEA (SEQ ID NO: 26), NNQKLVNIKEKVAQIEA(SEQ ID NO: 27), YPASYQR (SEQ ID NO: 28), YQATPLP (SEQ ID NO: 29), GSLLSAA (SEQ ID NO: 30), FSPHSRT (SEQ ID NO: 31), YPFLPTA (SEQ ID NO: 32), GCKLCAQ (SEQ ID NO: 33) are withdrawn from further consideration on the merits.
EXAMINER’S AMENDMENT
An examiner’s amendment to the record appears below. Should the changes and/or additions be unacceptable to applicant, an amendment may be filed as provided by 37 CFR 1.312. To ensure consideration of such an amendment, it MUST be submitted no later than the payment of the issue fee.
Authorization for this Examiner’s amendment was given by John Lopinsky on 1/21/2025.
Claims 21-32 are allowed.
Claims 1-20 (Canceled).
Claim 21. A fusion protein comprising:
five to ten tandemly connected intercellular adhesion molecule-1 (ICAM-1) targeting segments, wherein each ICAM-1 targeting segment comprises SEQ ID NO: 26 (NNQKIVNLKEKVAQLEA);
an enzyme segment that can be catalytically active at the pH of a lysosome, wherein the enzyme segment comprises Acid sphingomyelinase (ASM), Alpha galactosidase, or Glucocerebrosidase;
a first protease cleavage sequence segment between i) and ii), and optionally, one or more of:
iv) a secretion signal;
v) a protein purification tag; and
vi) a second protease cleavage sequence.
Claim 22. The fusion protein of claim 21, further comprising iv).
Claim 23. The fusion protein of claim 22, further comprising v).
Claim 24. The fusion protein of claim 22, further comprising vi).
Claim 25. The fusion protein of claim 21, wherein the enzyme segment comprises the ASM.
Claim 26. The fusion protein of claim 21, wherein the enzyme segment comprises the Alpha galactosidase.
Claim 27. The fusion protein of claim 21, wherein the enzyme segment comprises the Glucocerebrosidase.
Claim 28. A method comprising administering to an individual in need thereof a therapeutically effective amount of the fusion protein of claim 21.
Claim 29. The method of claim 28, wherein the fusion protein further comprises at least iv).
Claim 30. The method of claim 29, wherein the individual is in need of treatment for any of Pompe Disease, GM1 gangliosidosis, Tay-Sachs disease, GM2 gangliosidosis, Sandhoff disease, Fabry disease, Gaucher disease, metachromatic leukodystrophy, Krabbe disease, Niemann-Pick disease type A, Niemann-Pick disease type B, Niemann-Pick disease type C, Niemann-Pick disease type D, Farber disease, Wolman disease, Hurler Syndrome, Scheie Syndrome, Hurler-Scheie Syndrome, Hunter Syndrome, Sanfilippo A Syndrome, Sanfilippo B Syndrome, Sanfilippo C Syndrome, Sanfilippo D Syndrome, Morquio A disease, Morquio B disease, Maroteaux-Lamy disease, Sly Syndrome, α-mannosidosis, β-mannosidosis, fucosidosis, aspartylglucosaminuria, sialidosis, mucolipidosis II, mucolipidosis III, mucolipidosis IV, Goldberg Syndrome, Schindler disease, cystinosis, Salla disease, infantile sialic acid storage disease, Batten disease, infantile neuronal ceroid lipofuscinosis, and prosaposin, Parkinson's Disease, or a combination thereof.
Claim 31. An expression vector encoding the fusion protein of claim 21.
Claim 32. One or more modified cells that are modified to express the fusion protein of claim 21.
REASONS FOR ALLOWANCE
The following is an Examiner’s statement of reasons for allowance.  While Muro Galindo et al. (US Patent No. 8926946, see IDS) teach GMP having a fusion protein comprising ICAM-1 targeting peptide 2γ3 and an acid sphingomyelinase (ASM) (see Example 9 and Fig. 7), the Examiner has found no teaching or suggestion in the prior art directed to a fusion protein comprising: i) five to ten tandemly connected intercellular adhesion molecule-1 (ICAM-1) targeting segments, wherein each ICAM-1 targeting segment comprises SEQ ID NO: 26 (NNQKIVNLKEKVAQLEA); ii) an enzyme segment that can be catalytically active at the pH of a lysosome, wherein the enzyme segment comprises Acid sphingomyelinase (ASM), Alpha galactosidase, or Glucocerebrosidase; iii) a first protease cleavage sequence segment between i) and ii), and optionally, one or more of:  iv) a secretion signal; v) a protein purification tag; and vi) a second protease cleavage sequence.  It is noted by the Examiner that a person of ordinary skill in the art would not have been motivated to make and use a fusion protein comprising five to ten tandemly connected intercellular adhesion molecule-1 (ICAM-1) targeting segments, wherein each ICAM-1 targeting segment comprises SEQ ID NO: 26 (NNQKIVNLKEKVAQLEA) (italicized for added emphasis).  Therefore, the claimed invention is novel and unobvious over the prior art of record.
Any comments considered necessary by applicant must be submitted no later than the payment of the issue fee and, to avoid processing delays, should preferably accompany the issue fee.  Such submissions should be clearly labeled “Comments on Statement of Reasons for Allowance.”



CITED REFERENCE SUMMARIES: Ref US8926946: Claims:
1. A delivery composition for delivery of an agent into a cell, the composition comprising:
a) a targeting moiety comprising a peptide or protein having a sequence selected from the group consisting of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, and SEQ ID NO: 19; and an agent; or
b) a nucleic acid having a sequence encoding a targeting moiety having a sequence B selected from the group consisting of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, and SEQ ID NO: 19; and a second nucleic acid having a sequence encoding an agent,
wherein the targeting moiety recognizes and binds to a target on the cell, and is effective to deliver the agent into the cell.
2. The delivery composition of claim 1, wherein the agent comprises any of a biologically active compound, an imaging compound, a monitoring compound, therapeutic compound, a diagnostic compound, an enzyme, a peptide, a protein, a lipid, a lipoprotein, a sugar, a hormone, a vitamin, a nucleic acid, a virus, a bacteria, and a cell.
3. The delivery composition of claim 2, wherein the agent comprises a lysosomal enzyme.
4. The delivery composition of claim 3, wherein the agent comprises any of the enzymes involved in Pompe Disease, GM1 gangliosidosis, Tay-Sachs disease, GM2 gangliosidosis, Sandhoff disease, Fabry disease, Gaucher disease, metachromatic leukodystrophy, Krabbe disease, Niemann-Pick disease type A, Niemann-Pick disease type B, Niemann-Pick disease type C, Niemann-Pick disease type D, Farber disease, Wolman disease, Hurler Syndrome, Scheie Syndrome, Hurler-Scheie Syndrome, Hunter Syndrome, Sanfilippo A Syndrome, Sanfilippo B Syndrome, Sanfilippo C Syndrome, Sanfilippo D Syndrome, Morquio A disease, Morquio B disease, Maroteaux-Lamy disease, Sly Syndrome, α-mannosidosis, β-mannosidosis, fucosidosis, aspartylglucosaminuria, sialidosis, mucolipidosis II, mucolipidosis III, mucolipidosis IV, Goldberg Syndrome, Schindler disease, cystinosis, Salla disease, infantile sialic acid storage disease, Batten disease, infantile neuronal ceroid lipofuscinosis, and prosaposin.
5. The delivery composition of claim 1, wherein the agent comprises acid sphingomyelinase.
6. The delivery composition of claim 1, wherein the target on the cell comprises ICAM-1.
7. The delivery composition of claim 6, wherein the ICAM-1 comprises human or mouse ICAM-1.
8. The delivery composition of claim 1, wherein delivery of the agent to the cell comprises any of intracellular transport and transcellular transport of the agent.
9. The delivery composition of claim 1, further comprising a second targeting moiety.
10. The delivery composition of claim 9, wherein the second targeting moiety comprises a moiety selected from an antibody, an aptamer, a nucleic acid, a peptide, a carbohydrate, a lipid, a vitamin, a toxin, a component of a microorganism, a hormone, and a receptor ligand.
11. The delivery composition of claim 1, further comprising a delivery carrier.
12. The delivery composition of claim 11, wherein the delivery carrier comprises a carrier species selected from a natural virus or derived viral-like particle, dendrimer, carbon nanoassembly, liposome, a polymer carrier, a microbubble, a paramagnetic particle, a ferromagnetic particle, a self-assembled polymer, a polymersome, a filomicelle, a micelle, a micro particle or nanoparticle, an albumin particle, and a lipoprotein.
13. The delivery composition of claim 1, wherein the target organ is selected from kidney, spleen, heart, lung, liver, and brain.
14. A method for delivering an agent into a cell, the method comprising administration of a delivery composition of claim 1.
15. A method for delivering an agent to the surface of a cell, the method comprising administration of a delivery composition comprising:
a) a targeting moiety comprising a peptide or protein having a sequence selected from the group consisting of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, and SEQ ID NO: 19; and an agent; or
b) a nucleic acid having a sequence encoding a targeting moiety having a sequence selected from the group consisting of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, and SEQ ID NO: 19; and a second nucleic acid having a sequence encoding an agent.
16. A method for delivering an agent into a cell, the method comprising administration of a delivery composition comprising:
a) a targeting moiety comprising a peptide or protein having a sequence selected from the group consisting of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, and SEQ ID NO: 19; and an agent; or
b) a nucleic acid having a sequence encoding a targeting moiety having a sequence selected from the group consisting of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, and SEQ ID NO: 19; and a second nucleic acid having a sequence encoding an agent,
and further comprising a delivery carrier, wherein the targeting moiety recognizes and binds to a target on the cell, and the composition is effective to deliver the agent into the cell.
17. The method of claim 16, wherein the delivery carrier comprises a carrier species selected from a natural virus or derived viral-like particle, dendrimer, carbon nanoassembly, liposome, a polymer carrier, a microbubble, a paramagnetic particle, a ferromagnetic particle, a self-assembled polymer, a polymersome, a filomicelle, a micelle, a micro particle or nanoparticle, an albumin particle, and a lipoprotein.
18. The method of claim 17, wherein the delivery carrier comprises a polymer carrier.
19. The method of claim 18, wherein the delivery carrier is a polystyrene carrier or a poly-lactic co-glycolic acid carrier.
20. The method of claim 16, wherein a delivery composition is administered comprising a targeting moiety comprising a peptide or protein having a sequence selected from the group consisting of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, and SEQ ID NO: 19; and an agent.
21. The method of claim 16, wherein a delivery composition is administered comprising a nucleic acid having a sequence encoding a targeting moiety having a sequence selected from the group consisting of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, and SEQ ID NO: 19; and a second nucleic acid having a sequence encoding an agent.
22. The method of claim 16, wherein the targeting moiety is coupled to the delivery carrier.