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 .
Priority
This application is a continuation of U.S. Application No. 17/272393 (filed on 3/01/2021), which is a national stage entry of PCT/US2019/048698 (filed on 8/29/2019), which in turn claims priority benefit of U.S. Provisional Application No. 62/727420 (filed on 9/05/2018) under 35 U.S.C. 119(e).
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 4/21/2025, 7/22/2025, 10/22/2025, and 5/26/2026 are in compliance with the provisions of 37 C.F.R. 1.97. Accordingly, all references cited in the IDS have been fully considered.
Claim Objections
Claims 1,14, and 22 are objected to because of the following informality: space is missing after the colon in the sequence identifier “SEQ ID NO:”. To maintain consistency with the rest of the claims, “SEQ ID NO:32” should be amended to “SEQ ID NO: 32”.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-11, 14-17, 19-22, and 45 are rejected under 35 U.S.C. 102(a)(1)/102(a)(2) as being anticipated by Lang et al. (US 2015/0366949 A1).
Lang et al. teaches that chondroitin sulfate proteoglycan (CSPG) is a regeneration inhibitor in scar tissue formed by glia at the injury site that is involved not only in traumatic injury of the central nervous system (CSN) but also in CNS diseases (par. [0003]-[0004]). It forms dystrophic axonal retraction bulbs that fail to regenerate through the lesion and limit the sprouting of spared fibers. There is therefore a recognized need to modulate CSPG function (par. [0005]).
To address this need, Lang et al. provides methods of inhibiting and/or reducing the activity, signaling, and/or function of leukocyte-common antigen related (LAR) family of phosphatases in a subject’s cell induced by proteoglycans (par. [0006]). The methods comprise administering to a cell of the subject a therapeutic agent that inhibits one or more of catalytic activity, signaling, and function of the LAR family phosphatases without binding to or activation the LAR family phosphatases by proteoglycans (par. [0013]).
The therapeutic agent is a receptor protein tyrosine phosphatase sigma (PTP[Symbol font/0x73]) and includes a therapeutic peptide having an amino acid sequence that is at least about 65% to at least about 95% homologous to about 10-20 consecutive amino acids of the wedge domain of PTP[Symbol font/0x73] (par. [0007]). In some embodiments, the therapeutic peptide is at least about 65%-95% homologous to the amino acid sequence of SEQ ID NO: 37 (par. [0008]).
In other embodiments, the therapeutic agent has a transport moiety that is linked to the therapeutic peptide and facilitates uptake of said peptide by the cell. One example of a suitable transport moiety is an HIV Tat transport moiety (par. [0010]).
Lang et al. reads on the instant application as explained below:
Regarding claim 1: administering to a subject’s cell a therapeutic agent such as a therapeutic peptide selected from the group consisting of SEQ ID NOs: 9-33 such as SEQ ID NO: 17 (par. [0007]), or a therapeutic peptide that is at least about 65%-95% homologous to the amino acid sequence of SEQ ID NO: 37 (par. [0008]), is the same as the step “contacting the spared neural cells with an effective amount of a therapeutic agent comprising a therapeutic peptide, wherein the therapeutic peptide comprises an amino acid sequence with at least 70% identity to SEQ ID NO:32”.
The amino acid sequence of Applicant’s SEQ ID NO: 32 is EHXERLKANDSLKL where X is T or M.
Sequence-to-sequence analysis shows that Lang et al.’s SEQ ID NO: 17 and SEQ ID NO: 37 are 100% identical to applicant’s SEQ ID NO: 32 as shown below.
Applicant’s SEQ ID NO: 32 (Qy) vs. Lang et al.’s SEQ ID NO: 17 (Db)
Query Match 100.0%; Score 70; DB 1; Length 14;
Best Local Similarity 100.0%;
Matches 14; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EHTERLKANDSLKL 14
||||||||||||||
Db 1 EHTERLKANDSLKL 14
Applicant’s SEQ ID NO: 32 (Qy) vs. Lang et al.’s SEQ ID NO: 37 (Db)
Query Match 98.5%; Score 64; DB 1; Length 14;
Best Local Similarity 100.0%;
Matches 14; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EHXERLKANDSLKL 14
||||||||||||||
Db 1 EHXERLKANDSLKL 14
The therapeutic agent is capable of producing a neurosalutary effect that includes a response favorable to the health or function of neuron or part of the nervous system such as stimulating axonal outgrowth after injury to a neuron and promoting neural sprouting (par. [0084]-[0085]). Peptide mimetics of the LAR family, in particular, are found to inhibit and/or reduce LAR activity induced by CSPG activation when delivered into a neural cell. Inhibition of LAR family activity, signaling, and/or function leads to promotion of neural cell outgrowth, sprouting, neural cell survival and plasticity, as well as inhibition of neural cell dieback (par. [0087]). The term “neuronal outgrowth” is defined as a process by which axons or dendrites extend from a neuron and can result in a new neuritic projection or extension of a previously existing process (par. [0045]). Hence, the disclosed peptides are useful for promoting plasticity and functional recovery following neural injury and for treating a disease, disorder, and/or condition of the nervous system including neural injury, neural degenerative disorders, and neurological disorders such as traumatic/toxic injuries to nerves, spinal cord, or brain, as well as traumatic brain injury, cerebral aneurysm, stroke, and spinal cord injury (par. [0013]-[0016], [00181]-[0182]).
In some embodiments, Lang et al. teaches delivering the therapeutic agent to neurons of the CNS that are uninjured/healthy and located at the site of injury or at a site incident to the injury, wherein the neurons being targeted are neurons from which neuronal outgrowth is believed to be beneficial (par. [0156]).
Based on all these teachings, a person with ordinary skill in the art before the effective filing date of the claimed invention would have expected that administering one of the disclosed therapeutic peptides to uninjured/healthy neurons at the site of injury, or at a site incident to the injury, would stimulate neural sprouting or neuronal outgrowth, thereby forming new neuritic projections or extending a previously existing axonal process. Lang et al. therefore satisfies the claimed method’s intended function of “promoting compensatory plasticity of spared neural cells after a neural injury”.
Hence, claim 1 is anticipated by Lang et al..
Regarding claim 2: using the therapeutic agent to promote the growth, survival, and plasticity of a LAR family phosphatase-expressing cell such as neural stem cells and neural progenitor cells (par. [0081], [0195]) meets the requirement that “the spared neural cells are neural stem cells”.
Regarding claim 3: the embodiment of the cell being a glial progenitor cell (par. [0009]) is analogous to “the spared neural cells comprise oligodendrocyte progenitor cells (OPCs) and/or glial precursor cells (GPCs)”.
Regarding claim 4: the therapeutic agent being delivered to target cells, which include neurons that are either injured or uninjured (par. [0152], [0156]) satisfies “wherein the spared neural cells are neurons”.
Regarding claims 5-8: using the therapeutic agent comprising a therapeutic peptide to stimulate axonal outgrowth after injury to a neuron, reversing/reducing dieback, and/or promote neural sprouting (par. [0085], [0087]), wherein the term “axonal outgrowth” is defined as including the process by which axons or dendrites extend from a neuron that result in a new neuritic projection or extension of a previously existing axonal process (par. [0045]), fulfills the limitations “wherein the peptide induces compensatory neurite outgrowth of the spared neural cells”, “wherein the neurite outgrowth comprises axonal sprouting of the spared neural cells”, “wherein the neurite outgrowth comprises dendrite sprouting or branching of the spared neural cells”, and “wherein the peptide induces compensatory migration of spared neural cells toward the neural injury”.
Regarding claim 9: delivering the therapeutic agent to the neurons of the central nervous system, wherein said neurons may be injured (par. [0156]), satisfies “wherein the neural injury is in the central nervous system.
Regarding claim 10: treating injuries to nerves, spinal cord, or brain, as well as traumatic brain injury (par. [0013]-[0016], [00181]-[0182]) and the embodiment of administering the therapeutic agent to the subject’s brain when an injury occurs that results in a condition characterized by aberrant axonal outgrowth of the CNS neurons (par. [0165]) corresponds to “wherein the neural injury is in the brain”.
Regarding claim 11: treating a medical condition associated with a neural injury including cerebrovascular diseases like cerebral hemorrhage (par. [0185]-[1086]) is equivalent to “wherein the neural injury is caused by cerebral hemorrhage”.
Regarding claim 14: the therapeutic peptide being selected from the group consisting of SEQ ID NOs: 9-33 like SEQ ID NO: 17 (par. [0007]) or a therapeutic peptide having at least about 65%-95% homology to SEQ ID NO: 37 (par. [0008]), both of which are 100% identical to applicant’s SEQ ID NO: 32 reads on “wherein the amino acid sequence has at least 78% identity to SEQ ID NO:32”.
Regarding claim 15: some of the disclosed therapeutic peptides have an amino acid substitution at the 5th residue of SEQ ID NO: 32 such as the prior art’s SEQ ID NO: 16, which harbors amino acid residue H instead of R, thus satisfying “wherein the therapeutic peptide comprises a substitution of an amino acid of at least one of residue 4, 5, 6, 7, 9, 10, 12, or 13 of SEQ ID NO: 32 for another amino acid, wherein the amino acid residue 4E is substituted with D or Q, amino acid residue 5R is substituted with H, L or K…”.
Applicant’s SEQ ID NO: 32 (Qy) vs. Lang et al.’s SEQ ID NO: 16 (Db)
Query Match 88.6%; Score 62; DB 1; Length 24;
Best Local Similarity 85.7%;
Matches 12; Conservative 1; Mismatches 1; Indels 0; Gaps 0;
Qy 1 EHTERLKANDSLKL 14
|||| |||||:|||
Db 4 EHTEHLKANDNLKL 17
Regarding claim 16: the prior art’s SEQ ID NO: 17 and 37 have the amino acid sequence of applicant’s SEQ ID NO: 32 and therefore fulfills “wherein the therapeutic peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-25 and 32”.
Regarding claim 17: the embodiment of the therapeutic agent having a transport moiety that is linked to the therapeutic peptide and facilitates uptake of said peptide by the cell such as an HIV Tat transport moiety (par. [0010], [0121]-[0125]) is identical to “wherein the therapeutic agent further comprises a transport moiety linked to the therapeutic peptide and facilitates uptake of the therapeutic peptide by a cell”.
Regarding claim 19: the transport moiety can be linked to the therapeutic peptide via a linking polypeptide (par. [0121]) and therefore meets the limitation “wherein the transport moiety is linked to the therapeutic peptide by a peptide linker”.
Regarding claim 20: some of the disclosed therapeutic peptides contains a Tat-mediated protein delivery sequence and have the amino acid sequence of SEQ ID NOs: 42-66 and 70-74 (par. [0123]). For example, SEQ ID NO: 42 harbors the Tat-mediated protein sequence GRKKRRQRRR, which is the same as the transport moiety in applicant’s SEQ ID NO: 35 and thus satisfies “wherein the therapeutic agent comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 35-61”.
Applicant’s SEQ ID NO: 35 (Qy) vs. Lang et al.’s SEQ ID NO: 42 (Db)
Query Match 98.8%; Score 164; DB 1; Length 33;
Best Local Similarity 97.0%;
Matches 32; Conservative 0; Mismatches 1; Indels 0; Gaps 0;
Qy 1 GRKKRRQRRRXDLAEHTEHLKANDNLKSQEYES 33
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Db 1 GRKKRRQRRRCDLAEHTEHLKANDNLKSQEYES 33
Regarding claim 21: the therapeutic agent being administered at a therapeutically effective amount to the subject at the site of injury such as the nervous system up to about or within 100 hours (about 4 days) after occurrence of the injury (par. [0158], [0165]) satisfies “wherein the spared neural cells are contacted with the therapeutic agent within 7 days post injury”.
Regarding claim 22: as set forth above (see rejection on claim 1) and applied herein, Lang et al.’s method of treating a medical condition associated with a neural injury including cerebrovascular diseases like cerebral hemorrhage (par. [0185]-[1086]) is equivalent to “A method of treating a neural injury cerebral hemorrhage in a subject in need thereof”.
Performing the method to promote neural sprouting or neuronal outgrowth, which creates new neuritic projections or extends a previously existing axonal process, fulfills “promoting compensatory plasticity in spared neural cells after the cerebral hemorrhage”.
Administering to a subject’s cell a therapeutic agent such as a therapeutic peptide selected from the group consisting of SEQ ID NOs: 9-33 such as SEQ ID NO: 17 (par. [0007]) or a therapeutic peptide that is at least about 65%-95% homologous to the amino acid sequence of SEQ ID NO: 37 (par. [0008], [0156]-[0158]) at a therapeutically effective amount, wherein both sequences are 100% identical to applicant’s SEQ ID NO: 32, is the same as “administering to the subject an effective amount of a therapeutic agent comprising a therapeutic peptide, wherein the therapeutic peptide comprises an amino acid sequence with at least 70% identity to SEQ ID NO:32”.
Regarding claim 45: providing the therapeutic agent comprising a therapeutic peptide having the amino acid sequence of SEQ ID NO: 32 linked to a transport moiety as a pharmaceutical composition, wherein the transport moiety facilitates uptake of the therapeutic peptide by a cell (par. [0020]; claims 59-63), reads on “A composition comprising an effective amount of a therapeutic agent for treating a neural injury and pharmaceutically acceptable carrier, wherein the therapeutic agent comprises a therapeutic peptide and a transport moiety linked to the therapeutic peptide that facilitates uptake of the therapeutic peptide by a cell, wherein the therapeutic peptide comprises an amino acid sequence with at least 70% identity to SEQ ID NO: 32”.
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 1-11, 14-17, 19-22, and 45 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-27 of U.S. Patent No. 12,138,300.
The U.S. patent is directed to a method of promoting compensatory plasticity of spared neural cells of a subject's brain after a neural injury, wherein the neural injury is caused by cerebral focal ischemia, cerebral global ischemia, acute ischemic stroke, malignant stroke, chronic stroke disease, thrombus, or embolism, and wherein the therapeutic peptide induces compensatory neurite outgrowth in the spared neural cell. In one aspect, the method aims to treat a neural injury in a subject in need thereof by promoting compensatory plasticity in spared neural cells.
Similar to the claimed method which administers a therapeutic peptide comprising an amino acid sequence with at least 70% identity to SEQ ID NO: 32, the U.S. patent’s method comprises administering to the subject after the neural injury an effective amount of a therapeutic agent comprising a therapeutic peptide and a transport moiety linked to the therapeutic peptide that facilitates uptake of the therapeutic peptide by a cell, wherein the therapeutic peptide comprises an amino acid sequence with at least 70% identity to SEQ ID NO: 32. The transport moiety can be an HIV Tat transport moiety and linked to the therapeutic peptide by a peptide linker. Thus, the therapeutic peptide can comprise an amino acid sequence selected from the group consisting of SEQ ID NOs: 35-61.
One embodiment of the therapeutic peptide is that it comprises a substitution of an amino acid of at least one of residue 4, 5, 6, 7, 9, 10, 12, or 13 of SEQ ID NO: 32. The substitution includes: the amino acid residue 4E being substituted with D or Q; amino acid residue 5R being substituted with H, L or K; amino acid residue 6L being substituted with I, V or M; amino acid residue 7K being substituted with R or H; amino acid residue 9N being substituted with E or D; amino acid residue 10D being substituted with E or N; amino acid residue 12L being substituted with I, V or M; and/or amino acid residue 13K being substituted with R or H.
In some embodiments, the spared neural cells can be neurons, neural stem cells, oligodendrocyte progenitor cells (OPCs) and/or glial precursor cells (GPCs). Moreover, the spared neural cells can be contacted with the therapeutic agent within 7 days post injury.
Although none of the claims are directed to a composition, the method discloses use of a therapeutic agent comprising a therapeutic peptide having an amino acid sequence with at least 70% identity to SEQ ID NO: 32 and a therapeutic peptide linked to a transport moiety, wherein said transport moiety facilitates uptake of the therapeutic peptide by a cell. A person with ordinary skill in the art would have thus found it obvious to provide a composition comprising the disclosed therapeutic agent.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHELLE F PAGUIO FRISING whose telephone number is (571)272-6224. The examiner can normally be reached Monday-Friday, 8:00 a.m. - 4:00 p.m..
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Melenie L. Gordon can be reached at (571) 272-8037. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Michelle F. Paguio Frising/Primary Examiner, Art Unit 1651
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