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 .
DETAILED ACTION
RESPONSE TO AMENDMENT
Status of Application/Amendments/claims
2. Applicant’s amendment filed February 4, 2026 is acknowledged. Claim 4 is cancelled. Claim 6 is amended. Claims 12-13 are newly added. Claims 1-3, 5-11 and newly added claims 12-13 are pending in this application. Claims 1-2 and 8-9 are withdrawn with traverse (filed on 08/18/2025) from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on August 18, 2025.
3. Claims 3, 5-7 and 10-13 are under examination with respect to SEQ ID NO:53 for an epitope sequence, SEQ ID NOs: 58-63 for LCDRs1-3 and HCDRs1-3 in this office action.
4. Applicant’s arguments filed on February 4, 2026 have been fully considered but they are not deemed to be persuasive for the reasons set forth below.
Claim Rejections/Objections Maintained
In view of the amendment filed on February 4, 2026, the following rejections are maintained.
Claim Rejections - 35 USC § 112
5. 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 3, 5-7 and 10-13 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of reducing levels of CXCL10 and IL-2, and increasing levels of IL-10 in HTLV-1-associated myelopathy (HAM)-derived peripheral blood mononuclear cells (HAM-derived PBMCs) cultured in a culture medium supplemented with a structurally and functionally defined anti-RGMa antibody in vitro as compared to HAM-derived PMBCs without the anti-RGMa antibody or supplemented with normal IgG; or a method of reducing apoptosis in neuronal cells NB-1 cells co-cultured with JPX9+CdCl2 and a structurally and functionally defined anti-RGMa antibody in vitro as compared to NB-1 cells co-cultured with JPX9+CdCl2 and an normal mouse IgG2b in vitro, does not reasonably provide enablement for a method for treating HAM, comprising administering to an HAM patient in need thereof a pharmaceutically effective amount of an RGMa-inhibiting substance that is an anti-RGMa antibody including structurally and functionally undefined anti-RGMa antibodies as broadly claimed. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims. The rejection is maintained for the reasons made of record and the reasons set forth below.
Claims 3, 5-7 and 10-11 as amended are directed to a method for treating HTLV-1-associated myelopathy (HAM), comprising administering to an HAM patient in need thereof a pharmaceutically effective amount of an RGMa-inhibiting substance that is an anti-RGMa antibody or an antigen-binding fragment thereof, wherein the antibody includes an antibody recognizing one or more peptides having the amino acid sequences of SEQ ID NO: 53-57 or any position of 250th and the subsequent positions in the amino acid sequence of human RGMa or having SEQ ID NOs: 58-63 (elected) for LCDRs1-3 and HCDRs1-3 respectively or SEQ ID NOs: 64-68 and SFG for LCDRs1-3 and HCDRs1-3 or SEQ ID NOs: 95-96 or at least 90% identical to SEQ ID NOs:95-96 for VH and VL or SEQ ID NOs:84 and 88 or with 1-20 amino acids are substituted, deleted, added or inserted thereof for heavy chain and light chain.
Claims 12-13 as amended are directed to methods for suppressing, in an HTLV-1 associated myelopathy (HAM) patient, an inflammatory reaction associated with CXCL10 and/or neuronal cell death induced by HTLV-1-tax-expressing cells and suppressing injury and/or degeneration of spinal cord tissue in an HTLV-1-associated myelopathy (HAM) patient, comprising administering to an HAM patient in need thereof a pharmaceutically effective amount of an RGMa-inhibiting substance which is an anti-RGMa antibody or an antigen-binding fragment thereof.
Response to Arguments
On p. 7-12 of the response, Applicant arguses Dr. Yamano’s declaration filed 2/4/26 provides further evidence to support the enablement of the claimed invention. Applicant argues that: i) the inventors are the first to discover the relationship between HAM and RGMa and demonstrate the effect of anti-RGMa-antibodies for HAM (para. 12 of the declaration); ii) a skilled artisan would understand the in vitro data correlates to the in vivo treatment of HAM and a skilled artisan would have been able to treat HAM in vivo using anti-RGMa antibodies without undue experimentation (see para. 13 of the declaration) because:
a) CXCL10 plays a critical in the chronic inflammation mechanism, one of the causes of HAM;
b) no animal model can be reproduced natural HTLV-1 infection and human HLA-restricted CTL response (para.14 of the declaration);
c) the ex vivo or in vitro analyses using patient-derived PBMCs are used as standard and valid research methods for evaluating disease pathology and therapeutic effects and the clinical trials confirmed therapeutic efficacy against HAM, for example, the clinical trials for treatment of HAM using anti-CCR4 monoclonal antibody confirmed the effects of anti-CCR4 monoclonal antibody on the in vitro model from patient-derived PBMCs (see para. 14 of the declaration);
d) the neuronal apoptosis in co-cultured PBMCs derived from HAM patients with a neuronal cell line in Example 9 is consistent with neuronal damage in HAM induced by immune responses against HTLV-infected T cells (see para. 15 of the declaration);
e) reducing neuronal cell death in neural cells co-cultured with JPX-9 cells expressing Tax and RGMa by an RGMa antibody is shown in Example 10 (see para. 15 of the declaration);
f) HTLV-1-infected would be suppressed by anti-RGMa antibody (see para.15-16 of the declaration);
g) chronic inflammatory responses are associated with neuronal cell death in the spinal cord in HAM and administration of anti-RGMa antibody would suppress CXCL10 production and neuronal cell death caused by HTLV-1-infected cells (see para. 16 and 18 of the declaration);
h) HAM is a multifactorial disease involving multiple immunological factors including HTLV-1 proviral load, inflammatory cytokines (IFN-r and TNF-a) and activation and proliferation of CD4+ T cells, and administration of an anti-RGMa antibody suppress neuronal cell death caused by HTLV-1-infected cells and suppresses the production of CXCL10 which is for maintaining chronic inflammation (see para. 20 of the declaration);
i) CXLC10 is highly expressed in CSF and spinal cord lesions of HAM and maintains chronic inflammation, and the levels of IL-2 and IL-10 reflect qualitive changes in inflammatory immune environment, which indicate the overall disease state (see para. 22 of the declaration);
j) administration of an anti-RGMa antibody would suppress chronic inflammation and immunologically mediated neuronal cell damage in vivo, which are the essential pathology of HAM (see para. 23 of the declaration).
Applicant's arguments have been fully considered but they are not found persuasive. Contrary to Applicant's arguments, the examiner asserts that based on MPEP §2164, MPEP §§2164.01-2164.06(b) & 2164.08, neither the specification nor the prior art provides sufficient guidance to enable a skilled artisan to practice the claimed invention without undue experimentation because:
i. The Dr. Yamano’s declarations under 37 CFR 1.132 filed February 4, 2026 and May 14, 2025 are insufficient to overcome the rejection of claims 3, 5-7 and 10-13 based upon insufficiency of disclosure under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph as set forth in the last Office action because: the showings are not commensurate in scope with the claims. The declarations only include(s) statements which amount to an affirmation that the claimed subject matter functions as it was intended to function. This is not relevant to the issue of lack of enablement of the claimed subject matter and provides no objective evidence thereof. See MPEP § 716.
The Dr. Yamano’s declarations provide no well-established structural and functional relationship or correlation between the anti-CCR4 monoclonal antibody that is confirmed in a clinical trial taught by Nozum (p. 653) (p.9 of the response and para 14 of the declaration) and the claimed anti-RGMa antibody in the treatment of HAM.
The Dr. Yamano’s declarations provide no well-established correlation between the reduced levels of CXCL10 and IL-2, and the increased levels of IL-10 in cultured HAM-derived PBMCs treated with an anti-RGMa antibody in vitro as compared to no treatment or normal IgG and the treatment of HAM in an HAM patient in vivo using an anti-RGMa antibody.
The Dr. Yamano’s declarations provide no well-established correlation between the reduced apoptosis in neuronal cells NB-1 cells co-cultured with JPX9+CdCl2 treated with an anti-RGMa antibody in vitro as compared to a normal mouse IgG2b and the treatment of HAM in an HAM patient in vivo using an anti-RGMa antibody.
Note that the in vitro cultures of HAM-derived PBMCs are cultured under conditions optimized for cell survival whereas the affected cells in pathogeneses of HAM in vivo are not.
ii. Neither the specification nor the Dr. Yamano’s declarations provide sufficient evidence or data to demonstrate that administration of the claimed anti-RGMa can treat HAM in vivo or suppress an inflammatory reaction associated with CXCL10 and/or neuronal cell death induced by HTLV-1-tax-expresing cells or injury and/or degeneration in spinal cord tissue in HAM patient in vivo.
As admitted and acknowledged by Applicant on p. 11 of the response and para. 20 of the declaration, the increased expression of RGMa is not the only cause of HAM, and other factors including HTLV-1 proviral load, levels of IFN and TNF, and proliferative activity of CD4 cells are also involved in the pathogenesis of HAM.
Based on Applicant’s own admission, cultured HAM-derived PBMCs treated with an anti-RGMa antibody in vitro do not result in changes in HTLV-1 proviral load, levels of IFN and TNF, and proliferative activity of CD4 cells (see Examples 8, figures 9, 10 and 12).
The example of anti-CCR4 monoclonal antibody that is confirmed in a clinical trial taught by Nozum (p. 653) and as described in Applicant’s arguments (p.9) and the declaration (para.14) has different results from the claimed anti-RGMa antibody in vitro because the anti-CCR4 monoclonal antibody “effectively reduced the proviral load and proinflammatory cytokines in PBMCs from patients with HAM/TSP…”. However, in instant case, HTLV-1 proviral load, levels of IFN and TNF, and proliferative activity of CD4 cells are not changed in cultured HAM-derived PBMCs treated with an anti-RGMa antibody in vitro.
The Dr. Yamano’s declarations provide no well-established structural and functional relationship or correlation between the anti-CCR4 monoclonal antibody and the claimed anti-RGMa antibody, wherein the anti-CCR4 monoclonal antibody effectively reduces the proviral load and proinflammatory cytokines in HAM/TSP PBMCs whereas the claimed anti-RGMa antibody has no effects on HTLV-1 proviral load, levels of IFN and TNF, and proliferative activity of CD4 cells.
iii. Neither Dr. Yamano’s declarations nor the specification provides nexus between the collective in vitro data of detecting reduced CXCL10 and IL2, and increased IL-10 in cultured HAM-derived PBMCs treated with an anti-RGMa antibody in vitro as compared to no treatment and the pathogenesis of HAM including the HTLV-1 proviral load, levels of IFNg and TNF, and proliferative activity of CD4 cells or the symptoms of chronic progressive spastic paraparesis, urinary incontinence, mild sensory disturbance and inflammation and degeneration of the spinal cord in HAM patients treated with an anti-RGMa antibody in vivo.
There is no well-established correlation between the in vitro data obtained from cultured HAM-derived PBMCs treated with anti-RGMa antibody in vitro and the treatment of HAM using the claimed anti-RGMa antibody in vivo.
There is also no well-established correlation between the in vitro data obtained from neuronal cells NB-1 cells co-cultured with JPX9+CdCl2 and a commercially available anti-RGMa antibody in vitro and the treatment of HAM using the claimed anti-RGMa antibody in vivo.
Neither the specification nor the Dr. Yamano’s declarations provide evidence or data to demonstrate that administration of the claimed anti-RGMa can treat HAM in vivo or can suppress an inflammatory reaction associated with CXCL10 and/or neuronal cell death induced by HTLV-1-tax-expressing cells in vivo and suppressing injury and/or degeneration of spinal cord tissue in an HTLV-1-associated myelopathy (HAM) patient in vivo
Thus, it is unpredictable whether administration of the claimed anti-RGMa antibody to patients with HAM in vivo can treat HAM, indicating that undue experimentation is required by a skilled artisan to perform while practicing the claimed invention.
Note that the scope of the claims must bear a reasonable correlation with the scope of enablement (In re Fisher, 166 USPQ 19 24 (CCPA 1970)). Without such guidance, it is unpredictable whether HAM can be treated by administration of the claimed anti-RGMa antibody; and thus the experimentation left to those skilled in the art is extensive and undue. See Ex parte Forman, 230 USPQ 546 (Bd. Pat. App. & Int. 1986). Thus, the skilled artisan cannot readily know how to use the claimed invention as currently claimed without further undue experimentation. In re Marzocchi, 439 F.2d 220, 223-24, 169 USPQ 367, 369-70 (CCPA 1971)” See MPEP § 2164.03.
Therefore, in view of the breadth of the claims, the lack of guidance in the specification, no working examples, the unpredictability of inventions, and the current status of the art, undue experimentation would be required by a skilled artisan to perform in order to practice the claimed invention as it pertains to a method for treating HAM or suppressing an inflammatory reaction associated with CXCL10 and/or neuronal cell death induced by HTLV-1-tax-expressing cells or injury and/or degeneration of spinal cord tissue in an HTLV-1-associated myelopathy (HAM) patient by administration of the claimed anti-RGMa antibody to the HAM patient.
Accordingly, the rejection of claims 3, 5-7 and 10-13 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, lack of scope of enablement is maintained.
Claim Rejections - 35 USC § 112
6. Claims 3, 5-7 and 10-13 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. The rejection is maintained for the reasons made of record and the reasons set forth below.
Claims 3 and 12-13 as amended encompasses using a genus of structurally and functionally undefined anti-RGMa antibodies or antigen-binding fragments thereof for treating HTLV-1-associated myelopathy (HAM) or suppressing an inflammatory reaction associated with CXCL10 and/or neuronal cell death induced by HTLV-1-tax-expressing cells or injury and/or degeneration of spinal cord tissue in a HAM patient.
Claims 5-6 encompasses using a genus of structurally and functionally undefined anti-RGMa antibodies or antigen-binding fragments thereof binding to one or more peptides having the amino acid sequence of SEQ ID NO:53, 54, 55, 56 or 57 for treating HAM.
Claims 7 and 10-11 encompasses using a genus of anti-RGMa antibodies or antigen-binding fragments wherein the antibodies having SEQ ID NOs:58-63 for LCDRs1-3 and HCDRs1-3 respectively, or SEQ ID NOs:95-96 or at least 90% identical to SEQ ID NOs: 95-96 for VH and VL respectively, or SEQ ID NO:84 and 88 or variants thereof with 1-20 amino acids substituted, deleted, added or inserted for HC and LC respectively for treating HAM.
Response to Arguments
On p.13-15 of the response, Applicant argues that for the reasons set forth above, a skilled artisan would know Applicant had possession of the claimed method because: i) the specification discloses a variety of structures and features of anti-RGMa antibodies and substances including siRNA, shRNA, antisense that suppress the expression of RGMa. Applicant cites Examples 8-10, paragraphs [0016-0044] of the instant specification including a polyclonal binding aa 48-422 of human RGMa in Example 8 and antibody binding to C-terminal region of human RGMA and cites para. 25-26 of the declaration in support of the arguments.
Applicant's arguments have been fully considered but they are not found persuasive. Contrary to Applicant's arguments, the examiner asserts that based on MPEP §2163, MPEP §§2163.01-2163.03, the specification fails to provide sufficient description or information or evidence to demonstrate that Applicant is in possession of using the claimed genus of anti-RGMa antibodies or antigen-binding fragments thereof or variants thereof for treating HAM because:
i. There is no structural and functional relationship between the claimed genus of anti-RGMa antibodies or antigen-binding fragments thereof recited in claims 3, 5-6 and 12-13 and the anti-RGMa antibody (manufactured by R&D Systems, Inc) used in Example 8 or anti-RGMa antibody (IBL) used in Example 10.
There is no structural and functional relationship between the claimed genus of anti-RGMa variant antibodies or antigen-binding fragments thereof having at least 90% identity to SEQ ID NOs: 95-96 for VH and VL respectively or having SEQ ID NOs:84 and 88 with 1-20 amino acid substitution, deletion, addition or insertion recited in claims 10-11 and the anti-RGMa antibody (manufactured by R&D Systems, Inc) used in Example 8 or anti-RGMa antibody (IBL) used in Example 10.
The specification provides no structural and functional relationship or correlation between the claimed genus of anti-RGMa antibodies or antigen-binding fragments thereof or variants thereof with the recited SEQ ID NOs: and the anti-RGMa antibodies obtained from R&D Systems, Inc. used in Example 8 or anti-RGMa antibody (IBL) used in Example 10.
Applicant has not disclosed sufficient species for using the broad genus of anti-RGMa antibodies or antigen-binding fragments recited in instant claims 3, 5-6 and variants recited in instant claims 10-11 for treating HAM.
The specification provides no structures or sequences sufficiently detailed to show that he/she was in possession of the claimed invention as a whole. There was no known or disclosed correlation between the required function (binding to RGMa, or one or more peptide having the recited SEQ ID NOs: 53-57 or any position of 250th and the subsequent positions in human RGMa) and any particular structure or sequence for anti-RGMa antibodies antigen-binding fragments thereof or variants thereof for treating HAM. The specification fails to teach the detailed structures and sequences and characteristics for the claimed genus of anti-RGMa antibodies or antigen-binding fragments thereof or variants thereof or treating HAM.
The specification fails to teach what other structures/amino acid sequences can or cannot be included/changed in the claimed genus of anti-RGMa antibodies or antigen-binding fragments thereof or variants thereof in order to preserve the activity in reducing concentrations of CXCL10 and IL-2 and increasing a concentration of IL-10 in HAM-derived PBMCs in vitro as compared to HAM-derived PMBCs cultured without the anti-RGMa antibody or supplemented with normal IgG (See Example 8, Figures 11-12) or reducing apoptosis in NB-1 cells co-cultured with JPX9+CdCl2 as compared to the NB-1 cells co-cultured with JPX9+CdCl2 and a normal mouse IgG2b, or even for treating HAM.
Since the common characteristics/features of other anti-RGMa antibodies or antigen-binding fragments thereof or variants thereof are unknown, a skilled artisan cannot envision the functional correlations of the genus with the claimed invention.
ii. As stated in M.P.E.P. § 2163(II)(A)(3), a specification may describe an actual reduction to practice by showing that the inventor constructed an embodiment or performed a process that met all the limitations of the claim and determined that the invention would work for its intended purpose. Cooper v. Goldfarb, 154 F.3d 1321,1327, 47 USPQ2d 1896, 1901 (Fed. Cir. 1998). See also UMC Elecs. Co. v. United States, 816 F.2d 647, 652, 2 USPQ2d 1465, 1468 (Fed. Cir. 1987) (“[T]here cannot be a reduction to practice of the invention ... without a physical embodiment which includes all limitations of the claim.”); Estee Lauder Inc. v. L’Oreal, S.A., 129 F.3d 588, 593, 44 USPQ2d 1610, 1614 (Fed. Cir. 1997) (“[A] reduction to practice does not occur until the inventor has determined that the invention will work for its intended purpose.”); Mahurkar v. C.R. Bard, Inc., 79 F.3d 1572, 1578, 38 USPQ2d 1288, 1291 (Fed. Cir. 1996) (determining that the invention will work for its intended purpose may require testing depending on the character of the invention and the problem it solves).
To demonstrate the reduction to practice of a method of treating an HAM patient by administration of an anti-RGMa antibody requires either a working embodiment, a demonstration of operability in the treatment of an art accepted animal model of the condition to be treated wherein that animal model has been shown to be reliably predictive of efficacy in the treatment of the condition, or a demonstration that the therapeutic agent employed therein possesses an activity in which the majority of anti-RGMa antibodies possessing the activity have been shown to be effective in the treatment of the condition.
In the instant case, Applicant has provided none of these. Consequently, Applicant has failed to demonstrate possession of the claimed method or even a single species of using the genus of anti-RGMa antibodies or antigen-binding fragments thereof or variants thereof required thereby as of the earliest effective filing date of the instant application.
Applicant has failed to demonstrate a reduction to practice of a representative number of species of using the genus of “anti-RGMa antibody, or antigen-binding fragments thereof or variants thereof” in a method of treating HAM in an HAM patient in need thereof by the administration of such anti-RGMa antibodies or antigen-binding fragments thereof or variants thereto. The experimental results described in the specification consist primarily of the characterization of differences between an anti-RGMa antibody and a normal mouse IgG2b in HAM-derived PBMCs in vitro.
There is no well-established correlation between the in vitro data obtained from cultured HAM-derived PBMCs treated with anti-RGMa antibody in vitro and the treatment of HAM using the claimed anti-RGMa antibody in vivo.
There is also no well-established correlation between the in vitro data obtained from neuronal cells NB-1 cells co-cultured with JPX9+CdCl2 and a commercially available anti-RGMa antibody in vitro and the treatment of HAM using the claimed anti-RGMa antibody in vivo.
Neither the specification nor the Dr. Yamano’s declarations provide evidence or data to demonstrate that Applicant is in possession of the claimed method of treating HAM in vivo by administration of the claimed anti-RGMa or antigen-binding fragment thereof or suppressing an inflammatory reaction associated with CXCL10 and/or neuronal cell death induced by HTLV-1-tax-expressing cells and suppressing injury and/or degeneration of spinal cord tissue in an HTLV-1-associated myelopathy (HAM) patient in vivo by administration of the claimed anti-RGMa antibody or antigen-binding fragment thereof including structurally and functionally undefined anti-RGMa antibody or antigen-binding fragment thereof.
Based on MPEP § 2161.01 and §2163, “to satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116”.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116).
As discussed above, the skilled artisan cannot envision the detailed chemical structure of the encompassed genus of anti-RGMa antibodies for treatment of HAM or suppressing an inflammation reaction associated with CXCL10 and/or neuronal cell death induced by HTLV-1-tax-expression or injury and/or degeneration of spinal cord in an HAM patient in vivo, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483.
Therefore, the claimed methods hav not met the written description provision of 35 U.S.C. §112, first paragraph. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115). Applicant is directed to the Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, ¶ 1 "Written Description" Requirement. See MPEP § 2161.01 and 2163.
Accordingly, the rejection of claims 3, 5-7 and 10-13 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 is maintained.
Conclusion
7. NO CLAIM IS ALLOWED.
8. The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Paul et al. (US2019/0224339) teaches a method for treating various neurological disease including HTLV-1-associated myelopathy (HAM) listed in a disease list, comprising administering to an HAM patient in need thereof a pharmaceutical composition comprising AAV particles including an AAV encoding an antibody including anti-RGMa antibody in the list (see paragraphs [0478]; [0489]; [0528], p. 72-73, p. 80-81, table 3).
US10287346 teaches an anti-RGMa antibody comprising a VH of SEQ ID NO:41, which is 100% identical to instant SEQ ID NO:95 and a VL of SEQ ID NO: 42, which is 100% identical to instant SEQ ID NO:96 (see the sequence alignment below).
SEQ ID NO:95
US-15-569-382-41
(NOTE: this sequence has 1 duplicate in the database searched)
Sequence 41, US/15569382
Patent No. 10287346
GENERAL INFORMATION
APPLICANT: Mitsubishi Tanabe Pharma Corporation
APPLICANT: Osaka University
APPLICANT: National University Corporation Chiba University
TITLE OF INVENTION: RGMa BINDING PROTEIN AND USE THEREOF
FILE REFERENCE: 730591
CURRENT APPLICATION NUMBER: US/15/569,382
CURRENT FILING DATE: 2017-10-25
PRIOR APPLICATION NUMBER: PCT/JP2016/063166
PRIOR FILING DATE: 2016-04-27
PRIOR APPLICATION NUMBER: JP2015-091095
PRIOR FILING DATE: 2015-04-28
NUMBER OF SEQ ID NOS: 46
SEQ ID NO 41
LENGTH: 116
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Synthetic humanized antibody heavy chain
Query Match 100.0%; Score 612; Length 116;
Best Local Similarity 100.0%;
Matches 116; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLVQPGRSLRLSCTASGFTFSDAWMDWVRQAPGKGLEWVAEIRSKANNHAT 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVESGGGLVQPGRSLRLSCTASGFTFSDAWMDWVRQAPGKGLEWVAEIRSKANNHAT 60
Qy 61 YYAESVKGRFTISRDDSKSIVYLQMNSLRTEDTALYYCTRRDGAYWGKGTTVTVSS 116
||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 YYAESVKGRFTISRDDSKSIVYLQMNSLRTEDTALYYCTRRDGAYWGKGTTVTVSS 116
SEQ ID NO:96
US-15-569-382-42
(NOTE: this sequence has 1 duplicate in the database searched)
Sequence 42, US/15569382
Patent No. 10287346
GENERAL INFORMATION
APPLICANT: Mitsubishi Tanabe Pharma Corporation
APPLICANT: Osaka University
APPLICANT: National University Corporation Chiba University
TITLE OF INVENTION: RGMa BINDING PROTEIN AND USE THEREOF
FILE REFERENCE: 730591
CURRENT APPLICATION NUMBER: US/15/569,382
CURRENT FILING DATE: 2017-10-25
PRIOR APPLICATION NUMBER: PCT/JP2016/063166
PRIOR FILING DATE: 2016-04-27
PRIOR APPLICATION NUMBER: JP2015-091095
PRIOR FILING DATE: 2015-04-28
NUMBER OF SEQ ID NOS: 46
SEQ ID NO 42
LENGTH: 107
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Synthetic humanized antibody light chain
Query Match 100.0%; Score 562; Length 107;
Best Local Similarity 100.0%;
Matches 107; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIQMTQSPSSVSASVGDRVTITCRASQDISSYLNWYQQKPGKAPKLLIYYTSRLHSGVPS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DIQMTQSPSSVSASVGDRVTITCRASQDISSYLNWYQQKPGKAPKLLIYYTSRLHSGVPS 60
Qy 61 RFSGSGSGTDFTLTISSLQPEDFASYFCQQLNTLPWTFGGGTKVEME 107
|||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFSGSGSGTDFTLTISSLQPEDFASYFCQQLNTLPWTFGGGTKVEME 107
US11008388 teaches an anti-RGMa antibody comprising a VH of SEQ ID NO:41, which is 100% identical to instant SEQ ID NO:95 and a VL of SEQ ID NO:42, which is 100% identical to instant SEQ ID NO:96 (see the sequence alignment below). Hashimoto et al. (US11008388) teaches a method of treating or reducing relapse of a neurological or immunological disease selected from spinal cord injury, neurotrauma and multiple sclerosis using an anti-RGMa antibody (see col. 26, line 46-col. 27, line 41; claims 14-17).
SEQ ID NO:95
Sequence 41, US/16358657
Patent No. 11008388
GENERAL INFORMATION
APPLICANT: Mitsubishi Tanabe Pharma Corporation
APPLICANT: Osaka University
APPLICANT: National University Corporation Chiba University
TITLE OF INVENTION: RGMa BINDING PROTEIN AND USE THEREOF
FILE REFERENCE: 742239
CURRENT APPLICATION NUMBER: US/16/358,657
CURRENT FILING DATE: 2019-03-19
PRIOR APPLICATION NUMBER: 15/569,382
PRIOR FILING DATE: 2017-10-25
PRIOR APPLICATION NUMBER: PCT/JP2016/063166
PRIOR FILING DATE: 2016-04-27
PRIOR APPLICATION NUMBER: JP2015-091095
PRIOR FILING DATE: 2015-04-28
NUMBER OF SEQ ID NOS: 46
SEQ ID NO 41
LENGTH: 116
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Synthetic humanized antibody heavy chain
Query Match 100.0%; Score 612; Length 116;
Best Local Similarity 100.0%;
Matches 116; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLVQPGRSLRLSCTASGFTFSDAWMDWVRQAPGKGLEWVAEIRSKANNHAT 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVESGGGLVQPGRSLRLSCTASGFTFSDAWMDWVRQAPGKGLEWVAEIRSKANNHAT 60
Qy 61 YYAESVKGRFTISRDDSKSIVYLQMNSLRTEDTALYYCTRRDGAYWGKGTTVTVSS 116
||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 YYAESVKGRFTISRDDSKSIVYLQMNSLRTEDTALYYCTRRDGAYWGKGTTVTVSS 116
SEQ ID NO:96
Sequence 42, US/16358657
Patent No. 11008388
GENERAL INFORMATION
APPLICANT: Mitsubishi Tanabe Pharma Corporation
APPLICANT: Osaka University
APPLICANT: National University Corporation Chiba University
TITLE OF INVENTION: RGMa BINDING PROTEIN AND USE THEREOF
FILE REFERENCE: 742239
CURRENT APPLICATION NUMBER: US/16/358,657
CURRENT FILING DATE: 2019-03-19
PRIOR APPLICATION NUMBER: 15/569,382
PRIOR FILING DATE: 2017-10-25
PRIOR APPLICATION NUMBER: PCT/JP2016/063166
PRIOR FILING DATE: 2016-04-27
PRIOR APPLICATION NUMBER: JP2015-091095
PRIOR FILING DATE: 2015-04-28
NUMBER OF SEQ ID NOS: 46
SEQ ID NO 42
LENGTH: 107
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Synthetic humanized antibody light chain
Query Match 100.0%; Score 562; Length 107;
Best Local Similarity 100.0%;
Matches 107; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIQMTQSPSSVSASVGDRVTITCRASQDISSYLNWYQQKPGKAPKLLIYYTSRLHSGVPS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DIQMTQSPSSVSASVGDRVTITCRASQDISSYLNWYQQKPGKAPKLLIYYTSRLHSGVPS 60
Qy 61 RFSGSGSGTDFTLTISSLQPEDFASYFCQQLNTLPWTFGGGTKVEME 107
|||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFSGSGSGTDFTLTISSLQPEDFASYFCQQLNTLPWTFGGGTKVEME 107
WO2016175236 teaches an humanized anti-RGMa antibody comprising a VH of SEQ ID NO:41, which is 100% identical to instant SEQ ID NO:95 and a VL of SEQ ID NO:42, which is 100% identical to instant SEQ ID NO:96 (see the sequence alignment below).
SEQ ID NO:95
BDI27898
(NOTE: this sequence has 3 duplicates in the database searched)
ID BDI27898 standard; protein; 116 AA.
XX
AC BDI27898;
XX
DT 15-DEC-2016 (first entry)
XX
DE Humanized anti-RGMa antibody heavy chain variable region, SEQ ID 41.
XX
KW RGMa; Repulsive guidance molecule A; antibody production;
KW antibody therapy; heavy chain variable region; humanized antibody;
KW immune disorder; immunomodulator; neurological disease; neuroprotective;
KW prophylactic to disease; protein production; protein therapy.
XX
OS Mus musculus.
OS Homo sapiens.
OS Chimeric.
OS Synthetic.
XX
CC PN WO2016175236-A1.
XX
CC PD 03-NOV-2016.
XX
CC PF 27-APR-2016; 2016WO-JP063166.
XX
PR 28-APR-2015; 2015JP-00091095.
XX
CC PA (MTSB ) MITSUBISHI TANABE PHARMA CORP.
CC PA (OSAU ) UNIV OSAKA.
CC PA (UYCH-) UNIV CHIBA NAT CORP.
XX
CC PI Hashimoto M, Yamashita T;
XX
DR WPI; 2016-68867X/79.
DR N-PSDB; BDI27900.
XX
CC PT New isolated repulsive guidance molecule-A (RGMa) binding protein useful
CC PT in pharmaceutical composition for preventing neurological disease e.g.
CC PT amyloidosis and retina dystrophy, capable of not inhibiting binding of
CC PT RGMa and neogenin.
XX
CC PS Claim 18; SEQ ID NO 41; 74pp; Japanese.
XX
CC The present invention relates to a novel isolated RGMa binding protein
CC useful for preventing neurological disease. The invention further relates
CC to: (1) a nucleic acid molecule encoding protein part of the RGMa binding
CC protein; (2) a recombinant vector comprises the nucleic acid molecule;
CC (3) a host cell comprises the recombinant vector; (4) a method for
CC preparing the RGMa binding protein; (5) an isolated anti-RGMa antibody;
CC (5) an isolated anti-RGMa antibody; (6) a nucleic acid molecule encoding
CC protein part of the anti-RGMa antibody; (7) a recombinant vector
CC comprises the nucleic acid molecule; (8) a host cell comprises the
CC recombinant vector; and (9) a method for preparing the above-mentioned
CC anti-RGMa antibody. The RGMa binding protein of the invention is also
CC used for immunological disease. The present sequence is a humanized anti-
CC RGMa antibody heavy chain variable region, used in the invention for
CC preventing neurological disease.
XX
SQ Sequence 116 AA;
Query Match 100.0%; Score 612; Length 116;
Best Local Similarity 100.0%;
Matches 116; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLVQPGRSLRLSCTASGFTFSDAWMDWVRQAPGKGLEWVAEIRSKANNHAT 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVESGGGLVQPGRSLRLSCTASGFTFSDAWMDWVRQAPGKGLEWVAEIRSKANNHAT 60
Qy 61 YYAESVKGRFTISRDDSKSIVYLQMNSLRTEDTALYYCTRRDGAYWGKGTTVTVSS 116
||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 YYAESVKGRFTISRDDSKSIVYLQMNSLRTEDTALYYCTRRDGAYWGKGTTVTVSS 116
SEQ ID NO:96
BDI27899
(NOTE: this sequence has 3 duplicates in the database searched)
ID BDI27899 standard; protein; 107 AA.
XX
AC BDI27899;
XX
DT 15-DEC-2016 (first entry)
XX
DE Humanized anti-RGMa antibody light chain variable region, SEQ ID 42.
XX
KW RGMa; Repulsive guidance molecule A; antibody production;
KW antibody therapy; humanized antibody; immune disorder; immunomodulator;
KW light chain variable region; neurological disease; neuroprotective;
KW prophylactic to disease; protein production; protein therapy.
XX
OS Homo sapiens.
OS Mus musculus.
OS Chimeric.
OS Synthetic.
XX
CC PN WO2016175236-A1.
XX
CC PD 03-NOV-2016.
XX
CC PF 27-APR-2016; 2016WO-JP063166.
XX
PR 28-APR-2015; 2015JP-00091095.
XX
CC PA (MTSB ) MITSUBISHI TANABE PHARMA CORP.
CC PA (OSAU ) UNIV OSAKA.
CC PA (UYCH-) UNIV CHIBA NAT CORP.
XX
CC PI Hashimoto M, Yamashita T;
XX
DR WPI; 2016-68867X/79.
DR N-PSDB; BDI27901.
XX
CC PT New isolated repulsive guidance molecule-A (RGMa) binding protein useful
CC PT in pharmaceutical composition for preventing neurological disease e.g.
CC PT amyloidosis and retina dystrophy, capable of not inhibiting binding of
CC PT RGMa and neogenin.
XX
CC PS Claim 18; SEQ ID NO 42; 74pp; Japanese.
XX
CC The present invention relates to a novel isolated RGMa binding protein
CC useful for preventing neurological disease. The invention further relates
CC to: (1) a nucleic acid molecule encoding protein part of the RGMa binding
CC protein; (2) a recombinant vector comprises the nucleic acid molecule;
CC (3) a host cell comprises the recombinant vector; (4) a method for
CC preparing the RGMa binding protein; (5) an isolated anti-RGMa antibody;
CC (5) an isolated anti-RGMa antibody; (6) a nucleic acid molecule encoding
CC protein part of the anti-RGMa antibody; (7) a recombinant vector
CC comprises the nucleic acid molecule; (8) a host cell comprises the
CC recombinant vector; and (9) a method for preparing the above-mentioned
CC anti-RGMa antibody. The RGMa binding protein of the invention is also
CC used for immunological disease. The present sequence is a humanized anti-
CC RGMa antibody light chain variable region, used in the invention for
CC preventing neurological disease.
XX
SQ Sequence 107 AA;
Query Match 100.0%; Score 562; Length 107;
Best Local Similarity 100.0%;
Matches 107; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIQMTQSPSSVSASVGDRVTITCRASQDISSYLNWYQQKPGKAPKLLIYYTSRLHSGVPS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DIQMTQSPSSVSASVGDRVTITCRASQDISSYLNWYQQKPGKAPKLLIYYTSRLHSGVPS 60
Qy 61 RFSGSGSGTDFTLTISSLQPEDFASYFCQQLNTLPWTFGGGTKVEME 107
|||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFSGSGSGTDFTLTISSLQPEDFASYFCQQLNTLPWTFGGGTKVEME 107
9. This application contains claims 1-2 and 8-9 drawn to an invention nonelected with traverse in the reply filed on 08/18/2025. A complete reply to the final rejection must include cancellation of nonelected claims or other appropriate action (37 CFR 1.144) See MPEP § 821.01.
10. THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
11. Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHANG-YU WANG whose telephone number is (571)272-4521. The examiner can normally be reached Monday-Thursday, 7:00am-5:00pm EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Stucker can be reached at 571-272-0911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
Chang-Yu Wang
April 3, 2026
/CHANG-YU WANG/Primary Examiner, Art Unit 1675
Prosecution Insights