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
Status of Application/Election/Restrictions
Applicant’s election of Group I (claims 1-10, 17 and 19-20) in the reply filed on January 21, 2026 is acknowledged. 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)).
Claim 1 is amended. Claims 1-20 are pending in this application. Claims 11-16 and 18 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim. Election was treated as without traverse in the reply filed on January 21, 2026.
Claims 1-10, 17 and 19-20 are under examination in this office action.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of the first paragraph of 35 U.S.C. 112. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, provisional Application No. 63/056838 filed July 27, 2020, fails to provide adequate support or enablement in the manner provided by the first paragraph of 35 U.S.C. 112 for one or more claims of this application. The instant application claims an isolated human NGF mutein comprising an acid amino acid residue substitution at positive 34 relative to SEQ ID NO:2 and comprising a) greater than 80% sequence identity to SEQ ID NO:2 among the positions other than positions 32 and 34 or b) at least 80% sequence identity to a fragment of SEQ ID NO:2 that stimulates TrkA bio-activity, which is not presented in the provisional Application No. 63/056838, filed on July 27, 2020. The isolated human NGF mutein comprising an acid amino acid residue substitution at positive 34 relative to SEQ ID NO:2 and comprising a) greater than 80% sequence identity to SEQ ID NO:2 among the positions other than positions 32 and 34 or b) at least 80% sequence identity to a fragment of SEQ ID NO:2 that stimulates TrkA bio-activity recited in instant claim 1 was only disclosed in PCT/US2021/043316 filed on July 27, 2021 (see p.12 in the specification of PCT/US2021/043316).
Therefore, the priority for the claimed subject matter recited in claim 1 in the instant application is July 27, 2021.
Specification
The disclosure is objected to because of the following informalities: The wrong format for a sequence identifier is used in paragraphs [009], [0014], [0020]-[0021], [0053], [0056]-[0057], [0060], [0064], [00119], [00134] of the specification filed 10/06/2025. The recitation “SEQ ID NO.x” or “SEQ ID NO x” recited in the specification filed 10/06/2025 is incorrect. The correct format for a sequence identifier should be “SEQ ID NO:x”. Applicant is invited to view MPEP 2422 and 37 CFR 1.821 (d). Appropriate correction is required.
The recitation “BioCore3000” in paragraphs [0048], [0050], [0133], [0136] of the specification filed 10/06/2025 is objected to because it is unclear whether Applicant refers to the “BiaCore 3000” protein analyzer using Surface Plasmon Resonance (SPR) biosensor technology to study biomolecular interactions or other undefined devices or technology. Appropriate correction is required.
If the term ““BioCore3000” (p.) means “BiaCore 3000”, the term “BiaCore” “BiaCore3000” is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks. Appropriate correction is required.
Claim Objections
Claims 1, 9-10 and 19 are objected to because of the following informalities: The format for a sequence identifier recited in claim 1 is incorrect. The correct format for a sequence identifier is “SEQ ID NO:2”. Applicant is invited to view MPEP 2422 and 37 CFR 1.821 (d). Appropriate correction is required.
The recitation “TF1” recited in claim 9 or “WT” recited in claim 10 is not a unique or common abbreviation in the art. Applicants are required to spell out “TF1” or “WT” at the first usage. Appropriate correction is required.
The term “BioCore3000” recited in claim 19 is unclear whether Applicant refers to the “BiaCore 3000” protein analyzer using Surface Plasmon Resonance (SPR) biosensor technology to study biomolecular interactions or other undefined devices or technology. Appropriate correction is required.
If the term ““BioCore3000” recited in claim 19 means “BiaCore 3000”, the term “BiaCore” “BiaCore3000” is a trade name or a mark used in commerce. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term. 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 7 and 19 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
Claims 7 and 19 are indefinite because:
i. The limitations “the structure of Figure 2” and “the structure of Figure 2 by 5 substitutions….” recited in claim 7 are not concise to define the invention. Note that "Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table “is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience.” Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993)". See MPEP 2173.05(s). Note that the rejection can be obviated by copying the contents of the structure of Figure 2 into the claim itself.
ii. Claim 19 recites the term “BioCore3000”. It is unclear whether Applicant refers to the “BiaCore 3000” protein analyzer using Surface Plasmon Resonance (SPR) biosensor technology to study biomolecular interactions or other undefined devices or technology, which renders the claim indefinite. For examination purposes, the term “BioCore3000” is interpreted as “BiaCore3000” known for using Surface Plasmon Resonance (SPR) biosensor technology to study biomolecular interactions.
If the term ““BioCore3000” recited in claim 19 means “BiaCore 3000”, the term “BiaCore” “BiaCore3000” is a trade name or a mark used in commerce. The claim contains the trademark/trade name “BiaCore3000”. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112, second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe a Surface Plasmon Resonance (SPR) biosensor or protein analyzer to study or measure biomolecular interactions and, accordingly, the identification/description is indefinite.
Claim Rejections - 35 USC § 112
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 1-10, 17 and 19-20 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.
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof.
Claims 1-10, 17 and 19-20 encompass a genus of isolated human NGF mutein comprising an acid amino acid residue substitution at positive 34 relative to SEQ ID NO:2 and comprising a) greater than 80% sequence identity to SEQ ID NO:2 among the positions other than positions 32 and 34 or b) at least 80% sequence identity to a fragment of SEQ ID NO:2 that stimulates TrkA bio-activity.
Claims 8-10 encompass the claimed human NGF mutein with an acid amino acid substitution at position 34 and at least 80% identity to SEQ ID NO:2 or fragment of SEQ ID NO:2 and having at least 30% biological activity to TrkA, increased EC50 of not more than 170% based on a TF1 erythroleukemic cell-based proliferation assay or at least 30% expression level.
Claim 19 encompass a genus of the claimed human NGF mutein with an acid amino acid substitution at position 34 and at least 80% identity to SEQ ID NO:2 or fragment of SEQ ID NO:2 and having reduced biological activity toward p75NTR determined by BiaCore3000.
Applicant has not disclosed sufficient species for the broad genus of human NGF mutein comprising variants of SEQ ID NO:2 with at least 80% identity to SEQ ID NO:2 and having an acid amino acid substitution at position 34 and features recited in instant claim 1 or the broad genus of human NGF muteins having the features recited in claims 8-10 and 19.
In making a determination of whether the application complies with the written description requirement of 35 U.S.C. 112, first paragraph, it is necessary to understand what Applicant is in possession of and what Applicant is claiming.
M.P.E.P. § 2163 instructs:
An invention described solely in terms of a method of making and/or its function may lack written descriptive support where there is no described or art-recognized correlation between the disclosed function and the structure(s) responsible for the function. . . .
An applicant may show possession of an invention by disclosure of drawings or structural chemical formulas that are sufficiently detailed to show that applicant was in possession of the claimed invention as a whole. . . .
An applicant may also show that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics which provide evidence that applicant was in possession of the claimed invention, i.e., complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics.”
This standard has not been met in this case. From the specification, Applicant is in possession of human NGF muteins comprising SEQ ID NO: 2 with a mutation of K34D (NGF-K34D) or mutations K34D and K32D (NGF-K34D/K32D). However, Applicant is not in possession of other structural and functionally undefined human NGF mutein comprising variants of SEQ ID NO:2 with at least 80% identity to SEQ ID NO:2 and having an acid amino acid substitution at position 34 and features recited in instant claim 1 or the claimed human NGF mutein comprising a substitution with a glutamic acid or other derivatives recited in claim 2 because NGF with a mutation of K34E or K34A does not have neuroprotective activity as admitted by Applicant (see Example 4, para. [0157]).
Based on Applicant’s own admission, only NGF mutants with a specific single mutation of K34D (NGF-K34D) or mutations K34D and K32D (NGF-K34D/K32D) still possess activity and are effective to reduce RGC loss by 50% or optic nerve axon damage induced by elevated IOP in an animal model of glaucoma (see Examples 4-5 and 7-8).
Based on Applicant’s own admission, other NGF mutants with other substitutions at different locations cannot be expressed or lost the neuroprotective activities because:
i) the expression levels of NGF mutants with a single mutant K34D, K34E or R100E were comparable or higher compared to the wildtype NGF, and other single mutants (K34A, R69A, R69E, R100E) and all the double or triple mutants (i.e. K34A/R69A, K34D/R69A, K34D/R100E, K34A/R69A/R100E, K34D/R69A/R100D) showed reduced protein expression or no effects (see Example 2, para. [0147], Table 1);
ii) only NGF mutants with a mutation of K34A, K34D or K34E retained or increased thermostability relative to wild type (see Example 2, Table 1) but the thermostability of NGF mutants with a mutation of R100D or R100E was reduced;
iii) only NGF-K34D at 200 μg/mL effectively protected the structure and survival of RGCs and axons but the wildtype NGF and NGF-K34A or NGF-K34E at 200 μg/mL were not effective (see Example 4, para [0157]); and
iv) the NGF mutant with mutations of K34D/K32A was less stable and the EC50 was increased by 5-fold (see Example 6).
The specification provides no identification of any particular portion of the structure that must be conserved for the claimed genus of human NGF muteins with at least 80% identity to SEQ ID NO:2 and having an acid amino acid substitution at position 34 and features recited in instant claim 1 or having the features recited in claims 8-10 and 19.
The instant specification fails to provide sufficient descriptive information, such as definitive structural or functional features of the claimed genus of human NGF mutein comprising variants of SEQ ID NO:2 with at least 80% identity to SEQ ID NO:2 and having an acid amino acid substitution at position 34 and features recited in instant claim 1 or having the features recited in claims 8-10 and 19. There is no description of the conserved regions which are critical to the function of the claimed genus. There is no description of the sites at which variability may be tolerated and there is no information regarding the relation of structure of other human NGF muteins recited in instant claim 1 or in claims 8-10 and 19 to the function of NGF-K34D or NGF-K34D/K32D. The specification fails to teach provides no identification of any particular portion of the structure that must be conserved for the claimed genus of human NGF muteins with at least 80% identity to SEQ ID NO:2 and having an acid amino acid substitution at position 34 and features recited in instant claim 1 or having the features recited in claims 8-10 and 19.
The specification provides insufficient descriptive information to demonstrate that Applicant is in possession of the claimed genus of human NGF muteins recited in instant claim 1 or in claims 8-10 and 19 because a single amino acid change on a molecule or protein can abolish the activity or binding ability of the molecule and protein or expression of the protein, which is also evidenced by the data shown in Examples 2- 8 of the instant specification as admitted by Applicant.
It is known that a substitution of lysine residue by glutamic acid at position 118 of acidic fibroblast growth factor results in a substantial loss of its biological activity including the binding ability to heparin and its receptor (Burgess et al. J of Cell Bio. 1990, 111:2129-2138). Even if an active or binding site were identified in the specification, they may not be sufficient, as the ordinary artisan would not immediately recognize that an active or binding site must assume the proper three-dimensional configuration to be active because conformation is dependent upon surrounding residues; i.e. substitution of non-essential residues can often destroy activity. In addition to a core determinant sequence, the protein-protein interaction also relies on the flanking or noncontiguous residues (see p. 445 the second column, first paragraph, Pawson et al. 2003, Science 300:445-452). The optimal binding motif for a domain is not necessarily suitable for physiological or in vivo interaction. The predictive data always need to be validated by actual analyses in cells (see p. 445, the third column, second paragraph, Pawson et al. 2003, Science 300:445-452). Alaoui-lsmaili teaches that designing a mutein having predictable activities is difficult because of the complexity of the interactions between ligands and receptors (Alaoui-lsmaili et al., Cytokine Growth Factor Rev. 2009; 20:501-507). For example, given the complexity of BMP-BMP receptor interactions, it is difficult to design BMPs with improved affinity and/or specificity for one specific receptor. More importantly, predicting the in vivo biological activity of such altered BMPs remains a challenging undertaking (see p. 502, right col., 2th paragraph). Further, when multiple mutations are introduced, there is even less predictability because Guo et al. teaches that the effects of mutations on protein function are largely additive (see p. 9207, left col., 2th paragraph, Guo et al., PNAS 2004; 101:9205-9210).
The specification provides no structural and functional relationship between the claimed genus of human NGF muteins recited in instant claim 1 and NGF-K34D or NGF-K34D/K32D that still possesses activity in reducing RGC loss by 50% or optic nerve axon damage induced by elevated IOP in an animal model of glaucoma.
There is also no structural and functional relationship between the claimed genus of human NGF muteins recited in instant claim 1 and other NGF mutants including K34E or different mutations shown in Examples that cannot be expressed or lose neuroprotective activity as shown in Examples 2-6.
The specification fails to teach what other structures/amino acid sequences can or cannot be included/changed in the claimed genus of human NGF muteins recited in instant claim 1 in order to preserve the activity of NGF-K34D or NGF-K34D/K32D in reducing RGC loss by 50% or optic nerve axon damage induced by elevated IOP in an animal model of glaucoma as shown in Examples 4-5 and 7-8.
Furthermore, the prior art does not provide compensatory structural or correlative teachings sufficient to enable one of skill to identify what other human NGF mutein comprising variants of SEQ ID NO:2 with at least 80% identity to SEQ ID NO:2 and having an acid amino acid substitution at position 34 and features recited in instant claim 1 might be. Since the common characteristics/features of other human NGF mutein as recited in instant claim 1 are unknown, a skilled artisan cannot envision the functional correlations of the genus with the claimed invention. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the genus of human NGF mutein comprising variants of SEQ ID NO:2 with at least 80% identity to SEQ ID NO:2 and having an acid amino acid substitution at position 34 and features as recited in instant claim 1.
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 human NGF mutein as recited in instant claim 1, 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. In Fiddes, claims directed to mammalian FGF’s were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovine sequence.
Therefore, the claimed human NGF mutein has 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.
Conclusion
NO CLAIM IS ALLOWED.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Presta et al. (US7452863, issued Nov 18, 2008 or US8101571 issued on Jan 12, 2012) teaches that NGF with mutations at positions F12, I31, K32, K34, K50, Y52, R69, K74, K88, L112, S113, R114, and K115 all result in diminished p75 binding (see co.11, lines 19-21)
US6121235 teaches a human NGF comprising the amino acid sequence that is 98.9 identical to instant SEQ ID NO:2-K34D (see the sequence alignment below).
SEQ ID NO: 2-K34D
AAB29141
(NOTE: this sequence has 85 duplicates in the database searched)
ID AAB29141 standard; protein; 120 AA.
XX
AC AAB29141;
XX
DT 15-JUN-2007 (revised)
DT 02-FEB-2001 (first entry)
XX
DE N-terminal of neutrophic growth factor.
XX
KW Neutrophin; trkB; trkC; ototoxicity-related balance impairment;
KW Meniere's syndrome; myringitis; otitis media;
KW acute vestibular neuronitis; herpes zoster oticus; labyrinthitis; middle;
KW labyrinthe tumour; petrositis; otosclerosis; bacteria; BOND_PC;
KW nerve growth factor; GO7399; GO8083.
XX
OS Homo sapiens.
XX
CC PN US6121235-A.
XX
CC PD 19-SEP-2000.
XX
CC PF 29-DEC-1995; 95US-00581662.
XX
PR 29-DEC-1995; 95US-00581662.
XX
CC PA (GETH ) GENENTECH INC.
XX
CC PI Gao W;
XX
DR WPI; 2000-618200/59.
DR PC:NCBI; gi6137554.
XX
CC PT Treating ototoxin-induced neuronal-related balance impairment and
CC PT promoting vestibular ganglion neuron survival prior to, upon or after
CC PT exposure to an ototoxin, comprises administering a trkB or trkC agonist.
XX
CC PS Disclosure; Col 57-58; 40pp; English.
XX
CC The present invention relates to treating ototoxin-induced neuronal-
CC related balance impairment in a mammal by administering a trkB or trkC
CC agonist, particularly neurotrophin-4/5 (NT-4/5). Ototoxicity-related
CC balance impairments include Meniere's syndrome, myringitis, otitis media,
CC acute vestibular neuronitis, herpes zoster oticus, labyrinthitis, middle
CC or labyrinthe tumours, petrositis and otosclerosis. NT-4/5 may also be
CC used to treat diseases induced by gram positive, gram negative and acid-
CC fast bacteria. The present sequence is a protein used in the invention
CC
CC Revised record issued on 15-JUN-2007 : Enhanced with precomputed
CC information from BOND.
XX
SQ Sequence 120 AA;
Query Match 98.9%; Score 645; Length 120;
Best Local Similarity 99.2%;
Matches 119; Conservative 0; Mismatches 1; Indels 0; Gaps 0;
Qy 1 SSSHPIFHRGEFSVCDSVSVWVGDKTTATDIKGDEVMVLGEVNINNSVFKQYFFETKCRD 60
||||||||||||||||||||||||||||||||| ||||||||||||||||||||||||||
Db 1 SSSHPIFHRGEFSVCDSVSVWVGDKTTATDIKGKEVMVLGEVNINNSVFKQYFFETKCRD 60
Qy 61 PNPVDSGCRGIDSKHWNSYCTTTHTFVKALTMDGKQAAWRFIRIDTACVCVLSRKAVRRA 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 PNPVDSGCRGIDSKHWNSYCTTTHTFVKALTMDGKQAAWRFIRIDTACVCVLSRKAVRRA 120
CN112409471 teaches a human NGF mutant comprising SEQ ID NO:35 which is 100% identical to instant SEQ ID NO:2-K34A (see the sequence alignment below).
SEQ ID NO: 2-K34A
ID BIZ73688 standard; protein; 120 AA.
XX
AC BIZ73688;
XX
DT 15-APR-2021 (first entry)
XX
DE Human nerve growth factor mutant (K34A) SEQ ID 35.
XX
KW NGF; Nerve growth factor ligand; analgesic; expression; mutein;
KW neurological disease; neuroprotective; pain; protein engineering;
KW protein therapy; therapeutic; weight loss.
XX
OS Homo sapiens.
OS Synthetic.
XX
CC PN CN112409471-A.
XX
CC PD 26-FEB-2021.
XX
CC PF 07-APR-2017; 2020CN-11515637.
XX
PR 13-APR-2016; 2016CN-10228530.
PR 07-APR-2017; 2017CN-10225746.
XX
CC PA (STAI-) STAIDSON BEIJING PHARM CO LTD.
XX
CC PI Chen Z, Wang C;
XX
DR WPI; 2021-27900C/026.
XX
CC PT New low-pain nerve growth factor mutant in preparing of medicine for
CC PT treating neurological diseases, and effectively reducing body weight with
CC PT reducing pain side effect.
XX
CC PS Claim 1; SEQ ID NO 35; 43pp; Chinese.
XX
CC The present invention relates to a novel low-pain nerve growth factor
CC (NGF) mutant useful for preparing a medicine for treating neurological
CC disease. The NGF mutant comprises an amino acid sequence of SEQ ID No: 4-
CC 5 (see BIZ73657-BIZ73658), SEQ ID No: 7 (see BIZ73660), SEQ ID No: 15
CC (see BIZ73668), SEQ ID No: 17-18 (see BIZ73670-BIZ73671), SEQ ID No: 25
CC (see BIZ73678), SEQ ID No: 30 (see BIZ73683) or SEQ ID No: 33-36 (see
CC BIZ73686-BIZ73689). The invention further relates to: (1) a nucleotide
CC sequence encoding the NGF mutant; (2) an expression vector comprising the
CC nucleotide sequence; (3) a method for expressing the expression vector;
CC (4) a host cell containing the expression vector; (5) a medicinal
CC composition, comprising a medicinally acceptable excipient, the low-pain
CC NGF mutant, the expression vector or the host cell; and (6) the use of
CC the NGF mutant for preparing a low-pain NGF preparation and a painless
CC NGF preparation. The NGF mutant is useful for preparing a medicine for
CC treating neurological diseases, effectively reducing body weight, and
CC reducing pain. The mutant has low pain and reduces pain side effect.
CC Note: The present sequence is derived from the human nerve growth factor
CC (hNGF) sequence given in SEQ ID NO: 2 (see BIZ73655).
XX
SQ Sequence 120 AA;
Query Match 100.0%; Score 650; Length 120;
Best Local Similarity 100.0%;
Matches 120; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 SSSHPIFHRGEFSVCDSVSVWVGDKTTATDIKGAEVMVLGEVNINNSVFKQYFFETKCRD 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 SSSHPIFHRGEFSVCDSVSVWVGDKTTATDIKGAEVMVLGEVNINNSVFKQYFFETKCRD 60
Qy 61 PNPVDSGCRGIDSKHWNSYCTTTHTFVKALTMDGKQAAWRFIRIDTACVCVLSRKAVRRA 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 PNPVDSGCRGIDSKHWNSYCTTTHTFVKALTMDGKQAAWRFIRIDTACVCVLSRKAVRRA 120
CN115813951 teaches a human NGF mutant with mutations K34E/V87H/R100F/delN3 comprising the amino acid sequence that is 95.9% identical to instant SEQ ID NO:2-K34E/D(see the sequence alignment below).
SEQ ID NO: 2-K34E
BMP25456
ID BMP25456 standard; protein; 117 AA.
XX
AC BMP25456;
XX
DT 27-APR-2023 (first entry)
XX
DE Nerve growth factor (NGF) mutant protein, NGF-M07, K34E/V87H/R100F/delN3.
XX
KW NGF; Nerve growth factor ligand; analgesic; cell therapy;
KW genetic engineering; insomnia; mutein; nerve injury; pain;
KW pharmaceutical; site-specific mutagenesis; sleep maintenance insomnia;
KW stem cell; therapeutic; vulnerary.
XX
OS Synthetic.
OS Unidentified.
XX
FH Key Location/Qualifiers
FT Misc-difference 1
FT /note= "Wild-type Ser-Ser-Ser-His substituted by His (N-
FT terminal deletion)"
FT Misc-difference 31
FT /note= "Wild-type Lys substituted by Glu"
FT Misc-difference 84
FT /note= "Wild-type Val substituted by His"
FT Misc-difference 97
FT /note= "Wild-type Arg substituted by Phe"
XX
CC PN CN115813951-A.
XX
CC PD 21-MAR-2023.
XX
CC PF 10-NOV-2022; 2022CN-11406260.
XX
PR 10-NOV-2022; 2022CN-11406260.
XX
CC PA (GUAN-) GUANGZHOU LIANDA TECHNOLOGY CO LTD.
XX
CC PI Li Y, Li L, Wang J;
XX
DR WPI; 2023-32213L/029.
XX
CC PT Pharmaceutical composition used for treating insomnia and improving nerve
CC PT repair ability while reducing pain-inducing function, comprises
CC PT genetically modified stem cells, where stem cells contain polynucleotide
CC PT encoding nerve growth factor mutant having specific amino acid sequence.
XX
CC PS Example 1; Page; 13pp; Chinese.
XX
CC The present invention relates to a pharmaceutical composition, comprising
CC a genetically modified stem cells, where the stem cells contain a
CC polynucleotide encoding a nerve growth factor (NGF) mutant. The method
CC for preparing the bone marrow mesenchymal stem cells involves: (i) adding
CC a human bone marrow blood to a clean and sterile centrifuge tube, (ii)
CC inoculating the stem cells, (iii) observing the growth state of the cells
CC ; and (iv) detecting the expression of a cluster of differentiation 44
CC (CD44), CD90 and CD34 surface antigens on the cells. The pharmaceutical
CC composition is used for preparing medicine for treating insomnia, where
CC the insomnia comprises acute insomnia, subacute insomnia and chronic
CC insomnia. The site-directed mutation of the NGF amino acid sequence is
CC used for improving nerve repair ability while reducing pain-inducing
CC function. The mesenchymal stem cells are genetically modified to carry
CC the mutated NGF gene, which can exert a long-term effect in the body. The
CC medicine prolongs sleep period and improves sleep quality. Note: The
CC present sequence is not shown in the specification but is derived from
CC the nerve growth factor (NGF) protein (see BMP25448), based on the
CC information given in example 1.
XX
SQ Sequence 117 AA;
Query Match 95.9%; Score 624; Length 117;
Best Local Similarity 98.3%;
Matches 115; Conservative 0; Mismatches 2; Indels 0; Gaps 0;
Qy 4 HPIFHRGEFSVCDSVSVWVGDKTTATDIKGEEVMVLGEVNINNSVFKQYFFETKCRDPNP 63
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 HPIFHRGEFSVCDSVSVWVGDKTTATDIKGEEVMVLGEVNINNSVFKQYFFETKCRDPNP 60
Qy 64 VDSGCRGIDSKHWNSYCTTTHTFVKALTMDGKQAAWRFIRIDTACVCVLSRKAVRRA 120
||||||||||||||||||||||| |||||||||||| ||||||||||||||||||||
Db 61 VDSGCRGIDSKHWNSYCTTTHTFHKALTMDGKQAAWFFIRIDTACVCVLSRKAVRRA 117
CN107286233 teaches a human NGF mutant comprising SEQ ID NO:35 which is 100% identical to instant SEQ ID NO:2-K34A or 99.1% identical to instant SEQ ID NO:2-K34E/D(see the sequence alignment below).
SEQ ID NO:2-K34A
BEZ22878
(NOTE: this sequence has 1 duplicate in the database searched)
ID BEZ22878 standard; protein; 120 AA.
XX
AC BEZ22878;
XX
DT 22-MAR-2018 (first entry)
XX
DE Human mutant (K34A) nerve growth factor (NGF) protein, SEQ ID 35.
XX
KW NGFB protein; Nerve growth factor ligand; mutein; neurological disease;
KW neuroprotective; protein therapy; therapeutic; weight loss.
XX
OS Homo sapiens.
OS Synthetic.
XX
FH Key Location/Qualifiers
FT Misc-difference 34
FT /note= "Wild-type Lys substituted by Ala"
XX
CC PN CN107286233-A.
XX
CC PD 24-OCT-2017.
XX
CC PF 07-APR-2017; 2017CN-10225746.
XX
PR 07-APR-2017; 2017CN-10225746.
XX
CC PA (STAI-) STAIDSON BEIJING PHARM CO LTD.
XX
CC PI Chen Z, Wang C, Ma L, Du T;
XX
DR WPI; 2017-75323D/81.
XX
CC PT New low pain nerve growth factor mutants useful for preparing medicine
CC PT for curing nervous system disease in a patient and reducing weight in a
CC PT mammal.
XX
CC PS Claim 1; SEQ ID NO 35; 44pp; Chinese.
XX
CC The present invention relates to a novel mutant low-pain nerve growth
CC factor, useful for preparing a medicament capable of treating nervous
CC system disease in a subject. The invention further relates to: 1) a
CC nucleotide sequence encoding the nerve growth factor mutant; 2) an
CC expression vector; 3) a method for expressing the expression vector; and
CC 4) a pharmaceutical composition comprising a pharmaceutically acceptable
CC excipient and the low-pain nerve growth factor mutant. The mutant of the
CC invention is useful for preparing the medicament: to treat nervous system
CC disease; and for effective weight loss. The present sequence is a human
CC mutant (K34A) nerve growth factor (NGF) protein, useful for preparing
CC medicament to treat nervous system disease.
XX
SQ Sequence 120 AA;
Query Match 100.0%; Score 650; Length 120;
Best Local Similarity 100.0%;
Matches 120; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 SSSHPIFHRGEFSVCDSVSVWVGDKTTATDIKGAEVMVLGEVNINNSVFKQYFFETKCRD 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 SSSHPIFHRGEFSVCDSVSVWVGDKTTATDIKGAEVMVLGEVNINNSVFKQYFFETKCRD 60
Qy 61 PNPVDSGCRGIDSKHWNSYCTTTHTFVKALTMDGKQAAWRFIRIDTACVCVLSRKAVRRA 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 PNPVDSGCRGIDSKHWNSYCTTTHTFVKALTMDGKQAAWRFIRIDTACVCVLSRKAVRRA 120
SEQ ID NO:2-K34E
BEZ22878
(NOTE: this sequence has 1 duplicate in the database searched)
ID BEZ22878 standard; protein; 120 AA.
XX
AC BEZ22878;
XX
DT 22-MAR-2018 (first entry)
XX
DE Human mutant (K34A) nerve growth factor (NGF) protein, SEQ ID 35.
XX
KW NGFB protein; Nerve growth factor ligand; mutein; neurological disease;
KW neuroprotective; protein therapy; therapeutic; weight loss.
XX
OS Homo sapiens.
OS Synthetic.
XX
FH Key Location/Qualifiers
FT Misc-difference 34
FT /note= "Wild-type Lys substituted by Ala"
XX
CC PN CN107286233-A.
XX
CC PD 24-OCT-2017.
XX
CC PF 07-APR-2017; 2017CN-10225746.
XX
PR 07-APR-2017; 2017CN-10225746.
XX
CC PA (STAI-) STAIDSON BEIJING PHARM CO LTD.
XX
CC PI Chen Z, Wang C, Ma L, Du T;
XX
DR WPI; 2017-75323D/81.
XX
CC PT New low pain nerve growth factor mutants useful for preparing medicine
CC PT for curing nervous system disease in a patient and reducing weight in a
CC PT mammal.
XX
CC PS Claim 1; SEQ ID NO 35; 44pp; Chinese.
XX
CC The present invention relates to a novel mutant low-pain nerve growth
CC factor, useful for preparing a medicament capable of treating nervous
CC system disease in a subject. The invention further relates to: 1) a
CC nucleotide sequence encoding the nerve growth factor mutant; 2) an
CC expression vector; 3) a method for expressing the expression vector; and
CC 4) a pharmaceutical composition comprising a pharmaceutically acceptable
CC excipient and the low-pain nerve growth factor mutant. The mutant of the
CC invention is useful for preparing the medicament: to treat nervous system
CC disease; and for effective weight loss. The present sequence is a human
CC mutant (K34A) nerve growth factor (NGF) protein, useful for preparing
CC medicament to treat nervous system disease.
XX
SQ Sequence 120 AA;
Query Match 99.1%; Score 645; Length 120;
Best Local Similarity 99.2%;
Matches 119; Conservative 0; Mismatches 1; Indels 0; Gaps 0;
Qy 1 SSSHPIFHRGEFSVCDSVSVWVGDKTTATDIKGEEVMVLGEVNINNSVFKQYFFETKCRD 60
||||||||||||||||||||||||||||||||| ||||||||||||||||||||||||||
Db 1 SSSHPIFHRGEFSVCDSVSVWVGDKTTATDIKGAEVMVLGEVNINNSVFKQYFFETKCRD 60
Qy 61 PNPVDSGCRGIDSKHWNSYCTTTHTFVKALTMDGKQAAWRFIRIDTACVCVLSRKAVRRA 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 PNPVDSGCRGIDSKHWNSYCTTTHTFVKALTMDGKQAAWRFIRIDTACVCVLSRKAVRRA 120
WO2018140792 teaches a human NGF mutant with mutations K32A/K34A/E35A/F7A/N45A/R103A, comprising SEQ ID NO:11 which is 93.9% identical to instant SEQ ID NO:2-K34E or 94.8% identical to SEQ ID NO:2-K34A
(see the sequence alignment below).
SEQ ID NO:2-K34E
BFM79892
(NOTE: this sequence has 4 duplicates in the database searched)
ID BFM79892 standard; protein; 120 AA.
XX
AC BFM79892;
XX
DT 20-SEP-2018 (first entry)
XX
DE Human mutant NGF protein (K32A/K34A/E35A/F7A/N45A/R103A), SEQ ID 11.
XX
KW Nerve growth factor ligand; auditory; hearing loss; labyrinthitis;
KW meniere disease; mutein; neurodegenerative disease;
KW noise induced hearing loss; otitis; presbycusis; protein therapy;
KW sensorineural hearing loss; therapeutic; tinnitus;
KW vestibulocochlear nerve disorder.
XX
OS Homo sapiens.
OS Synthetic.
XX
FH Key Location/Qualifiers
FT Misc-difference 7
FT /note= "Wild type Phe substituted by Ala"
FT Misc-difference 32
FT /note= "Wild type Lys substituted by Ala"
FT Misc-difference 34
FT /note= "Wild type Lys substituted by Ala"
FT Misc-difference 35
FT /note= "Wild type Glu substituted by Ala"
FT Misc-difference 45
FT /note= "Wild type Asn substituted by Ala"
FT Misc-difference 103
FT /note= "Wild type Arg substituted by Ala"
XX
CC PN WO2018140792-A2.
XX
CC PD 02-AUG-2018.
XX
CC PF 26-JAN-2018; 2018WO-US015548.
XX
PR 27-JAN-2017; 2017US-0451570P.
XX
CC PA (OTON-) OTONOMY INC.
XX
CC PI Foster A, Szobota S, Saragovi HU;
XX
DR WPI; 2018-603668/55.
XX
CC PT Treating an otic condition, e.g. hearing loss, endolymphatic hydrops,
CC PT labyrinthitis, vestibular neuronitis, and tinnitus, involves
CC PT administering an otic composition comprising a non-natural neurotrophic
CC PT agent.
XX
CC PS Claim 9; SEQ ID NO 11; 160pp; English.
XX
CC The present invention relates to a method for treating an otic condition
CC in a subject. The method involves administering an otic composition
CC comprising a non-natural neurotrophic agent (mutant nerve growth factor
CC protein). The invention further relates to an otic pharmaceutical
CC composition comprising a non-natural neurotrophic agent and an auris-
CC acceptable vehicle. The method is used for treating an otic condition.
CC The otic condition is selected from ototoxicity, chemotherapy induced
CC hearing loss, excitotoxicity, sensorineural hearing loss, noise induced
CC hearing loss, hidden hearing loss, Meniere's disease or syndrome,
CC endolymphatic hydrops, labyrinthitis, Ramsay Hunt's Syndrome, vestibular
CC neuronitis, tinnitus, age-related hearing loss (presbycusis),
CC microvascular compression syndrome, genetic hearing loss, and balance
CC disorder; or characterized by damaged ribbon synapse, neurodegeneration,
CC hair cell loss, or synaptopathy. The present sequence represents a human
CC mutant nerve growth factor (K32A/K34A/E35A/F7A/N45A/R103A) protein
CC (derived from BFM79882), useful for treating otic condition.
XX
SQ Sequence 120 AA;
Query Match 93.9%; Score 611; Length 120;
Best Local Similarity 95.0%;
Matches 114; Conservative 0; Mismatches 6; Indels 0; Gaps 0;
Qy 1 SSSHPIFHRGEFSVCDSVSVWVGDKTTATDIKGEEVMVLGEVNINNSVFKQYFFETKCRD 60
|||||| |||||||||||||||||||||||| | ||||||||| |||||||||||||||
Db 1 SSSHPIAHRGEFSVCDSVSVWVGDKTTATDIAGAAVMVLGEVNIANSVFKQYFFETKCRD 60
Qy 61 PNPVDSGCRGIDSKHWNSYCTTTHTFVKALTMDGKQAAWRFIRIDTACVCVLSRKAVRRA 120
|||||||||||||||||||||||||||||||||||||||||| |||||||||||||||||
Db 61 PNPVDSGCRGIDSKHWNSYCTTTHTFVKALTMDGKQAAWRFIAIDTACVCVLSRKAVRRA 120
SEQ ID NO:2-K34A
BFM79892
(NOTE: this sequence has 4 duplicates in the database searched)
ID BFM79892 standard; protein; 120 AA.
XX
AC BFM79892;
XX
DT 20-SEP-2018 (first entry)
XX
DE Human mutant NGF protein (K32A/K34A/E35A/F7A/N45A/R103A), SEQ ID 11.
XX
KW Nerve growth factor ligand; auditory; hearing loss; labyrinthitis;
KW meniere disease; mutein; neurodegenerative disease;
KW noise induced hearing loss; otitis; presbycusis; protein therapy;
KW sensorineural hearing loss; therapeutic; tinnitus;
KW vestibulocochlear nerve disorder.
XX
OS Homo sapiens.
OS Synthetic.
XX
FH Key Location/Qualifiers
FT Misc-difference 7
FT /note= "Wild type Phe substituted by Ala"
FT Misc-difference 32
FT /note= "Wild type Lys substituted by Ala"
FT Misc-difference 34
FT /note= "Wild type Lys substituted by Ala"
FT Misc-difference 35
FT /note= "Wild type Glu substituted by Ala"
FT Misc-difference 45
FT /note= "Wild type Asn substituted by Ala"
FT Misc-difference 103
FT /note= "Wild type Arg substituted by Ala"
XX
CC PN WO2018140792-A2.
XX
CC PD 02-AUG-2018.
XX
CC PF 26-JAN-2018; 2018WO-US015548.
XX
PR 27-JAN-2017; 2017US-0451570P.
XX
CC PA (OTON-) OTONOMY INC.
XX
CC PI Foster A, Szobota S, Saragovi HU;
XX
DR WPI; 2018-603668/55.
XX
CC PT Treating an otic condition, e.g. hearing loss, endolymphatic hydrops,
CC PT labyrinthitis, vestibular neuronitis, and tinnitus, involves
CC PT administering an otic composition comprising a non-natural neurotrophic
CC PT agent.
XX
CC PS Claim 9; SEQ ID NO 11; 160pp; English.
XX
CC The present invention relates to a method for treating an otic condition
CC in a subject. The method involves administering an otic composition
CC comprising a non-natural neurotrophic agent (mutant nerve growth factor
CC protein). The invention further relates to an otic pharmaceutical
CC composition comprising a non-natural neurotrophic agent and an auris-
CC acceptable vehicle. The method is used for treating an otic condition.
CC The otic condition is selected from ototoxicity, chemotherapy induced
CC hearing loss, excitotoxicity, sensorineural hearing loss, noise induced
CC hearing loss, hidden hearing loss, Meniere's disease or syndrome,
CC endolymphatic hydrops, labyrinthitis, Ramsay Hunt's Syndrome, vestibular
CC neuronitis, tinnitus, age-related hearing loss (presbycusis),
CC microvascular compression syndrome, genetic hearing loss, and balance
CC disorder; or characterized by damaged ribbon synapse, neurodegeneration,
CC hair cell loss, or synaptopathy. The present sequence represents a human
CC mutant nerve growth factor (K32A/K34A/E35A/F7A/N45A/R103A) protein
CC (derived from BFM79882), useful for treating otic condition.
XX
SQ Sequence 120 AA;
Query Match 94.8%; Score 616; Length 120;
Best Local Similarity 95.8%;
Matches 115; Conservative 0; Mismatches 5; Indels 0; Gaps 0;
Qy 1 SSSHPIFHRGEFSVCDSVSVWVGDKTTATDIKGAEVMVLGEVNINNSVFKQYFFETKCRD 60
|||||| |||||||||||||||||||||||| || ||||||||| |||||||||||||||
Db 1 SSSHPIAHRGEFSVCDSVSVWVGDKTTATDIAGAAVMVLGEVNIANSVFKQYFFETKCRD 60
Qy 61 PNPVDSGCRGIDSKHWNSYCTTTHTFVKALTMDGKQAAWRFIRIDTACVCVLSRKAVRRA 120
|||||||||||||||||||||||||||||||||||||||||| |||||||||||||||||
Db 61 PNPVDSGCRGIDSKHWNSYCTTTHTFVKALTMDGKQAAWRFIAIDTACVCVLSRKAVRRA 120
WO2018140799 (as in IDS) teaches a human NGF mutant with mutations K32A/K34A/E35A, comprising SEQ ID NO:17 which is 80.7% identical to instant SEQ ID NO:2-K34A (see the sequence alignment below).
SEQ ID NO:2-K34A
BFM79932
(NOTE: this sequence has 3 duplicates in the database searched)
ID BFM79932 standard; protein; 121 AA.
XX
AC BFM79932;
XX
DT 20-SEP-2018 (first entry)
XX
DE Human mutant NGF/BDNF chimera 3 protein (K32A/K34A/E35A), SEQ ID 17.
XX
KW Brain derived neurotrophic factor ligand; Nerve growth factor ligand;
KW alzheimers disease; auditory; cancer; corneal disease; corneal ulcer;
KW glaucoma; ischemic stroke; motor neurone disease; mutein;
KW neurodegenerative disease; neuroprotective; osteoarthritis; otitis;
KW parkinsons disease; protein activation; protein therapy;
KW psychiatric disorder; psychiatric-gen.; retinitis pigmentosa;
KW rheumatoid arthritis; spinal cord injury; spinal muscular atrophy;
KW therapeutic.
XX
OS Homo sapiens.
OS Synthetic.
XX
FH Key Location/Qualifiers
FT Misc-difference 32
FT /note= "Wild type Arg substituted by Ala"
FT Misc-difference 34
FT /note= "Wild type Lys substituted by Ala"
FT Misc-difference 35
FT /note= "Wild type Glu substituted by Ala"
XX
CC PN WO2018140799-A2.
XX
CC PD 02-AUG-2018.
XX
CC PF 26-JAN-2018; 2018WO-US015562.
XX
PR 27-JAN-2017; 2017US-0451560P.
XX
CC PA (URIS/) HORACIO URI S.
XX
CC PI Horacio Uri S;
XX
DR WPI; 2018-603664/55.
XX
CC PT New modified neurotrophic agent, useful for activating a Trk receptor and
CC PT for treating a non-otic disease or condition, e.g. neurodegenerative
CC PT disease, corneal ulcer, spinal muscular atrophy, glaucoma, and
CC PT psychiatric disorder.
XX
CC PS Claim 27; SEQ ID NO 17; 99pp; English.
XX
CC The present invention relates to a method for treating non-otic condition
CC in a subject. The method involves administering an otic composition
CC comprising a non-natural neurotrophic agent (mutant NGF/BDNF chimera 3
CC protein). The invention further relates to: (1) a method for activating a
CC tropomyosin receptor kinase (Trk) receptor by (a) contacting a cell with
CC a neurotrophic agent, and (b) facilitating binding between the
CC neurotrophic agent and the Trk receptor; and (2) a method for treating a
CC non-otic disease or condition by administering to a subject a
CC neurotrophic agent. The non-otic condition comprises: (i) a
CC neurodegenerative disease or a symptomatic or pre-symptomatic condition
CC with alterations to synapses; (ii) a corneal epithelial and Goblet cell
CC defect; (iii) corneal ulcer; (iv) pain associated with osteoarthritis,
CC rheumatoid arthritis, or cancer; (v) amyotrophic lateral sclerosis (ALS),
CC spinal muscular atrophy (SMA), glaucoma, spinal cord injury (SCI), or
CC retinitis pigmentosa; or (vi) a psychiatric disorder. The
CC neurodegenerative disease includes Alzheimer's disease, glaucoma,
CC ischemia stroke, Parkinson's disease, and progressive muscular atrophy.
CC The present sequence represents a human mutant NGF/BDNF chimera 3
CC (K32A/K34A/E35A) protein (derived from BFM79922), useful for treating
CC otic condition.
XX
SQ Sequence 121 AA;
Query Match 80.7%; Score 524.5; Length 121;
Best Local Similarity 82.6%;
Matches 100; Conservative 4; Mismatches 16; Indels 1; Gaps 1;
Qy 1 SSSHPIFHRGEFSVCDSVSVWVGDKTTATDIKGAEVMVLGEVNINNSVFKQYFFETKCRD 60
||||||||||||||||||||||||||||||| || |||||||||||||||||||||||
Db 1 SSSHPIFHRGEFSVCDSVSVWVGDKTTATDIAGAAVMVLGEVNINNSVFKQYFFETKCNP 60
Qy 61 PNPVDSGCRGIDSKHWNSYCTTTHTFVKALTMDG-KQAAWRFIRIDTACVCVLSRKAVRR 119
|||||||||||| | || ::|:||||| |: |||||||||||||||||||||
Db 61 MGYTKEGCRGIDSKHWNSQCRTTQSYVRALTMDSKKRIGWRFIRIDTACVCVLSRKAVRR 120
Qy 120 A 120
|
Db 121 A 121
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 on 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 on 571-272-0911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Chang-Yu Wang
March 21, 2026
/CHANG-YU WANG/Primary Examiner, Art Unit 1675