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 without traverse of Group I (claims 1-16 and 23), SEQ ID NO:361 for species of HCDRH3 of VH2, SEQ ID NO:381 for species of VH2, substitutions L234A, L235A and P329G for species of substitutions in Fc, SEQ ID NO:81 for species of Fc, SEQ ID NO:101 for species of linker, SEQ ID NO:2 for species of first polypeptide, multispecific antibody for species of agent, retinopathy/retinal vascular disease for species of disease, diabetic edema for species of vascular disorder, cancer-associated osteolysis for species of bone disease, sarcopenia for species of muscle wasting disease, Alzheimer’s disease for species of neural or neurodegenerative disease in the reply filed on January 9, 2026 is acknowledged.
Claims 32-34 are canceled. Claims 1-31 and 35-42 are pending in this application. Claims 17-22, 24-31 and 35-42 are withdrawn without traverse (filed 01/09/2026) from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable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 made without traverse in the reply filed on January 9, 2026.
Claims 1-16 and 23 are under examination with respect to SEQ ID NO:361 for HCDRH3 of VH2, SEQ ID NO:381 for VH2, L234A, L235A and P329G for substitutions in Fc, SEQ ID NO:81 for Fc, SEQ ID NO:101 for linker, SEQ ID NO:2 for first polypeptide in this office action.
Specification
The disclosure is objected to because of the following informalities: The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (see p. 47, [00201]; p. 54, [00226]; p. 56, [00233]; p. 57, [00236]; p. 58, [00239]). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. Appropriate correction is required.
Claim Objections
Claims 17-22, 24-31 and 35-42 are objected to because of the following informalities: the status of the claims 17-22, 24-31 and 35-42 is incorrect because these claims are withdrawn from consideration. Appropriate correction is required.
See MPEP 714 & 37 CFR 1.121.
“In the claim listing, the status of every claim must be indicated after its claim number by using one of the following identifiers in a parenthetical expression: (Original), (Currently amended), (Canceled), (Withdrawn), (Previously presented), (New), and (Not entered).”
6. Claims 1, 2, 4, 10 and 23 are objected to because of the following informalities:
i. the recitations “IMGT”, “Kabat” and “EU numbering” recited in claims 1, 4 and 10 are not unique or common abbreviations in the art. Applicants are required to spell out “IMGT”, “Kabat” and “EU numbering” at the first usage. Appropriate correction is required.
ii. The use of the term “nanobody” in claim 2, which 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.
iii. Claim 23 is objected to because the claim encompasses nonelected inventions. Appropriate correction is required.
Improper Markush Grouping
7. Claim 23 is rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 706.03(y).
The Markush grouping of different agents including multispecific antibody/antibody fragment thereof, a nucleic acid/a combination of nucleic acids/vectors and host cells recited in claim 23 is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons:
The recited alternative species do not share a single structural similarity, as each species recited in the Markush group has a different chemical structure because the structure and composition of the recited multispecific antibody/antibody fragment thereof are different from those of polynucleotides/vectors or host cells, each type of agents or molecules/components has different activities, functions and effects. Thus, the different agents/components recited in the Markush grouping do not share a single structural similarity or biological activity. Accordingly, different agents or molecules/components recited in the Markush group do not share a single structural similarity essential to this activity. See MPEP § 706.03(y).
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Claim Rejections - 35 USC § 112
8. 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 2, 8, 11 and 14-16 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 2, 8, 11 and 14-16 are indefinite because:
i. Claim 2 contains the trademark/trade name “nanobody”. 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 single monomeric heavy chain variable domain antibody or VHH antibody and, accordingly, the identification/description is indefinite
ii. The article “A” recited in claim 8 connotes that there is more than a single multispecific antibody encompassed within the base claim and since only a single multispecific antibody was set forth therein, it is unclear what, if any, additional multispecific antibodies are encompassed, which renders the claim indefinite.
iii. Regarding claims 11 and 14-16, it is unclear whether the limitations “said VH1”, “said VH2” and “said VL1” recited in claim 11 and the limitations “the VH1”, “the VH2” and “the VL1” refer to the same “VH1”, “VH2” and “VL1”, which renders the claim indefinite. The same issue applies to the limitations “said first polypeptide” and “said second polypeptide” and “the limitations “the first polypeptide” and “the second polypeptide” recited in claim 14; the limitations “said Fzd4-binding regions” and “said LRP5 and/or LRP6-binding regions” and “the limitations “the Fzd4-binding regions” and “the LRP5 and/or LRP6-binding regions”; limitations “said first antigen-binding region” and “said second antigen-binding region” and “the limitations “the first polypeptide” and “the second polypeptide” recited in claims 15-16. Thus, claims 11 and 14-16 are indefinite.
iv. Claim 16 recites the limitations "the ratio" and “the number” in line 2, (I) and line 6, (II) of the claim. There is insufficient antecedent basis for this limitation in the claim.
Claim Rejections - 35 USC § 112
9. 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 1-5, 8, 10-12, 14-16 and 23 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 1-5, 8, 10-12, 14-16 and 23 are directed to a multispecific antibody or antibody fragment thereof comprising at least (A) a first antigen-binding region binding to Fzd4 and comprising VH1 and VL1, (B) a second antigen-binding region binding to LRP5/LRP6 and comprising VH2, wherein the VH1 comprises a CDRH1 having an amino acid sequence with at least 80% identity to SEQ ID NO:121, a CDRH2 having an amino acid with at least 90% identity to SEQ ID NO:121 and a CDRH3 having an amino acid sequence with at least 90% identity to SEQ ID NO:161 or the VH1 comprises CDRH1-3 of SEQ ID NO:181 defined according to Kabat; wherein the VL1 comprises a CDRL1 having an amino acid sequence with at least 90% identity to SE ID NO:221, a CDRL2 having the sequence of SEQ ID NO:241 and a CDRL3 having the sequence of SEQ ID NO:261 or the VL1 comprises CDRL1-3 of SEQ ID NO:281 defined according to Kabat; and wherein the VH2 comprises a CDRH1 having the amino acid sequence of SEQ ID NO:321, a CDRH2 having at least 90% identity to SEQ ID NO:341 and a CDRH3 having an amino acid sequence with at least 90% identity to SEQ ID NO:361 or comprising any one of SEQ ID NOs:361 and 363-366 or the VH2 comprises CDRH1-3 of SEQ ID NO:381 defined according to IMGT or Kaba.
The claims encompasses a genus of multispecific antibody or antibody fragment thereof comprising at least (A) a first antigen-binding region binding to Fzd4 and comprising VH1 and VL1, (B) a second antigen-binding region binding to LRP5/LRP6 and comprising VH2, wherein the VH1 comprises variants having at least 80% identity to SEQ ID NO:121 for CDRH1, variants having at least 90% identity to SEQ ID NO: 141 for CDRH2 and variants having at least 90% identity to SEQ ID NO:161 for CDRH3; the VL comprises variants having at least 90% identity to SEQ ID NO:221 for CDRL1; and the VH2 comprises variants having at least 90% identity to SEQ ID NO:341 for CDRH2 and variants having at least 90% identity to SEQ ID NO:361 for CDRH3. Claim 5 encompasses a genus of multispecific antibody or antibody fragment thereof comprising variants having at least 80% identity to SEQ ID NO:181 for VH1, variants having at least 80% identity to SEQ ID NO:281 for VL1 and variants having at least 80% identity to recited SEQ ID NOs: including SDEQ ID NO:381 for VH2.
The specification fails to provide sufficient species for the broad genus of multispecific antibody or antibody fragment thereof comprising variants of recited SEQ ID NOs: in CDRH1-3 of VH1 and variants of recited SEQ ID NOs: for CDRL1-3 of VL1 and variants of recited SEQ ID NOs: for CDRH1-3 or comprising variants of recited SEQ ID NOs: for VH1, VL1 and VH2.
The specification only discloses a bispecific antibody, 4SD1-03_LALAPG, and humanized 4SD1-03_LALAPG: hp4SD1-03, hp4SD1-03 AAQ and hp4SD1-03 AAA antibodies, wherein the 4SD1-03_LALAPG comprises two heavy chains and two light chains of anti-Fzd4 antibody, 4SD1, and an anti-LRP5/6 VHH domain, wherein the anti-LRP5/6 VHH domain is fused to the N-terminus of each anti-Fzd4 antibody light chain via a linker, GGSGS (SEQ ID NO:102) (figures 1 and 6-9).
The specification teaches that the hsp4SD1-03 comprises a light chain having the amino acid sequence of SEQ ID NO:1 and a heavy chain having the amino acid sequence of SEQ ID NO:2. The specification teaches that the anti-LRP5/6 VHH domain encompassed within the hsp4SD1-03 comprises the amino acid sequence of SEQ ID NO:381, the anti-Fzd4 VL domain encompassed within the hsp4SD1-03 comprises the amino acid sequence of SEQ ID NO:281 and anti-Fzd4 VH domain encompassed within the hsp4SD1-03 comprises the amino acid sequence of SEQ ID NO:181, and the Fc domain encompassed within the hsp4SD1-03 comprises the amino acid sequence of SEQ ID NO:81 (p.78-80). The hp4SD1-03 AAQ comprises SEQ ID NO:1 for the light chain and SEQ ID NO:450 for the heavy chain. The hp4SD1-03 AAA comprises SEQ ID NO:1 for the light chain and SEQ ID NO:451 for the heavy chain (p. 80). The specification discloses that intravitreal injection of hp4SD1-03 to an animal model of injured retina resulted in a better outcome of reducing vascular leakage as compared to 4SD1-03_LALAPG (Figure 11), or administering hp4SD1-03 to a rabbit model of VEGF-induced retinal vascular leakage resulted in reducing vascular leakage as compared to a vehicle control (Figure 12). The specification discloses that monovalent binding of human Fzd4 CRD to 4SD1-03_LALAPG or hp4SD1-03 (Example 8, Figures 17-18).
However, the specification fails to provide sufficient support to demonstrate that Applicant is in possession of the claimed genus of multispecific antibody or antibody fragment thereof comprising variants of recited SEQ ID NOs: in CDRH1-3 of VH1 and variants of recited SEQ ID NOs: for CDRL1-3 of VL1 for binding Fzd4 and variants of recited SEQ ID NOs: for CDRH1-3 of VH2 for binding to LRP5/6 or comprising variants of recited SEQ ID NOs: for VH1 and VL1 for binding to Fzd4 and variants of recited SEQ ID NOs: for VH2 for binding to LRP5/6.
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 a bispecific anti-Fzd4 and anti-LRP5/6 antibody: 4SD1-03_LALAPG and humanized 4SD1-03_LALAPG: hp4SD1-03, hp4SD1-03 AAQ and hp4SD1-03 AAA, wherein 4SD1-03_LALAPG comprises two heavy chains and two light chains of anti-Fzd4 antibody, 4SD1 and wherein an anti-LRP5/6 VHH domain is fused to the N-terminus of each anti-Fzd4 antibody light chain via a linker, GGSGS (SEQ ID NO:102) as shown in figures 1 and 6-9. The hsp4SD1-03 comprises a light chain having the amino acid sequence of SEQ ID NO:1 and a heavy chain having the amino acid sequence of SEQ ID NO:2, and wherein the anti-LRP5/6 VHH domain of hsp4SD1-03 comprises the amino acid sequence of SEQ ID NO:381, the VL domain of anti-Fzd4 antibody in hsp4SD1-03 comprises the amino acid sequence of SEQ ID NO:281 and the VH domain of anti-Fzd4 antibody in hsp4SD1-03 comprises the amino acid sequence of SEQ ID NO:181, and the Fc domain of hsp4SD1-03 comprises the amino acid sequence of SEQ ID NO:81. The hp4SD1-03 AAQ comprises a light chain having the amino acid sequence of SEQ ID NO:1 and a heavy chain having the amino acid sequence of SEQ ID NO:450; and the hp4SD1-03 AAA comprises a light chain having the amino acid sequence of SEQ ID NO:1 and a heavy chain having the amino acid sequence of SEQ ID NO:451.
However, Applicant is not in possession of other multispecific antibodies or antibody fragments thereof comprising structural and functionally undefined variants of recited SEQ ID NOs: in CDRH1-3 of VH1 and variants of recited SEQ ID NOs: for CDRL1-3 of VL1 for binding Fzd4 and variants of recited SEQ ID NOs: for CDRH1-3 of VH2 for binding to LRP5/6 or comprising variants of recited SEQ ID NOs: for VH1 and VL1 for binding to Fzd4 and variants of recited SEQ ID NOs: for VH2 for binding to LRP5/6.
It is well established in the art that the formation of an intact antigen-binding site generally requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three CDRs which provide the majority of the contact residues for the binding of the antibody to its target epitope. The amino acid sequences and conformations of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity which is characteristic of the parent immunoglobulin. It is expected that all of the heavy and light chain CDRs in their proper order and in the context of framework sequences which maintain their required conformation, are required in order to produce a protein having antigen-binding function and that proper association of heavy and light chain variable regions is required in order to form functional antigen binding sites. MacCallum et al. (J. Mol. Biol.,1996; 262: 732-745) teaches that although CDR3 of the heavy and light chain dominates, a number of residues outside the standard CDR definitions make antigen contacts (see p. 733, right col) and non-contacting residues within the CDRs coincide with residues as important in defining canonical backbone conformations (see page 735, left col.). Pascalis et al. (The Journal of Immunology, 2002; 169: 3076-3084) teaches that grafting of the CDRs into a human framework was performed by grafting CDR residues and maintaining framework residues that were deemed essential for preserving the structural integrity of the antigen binding site (see page 3079, right col.) and that although abbreviated CDR residues were used in the constructs, some residues in all 6 CDRs were used for the constructs (see page 3080, left col.). The fact that not just one CDR is essential for antigen binding or maintaining the conformation of the antigen binding site because although CDR H3 is at the center of most if not all antigen interactions, clearly other CDRs play an important role in the recognition process (page 199, left col.) and this is demonstrated in this work by using all CDRs except L2 and additionally using a framework residue located just before the H3 (see page 202, left col.; Casset et al., BBRC, 2003; 307: 198-205). Vajdos et al. (J. Mol. Biol. 2002; 320: 415-428) also teaches that antigen binding is primarily mediated by the CDRs more highly conserved framework segments which connect the CDRs are mainly involved in supporting the CDR loop conformations and in some cases framework residues also contact antigen (page 416, left col.). Holm et al. (Mol. Immunol., 2007; 44: 1075-1084) teaches that although residues in the CDR3 of the heavy chain were involved in antigen binding, unexpectedly a residue in CDR2 of the light chain was also involved (abstract). Chen et al. (J. Mol. Bio., 1999; 293: 865-881) teaches that the antigen binding site is almost entirely composed of residues from heavy chain CDRs, CDR-H1, H2, H3 (page 866). Wu et al. (J. Mol. Biol., 1999; 294:151-162) teaches that it is difficult to predict which framework residues serve a critical role in maintaining affinity and specificity due in part to the large conformational change in antibodies that accompany antigen binding (page 152 left col.) but certain residues have been identified as important for maintaining conformation. These references demonstrate that in order to generate an antibody with the claimed binding activity or features, the antibody must comprise all 6 CDRs with defined sequences or structures in order to maintain the claimed antigen binding specificity and affinity. However, no such information is provided by the specification.
It is also known in the art that a single amino acid change on a molecule or a protein can abolish the binding ability or activity of the molecule or the protein. For example, 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). Although many amino acid substitutions are possible in any given protein, the position of where such amino acid substitutions can be made is critical for maintaining the function of a protein; i.e. only certain positions can tolerate conservative substitutions without changing the relationship of three dimensional structure and function of the protein (col 2, p. 1306, Bowie et al. Science, 1990, 247:1306-1310). 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). Moreover, even minor changes in the amino acid sequences of the heavy and light variable regions, particularly in the CDRs, may dramatically affect antigen-binding function as evidenced by Rudikoff et al. (Proc. Natl. Acad. Sci. USA 1982 Vol. 79: page 1979). Rudikoff et al teach that the alteration of a single amino acid in the CDR of a phosphocholine-binding myeloma protein resulted in the loss of antigen-binding function.
Applicant fails to teach what other structures/amino acid sequences are required by the claimed genus of other multspecific antibodies or antibody fragments thereof comprising variants of recited SEQ ID NOs: in CDRH1-3 of VH1 and variants of recited SEQ ID NOs: for CDRL1-3 of VL1 for binding Fzd4 and variants of recited SEQ ID NOs: for CDRH1-3 of VH2 for binding to LRP5/6 or comprising variants of recited SEQ ID NOs: for VH1 and VL1 for binding to Fzd4 and variants of recited SEQ ID NOs: for VH2 for binding to LRP5/6.
Neither the specification nor the prior art teaches what other structurally and functionally undefined multspecific variant antibodies are and can possess the claimed biological binding properties as claimed. The specification provides no identification of any particular portion of the structure that must be conserved. The instant specification fails to provide sufficient descriptive information, such as definitive structural or functional features of the claimed genus of multspecific variant antibodies comprising variants of recited SEQ ID NOs: in CDRH1-3 of VH1 and variants of recited SEQ ID NOs: for CDRL1-3 of VL1 for binding Fzd4 and variants of recited SEQ ID NOs: for CDRH1-3 of VH2 for binding to LRP5/6 or comprising variants of recited SEQ ID NOs: for VH1 and VL1 for binding to Fzd4 and variants of recited SEQ ID NOs: for VH2 for binding to LRP5/6.
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 the structure of other variant antibodies comprising variants of recited SEQ ID NOs: in CDRH1-3 of VH1 and CDRL1-3 of VL1 for binding Fzd4 and variants of recited SEQ ID NOs: for CDRH1-3 of VH2 for binding to LRP5/6 to the function of 4SD1-03_LALAPG, or hp4SD1-03, or hp4SD1-03 AAQ or hp4SD1-03 AAA.
Furthermore, the prior art does not provide compensatory structural or correlative teachings sufficient to enable one of skill to isolate and identify what other multispecific variant antibodies comprising variants of recited SEQ ID NOs: in CDRH1-3 of VH1 and variants of recited SEQ ID NOs: for CDRL1-3 of VL1 for binding Fzd4 and variants of recited SEQ ID NOs: for CDRH1-3 of VH2 for binding to LRP5/6 or comprising variants of recited SEQ ID NOs: for VH1 and VL1 for binding to Fzd4 and variants of recited SEQ ID NOs: for VH2 for binding to LRP5/6 might be.
Since the common characteristics/features of other mutispecific variant antibodies comprising variants of recited SEQ ID NOs: in CDRH1-3 of VH1 and variants of recited SEQ ID NOs: for CDRL1-3 of VL1 for binding Fzd4 and variants of recited SEQ ID NOs: for CDRH1-3 of VH2 for binding to LRP5/6 or comprising variants of recited SEQ ID NOs: for VH1 and VL1 for binding to Fzd4 and variants of recited SEQ ID NOs: for VH2 for binding to LRP5/6 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 multispecific variant antibodies.
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 multispecific variant antibodies, 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 and Centocor v. Abbott, 636 F.3d1341 (Fed. Cir. 2011) and AbbVie v. Janssen, 759 F.3d 1285 (Fed. Cir.2014). One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483.
Therefore, the claimed multispecific antibodies or antibody fragments thereof have 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.
10. In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Claim Rejections - 35 USC § 102
11. 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 5 and 12 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Li (WO2019126398, published June 27, 2019, priority Dec 19, 2017, as in IDS).
Claims 5 and 12 are drawn to a multispecific antibody or antibody fragment thereof comprising at least (A) a first antigen-binding region binding to Fzd4 and comprising VH1 (anti-Fzd4-VH1) and VL1 (anti-Fzd4-VL1), (B) a second antigen-binding region binding to LRP5/6 and comprising VH2 (anti-LRP5/6-VH2), wherein the anti-Fzd4-VH1 comprises an amino acid sequence which has at least 80% identity to the amino acid sequence of instant SEQ ID NO:181; the anti-Fzd4-VL comprises an amino acid sequence which has at least 80% identity to instant SEQ ID NO:281; and wherein the anti-LRP5/6-VH2 comprises an amino acid sequence which has at least 80% identity to SEQ ID NO: instant 381 (elected). Claim 12 is drawn to the multispecific antibody or antibody fragment thereof that comprises a first polypeptide comprising an amino acid sequence which has at least 80% identity to instant SEQ ID NO:2 (elected) and a second polypeptide comprising an amino acid sequence which has at least 80% identity to instant SEQ ID NO:1 (elected).
Li et al. (WO2019126398) teaches a multispecific Wnt surrogate molecule comprising (a) one or more region that specifically binds to one or more frizzled (Fzd) receptor including Fzd4 (i.e. a Fzd4 binding region); and (b) one or more region that specifically binds to a LRP5 and/or a LRP6 (i.e. a LRP5/6 binding region), wherein the Wnt surrogate molecule comprises a first polypeptide and a second polypeptide, wherein the first polypeptide comprises the amino acid sequence of SEQ ID NO:155 (which is 99.1% identical to instant SEQ ID NO:2) and comprises a VH having the amino acid sequence that is 96.5% identical to instant SEQ ID NO:181 (the claimed VH1), and wherein the second polypeptide comprises the amino acid sequence of SEQ ID NO:144 or 147 (which is 97.2% identical to instant SEQ ID NO:1) and comprises an amino acid sequence that is 93.1% identical to instant SEQ ID NO:381 (the claimed VH2), a linker (i.e. -GGSGS-) and an amino acid that is 100% identical to instant SEQ ID NO:281 (the claimed VL1), which meets the limitations recited in claims 5 and 12 (see the sequence alignment below, figure 1) because claims 5 and 12 do not specify that the sequences of CDRH1-3 in the VH of the anti-Fzd4 and the sequences of CDRH1-3 in the VH of the anti-LRP5/6 cannot be changed. Thus, claims 5 and 12 are anticipated by Li (WO2019126398).
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SEQ ID NO:2
BGM03008
(NOTE: this sequence has 2 duplicates in the database searched)
ID BGM03008 standard; protein; 472 AA.
XX
AC BGM03008;
XX
DT 08-AUG-2019 (first entry)
XX
DE Wnt surrogate molecule construct, SEQ ID 155.
XX
KW Immunoglobulin; LDL receptor related protein-5;
KW LDL receptor related protein-6; LRP5 protein; LRP6 protein;
KW Low-density lipoprotein receptor-related protein 5;
KW Low-density lipoprotein receptor-related protein 6; antibody therapy;
KW antiinflammatory; antimicrobial-gen.; antiulcer; bone; bone disease;
KW bone injury; bone resorption; cardiovascular disease;
KW cardiovascular-gen.; cell proliferation; cell signaling; degeneration;
KW dermatological; dermatological disease; endocrine disease;
KW endocrine-gen.; fusion protein; gastrointestinal disease;
KW gastrointestinal-gen.; growth disorder; growth-disorder-gen.;
KW heavy chain constant region; heavy chain variable region; hepatocyte;
KW hepatotropic; immune disorder; immunomodulator; immunotherapy;
KW infectious disease; inflammatory disease; injury; liver disease;
KW liver fibrosis; liver injury; metabolic disorder; metabolic-gen.;
KW mitosis; mouth disease; musculoskeletal disease; musculoskeletal-gen.;
KW neurological disease; neuroprotective; nutrition-disorder-gen.;
KW nutritional disorder; ocular disease; ophthalmological; oral-dental-gen.;
KW osteopathic; otorhinolaryngological disease; otorhinolaryngological-gen.;
KW respiratory disease; respiratory-gen.; single domain antibody;
KW surgical procedure; surgical-gen.; therapeutic; tissue regeneration;
KW ulcer; vulnerary.
XX
OS Synthetic.
OS Unidentified.
XX
FH Key Location/Qualifiers
FT Peptide 1..22
FT /label= Signal_peptide
FT Region 23..142
FT /note= "Single domain antibody"
FT Region 143..472
FT /note= "Heavy chain constant region"
XX
CC PN WO2019126398-A1.
XX
CC PD 27-JUN-2019.
XX
CC PF 19-DEC-2018; 2018WO-US066616.
XX
PR 19-DEC-2017; 2017US-0607875P.
PR 09-MAR-2018; 2018US-0641217P.
PR 04-JUN-2018; 2018US-0680522P.
XX
CC PA (SURR-) SURROZEN INC.
XX
CC PI Li Y, Yuan TZ, Sato AK, Yeh W, Janda CY, Fowler TW, Baribault H;
CC PI Lai K, Xie L, Brezski RJ, Lu C;
XX
DR WPI; 2019-55460J/53.
XX
CC PT New soluble, multivalent, multispecific Wnt surrogate molecule comprising
CC PT regions that binds to Frizzled receptor and low-density lipoprotein
CC PT receptor-related protein (LRP) 5 or LRP6) is useful for treating e.g.
CC PT bone disease and fractures.
XX
CC PS Claim 14; SEQ ID NO 155; 353pp; English.
XX
CC The present invention relates to a novel soluble, multivalent,
CC multispecific Wnt surrogate molecule. The Wnt surrogate molecule
CC comprises: (a) one or more region that specifically binds to one or more
CC frizzled (Fzd) receptor (a Fzd binding region); and (b) one or more
CC region that specifically binds to a low-density lipoprotein (LDL)
CC receptor-related protein 5 (LRP5) and/or a low-density lipoprotein (LDL)
CC receptor-related protein 6 (LRP6) (a LRP5/6 binding region). The
CC invention further provides: (1) an isolated polynucleotide encoding a
CC polypeptide sequence comprising one or more of the Fzd binding regions
CC and/or one or more of the LRP5/6 binding regions of a Wnt surrogate
CC molecule; (2) an expression vector comprising the isolated polynucleotide
CC ; (3) an isolated host cell comprising the expression vector; (4) a
CC pharmaceutical composition comprising a physiologically acceptable
CC excipient, diluent, or carrier, and the Wnt surrogate molecule, the
CC polynucleotide, the expression cell, or the host cell; (5) a method for
CC agonizing a Wnt signaling pathway in a cell, which comprises contacting
CC the Wnt surrogate molecule, the polynucleotide, the expression cell, or
CC the host cell, wherein the Wnt surrogate molecule is an agonist of a Wnt
CC signaling pathway; (6) a method for treating a subject having a disease
CC or disorder associated with reduced Wnt signaling, which comprises
CC administering the Wnt surrogate molecule, the polynucleotide, the
CC expression cell, the host cell, or the pharmaceutical composition,
CC wherein the disease or disorder is selected from bone disease or
CC disorder, injury, musculoskeletal disease, degeneration, endocrine
CC disease, growth disorder, mouth disease, dermatological disease,
CC otorhinolaryngological disease, ocular disease, cardiovascular disease,
CC neurological disease, immune disorder, gastrointestinal disease,
CC nutritional disorder, inflammatory disease, metabolic disorder, ulcer,
CC respiratory disease, infectious disease, and surgical procedure; (7) a
CC method for increasing bone mineral density, increasing bone volume,
CC increasing bone cortical thickness, increasing bone mineral apposition
CC rate, increasing bone stiffness, increasing bone biomechanical strength,
CC increasing resistance to bone fracture, or decreasing bone loss
CC associated with osteoporosis; and (8) a method for increasing liver to
CC body weight ratio, promoting liver regeneration, increasing liver cell
CC proliferation or mitosis, decreasing liver fibrosis, optionally following
CC a chronic liver injury, increasing hepatocyte function, or decreasing
CC coagulation time in liver; and (9) a method for inhibiting or reducing
CC bone resorption in a subject. The present sequence represents a Wnt
CC surrogate molecule construct comprising a signal peptide, an anti-LRP5/6
CC single domain antibody (VHH/sdAb), and a heavy chain constant region,
CC which is used for treating the above-mentioned diseases.
XX
SQ Sequence 472 AA;
Query Match 99.1%; Score 2367; Length 472;
Best Local Similarity 98.7%;
Matches 444; Conservative 5; Mismatches 1; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLVQPGGSLRLSCAASGFTFTSYAMSWVRQAPGKGLEWVSAISGSGGSTYY 60
||||||||||||:|||||||||||||||||:|||||||||||||||||||||||||||||
Db 23 EVQLVESGGGLVKPGGSLRLSCAASGFTFTNYAMSWVRQAPGKGLEWVSAISGSGGSTYY 82
Qy 61 AESVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARATGFGTVVFDYWGQGTLVTVSS 120
|:|||||||||||:||||||||||||: ||||||||||||||||||||||||||||||||
Db 83 ADSVKGRFTISRDDSKNTLYLQMNSLKTEDTAVYYCARATGFGTVVFDYWGQGTLVTVSS 142
Qy 121 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 143 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 202
Qy 181 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGG 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 203 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGG 262
Qy 241 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 263 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN 322
Qy 301 STYRVVSVLTVLHQDWLNGKEYKCKVSNKALGAPIEKTISKAKGQPREPQVYTLPPSREE 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 323 STYRVVSVLTVLHQDWLNGKEYKCKVSNKALGAPIEKTISKAKGQPREPQVYTLPPSREE 382
Qy 361 MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 383 MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW 442
Qy 421 QQGNVFSCSVMHEALHNHYTQKSLSLSPGK 450
||||||||||||||||||||||||||||||
Db 443 QQGNVFSCSVMHEALHNHYTQKSLSLSPGK 472
SEQ ID NO:181 (Anti-Fzd4-VH1)
Query Match 96.5%; Score 601; Length 472;
Best Local Similarity 95.0%;
Matches 114; Conservative 5; Mismatches 1; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLVQPGGSLRLSCAASGFTFTSYAMSWVRQAPGKGLEWVSAISGSGGSTYY 60
||||||||||||:|||||||||||||||||:|||||||||||||||||||||||||||||
Db 23 EVQLVESGGGLVKPGGSLRLSCAASGFTFTNYAMSWVRQAPGKGLEWVSAISGSGGSTYY 82
Qy 61 AESVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARATGFGTVVFDYWGQGTLVTVSS 120
|:|||||||||||:||||||||||||: ||||||||||||||||||||||||||||||||
Db 83 ADSVKGRFTISRDDSKNTLYLQMNSLKTEDTAVYYCARATGFGTVVFDYWGQGTLVTVSS 142
SEQ ID NO:1
BGM02997
(NOTE: this sequence has 3 duplicates in the database searched)
ID BGM02997 standard; protein; 358 AA.
XX
AC BGM02997;
XX
DT 08-AUG-2019 (first entry)
XX
DE Wnt surrogate molecule construct, SEQ ID 144.
XX
KW Frizzled receptor; Fzd receptor; LDL receptor related protein-5;
KW LDL receptor related protein-6; LRP5 protein; LRP6 protein;
KW Low-density lipoprotein receptor-related protein 5;
KW Low-density lipoprotein receptor-related protein 6; antibody;
KW antibody therapy; antiinflammatory; antimicrobial-gen.; antiulcer; bone;
KW bone disease; bone injury; bone resorption; cardiovascular disease;
KW cardiovascular-gen.; cell proliferation; cell signaling; degeneration;
KW dermatological; dermatological disease; endocrine disease;
KW endocrine-gen.; fusion protein; gastrointestinal disease;
KW gastrointestinal-gen.; growth disorder; growth-disorder-gen.;
KW heavy chain variable region; hepatocyte; hepatotropic; immune disorder;
KW immunomodulator; immunotherapy; infectious disease; inflammatory disease;
KW injury; light chain; liver disease; liver fibrosis; liver injury;
KW metabolic disorder; metabolic-gen.; mitosis; mouth disease;
KW musculoskeletal disease; musculoskeletal-gen.; neurological disease;
KW neuroprotective; nutrition-disorder-gen.; nutritional disorder;
KW ocular disease; ophthalmological; oral-dental-gen.; osteopathic;
KW otorhinolaryngological disease; otorhinolaryngological-gen.;
KW respiratory disease; respiratory-gen.; single domain antibody;
KW surgical procedure; surgical-gen.; therapeutic; tissue regeneration;
KW ulcer; vulnerary.
XX
OS Synthetic.
OS Unidentified.
XX
FH Key Location/Qualifiers
FT Peptide 1..22
FT /label= Signal_peptide
FT Region 23..139
FT /note= "Single domain antibody"
FT Region 140..144
FT /note= "Linker"
FT Region 145..358
FT /note= "Light chain"
XX
CC PN WO2019126398-A1.
XX
CC PD 27-JUN-2019.
XX
CC PF 19-DEC-2018; 2018WO-US066616.
XX
PR 19-DEC-2017; 2017US-0607875P.
PR 09-MAR-2018; 2018US-0641217P.
PR 04-JUN-2018; 2018US-0680522P.
XX
CC PA (SURR-) SURROZEN INC.
XX
CC PI Li Y, Yuan TZ, Sato AK, Yeh W, Janda CY, Fowler TW, Baribault H;
CC PI Lai K, Xie L, Brezski RJ, Lu C;
XX
DR WPI; 2019-55460J/53.
XX
CC PT New soluble, multivalent, multispecific Wnt surrogate molecule comprising
CC PT regions that binds to Frizzled receptor and low-density lipoprotein
CC PT receptor-related protein (LRP) 5 or LRP6) is useful for treating e.g.
CC PT bone disease and fractures.
XX
CC PS Claim 14; SEQ ID NO 144; 353pp; English.
XX
CC The present invention relates to a novel soluble, multivalent,
CC multispecific Wnt surrogate molecule. The Wnt surrogate molecule
CC comprises: (a) one or more region that specifically binds to one or more
CC frizzled (Fzd) receptor (a Fzd binding region); and (b) one or more
CC region that specifically binds to a low-density lipoprotein (LDL)
CC receptor-related protein 5 (LRP5) and/or a low-density lipoprotein (LDL)
CC receptor-related protein 6 (LRP6) (a LRP5/6 binding region). The
CC invention further provides: (1) an isolated polynucleotide encoding a
CC polypeptide sequence comprising one or more of the Fzd binding regions
CC and/or one or more of the LRP5/6 binding regions of a Wnt surrogate
CC molecule; (2) an expression vector comprising the isolated polynucleotide
CC ; (3) an isolated host cell comprising the expression vector; (4) a
CC pharmaceutical composition comprising a physiologically acceptable
CC excipient, diluent, or carrier, and the Wnt surrogate molecule, the
CC polynucleotide, the expression cell, or the host cell; (5) a method for
CC agonizing a Wnt signaling pathway in a cell, which comprises contacting
CC the Wnt surrogate molecule, the polynucleotide, the expression cell, or
CC the host cell, wherein the Wnt surrogate molecule is an agonist of a Wnt
CC signaling pathway; (6) a method for treating a subject having a disease
CC or disorder associated with reduced Wnt signaling, which comprises
CC administering the Wnt surrogate molecule, the polynucleotide, the
CC expression cell, the host cell, or the pharmaceutical composition,
CC wherein the disease or disorder is selected from bone disease or
CC disorder, injury, musculoskeletal disease, degeneration, endocrine
CC disease, growth disorder, mouth disease, dermatological disease,
CC otorhinolaryngological disease, ocular disease, cardiovascular disease,
CC neurological disease, immune disorder, gastrointestinal disease,
CC nutritional disorder, inflammatory disease, metabolic disorder, ulcer,
CC respiratory disease, infectious disease, and surgical procedure; (7) a
CC method for increasing bone mineral density, increasing bone volume,
CC increasing bone cortical thickness, increasing bone mineral apposition
CC rate, increasing bone stiffness, increasing bone biomechanical strength,
CC increasing resistance to bone fracture, or decreasing bone loss
CC associated with osteoporosis; and (8) a method for increasing liver to
CC body weight ratio, promoting liver regeneration, increasing liver cell
CC proliferation or mitosis, decreasing liver fibrosis, optionally following
CC a chronic liver injury, increasing hepatocyte function, or decreasing
CC coagulation time in liver; and (9) a method for inhibiting or reducing
CC bone resorption in a subject. The present sequence represents a Wnt
CC surrogate molecule construct comprising a signal peptide, an anti-LRP5/6
CC single domain antibody (VHH/sdAb), and an anti-Fzd antibody sequence,
CC which is used for treating the above-mentioned diseases.
XX
SQ Sequence 358 AA;
Query Match 97.2%; Score 1685; Length 358;
Best Local Similarity 96.7%;
Matches 325; Conservative 6; Mismatches 5; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLVQPGGSLRLSCASSANIQSIETLGWYRQAPGKQRELIANMRGGGYMKYA 60
:||||||||||||||||||||| ||||| |||||||||||||||||||||||||||||||
Db 23 DVQLVESGGGLVQPGGSLRLSCTSSANINSIETLGWYRQAPGKQRELIANMRGGGYMKYA 82
Qy 61 DSLKGRFTMSTDNSKNTMYLQMNSLRAEDTAVYYCYVKLRDEDYVYRGQGTQVTVSSGGG 120
||||||||||:::|||||||||||: ||||||||||||||:|||||||||||||||||
Db 83 GSLKGRFTMSTESAKNTMYLQMNSLKPEDTAVYYCYVKLRDDDYVYRGQGTQVTVSSGGS 142
Qy 121 GSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGV 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 143 GSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGV 202
Qy 181 PSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIKRTVAAPSVFIF 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 203 PSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIKRTVAAPSVFIF 262
Qy 241 PPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSST 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 263 PPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSST 322
Qy 301 LTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 336
||||||||||||||||||||||||||||||||||||
Db 323 LTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 358
SEQ ID NO:1
ID BGM03000 standard; protein; 358 AA.
XX
AC BGM03000;
XX
DT 08-AUG-2019 (first entry)
XX
DE Wnt surrogate molecule construct, SEQ ID 147.
XX
KW Frizzled receptor; Fzd receptor; LDL receptor related protein-5;
KW LDL receptor related protein-6; LRP5 protein; LRP6 protein;
KW Low-density lipoprotein receptor-related protein 5;
KW Low-density lipoprotein receptor-related protein 6; antibody;
KW antibody therapy; antiinflammatory; antimicrobial-gen.; antiulcer; bone;
KW bone disease; bone injury; bone resorption; cardiovascular disease;
KW cardiovascular-gen.; cell proliferation; cell signaling; degeneration;
KW dermatological; dermatological disease; endocrine disease;
KW endocrine-gen.; fusion protein; gastrointestinal disease;
KW gastrointestinal-gen.; growth disorder; growth-disorder-gen.;
KW heavy chain variable region; hepatocyte; hepatotropic; immune disorder;
KW immunomodulator; immunotherapy; infectious disease; inflammatory disease;
KW injury; light chain; liver disease; liver fibrosis; liver injury;
KW metabolic disorder; metabolic-gen.; mitosis; mouth disease;
KW musculoskeletal disease; musculoskeletal-gen.; neurological disease;
KW neuroprotective; nutrition-disorder-gen.; nutritional disorder;
KW ocular disease; ophthalmological; oral-dental-gen.; osteopathic;
KW otorhinolaryngological disease; otorhinolaryngological-gen.;
KW respiratory disease; respiratory-gen.; single domain antibody;
KW surgical procedure; surgical-gen.; therapeutic; tissue regeneration;
KW ulcer; vulnerary.
XX
OS Synthetic.
OS Unidentified.
XX
FH Key Location/Qualifiers
FT Peptide 1..22
FT /label= Signal_peptide
FT Region 23..139
FT /note= "Single domain antibody"
FT Region 140..144
FT /note= "Linker"
FT Region 145..358
FT /note= "Light chain"
XX
CC PN WO2019126398-A1.
XX
CC PD 27-JUN-2019.
XX
CC PF 19-DEC-2018; 2018WO-US066616.
XX
PR 19-DEC-2017; 2017US-0607875P.
PR 09-MAR-2018; 2018US-0641217P.
PR 04-JUN-2018; 2018US-0680522P.
XX
CC PA (SURR-) SURROZEN INC.
XX
CC PI Li Y, Yuan TZ, Sato AK, Yeh W, Janda CY, Fowler TW, Baribault H;
CC PI Lai K, Xie L, Brezski RJ, Lu C;
XX
DR WPI; 2019-55460J/53.
XX
CC PT New soluble, multivalent, multispecific Wnt surrogate molecule comprising
CC PT regions that binds to Frizzled receptor and low-density lipoprotein
CC PT receptor-related protein (LRP) 5 or LRP6) is useful for treating e.g.
CC PT bone disease and fractures.
XX
CC PS Claim 14; SEQ ID NO 147; 353pp; English.
XX
CC The present invention relates to a novel soluble, multivalent,
CC multispecific Wnt surrogate molecule. The Wnt surrogate molecule
CC comprises: (a) one or more region that specifically binds to one or more
CC frizzled (Fzd) receptor (a Fzd binding region); and (b) one or more
CC region that specifically binds to a low-density lipoprotein (LDL)
CC receptor-related protein 5 (LRP5) and/or a low-density lipoprotein (LDL)
CC receptor-related protein 6 (LRP6) (a LRP5/6 binding region). The
CC invention further provides: (1) an isolated polynucleotide encoding a
CC polypeptide sequence comprising one or more of the Fzd binding regions
CC and/or one or more of the LRP5/6 binding regions of a Wnt surrogate
CC molecule; (2) an expression vector comprising the isolated polynucleotide
CC ; (3) an isolated host cell comprising the expression vector; (4) a
CC pharmaceutical composition comprising a physiologically acceptable
CC excipient, diluent, or carrier, and the Wnt surrogate molecule, the
CC polynucleotide, the expression cell, or the host cell; (5) a method for
CC agonizing a Wnt signaling pathway in a cell, which comprises contacting
CC the Wnt surrogate molecule, the polynucleotide, the expression cell, or
CC the host cell, wherein the Wnt surrogate molecule is an agonist of a Wnt
CC signaling pathway; (6) a method for treating a subject having a disease
CC or disorder associated with reduced Wnt signaling, which comprises
CC administering the Wnt surrogate molecule, the polynucleotide, the
CC expression cell, the host cell, or the pharmaceutical composition,
CC wherein the disease or disorder is selected from bone disease or
CC disorder, injury, musculoskeletal disease, degeneration, endocrine
CC disease, growth disorder, mouth disease, dermatological disease,
CC otorhinolaryngological disease, ocular disease, cardiovascular disease,
CC neurological disease, immune disorder, gastrointestinal disease,
CC nutritional disorder, inflammatory disease, metabolic disorder, ulcer,
CC respiratory disease, infectious disease, and surgical procedure; (7) a
CC method for increasing bone mineral density, increasing bone volume,
CC increasing bone cortical thickness, increasing bone mineral apposition
CC rate, increasing bone stiffness, increasing bone biomechanical strength,
CC increasing resistance to bone fracture, or decreasing bone loss
CC associated with osteoporosis; and (8) a method for increasing liver to
CC body weight ratio, promoting liver regeneration, increasing liver cell
CC proliferation or mitosis, decreasing liver fibrosis, optionally following
CC a chronic liver injury, increasing hepatocyte function, or decreasing
CC coagulation time in liver; and (9) a method for inhibiting or reducing
CC bone resorption in a subject. The present sequence represents a Wnt
CC surrogate molecule construct comprising a signal peptide, an anti-LRP5/6
CC single domain antibody (VHH/sdAb), and an anti-Fzd antibody sequence,
CC which is used for treating the above-mentioned diseases.
XX
SQ Sequence 358 AA;
Query Match 97.2%; Score 1685; Length 358;
Best Local Similarity 96.7%;
Matches 325; Conservative 6; Mismatches 5; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLVQPGGSLRLSCASSANIQSIETLGWYRQAPGKQRELIANMRGGGYMKYA 60
:||||||||||||||||||||| ||||| |||||||||||||||||||||||||||||||
Db 23 DVQLVESGGGLVQPGGSLRLSCTSSANINSIETLGWYRQAPGKQRELIANMRGGGYMKYA 82
Qy 61 DSLKGRFTMSTDNSKNTMYLQMNSLRAEDTAVYYCYVKLRDEDYVYRGQGTQVTVSSGGG 120
||||||||||:::|||||||||||: ||||||||||||||:|||||||||||||||||
Db 83 GSLKGRFTMSTESAKNTMYLQMNSLKPEDTAVYYCYVKLRDDDYVYRGQGTQVTVSSGGS 142
Qy 121 GSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGV 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 143 GSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGV 202
Qy 181 PSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIKRTVAAPSVFIF 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 203 PSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIKRTVAAPSVFIF 262
Qy 241 PPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSST 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 263 PPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSST 322
Qy 301 LTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 336
||||||||||||||||||||||||||||||||||||
Db 323 LTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 358
SEQ ID NO:321-SEQ ID NO:341-SEQ ID NO:361
ID BGM02986 standard; protein; 117 AA.
XX
AC BGM02986;
XX
DT 08-AUG-2019 (first entry)
XX
DE Anti-LRP5 single domain antibody (VHH/sdAb), SEQ ID 133.
XX
KW LDL receptor related protein-5; LRP5 protein;
KW Low-density lipoprotein receptor-related protein 5; antibody therapy;
KW antiinflammatory; antimicrobial-gen.; antiulcer; bone; bone disease;
KW bone injury; bone resorption; cardiovascular disease;
KW cardiovascular-gen.; cell proliferation; cell signaling; degeneration;
KW dermatological; dermatological disease; endocrine disease;
KW endocrine-gen.; gastrointestinal disease; gastrointestinal-gen.;
KW growth disorder; growth-disorder-gen.; heavy chain variable region;
KW hepatocyte; hepatotropic; immune disorder; immunomodulator;
KW immunotherapy; infectious disease; inflammatory disease; injury;
KW liver disease; liver fibrosis; liver injury; metabolic disorder;
KW metabolic-gen.; mitosis; mouth disease; musculoskeletal disease;
KW musculoskeletal-gen.; neurological disease; neuroprotective;
KW nutrition-disorder-gen.; nutritional disorder; ocular disease;
KW ophthalmological; oral-dental-gen.; osteopathic;
KW otorhinolaryngological disease; otorhinolaryngological-gen.;
KW respiratory disease; respiratory-gen.; single domain antibody;
KW surgical procedure; surgical-gen.; therapeutic; tissue regeneration;
KW ulcer; vulnerary.
XX
OS Unidentified.
XX
CC PN WO2019126398-A1.
XX
CC PD 27-JUN-2019.
XX
CC PF 19-DEC-2018; 2018WO-US066616.
XX
PR 19-DEC-2017; 2017US-0607875P.
PR 09-MAR-2018; 2018US-0641217P.
PR 04-JUN-2018; 2018US-0680522P.
XX
CC PA (SURR-) SURROZEN INC.
XX
CC PI Li Y, Yuan TZ, Sato AK, Yeh W, Janda CY, Fowler TW, Baribault H;
CC PI Lai K, Xie L, Brezski RJ, Lu C;
XX
DR WPI; 2019-55460J/53.
XX
CC PT New soluble, multivalent, multispecific Wnt surrogate molecule comprising
CC PT regions that binds to Frizzled receptor and low-density lipoprotein
CC PT receptor-related protein (LRP) 5 or LRP6) is useful for treating e.g.
CC PT bone disease and fractures.
XX
CC PS Claim 13; SEQ ID NO 133; 353pp; English.
XX
CC The present invention relates to a novel soluble, multivalent,
CC multispecific Wnt surrogate molecule. The Wnt surrogate molecule
CC comprises: (a) one or more region that specifically binds to one or more
CC frizzled (Fzd) receptor (a Fzd binding region); and (b) one or more
CC region that specifically binds to a low-density lipoprotein (LDL)
CC receptor-related protein 5 (LRP5) and/or a low-density lipoprotein (LDL)
CC receptor-related protein 6 (LRP6) (a LRP5/6 binding region). The
CC invention further provides: (1) an isolated polynucleotide encoding a
CC polypeptide sequence comprising one or more of the Fzd binding regions
CC and/or one or more of the LRP5/6 binding regions of a Wnt surrogate
CC molecule; (2) an expression vector comprising the isolated polynucleotide
CC ; (3) an isolated host cell comprising the expression vector; (4) a
CC pharmaceutical composition comprising a physiologically acceptable
CC excipient, diluent, or carrier, and the Wnt surrogate molecule, the
CC polynucleotide, the expression cell, or the host cell; (5) a method for
CC agonizing a Wnt signaling pathway in a cell, which comprises contacting
CC the Wnt surrogate molecule, the polynucleotide, the expression cell, or
CC the host cell, wherein the Wnt surrogate molecule is an agonist of a Wnt
CC signaling pathway; (6) a method for treating a subject having a disease
CC or disorder associated with reduced Wnt signaling, which comprises
CC administering the Wnt surrogate molecule, the polynucleotide, the
CC expression cell, the host cell, or the pharmaceutical composition,
CC wherein the disease or disorder is selected from bone disease or
CC disorder, injury, musculoskeletal disease, degeneration, endocrine
CC disease, growth disorder, mouth disease, dermatological disease,
CC otorhinolaryngological disease, ocular disease, cardiovascular disease,
CC neurological disease, immune disorder, gastrointestinal disease,
CC nutritional disorder, inflammatory disease, metabolic disorder, ulcer,
CC respiratory disease, infectious disease, and surgical procedure; (7) a
CC method for increasing bone mineral density, increasing bone volume,
CC increasing bone cortical thickness, increasing bone mineral apposition
CC rate, increasing bone stiffness, increasing bone biomechanical strength,
CC increasing resistance to bone fracture, or decreasing bone loss
CC associated with osteoporosis; and (8) a method for increasing liver to
CC body weight ratio, promoting liver regeneration, increasing liver cell
CC proliferation or mitosis, decreasing liver fibrosis, optionally following
CC a chronic liver injury, increasing hepatocyte function, or decreasing
CC coagulation time in liver; and (9) a method for inhibiting or reducing
CC bone resorption in a subject.
XX
SQ Sequence 117 AA;
Query Match 76.6%; Score 109.6; Length 117;
Best Local Similarity 30.9%;
Matches 25; Conservative 1; Mismatches 1; Indels 54; Gaps 2;
Qy 1 ANIQSIET----------------NMRGGGYM---------------------------- 16
||| |||| ||||||||
Db 26 ANINSIETLGWYRQAPGKQRELIANMRGGGYMKYAGSLKGRFTMSTESAKNTMYLQMNSL 85
Qy 17 ----------YVKLRDEDYVY 27
||||||:||||
Db 86 KPEDTAVYYCYVKLRDDDYVY 106
SEQ ID NO:381 (Ant-LRP5/6-VH2)
ID BGM02986 standard; protein; 117 AA.
XX
AC BGM02986;
XX
DT 08-AUG-2019 (first entry)
XX
DE Anti-LRP5 single domain antibody (VHH/sdAb), SEQ ID 133.
XX
Query Match 93.1%; Score 563; Length 117;
Best Local Similarity 91.5%;
Matches 107; Conservative 6; Mismatches 4; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLVQPGGSLRLSCASSANIQSIETLGWYRQAPGKQRELIANMRGGGYMKYA 60
:||||||||||||||||||||| ||||| |||||||||||||||||||||||||||||||
Db 1 DVQLVESGGGLVQPGGSLRLSCTSSANINSIETLGWYRQAPGKQRELIANMRGGGYMKYA 60
Qy 61 DSLKGRFTMSTDNSKNTMYLQMNSLRAEDTAVYYCYVKLRDEDYVYRGQGTQVTVSS 117
||||||||||:::|||||||||||: ||||||||||||||:|||||||||||||||
Db 61 GSLKGRFTMSTESAKNTMYLQMNSLKPEDTAVYYCYVKLRDDDYVYRGQGTQVTVSS 117
Double Patenting
12. 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 1-16 and 23 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of copending Application No. 18/397892. Although the claims at issue are not identical, they are not patentably distinct from each other because the Wnt surrogate molecule recited in the claims of Application No. 18/397892 (the ‘892 Application) anticipates the multispecific antibody or antibody fragment recited in the claims of instant Application.
Claims 1-11 of the ‘892 Applicant claim a Wnt surrogate molecule, an expression vector and a host cell encoding the Wnt surrogate molecule and a method of treatment using the Wnt surrogate molecule, wherein the Wnt surrogate molecule comprises one or more Fdz binding regions and one or more LRP5/6 binding regions, and an Fc region of an immunoglobulin molecule, wherein the Fc has at least one medication resulting in reduced affinity to FcRn including substitutions I253A, H310A and H435Q or L234A, L235A and P329G; and wherein the Wnt surrogate molecule comprises a polypeptide comprising one or more Fdz binding regions and comprising the sequence of SEQ ID NO:10, which is 99.3% identical to instant SEQ ID NO:2 and comprising a VH1 having the sequence that is 100% identical to instant SEQ ID NO: 181 and a polypeptide comprising one or more LRP5/6 binding regions and comprising the sequence of SEQ ID NO:9, which is 100% identical to instant SEQ ID NO:1, and comprising a VH2 having the sequence that is 100% identical to instant SEQ ID NO:381, and a VL1 having the sequence that is 100% identical to instant SEQ ID NO:281 (see the sequence alignment below).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
SEQ ID NO:2
Sequence 10, US/18397892
Publication No. US20240262918A1
GENERAL INFORMATION
APPLICANT: Surrozen Operating, Inc. (en)
TITLE OF INVENTION: FC-MODIFIED WNT SURROGATE MOLECULES AND USES THEREOF (en)
FILE REFERENCE: SRZN-027/01US
CURRENT APPLICATION NUMBER: US/18/397,892
CURRENT FILING DATE: 2023-12-27
NUMBER OF SEQ ID NOS: 23
SEQ ID NO 10
LENGTH: 450
TYPE: PRT
FEATURE:
NAME/KEY: source
LOCATION: 1..450
QUALIFIERS: mol_type = protein
organism = synthetic construct
FEATURE:
NAME/KEY: REGION
LOCATION: 1..450
QUALIFIERS: note = WNT mimetic construct hp4SD1-03-IgG1-AAQ heavy chain
Query Match 99.0%; Score 2366; Length 450;
Best Local Similarity 99.3%;
Matches 447; Conservative 0; Mismatches 3; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLVQPGGSLRLSCAASGFTFTSYAMSWVRQAPGKGLEWVSAISGSGGSTYY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVESGGGLVQPGGSLRLSCAASGFTFTSYAMSWVRQAPGKGLEWVSAISGSGGSTYY 60
Qy 61 AESVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARATGFGTVVFDYWGQGTLVTVSS 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 AESVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARATGFGTVVFDYWGQGTLVTVSS 120
Qy 121 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 180
Qy 181 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGG 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGG 240
Qy 241 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN 300
||||||||||||||| ||||||||||||||||||||||||||||||||||||||||||||
Db 241 PSVFLFPPKPKDTLMASRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN 300
Qy 301 STYRVVSVLTVLHQDWLNGKEYKCKVSNKALGAPIEKTISKAKGQPREPQVYTLPPSREE 360
|||||||||||| |||||||||||||||||||||||||||||||||||||||||||||||
Db 301 STYRVVSVLTVLAQDWLNGKEYKCKVSNKALGAPIEKTISKAKGQPREPQVYTLPPSREE 360
Qy 361 MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW 420
Qy 421 QQGNVFSCSVMHEALHNHYTQKSLSLSPGK 450
||||||||||||||||| ||||||||||||
Db 421 QQGNVFSCSVMHEALHNQYTQKSLSLSPGK 450
SEQ ID NO:181
Sequence 10, US/18397892
Publication No. US20240262918A1
GENERAL INFORMATION
APPLICANT: Surrozen Operating, Inc. (en)
TITLE OF INVENTION: FC-MODIFIED WNT SURROGATE MOLECULES AND USES THEREOF (en)
FILE REFERENCE: SRZN-027/01US
CURRENT APPLICATION NUMBER: US/18/397,892
CURRENT FILING DATE: 2023-12-27
NUMBER OF SEQ ID NOS: 23
SEQ ID NO 10
LENGTH: 450
TYPE: PRT
FEATURE:
NAME/KEY: source
LOCATION: 1..450
QUALIFIERS: mol_type = protein
organism = synthetic construct
FEATURE:
NAME/KEY: REGION
LOCATION: 1..450
QUALIFIERS: note = WNT mimetic construct hp4SD1-03-IgG1-AAQ heavy chain
Query Match 100.0%; Score 623; Length 450;
Best Local Similarity 100.0%;
Matches 120; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLVQPGGSLRLSCAASGFTFTSYAMSWVRQAPGKGLEWVSAISGSGGSTYY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVESGGGLVQPGGSLRLSCAASGFTFTSYAMSWVRQAPGKGLEWVSAISGSGGSTYY 60
Qy 61 AESVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARATGFGTVVFDYWGQGTLVTVSS 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 AESVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARATGFGTVVFDYWGQGTLVTVSS 120
SEQ ID NO:1
Sequence 9, US/18397892
Publication No. US20240262918A1
GENERAL INFORMATION
APPLICANT: Surrozen Operating, Inc. (en)
TITLE OF INVENTION: FC-MODIFIED WNT SURROGATE MOLECULES AND USES THEREOF (en)
FILE REFERENCE: SRZN-027/01US
CURRENT APPLICATION NUMBER: US/18/397,892
CURRENT FILING DATE: 2023-12-27
NUMBER OF SEQ ID NOS: 23
SEQ ID NO 9
LENGTH: 336
TYPE: PRT
FEATURE:
NAME/KEY: source
LOCATION: 1..336
QUALIFIERS: mol_type = protein
organism = synthetic construct
FEATURE:
NAME/KEY: REGION
LOCATION: 1..336
QUALIFIERS: note = WNT mimetic construct hp4SD1-03-IgG1-AAQ light chain
Query Match 100.0%; Score 1733; Length 336;
Best Local Similarity 100.0%;
Matches 336; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLVQPGGSLRLSCASSANIQSIETLGWYRQAPGKQRELIANMRGGGYMKYA 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVESGGGLVQPGGSLRLSCASSANIQSIETLGWYRQAPGKQRELIANMRGGGYMKYA 60
Qy 61 DSLKGRFTMSTDNSKNTMYLQMNSLRAEDTAVYYCYVKLRDEDYVYRGQGTQVTVSSGGG 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 DSLKGRFTMSTDNSKNTMYLQMNSLRAEDTAVYYCYVKLRDEDYVYRGQGTQVTVSSGGG 120
Qy 121 GSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGV 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 GSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGV 180
Qy 181 PSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIKRTVAAPSVFIF 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 PSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIKRTVAAPSVFIF 240
Qy 241 PPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSST 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 PPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSST 300
Qy 301 LTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 336
||||||||||||||||||||||||||||||||||||
Db 301 LTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 336
Sequence 11, US/18397892
Publication No. US20240262918A1
GENERAL INFORMATION
APPLICANT: Surrozen Operating, Inc. (en)
TITLE OF INVENTION: FC-MODIFIED WNT SURROGATE MOLECULES AND USES THEREOF (en)
FILE REFERENCE: SRZN-027/01US
CURRENT APPLICATION NUMBER: US/18/397,892
CURRENT FILING DATE: 2023-12-27
NUMBER OF SEQ ID NOS: 23
SEQ ID NO 11
LENGTH: 336
TYPE: PRT
FEATURE:
NAME/KEY: source
LOCATION: 1..336
QUALIFIERS: mol_type = protein
organism = synthetic construct
FEATURE:
NAME/KEY: REGION
LOCATION: 1..336
QUALIFIERS: note = WNT mimetic construct hp4SD1-03-IgG1-AAA light chain
Query Match 100.0%; Score 1733; Length 336;
Best Local Similarity 100.0%;
Matches 336; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLVQPGGSLRLSCASSANIQSIETLGWYRQAPGKQRELIANMRGGGYMKYA 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVESGGGLVQPGGSLRLSCASSANIQSIETLGWYRQAPGKQRELIANMRGGGYMKYA 60
Qy 61 DSLKGRFTMSTDNSKNTMYLQMNSLRAEDTAVYYCYVKLRDEDYVYRGQGTQVTVSSGGG 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 DSLKGRFTMSTDNSKNTMYLQMNSLRAEDTAVYYCYVKLRDEDYVYRGQGTQVTVSSGGG 120
Qy 121 GSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGV 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 GSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGV 180
Qy 181 PSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIKRTVAAPSVFIF 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 PSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIKRTVAAPSVFIF 240
Qy 241 PPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSST 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 PPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSST 300
Qy 301 LTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 336
||||||||||||||||||||||||||||||||||||
Db 301 LTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 336
SEQ ID NO:321-SEQ ID NO:341-SEQ ID NO:-361
Sequence 11, US/18397892
Publication No. US20240262918A1
GENERAL INFORMATION
APPLICANT: Surrozen Operating, Inc. (en)
TITLE OF INVENTION: FC-MODIFIED WNT SURROGATE MOLECULES AND USES THEREOF (en)
FILE REFERENCE: SRZN-027/01US
CURRENT APPLICATION NUMBER: US/18/397,892
CURRENT FILING DATE: 2023-12-27
NUMBER OF SEQ ID NOS: 23
SEQ ID NO 11
LENGTH: 336
TYPE: PRT
FEATURE:
NAME/KEY: source
LOCATION: 1..336
QUALIFIERS: mol_type = protein
organism = synthetic construct
FEATURE:
NAME/KEY: REGION
LOCATION: 1..336
QUALIFIERS: note = WNT mimetic construct hp4SD1-03-IgG1-AAA light chain
Query Match 82.2%; Score 117.6; Length 336;
Best Local Similarity 33.3%;
Matches 27; Conservative 0; Mismatches 0; Indels 54; Gaps 2;
Qy 1 ANIQSIET----------------NMRGGGYM---------------------------- 16
|||||||| ||||||||
Db 26 ANIQSIETLGWYRQAPGKQRELIANMRGGGYMKYADSLKGRFTMSTDNSKNTMYLQMNSL 85
Qy 17 ----------YVKLRDEDYVY 27
|||||||||||
Db 86 RAEDTAVYYCYVKLRDEDYVY 106
Sequence 9, US/18397892
Publication No. US20240262918A1
GENERAL INFORMATION
APPLICANT: Surrozen Operating, Inc. (en)
TITLE OF INVENTION: FC-MODIFIED WNT SURROGATE MOLECULES AND USES THEREOF (en)
FILE REFERENCE: SRZN-027/01US
CURRENT APPLICATION NUMBER: US/18/397,892
CURRENT FILING DATE: 2023-12-27
NUMBER OF SEQ ID NOS: 23
SEQ ID NO 9
LENGTH: 336
TYPE: PRT
FEATURE:
NAME/KEY: source
LOCATION: 1..336
QUALIFIERS: mol_type = protein
organism = synthetic construct
FEATURE:
NAME/KEY: REGION
LOCATION: 1..336
QUALIFIERS: note = WNT mimetic construct hp4SD1-03-IgG1-AAQ light chain
Query Match 82.2%; Score 117.6; Length 336;
Best Local Similarity 33.3%;
Matches 27; Conservative 0; Mismatches 0; Indels 54; Gaps 2;
Qy 1 ANIQSIET----------------NMRGGGYM---------------------------- 16
|||||||| ||||||||
Db 26 ANIQSIETLGWYRQAPGKQRELIANMRGGGYMKYADSLKGRFTMSTDNSKNTMYLQMNSL 85
Qy 17 ----------YVKLRDEDYVY 27
|||||||||||
Db 86 RAEDTAVYYCYVKLRDEDYVY 106
SEQ ID NO:381
Sequence 11, US/18397892
Publication No. US20240262918A1
GENERAL INFORMATION
APPLICANT: Surrozen Operating, Inc. (en)
TITLE OF INVENTION: FC-MODIFIED WNT SURROGATE MOLECULES AND USES THEREOF (en)
FILE REFERENCE: SRZN-027/01US
CURRENT APPLICATION NUMBER: US/18/397,892
CURRENT FILING DATE: 2023-12-27
NUMBER OF SEQ ID NOS: 23
SEQ ID NO 11
LENGTH: 336
TYPE: PRT
FEATURE:
NAME/KEY: source
LOCATION: 1..336
QUALIFIERS: mol_type = protein
organism = synthetic construct
FEATURE:
NAME/KEY: REGION
LOCATION: 1..336
QUALIFIERS: note = WNT mimetic construct hp4SD1-03-IgG1-AAA light chain
Query Match 100.0%; Score 605; Length 336;
Best Local Similarity 100.0%;
Matches 117; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLVQPGGSLRLSCASSANIQSIETLGWYRQAPGKQRELIANMRGGGYMKYA 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVESGGGLVQPGGSLRLSCASSANIQSIETLGWYRQAPGKQRELIANMRGGGYMKYA 60
Qy 61 DSLKGRFTMSTDNSKNTMYLQMNSLRAEDTAVYYCYVKLRDEDYVYRGQGTQVTVSS 117
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 DSLKGRFTMSTDNSKNTMYLQMNSLRAEDTAVYYCYVKLRDEDYVYRGQGTQVTVSS 117
Sequence 9, US/18397892
Publication No. US20240262918A1
GENERAL INFORMATION
APPLICANT: Surrozen Operating, Inc. (en)
TITLE OF INVENTION: FC-MODIFIED WNT SURROGATE MOLECULES AND USES THEREOF (en)
FILE REFERENCE: SRZN-027/01US
CURRENT APPLICATION NUMBER: US/18/397,892
CURRENT FILING DATE: 2023-12-27
NUMBER OF SEQ ID NOS: 23
SEQ ID NO 9
LENGTH: 336
TYPE: PRT
FEATURE:
NAME/KEY: source
LOCATION: 1..336
QUALIFIERS: mol_type = protein
organism = synthetic construct
FEATURE:
NAME/KEY: REGION
LOCATION: 1..336
QUALIFIERS: note = WNT mimetic construct hp4SD1-03-IgG1-AAQ light chain
Query Match 100.0%; Score 605; Length 336;
Best Local Similarity 100.0%;
Matches 117; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLVQPGGSLRLSCASSANIQSIETLGWYRQAPGKQRELIANMRGGGYMKYA 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVESGGGLVQPGGSLRLSCASSANIQSIETLGWYRQAPGKQRELIANMRGGGYMKYA 60
Qy 61 DSLKGRFTMSTDNSKNTMYLQMNSLRAEDTAVYYCYVKLRDEDYVYRGQGTQVTVSS 117
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 DSLKGRFTMSTDNSKNTMYLQMNSLRAEDTAVYYCYVKLRDEDYVYRGQGTQVTVSS 117
Conclusion
13. NO CLAIM IS ALLOWED.
Sequence alignment
VH1-Anti-Fzd4
SEQ ID NO:181 1 EVQLVESGGGLVQPGGSLRLSCAASGFTFTSYAMSWVRQAPGKGLEWVSAISGSGGSTYY 60
SEQ ID NO:121 1 ------------------------------SYAMS------------------------- 5
SEQ ID NO:141 1 -------------------------------------------------AISGSGGSTYY 12
SEQ ID NO:161 ------------------------------------------------------------
SEQ ID NO:181 61 AESVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARATGFGTVVFDYWGQGTLVTVSS 120
SEQ ID NO:121 ------------------------------------------------------------
SEQ ID NO:141 13 AESVKG------------------------------------------------------ 18
SEQ ID NO:161 1 --------------------------------------ATGFGTVVFDY----------- 11
VL1-Anti-Fzd4
SEQ ID NO:281 1 DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPS 60
SEQ ID NO:221 1 -----------------------RASQSISSYLN-------------------------- 11
SEQ ID NO:241 1 -------------------------------------------------AASSLQS---- 7
SEQ ID NO:261 ------------------------------------------------------------
SEQ ID NO:281 61 RFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIK 107
SEQ ID NO:221 -----------------------------------------------
SEQ ID NO:241 -----------------------------------------------
SEQ ID NO:261 1 ----------------------------QQSYSTPLT---------- 9
VH2-anti-LRP5/6
SEQ ID NO:381 1 EVQLVESGGGLVQPGGSLRLSCASSANIQSIETLGWYRQAPGKQRELIANMRGGGYMKYA 60
SEQ ID NO:393 1 EVQLVESGGGLVQPGGSLRLSCASSANIQSIETLGWYRQAPGKQRELIANMRGGGYMKYA 60
SEQ ID NO:394 1 EVQLVESGGGLVQPGGSLRLSCASSANIQSIETLGWYRQAPGKQRELIANMRGGGYMKYA 60
SEQ ID NO:395 1 EVQLVESGGGLVQPGGSLRLSCASSANIQSIETLGWYRQAPGKQRELIANMRGGGYMKYA 60
SEQ ID NO:396 1 EVQLVESGGGLVQPGGSLRLSCASSANIQSIETLGWYRQAPGKQRELIANMRGGGYMKYA 60
SEQ ID NO:321 1 -------------------------ANIQSIET--------------------------- 8
SEQ ID NO:341 1 -------------------------------------------------NMRGGGYM--- 8
SEQ ID NO:361 ------------------------------------------------------------
SEQ ID NO:381 61 DSLKGRFTMSTDNSKNTMYLQMNSLRAEDTAVYYCYVKLRDEDYVYRGQGTQVTVSS 117
SEQ ID NO:393 61 DSLKGRFTMSTDNSKNTMYLQMNSLRAEDTAVYYCYVKLRDEEYVYRGQGTQVTVSS 117
SEQ ID NO:394 61 DSLKGRFTMSTDNSKNTMYLQMNSLRAEDTAVYYCYVKLRDESYVYRGQGTQVTVSS 117
SEQ ID NO:395 61 DSLKGRFTMSTDNSKNTMYLQMNSLRAEDTAVYYCYVKLRDEAYVYRGQGTQVTVSS 117
SEQ ID NO:396 61 DSLKGRFTMSTDNSKNTMYLQMNSLRAEDTAVYYCYVKLRDETYVYRGQGTQVTVSS 117
SEQ ID NO:321 ---------------------------------------------------------
SEQ ID NO:341 ---------------------------------------------------------
SEQ ID NO:361 1 -------------------------------------------YVKLRDEDYVY--- 11
Anti-LRP5/6-VH2+anti-Fzd4-VL1
SEQ ID NO:1(Anti-LRP5/6-VH2+anti-Fzd4-VL1) 1 EVQLVESGGGLVQPGGSLRLSCASSANIQSIETLGWYRQAPGKQRELIANMRGGGYMKYA 60
SEQ ID NO:381(Anti-LRP5/6-VH2) 1 EVQLVESGGGLVQPGGSLRLSCASSANIQSIETLGWYRQAPGKQRELIANMRGGGYMKYA 60
SEQ ID NO:1(Anti-LRP5/6-VH2+anti-Fzd4-VL1) 61 DSLKGRFTMSTDNSKNTMYLQMNSLRAEDTAVYYCYVKLRDEDYVYRGQGTQVTVSSGGG 120
SEQ ID NO:381(Anti-LRP5/6-VH2) 61 DSLKGRFTMSTDNSKNTMYLQMNSLRAEDTAVYYCYVKLRDEDYVYRGQGTQVTVSS--- 117
SEQ ID NO:1(Anti-LRP5/6-VH2+anti-Fzd4-VL1) 121 GSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGV 180
SEQ ID NO:281(Anti-Fzd4-VL1) 1 --DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGV 58
SEQ ID NO:1(Anti-LRP5/6-VH2+anti-Fzd4-VL1) 181 PSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIKRTVAAPSVFIF 240
SEQ ID NO:281(Anti-Fzd4-VL1) PSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIK----------- 107
SEQ ID NO:1(Anti-LRP5/6-VH2+anti-Fzd4-VL1) 241 PPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSST 300
SEQ ID NO:1(Anti-LRP5/6-VH2+anti-Fzd4-VL1) 301 LTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 336
Anti-Fzd4-VH1-Fc
SEQ ID NO:2(Anti-Fzd4-VH1) 1 EVQLVESGGGLVQPGGSLRLSCAASGFTFTSYAMSWVRQAPGKGLEWVSAISGSGGSTYY 60
SEQ ID NO:181(Anti-Fzd4-VH1) 1 EVQLVESGGGLVQPGGSLRLSCAASGFTFTSYAMSWVRQAPGKGLEWVSAISGSGGSTYY 60
SEQ ID NO:2(Anti-Fzd4-VH1) 61 AESVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARATGFGTVVFDYWGQGTLVTVSS 120
SEQ ID NO:181(Anti-Fzd4-VH1) 61 AESVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARATGFGTVVFDYWGQGTLVTVSS 120
SEQ ID NO:2(Anti-Fzd4-VH1) 121 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 180
SEQ ID NO:2(Anti-Fzd4-VH1) 181 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGG 240
SEQ ID NO:2(Anti-Fzd4-VH1) 241 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN 300
SEQ ID NO:2(Anti-Fzd4-VH1) 301 STYRVVSVLTVLHQDWLNGKEYKCKVSNKALGAPIEKTISKAKGQPREPQVYTLPPSREE 360
SEQ ID NO:2(Anti-Fzd4-VH1) 361 MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW 420
SEQ ID NO:2(Anti-Fzd4-VH1) 421 QQGNVFSCSVMHEALHNHYTQKSLSLSPGK 450
14. The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Li (WO2020010308 as in IDS) teaches a multispecific Wnt surrogate molecule 4SD1-3 binding to Fzd4 and LRP5/6, wherein the multispecific Wnt surrogate molecule comprises at least (A) a first antigen-binding region binding to Fzd4 (anti-Fzd4) and comprising VH1 (anti-Fzd4-VH1) and VL1 (anti-Fzd4 VL1), (B) a second antigen-binding region binding to LRP5/LRP6 (anti-LRP5/6) and comprising VH2 (anti-LRP5/6 VH2), and has a structure of a multispecific antibody or antigen-binding fragment as in figure 1 or 2B or 3A (see p. 2-6 Figures 1, 2B and 3A). Li teaches that the multispecific Wnt surrogate molecule 4SD1-3 comprises a first polypeptide (i.e.4SD1-3 HC), and a second polypeptide (i.e a 4SD1-3 LC), wherein the 4SD1-3 HC has the amino acid sequence of SEQ ID NO:116 (which is 99.1% identical to instant SEQ ID NO:2 and comprises an amino acid sequence that is 96.5% identical to instant SEQ ID NO:181(the claimed VH1) which comprises an amino acid sequence that is 80% identical to instant SEQ ID NO:121 for CDRH1, an amino acid sequence that is at least 90% identical to instant SEQ ID NO: 141 for CDRH2 and an amino acid sequence that is 100% identical to SEQ ID NO:161 for CDRH3), and the 4SD1-3 LC has the amino acid sequence of SEQ 115 (which is 96.7% identical to instant SEQ ID NO:1 and comprises an amino acid sequence that is 93.1% identical to instant SEQ ID NO:381(the claimed VH2) which comprises an amino acid sequence 87.5% identical to instant SEQ ID NO:321 for CDRH1, an amino acid sequence that is 100% identical to instant SEQ ID NO:341 for CDRH2 and an amino acid sequence that is at least 90% identical to instant SEQ ID NO:361 and an amino acid sequence that is 100% identical to instant SEQ ID NO:281 (the claimed VL1) (see the sequence alignment below; p. 159-, table 5).
SEQ ID NO:2
ID BHD71239 standard; protein; 472 AA.
XX
AC BHD71239;
XX
DT 05-MAR-2020 (first entry)
XX
DE Multispecific Wnt surrogate molecule (4SD1-3 HC), SEQ 116.
XX
KW Frizzled protein; Fzd protein; antibody; antibody therapy;
KW antiinflammatory; antiulcer; cardiovascular disease; cardiovascular-gen.;
KW cell signaling; degeneration; dermatological; dermatological disease;
KW endocrine disease; endocrine-gen.; fusion protein;
KW gastrointestinal disease; gastrointestinal-gen.; genetic disorder;
KW genetic-disease-gen.; genitourinary disease; growth disorder;
KW growth-disorder-gen.; heavy chain; immune disorder; immunomodulator;
KW inflammatory disease; injury; metabolic disorder; metabolic-gen.;
KW mouth disease; musculoskeletal disease; musculoskeletal-gen.;
KW neurological disease; neuroprotective; nutrition-disorder-gen.;
KW nutritional disorder; ocular disease; ophthalmological; oral-dental-gen.;
KW otorhinolaryngological disease; otorhinolaryngological-gen.;
KW respiratory disease; respiratory-gen.; surgical procedure; surgical-gen.;
KW therapeutic; ulcer; uropathic; vulnerary.
XX
OS Synthetic.
OS Unidentified.
XX
CC PN WO2020010308-A1.
XX
CC PD 09-JAN-2020.
XX
CC PF 05-JUL-2019; 2019WO-US040687.
XX
PR 05-JUL-2018; 2018US-0694339P.
PR 19-DEC-2018; 2018US-0782122P.
PR 28-JAN-2019; 2019US-0797772P.
XX
CC PA (SURR-) SURROZEN INC.
XX
CC PI Li Y;
XX
DR WPI; 2020-046200/007.
XX
CC PT New multispecific Wnt surrogate molecule containing several regions
CC PT specifically bind to set of frizzled receptor epitopes, used treating
CC PT subject having disease or disorder associated with reduced or impaired
CC PT Wnt signaling e.g. osteoporosis.
XX
CC PS Claim 39; SEQ ID NO 116; 253pp; English.
XX
CC The present invention relates to a novel multispecific Wnt surrogate
CC molecule useful for treating a subject having disease or disorder
CC associated with reduced or impaired Wnt signaling. The multispecific Wnt
CC surrogate molecule comprises a plurality of regions that each
CC specifically bind to a set of Frizzled (Fzd) receptor epitopes (Fzd
CC binding regions), wherein at least two Fzd binding regions binds to
CC different sets of Fzd receptor epitopes; and one or more regions that
CC specifically bind to a Low-density lipoprotein (LDL) receptor-related
CC protein 5 (LRP5) and/or a LDL receptor-related protein 6 (LRP6) (LRP5/6
CC binding regions). The invention further provides: a pharmaceutical
CC composition comprising a pharmaceutically acceptable excipient, diluent
CC or carrier, and the Wnt surrogate molecule; a method for agonizing the
CC Wnt signaling pathway in a cell; and a method for treating the subject
CC having a disease or disorder, by administering an effective amount of the
CC Wnt surrogate molecule. The present sequence represents a multispecific
CC Wnt surrogate molecule comprising a signal peptide and an anti-Fzd
CC antibody heavy chain region.
XX
SQ Sequence 472 AA;
Query Match 99.1%; Score 2367; Length 472;
Best Local Similarity 98.7%;
Matches 444; Conservative 5; Mismatches 1; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLVQPGGSLRLSCAASGFTFTSYAMSWVRQAPGKGLEWVSAISGSGGSTYY 60
||||||||||||:|||||||||||||||||:|||||||||||||||||||||||||||||
Db 23 EVQLVESGGGLVKPGGSLRLSCAASGFTFTNYAMSWVRQAPGKGLEWVSAISGSGGSTYY 82
Qy 61 AESVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARATGFGTVVFDYWGQGTLVTVSS 120
|:|||||||||||:||||||||||||: ||||||||||||||||||||||||||||||||
Db 83 ADSVKGRFTISRDDSKNTLYLQMNSLKTEDTAVYYCARATGFGTVVFDYWGQGTLVTVSS 142
Qy 121 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 143 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 202
Qy 181 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGG 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 203 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGG 262
Qy 241 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 263 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN 322
Qy 301 STYRVVSVLTVLHQDWLNGKEYKCKVSNKALGAPIEKTISKAKGQPREPQVYTLPPSREE 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 323 STYRVVSVLTVLHQDWLNGKEYKCKVSNKALGAPIEKTISKAKGQPREPQVYTLPPSREE 382
Qy 361 MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 383 MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW 442
Qy 421 QQGNVFSCSVMHEALHNHYTQKSLSLSPGK 450
||||||||||||||||||||||||||||||
Db 443 QQGNVFSCSVMHEALHNHYTQKSLSLSPGK 472
SEQ ID NO:181 (Anti-Fzd4-VH)
ID BHD71239 standard; protein; 472 AA.
XX
AC BHD71239;
XX
DT 05-MAR-2020 (first entry)
XX
DE Multispecific Wnt surrogate molecule (4SD1-3 HC), SEQ 116.
XX
KW Frizzled protein; Fzd protein; antibody; antibody therapy;
KW antiinflammatory; antiulcer; cardiovascular disease; cardiovascular-gen.;
KW cell signaling; degeneration; dermatological; dermatological disease;
KW endocrine disease; endocrine-gen.; fusion protein;
KW gastrointestinal disease; gastrointestinal-gen.; genetic disorder;
KW genetic-disease-gen.; genitourinary disease; growth disorder;
KW growth-disorder-gen.; heavy chain; immune disorder; immunomodulator;
KW inflammatory disease; injury; metabolic disorder; metabolic-gen.;
KW mouth disease; musculoskeletal disease; musculoskeletal-gen.;
KW neurological disease; neuroprotective; nutrition-disorder-gen.;
KW nutritional disorder; ocular disease; ophthalmological; oral-dental-gen.;
KW otorhinolaryngological disease; otorhinolaryngological-gen.;
KW respiratory disease; respiratory-gen.; surgical procedure; surgical-gen.;
KW therapeutic; ulcer; uropathic; vulnerary.
XX
OS Synthetic.
OS Unidentified.
XX
CC PN WO2020010308-A1.
XX
CC PD 09-JAN-2020.
XX
CC PF 05-JUL-2019; 2019WO-US040687.
XX
PR 05-JUL-2018; 2018US-0694339P.
PR 19-DEC-2018; 2018US-0782122P.
PR 28-JAN-2019; 2019US-0797772P.
XX
CC PA (SURR-) SURROZEN INC.
XX
CC PI Li Y;
XX
DR WPI; 2020-046200/007.
XX
CC PT New multispecific Wnt surrogate molecule containing several regions
CC PT specifically bind to set of frizzled receptor epitopes, used treating
CC PT subject having disease or disorder associated with reduced or impaired
CC PT Wnt signaling e.g. osteoporosis.
XX
CC PS Claim 39; SEQ ID NO 116; 253pp; English.
XX
CC The present invention relates to a novel multispecific Wnt surrogate
CC molecule useful for treating a subject having disease or disorder
CC associated with reduced or impaired Wnt signaling. The multispecific Wnt
CC surrogate molecule comprises a plurality of regions that each
CC specifically bind to a set of Frizzled (Fzd) receptor epitopes (Fzd
CC binding regions), wherein at least two Fzd binding regions binds to
CC different sets of Fzd receptor epitopes; and one or more regions that
CC specifically bind to a Low-density lipoprotein (LDL) receptor-related
CC protein 5 (LRP5) and/or a LDL receptor-related protein 6 (LRP6) (LRP5/6
CC binding regions). The invention further provides: a pharmaceutical
CC composition comprising a pharmaceutically acceptable excipient, diluent
CC or carrier, and the Wnt surrogate molecule; a method for agonizing the
CC Wnt signaling pathway in a cell; and a method for treating the subject
CC having a disease or disorder, by administering an effective amount of the
CC Wnt surrogate molecule. The present sequence represents a multispecific
CC Wnt surrogate molecule comprising a signal peptide and an anti-Fzd
CC antibody heavy chain region.
XX
SQ Sequence 472 AA;
Query Match 96.5%; Score 601; Length 472;
Best Local Similarity 95.0%;
Matches 114; Conservative 5; Mismatches 1; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLVQPGGSLRLSCAASGFTFTSYAMSWVRQAPGKGLEWVSAISGSGGSTYY 60
||||||||||||:|||||||||||||||||:|||||||||||||||||||||||||||||
Db 23 EVQLVESGGGLVKPGGSLRLSCAASGFTFTNYAMSWVRQAPGKGLEWVSAISGSGGSTYY 82
Qy 61 AESVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARATGFGTVVFDYWGQGTLVTVSS 120
|:|||||||||||:||||||||||||: ||||||||||||||||||||||||||||||||
Db 83 ADSVKGRFTISRDDSKNTLYLQMNSLKTEDTAVYYCARATGFGTVVFDYWGQGTLVTVSS 142
SEQ ID NO:1
BHD71238
(NOTE: this sequence has 3 duplicates in the database searched)
ID BHD71238 standard; protein; 358 AA.
XX
AC BHD71238;
XX
DT 05-MAR-2020 (first entry)
XX
DE Multispecific Wnt surrogate molecule (4SD1-3 LC), SEQ 115.
XX
KW Frizzled protein; Fzd protein; LDL receptor-related protein; LRP;
KW Low-density lipoprotein receptor-related protein; antibody;
KW antibody therapy; antiinflammatory; antiulcer; cardiovascular disease;
KW cardiovascular-gen.; cell signaling; degeneration; dermatological;
KW dermatological disease; endocrine disease; endocrine-gen.;
KW fusion protein; gastrointestinal disease; gastrointestinal-gen.;
KW genetic disorder; genetic-disease-gen.; genitourinary disease;
KW growth disorder; growth-disorder-gen.; heavy chain variable region;
KW immune disorder; immunomodulator; inflammatory disease; injury;
KW light chain variable region; metabolic disorder; metabolic-gen.;
KW mouth disease; musculoskeletal disease; musculoskeletal-gen.;
KW neurological disease; neuroprotective; nutrition-disorder-gen.;
KW nutritional disorder; ocular disease; ophthalmological; oral-dental-gen.;
KW otorhinolaryngological disease; otorhinolaryngological-gen.;
KW respiratory disease; respiratory-gen.; single domain antibody;
KW surgical procedure; surgical-gen.; therapeutic; ulcer; uropathic;
KW vulnerary.
XX
OS Synthetic.
OS Unidentified.
XX
CC PN WO2020010308-A1.
XX
CC PD 09-JAN-2020.
XX
CC PF 05-JUL-2019; 2019WO-US040687.
XX
PR 05-JUL-2018; 2018US-0694339P.
PR 19-DEC-2018; 2018US-0782122P.
PR 28-JAN-2019; 2019US-0797772P.
XX
CC PA (SURR-) SURROZEN INC.
XX
CC PI Li Y;
XX
DR WPI; 2020-046200/007.
XX
CC PT New multispecific Wnt surrogate molecule containing several regions
CC PT specifically bind to set of frizzled receptor epitopes, used treating
CC PT subject having disease or disorder associated with reduced or impaired
CC PT Wnt signaling e.g. osteoporosis.
XX
CC PS Claim 39; SEQ ID NO 115; 253pp; English.
XX
CC The present invention relates to a novel multispecific Wnt surrogate
CC molecule useful for treating a subject having disease or disorder
CC associated with reduced or impaired Wnt signaling. The multispecific Wnt
CC surrogate molecule comprises a plurality of regions that each
CC specifically bind to a set of Frizzled (Fzd) receptor epitopes (Fzd
CC binding regions), wherein at least two Fzd binding regions binds to
CC different sets of Fzd receptor epitopes; and one or more regions that
CC specifically bind to a Low-density lipoprotein (LDL) receptor-related
CC protein 5 (LRP5) and/or a LDL receptor-related protein 6 (LRP6) (LRP5/6
CC binding regions). The invention further provides: a pharmaceutical
CC composition comprising a pharmaceutically acceptable excipient, diluent
CC or carrier, and the Wnt surrogate molecule; a method for agonizing the
CC Wnt signaling pathway in a cell; and a method for treating the subject
CC having a disease or disorder, by administering an effective amount of the
CC Wnt surrogate molecule. The present sequence represents a multispecific
CC Wnt surrogate molecule comprising a signal peptide, an anti-Lrp VHH or
CC sdAb antibody and an anti-Fzd antibody light chain region.
XX
SQ Sequence 358 AA;
Query Match 96.7%; Score 1675; Length 358;
Best Local Similarity 96.1%;
Matches 323; Conservative 6; Mismatches 7; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLVQPGGSLRLSCASSANIQSIETLGWYRQAPGKQRELIANMRGGGYMKYA 60
:||||||||||||||||||||| ||||| |||||||||||||||||||||||||||||||
Db 23 DVQLVESGGGLVQPGGSLRLSCTSSANINSIETLGWYRQAPGKQRELIANMRGGGYMKYA 82
Qy 61 DSLKGRFTMSTDNSKNTMYLQMNSLRAEDTAVYYCYVKLRDEDYVYRGQGTQVTVSSGGG 120
||||||||||:::|||||||||||: ||||||||||||||:|||||||||||||||| |
Db 83 GSLKGRFTMSTESAKNTMYLQMNSLKPEDTAVYYCYVKLRDDDYVYRGQGTQVTVSSGSG 142
Qy 121 GSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGV 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 143 SGDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGV 202
Qy 181 PSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIKRTVAAPSVFIF 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 203 PSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIKRTVAAPSVFIF 262
Qy 241 PPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSST 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 263 PPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSST 322
Qy 301 LTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 336
||||||||||||||||||||||||||||||||||||
Db 323 LTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 358
SEQ ID NO:381 (Anti-LRP5/6-VH)
BHD71238
(NOTE: this sequence has 3 duplicates in the database searched)
ID BHD71238 standard; protein; 358 AA.
XX
AC BHD71238;
XX
DT 05-MAR-2020 (first entry)
XX
DE Multispecific Wnt surrogate molecule (4SD1-3 LC), SEQ 115.
XX
KW Frizzled protein; Fzd protein; LDL receptor-related protein; LRP;
KW Low-density lipoprotein receptor-related protein; antibody;
KW antibody therapy; antiinflammatory; antiulcer; cardiovascular disease;
KW cardiovascular-gen.; cell signaling; degeneration; dermatological;
KW dermatological disease; endocrine disease; endocrine-gen.;
KW fusion protein; gastrointestinal disease; gastrointestinal-gen.;
KW genetic disorder; genetic-disease-gen.; genitourinary disease;
KW growth disorder; growth-disorder-gen.; heavy chain variable region;
KW immune disorder; immunomodulator; inflammatory disease; injury;
KW light chain variable region; metabolic disorder; metabolic-gen.;
KW mouth disease; musculoskeletal disease; musculoskeletal-gen.;
KW neurological disease; neuroprotective; nutrition-disorder-gen.;
KW nutritional disorder; ocular disease; ophthalmological; oral-dental-gen.;
KW otorhinolaryngological disease; otorhinolaryngological-gen.;
KW respiratory disease; respiratory-gen.; single domain antibody;
KW surgical procedure; surgical-gen.; therapeutic; ulcer; uropathic;
KW vulnerary.
XX
OS Synthetic.
OS Unidentified.
XX
CC PN WO2020010308-A1.
XX
CC PD 09-JAN-2020.
XX
CC PF 05-JUL-2019; 2019WO-US040687.
XX
PR 05-JUL-2018; 2018US-0694339P.
PR 19-DEC-2018; 2018US-0782122P.
PR 28-JAN-2019; 2019US-0797772P.
XX
CC PA (SURR-) SURROZEN INC.
XX
CC PI Li Y;
XX
DR WPI; 2020-046200/007.
XX
CC PT New multispecific Wnt surrogate molecule containing several regions
CC PT specifically bind to set of frizzled receptor epitopes, used treating
CC PT subject having disease or disorder associated with reduced or impaired
CC PT Wnt signaling e.g. osteoporosis.
XX
CC PS Claim 39; SEQ ID NO 115; 253pp; English.
XX
CC The present invention relates to a novel multispecific Wnt surrogate
CC molecule useful for treating a subject having disease or disorder
CC associated with reduced or impaired Wnt signaling. The multispecific Wnt
CC surrogate molecule comprises a plurality of regions that each
CC specifically bind to a set of Frizzled (Fzd) receptor epitopes (Fzd
CC binding regions), wherein at least two Fzd binding regions binds to
CC different sets of Fzd receptor epitopes; and one or more regions that
CC specifically bind to a Low-density lipoprotein (LDL) receptor-related
CC protein 5 (LRP5) and/or a LDL receptor-related protein 6 (LRP6) (LRP5/6
CC binding regions). The invention further provides: a pharmaceutical
CC composition comprising a pharmaceutically acceptable excipient, diluent
CC or carrier, and the Wnt surrogate molecule; a method for agonizing the
CC Wnt signaling pathway in a cell; and a method for treating the subject
CC having a disease or disorder, by administering an effective amount of the
CC Wnt surrogate molecule. The present sequence represents a multispecific
CC Wnt surrogate molecule comprising a signal peptide, an anti-Lrp VHH or
CC sdAb antibody and an anti-Fzd antibody light chain region.
XX
SQ Sequence 358 AA;
Query Match 93.1%; Score 563; Length 358;
Best Local Similarity 91.5%;
Matches 107; Conservative 6; Mismatches 4; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLVQPGGSLRLSCASSANIQSIETLGWYRQAPGKQRELIANMRGGGYMKYA 60
:||||||||||||||||||||| ||||| |||||||||||||||||||||||||||||||
Db 23 DVQLVESGGGLVQPGGSLRLSCTSSANINSIETLGWYRQAPGKQRELIANMRGGGYMKYA 82
Qy 61 DSLKGRFTMSTDNSKNTMYLQMNSLRAEDTAVYYCYVKLRDEDYVYRGQGTQVTVSS 117
||||||||||:::|||||||||||: ||||||||||||||:|||||||||||||||
Db 83 GSLKGRFTMSTESAKNTMYLQMNSLKPEDTAVYYCYVKLRDDDYVYRGQGTQVTVSS 139
SEQ ID NO:281 (Anti-Fzd4-VL)
BHD71238
(NOTE: this sequence has 3 duplicates in the database searched.
See complete list at the end of this report)
ID BHD71238 standard; protein; 358 AA.
XX
AC BHD71238;
XX
DT 05-MAR-2020 (first entry)
XX
DE Multispecific Wnt surrogate molecule (4SD1-3 LC), SEQ 115.
XX
KW Frizzled protein; Fzd protein; LDL receptor-related protein; LRP;
KW Low-density lipoprotein receptor-related protein; antibody;
KW antibody therapy; antiinflammatory; antiulcer; cardiovascular disease;
KW cardiovascular-gen.; cell signaling; degeneration; dermatological;
KW dermatological disease; endocrine disease; endocrine-gen.;
KW fusion protein; gastrointestinal disease; gastrointestinal-gen.;
KW genetic disorder; genetic-disease-gen.; genitourinary disease;
KW growth disorder; growth-disorder-gen.; heavy chain variable region;
KW immune disorder; immunomodulator; inflammatory disease; injury;
KW light chain variable region; metabolic disorder; metabolic-gen.;
KW mouth disease; musculoskeletal disease; musculoskeletal-gen.;
KW neurological disease; neuroprotective; nutrition-disorder-gen.;
KW nutritional disorder; ocular disease; ophthalmological; oral-dental-gen.;
KW otorhinolaryngological disease; otorhinolaryngological-gen.;
KW respiratory disease; respiratory-gen.; single domain antibody;
KW surgical procedure; surgical-gen.; therapeutic; ulcer; uropathic;
KW vulnerary.
XX
OS Synthetic.
OS Unidentified.
XX
CC PN WO2020010308-A1.
XX
CC PD 09-JAN-2020.
XX
CC PF 05-JUL-2019; 2019WO-US040687.
XX
PR 05-JUL-2018; 2018US-0694339P.
PR 19-DEC-2018; 2018US-0782122P.
PR 28-JAN-2019; 2019US-0797772P.
XX
CC PA (SURR-) SURROZEN INC.
XX
CC PI Li Y;
XX
DR WPI; 2020-046200/007.
XX
CC PT New multispecific Wnt surrogate molecule containing several regions
CC PT specifically bind to set of frizzled receptor epitopes, used treating
CC PT subject having disease or disorder associated with reduced or impaired
CC PT Wnt signaling e.g. osteoporosis.
XX
CC PS Claim 39; SEQ ID NO 115; 253pp; English.
XX
CC The present invention relates to a novel multispecific Wnt surrogate
CC molecule useful for treating a subject having disease or disorder
CC associated with reduced or impaired Wnt signaling. The multispecific Wnt
CC surrogate molecule comprises a plurality of regions that each
CC specifically bind to a set of Frizzled (Fzd) receptor epitopes (Fzd
CC binding regions), wherein at least two Fzd binding regions binds to
CC different sets of Fzd receptor epitopes; and one or more regions that
CC specifically bind to a Low-density lipoprotein (LDL) receptor-related
CC protein 5 (LRP5) and/or a LDL receptor-related protein 6 (LRP6) (LRP5/6
CC binding regions). The invention further provides: a pharmaceutical
CC composition comprising a pharmaceutically acceptable excipient, diluent
CC or carrier, and the Wnt surrogate molecule; a method for agonizing the
CC Wnt signaling pathway in a cell; and a method for treating the subject
CC having a disease or disorder, by administering an effective amount of the
CC Wnt surrogate molecule. The present sequence represents a multispecific
CC Wnt surrogate molecule comprising a signal peptide, an anti-Lrp VHH or
CC sdAb antibody and an anti-Fzd antibody light chain region.
XX
SQ Sequence 358 AA;
Query Match 100.0%; Score 547; Length 358;
Best Local Similarity 100.0%;
Matches 107; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 145 DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPS 204
Qy 61 RFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIK 107
|||||||||||||||||||||||||||||||||||||||||||||||
Db 205 RFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIK 251
WO2020167848 teaches a multispecific Wnt agonist polypeptide comprising (a) one or more region that specifically binds to one or more frizzled (Fzd) receptor including Fzd4 (a Fzd4 binding region); and (b) one or more region that specifically binds to a LRP5 and/or a LRP6 (a LRP5/6 binding region), wherein the Wnt agonist polypeptide comprises a first polypeptide comprising the amino acid sequence of SEQ ID NO:6,which is 99.1% identical to instant SEQ ID NO:2 and comprises the claimed VH1, and a second polypeptide comprising the amino acid sequence of SEQ ID NO:5, which is 97.2% identical to instant SEQ ID NO:1 and comprises VH2, a linker and a VL1 (see the sequence alignment below).
SEQ ID NO:2
ID BIF28720 standard; protein; 472 AA.
XX
AC BIF28720;
XX
DT 15-OCT-2020 (first entry)
XX
DE Retinopathy treatment related WNT agonist polypeptide, SEQ 6.
XX
KW WNT protein agonist; antibody; fusion protein; heavy chain;
KW immunomodulator; ocular disease; ophthalmological; protein therapy;
KW retinopathy; therapeutic; vascular disease; vasotropic.
XX
OS Synthetic.
OS Unidentified.
XX
CC PN WO2020167848-A1.
XX
CC PD 20-AUG-2020.
XX
CC PF 11-FEB-2020; 2020WO-US017769.
XX
PR 11-FEB-2019; 2019US-0803835P.
XX
CC PA (SURR-) SURROZEN INC.
XX
CC PI Li Y, Tu S, Lee S, Yeh W;
XX
DR WPI; 2020-79727E/073.
XX
CC PT Treating retinopathy includes retinal vascular disease such as familiar
CC PT exudative vitreoretionopathy, involves administering engineered WNT
CC PT signaling modulator to subject.
XX
CC PS Example 1; SEQ ID NO 6; 56pp; English.
XX
CC The present invention relates to a novel method for treating retinopathy
CC in a subject. The method involves administering an engineered WNT
CC signaling modulator to a subject. The method is useful for treating
CC retinal vascular disease such as retinopathy, where retinal vascular
CC disease is selected from familiar exudative vitreoretionopathy (FEVR),
CC exudative vitreoretinopathy, Nome disease, diabetic retinopathy (DR), age
CC -related macular degeneration (AMD), retinopathy of prematurity (ROP),
CC osteoporosis-psuedoglioma syndrome (OPPG), retinal vein occlusion, and
CC Coats disease. The method enables to treat retinopathy which regulate
CC aberrant vascular formation in retinopathy indication. The present
CC sequence is a WNT agonist comprising leader sequence, heavy chain
CC variable region (VHH), Gly-Ser linker, and heavy chain region, which can
CC be useful for treating retinopathy in a subject.
XX
SQ Sequence 472 AA;
Query Match 99.1%; Score 2367; Length 472;
Best Local Similarity 98.7%;
Matches 444; Conservative 5; Mismatches 1; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLVQPGGSLRLSCAASGFTFTSYAMSWVRQAPGKGLEWVSAISGSGGSTYY 60
||||||||||||:|||||||||||||||||:|||||||||||||||||||||||||||||
Db 23 EVQLVESGGGLVKPGGSLRLSCAASGFTFTNYAMSWVRQAPGKGLEWVSAISGSGGSTYY 82
Qy 61 AESVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARATGFGTVVFDYWGQGTLVTVSS 120
|:|||||||||||:||||||||||||: ||||||||||||||||||||||||||||||||
Db 83 ADSVKGRFTISRDDSKNTLYLQMNSLKTEDTAVYYCARATGFGTVVFDYWGQGTLVTVSS 142
Qy 121 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 143 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 202
Qy 181 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGG 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 203 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGG 262
Qy 241 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 263 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN 322
Qy 301 STYRVVSVLTVLHQDWLNGKEYKCKVSNKALGAPIEKTISKAKGQPREPQVYTLPPSREE 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 323 STYRVVSVLTVLHQDWLNGKEYKCKVSNKALGAPIEKTISKAKGQPREPQVYTLPPSREE 382
Qy 361 MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 383 MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW 442
Qy 421 QQGNVFSCSVMHEALHNHYTQKSLSLSPGK 450
||||||||||||||||||||||||||||||
Db 443 QQGNVFSCSVMHEALHNHYTQKSLSLSPGK 472
SEQ ID NO:1
ID BIF28719 standard; protein; 358 AA.
XX
AC BIF28719;
XX
DT 15-OCT-2020 (first entry)
XX
DE Retinopathy treatment related WNT agonist polypeptide, SEQ 5.
XX
KW WNT protein agonist; antibody; fusion protein;
KW heavy chain variable region; immunomodulator; light chain;
KW ocular disease; ophthalmological; protein therapy; retinopathy;
KW therapeutic; vascular disease; vasotropic.
XX
OS Synthetic.
OS Unidentified.
XX
CC PN WO2020167848-A1.
XX
CC PD 20-AUG-2020.
XX
CC PF 11-FEB-2020; 2020WO-US017769.
XX
PR 11-FEB-2019; 2019US-0803835P.
XX
CC PA (SURR-) SURROZEN INC.
XX
CC PI Li Y, Tu S, Lee S, Yeh W;
XX
DR WPI; 2020-79727E/073.
XX
CC PT Treating retinopathy includes retinal vascular disease such as familiar
CC PT exudative vitreoretionopathy, involves administering engineered WNT
CC PT signaling modulator to subject.
XX
CC PS Example 1; SEQ ID NO 5; 56pp; English.
XX
CC The present invention relates to a novel method for treating retinopathy
CC in a subject. The method involves administering an engineered WNT
CC signaling modulator to a subject. The method is useful for treating
CC retinal vascular disease such as retinopathy, where retinal vascular
CC disease is selected from familiar exudative vitreoretionopathy (FEVR),
CC exudative vitreoretinopathy, Nome disease, diabetic retinopathy (DR), age
CC -related macular degeneration (AMD), retinopathy of prematurity (ROP),
CC osteoporosis-psuedoglioma syndrome (OPPG), retinal vein occlusion, and
CC Coats disease. The method enables to treat retinopathy which regulate
CC aberrant vascular formation in retinopathy indication. The present
CC sequence is a WNT agonist comprising leader sequence, heavy chain
CC variable region (VHH), Gly-Ser linker, and light chain region, which can
CC be useful for treating retinopathy in a subject.
XX
SQ Sequence 358 AA;
Query Match 97.2%; Score 1685; Length 358;
Best Local Similarity 96.7%;
Matches 325; Conservative 6; Mismatches 5; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLVQPGGSLRLSCASSANIQSIETLGWYRQAPGKQRELIANMRGGGYMKYA 60
:||||||||||||||||||||| ||||| |||||||||||||||||||||||||||||||
Db 23 DVQLVESGGGLVQPGGSLRLSCTSSANINSIETLGWYRQAPGKQRELIANMRGGGYMKYA 82
Qy 61 DSLKGRFTMSTDNSKNTMYLQMNSLRAEDTAVYYCYVKLRDEDYVYRGQGTQVTVSSGGG 120
||||||||||:::|||||||||||: ||||||||||||||:|||||||||||||||||
Db 83 GSLKGRFTMSTESAKNTMYLQMNSLKPEDTAVYYCYVKLRDDDYVYRGQGTQVTVSSGGS 142
Qy 121 GSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGV 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 143 GSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGV 202
Qy 181 PSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIKRTVAAPSVFIF 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 203 PSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIKRTVAAPSVFIF 262
Qy 241 PPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSST 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 263 PPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSST 322
Qy 301 LTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 336
||||||||||||||||||||||||||||||||||||
Db 323 LTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 358
WO2022192445 teaches an anti-Wnt agonist humanized mAb R2M13-03 IgG1 light chain having the amino acid sequence of SEQ ID NO:4, which is 100% identical to instant SEQ ID NO:1 and comprises the sequence of instant SEQ ID NO:381 (see the sequence alignment below).
SEQ ID NO:1
BLT69748
(NOTE: this sequence has 4 duplicates in the database searched)
ID BLT69748 standard; protein; 336 AA.
XX
AC BLT69748;
XX
DT 03-NOV-2022 (first entry)
XX
DE Anti-WNT agonist humanized mAb R2M13-03 IgG1 light chain, SEQ:4.
XX
KW Agonist; FZD5 protein; FZD8 protein; Frizzed 5; Frizzed 8;
KW Frizzled-5 receptor; Frizzled-8 receptor; Immunoglobulin G1;
KW Immunoglobulin gamma 1; Light chain; Wnt ligand; antiinflammatory;
KW cell differentiation; cell signaling; crohns disease; fistula;
KW gastric secretion stimulant; gastrointestinal disease;
KW gastrointestinal-gen.; gene expression; genetic engineering;
KW humanized antibody; inflammatory bowel disease; inflammatory disease;
KW protein therapy; therapeutic; tissue regeneration; ulcerative colitis.
XX
OS Homo sapiens.
OS Chimeric.
OS Synthetic.
OS Unidentified.
XX
CC PN WO2022192445-A1.
XX
CC PD 15-SEP-2022.
XX
CC PF 09-MAR-2022; 2022WO-US019614.
XX
PR 10-MAR-2021; 2021US-0159010P.
PR 19-MAY-2021; 2021US-0190535P.
PR 22-SEP-2021; 2021US-0247151P.
XX
CC PA (SURR-) SURROZEN OPERATING INC.
XX
CC PI Fletcher R, Lee S, Li Y, Lu C, Sampathkumar P, Vanhove G, Yeh W;
CC PI Xie L, Presta L;
XX
DR WPI; 2022-B6717F/079.
XX
CC PT New engineered WNT agonist comprising binding domains that bind to
CC PT frizzled and binding domains that bind to low-density lipoprotein
CC PT receptor-related protein 5 (LRP5) and/or LRP6, used for e.g. treating
CC PT disease or disorder e.g. Crohn's disease.
XX
CC PS Claim 1; SEQ ID NO 4; 195pp; English.
XX
CC The present invention relates to an engineered WNT agonist useful for
CC treating disease or disorder. The engineered WNT agonist comprises (a)
CC one or more binding domains that bind to one or more frizzled (FZD) and
CC (b) one or more binding domains that bind to low-density lipoprotein
CC receptor-related protein 5 (LRP5), LRP6, or both LRP5 and LRP6 of SEQ ID
CC Nos:1-25 (see BLT69745-BLT69769). The invention further discloses: (1) a
CC method for modulating expression of a WNT pathway molecule in one or more
CC tissues or cells in a subject having a gastrointestinal disorder, and
CC stimulating tissue repair, reducing inflammation, restoring
CC gastrointestinal epithelial barrier in a subject; and (2) a method for
CC generating, culturing, or maintaining an organ, tissue, cell, or organoid
CC culture, involves contacting the organ, tissue, cell, or organoid culture
CC with the engineered WNT agonist. The engineered WNT agonist of the
CC invention is useful in pharmaceutical composition for treating a disease
CC or disorder amenable to treatment by increased WNT pathway signaling,
CC increasing WNT signaling in a cell, stimulating tissue repair, reducing
CC inflammation, restoring gastrointestinal epithelial barrier in a subject
CC having injured epithelium and inducing epithelial progenitor cell
CC differentiation in a subject having a gastrointestinal disorder, where
CC the gastrointestinal disorder is an inflammatory bowel disease chosen
CC from Crohn's disease (CD), CD with fistula formation, and ulcerative
CC colitis (UC).
XX
SQ Sequence 336 AA;
Query Match 100.0%; Score 1733; Length 336;
Best Local Similarity 100.0%;
Matches 336; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLVQPGGSLRLSCASSANIQSIETLGWYRQAPGKQRELIANMRGGGYMKYA 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVESGGGLVQPGGSLRLSCASSANIQSIETLGWYRQAPGKQRELIANMRGGGYMKYA 60
Qy 61 DSLKGRFTMSTDNSKNTMYLQMNSLRAEDTAVYYCYVKLRDEDYVYRGQGTQVTVSSGGG 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 DSLKGRFTMSTDNSKNTMYLQMNSLRAEDTAVYYCYVKLRDEDYVYRGQGTQVTVSSGGG 120
Qy 121 GSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGV 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 GSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGV 180
Qy 181 PSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIKRTVAAPSVFIF 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 PSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIKRTVAAPSVFIF 240
Qy 241 PPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSST 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 PPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSST 300
Qy 301 LTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 336
||||||||||||||||||||||||||||||||||||
Db 301 LTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 336
WO2020206005 teaches an engineered WNT agonist comprising an anti-Fzd antibody heavy chain comprising the amino acid sequence of SEQ ID NO:7, which is 99.1% identical to instant SEQ ID NO:2 (see the sequence alignment below), and an anti-LRP VH-anti-FZD antibody light chain fusion protein comprising the amino acid sequence of SEQ ID 8, which is 97.2 % identical to instant SEQ ID NO:8 (see the sequence alignment below).
SEQ ID NO:2
BIK87194
(NOTE: this sequence has 1 duplicate in the database searched)
ID BIK87194 standard; protein; 450 AA.
XX
AC BIK87194;
XX
DT 26-NOV-2020 (first entry)
XX
DE Anti-FZD antibody heavy chain SEQ ID 7.
XX
KW FZD-4 receptor; Frizzled-4 receptor; WNT signalling pathway; antibody;
KW antibody therapy; antisense therapy; auditory; hearing loss; heavy chain;
KW sensorineural hearing loss; therapeutic.
XX
OS Unidentified.
XX
FH Key Location/Qualifiers
FT Region 1..120
FT /note= "Frizzled receptor-VH (FZD-VH) region"
FT Region 121..218
FT /note= "Frizzled receptor-CH1 (FZD-CH1) region"
FT Region 218..230
FT /note= "hinge"
FT Region 231..343
FT /note= "Frizzled receptor-CH2 (FZD-CH2) region"
FT Region 344..450
FT /note= "Frizzled receptor-CH3 (FZD-CH3) region"
XX
CC PN WO2020206005-A1.
XX
CC PD 08-OCT-2020.
XX
CC PF 01-APR-2020; 2020WO-US026227.
XX
PR 02-APR-2019; 2019US-0828100P.
XX
CC PA (SURR-) SURROZEN INC.
XX
CC PI Lee S, Li Y, Yeh W;
XX
DR WPI; 2020-981092/088.
XX
CC PT Treating human suffering from auditory disorder, involves administering
CC PT engineered wingless-type MMTV integration site family (WNT) signaling
CC PT modulator, or tissue-specific WNT signal enhancing molecule.
XX
CC PS Example; SEQ ID NO 7; 60pp; English.
XX
CC The present invention relates to a method for treating a human suffering
CC from auditory disorder using a wingless-int site (WNT) signaling
CC modulator. The signal modulator is a tissue specific WNT signal enhancing
CC molecule or an engineered WNT agonist (antibody or a small molecule or a
CC siRNA or an antisense molecule) and an engineered tissue specific WNT
CC signal enhancing combination molecule. The method involves administering
CC the signal modulator to the suffering subject. The method is useful in
CC treating hearing loss due to cochlear tissue damage, hearing loss caused
CC by exposure to loud noise, aging, ototoxicity, head trauma, virus
CC infection.
XX
SQ Sequence 450 AA;
Query Match 99.1%; Score 2367; Length 450;
Best Local Similarity 98.7%;
Matches 444; Conservative 5; Mismatches 1; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLVQPGGSLRLSCAASGFTFTSYAMSWVRQAPGKGLEWVSAISGSGGSTYY 60
||||||||||||:|||||||||||||||||:|||||||||||||||||||||||||||||
Db 1 EVQLVESGGGLVKPGGSLRLSCAASGFTFTNYAMSWVRQAPGKGLEWVSAISGSGGSTYY 60
Qy 61 AESVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARATGFGTVVFDYWGQGTLVTVSS 120
|:|||||||||||:||||||||||||: ||||||||||||||||||||||||||||||||
Db 61 ADSVKGRFTISRDDSKNTLYLQMNSLKTEDTAVYYCARATGFGTVVFDYWGQGTLVTVSS 120
Qy 121 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 180
Qy 181 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGG 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGG 240
Qy 241 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN 300
Qy 301 STYRVVSVLTVLHQDWLNGKEYKCKVSNKALGAPIEKTISKAKGQPREPQVYTLPPSREE 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 STYRVVSVLTVLHQDWLNGKEYKCKVSNKALGAPIEKTISKAKGQPREPQVYTLPPSREE 360
Qy 361 MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW 420
Qy 421 QQGNVFSCSVMHEALHNHYTQKSLSLSPGK 450
||||||||||||||||||||||||||||||
Db 421 QQGNVFSCSVMHEALHNHYTQKSLSLSPGK 450
SEQ ID NO:1
BIK87195
(NOTE: this sequence has 1 duplicate in the database searched)
ID BIK87195 standard; protein; 336 AA.
XX
AC BIK87195;
XX
DT 26-NOV-2020 (first entry)
XX
DE Anti-LRP VH-anti-FZD antibody light chain fusion protein SEQ ID 8.
XX
KW FZD-4 receptor; Frizzled-4 receptor; LRP protein; WNT signalling pathway;
KW antibody; antibody therapy; antisense therapy; auditory; fusion protein;
KW hearing loss; heavy chain variable region; light chain;
KW sensorineural hearing loss; therapeutic.
XX
OS Synthetic.
OS Unidentified.
XX
FH Key Location/Qualifiers
FT Region 1..117
FT /note= "LRP VHH sequence"
FT Region 118..122
FT /note= "linker"
FT Region 123..234
FT /note= "Frizzled receptor-VL (FZD-VL) region"
FT Region 235..336
FT /note= "Frizzled receptor-CL (FZD-CL)"
XX
CC PN WO2020206005-A1.
XX
CC PD 08-OCT-2020.
XX
CC PF 01-APR-2020; 2020WO-US026227.
XX
PR 02-APR-2019; 2019US-0828100P.
XX
CC PA (SURR-) SURROZEN INC.
XX
CC PI Lee S, Li Y, Yeh W;
XX
DR WPI; 2020-981092/088.
XX
CC PT Treating human suffering from auditory disorder, involves administering
CC PT engineered wingless-type MMTV integration site family (WNT) signaling
CC PT modulator, or tissue-specific WNT signal enhancing molecule.
XX
CC PS Example; SEQ ID NO 8; 60pp; English.
XX
CC The present invention relates to a method for treating a human suffering
CC from auditory disorder using a wingless-int site (WNT) signaling
CC modulator. The signal modulator is a tissue specific WNT signal enhancing
CC molecule or an engineered WNT agonist (antibody or a small molecule or a
CC siRNA or an antisense molecule) and an engineered tissue specific WNT
CC signal enhancing combination molecule. The method involves administering
CC the signal modulator to the suffering subject. The method is useful in
CC treating hearing loss due to cochlear tissue damage, hearing loss caused
CC by exposure to loud noise, aging, ototoxicity, head trauma, virus
CC infection.
XX
SQ Sequence 336 AA;
Query Match 97.2%; Score 1685; Length 336;
Best Local Similarity 96.7%;
Matches 325; Conservative 6; Mismatches 5; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLVQPGGSLRLSCASSANIQSIETLGWYRQAPGKQRELIANMRGGGYMKYA 60
:||||||||||||||||||||| ||||| |||||||||||||||||||||||||||||||
Db 1 DVQLVESGGGLVQPGGSLRLSCTSSANINSIETLGWYRQAPGKQRELIANMRGGGYMKYA 60
Qy 61 DSLKGRFTMSTDNSKNTMYLQMNSLRAEDTAVYYCYVKLRDEDYVYRGQGTQVTVSSGGG 120
||||||||||:::|||||||||||: ||||||||||||||:|||||||||||||||||
Db 61 GSLKGRFTMSTESAKNTMYLQMNSLKPEDTAVYYCYVKLRDDDYVYRGQGTQVTVSSGGS 120
Qy 121 GSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGV 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 GSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGV 180
Qy 181 PSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIKRTVAAPSVFIF 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 PSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIKRTVAAPSVFIF 240
Qy 241 PPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSST 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 PPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSST 300
Qy 301 LTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 336
||||||||||||||||||||||||||||||||||||
Db 301 LTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 336
US12006368 teaches an anti-Fzd antibody comprising an anti-Fzd antibody heavy chain comprising the amino acid sequence of SEQ ID NO:66, which is 96.51% identical to instant SEQ ID NO:181 (see the sequence alignment below).
SEQ ID NO:181
US-16-954-482-66
(NOTE: this sequence has 2 duplicates in the database searched)
Sequence 66, US/16954482
Patent No. 12006368
GENERAL INFORMATION
APPLICANT: Surrozen, Inc.
APPLICANT: Li, Yang
APPLICANT: Yuan, Tom Zhiye
APPLICANT: Sato, Aaron Ken
APPLICANT: Yeh, Wen-Chen
APPLICANT: Lu, Chenggang
APPLICANT: Sampathkumar, Partha
TITLE OF INVENTION: ANTI-FRIZZLED ANTIBODIES AND METHODS OF USE
FILE REFERENCE: SRZN-004/02WO 328202-2031
CURRENT APPLICATION NUMBER: US/16/954,482
CURRENT FILING DATE: 2020-06-16
PRIOR APPLICATION NUMBER: US 62/680,508
PRIOR FILING DATE: 2018-06-04
PRIOR APPLICATION NUMBER: US 62/607,877
PRIOR FILING DATE: 2017-12-19
NUMBER OF SEQ ID NOS: 1485
SEQ ID NO 66
LENGTH: 120
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Made in Lab - 004S-D01 Heavy Chain
Query Match 96.5%; Score 601; Length 120;
Best Local Similarity 95.0%;
Matches 114; Conservative 5; Mismatches 1; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLVQPGGSLRLSCAASGFTFTSYAMSWVRQAPGKGLEWVSAISGSGGSTYY 60
||||||||||||:|||||||||||||||||:|||||||||||||||||||||||||||||
Db 1 EVQLVESGGGLVKPGGSLRLSCAASGFTFTNYAMSWVRQAPGKGLEWVSAISGSGGSTYY 60
Qy 61 AESVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARATGFGTVVFDYWGQGTLVTVSS 120
|:|||||||||||:||||||||||||: ||||||||||||||||||||||||||||||||
Db 61 ADSVKGRFTISRDDSKNTLYLQMNSLKTEDTAVYYCARATGFGTVVFDYWGQGTLVTVSS 120
US11773171 teaches a Wnt surrogate molecule comprising an anti-Fzd antibody heavy chain comprising the amino acid sequence of SEQ ID NO:129, which is 96.5% identical to instant SEQ ID NO:181 and an anti-LRP5/6 having the amino acid sequence of SEQ ID NO:2245, which is 100% identical to instant SEQ ID NO:381 (see the sequence alignment below).
SEQ ID NO:181
Sequence 129, US/16954484
Patent No. 11773171
GENERAL INFORMATION
APPLICANT: Surrozen, Inc.
APPLICANT: Li, Yang
APPLICANT: Yuan, Tom Zhiye
APPLICANT: Sato, Aaron Ken
APPLICANT: Yeh, Wen-Chen
APPLICANT: Xie, Liqin
APPLICANT: Brezski, Randall J.
APPLICANT: Lu, Chenggang
TITLE OF INVENTION: WNT SURROGATE MOLECULES AND USES THEREOEOF
FILE REFERENCE: SRZN-006/03WO 328202-2033
CURRENT APPLICATION NUMBER: US/16/954,484
CURRENT FILING DATE: 2020-06-16
PRIOR APPLICATION NUMBER: US 62/607,875
PRIOR FILING DATE: 2017-12-19
PRIOR APPLICATION NUMBER: US 62/641,217
PRIOR FILING DATE: 2018-03-09
PRIOR APPLICATION NUMBER: US 62/680,522
PRIOR FILING DATE: 2018-06-04
NUMBER OF SEQ ID NOS: 2267
SEQ ID NO 129
LENGTH: 120
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Made in Lab - 004S-D01 Heavy Chain
Query Match 96.5%; Score 601; Length 120;
Best Local Similarity 95.0%;
Matches 114; Conservative 5; Mismatches 1; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLVQPGGSLRLSCAASGFTFTSYAMSWVRQAPGKGLEWVSAISGSGGSTYY 60
||||||||||||:|||||||||||||||||:|||||||||||||||||||||||||||||
Db 1 EVQLVESGGGLVKPGGSLRLSCAASGFTFTNYAMSWVRQAPGKGLEWVSAISGSGGSTYY 60
Qy 61 AESVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARATGFGTVVFDYWGQGTLVTVSS 120
|:|||||||||||:||||||||||||: ||||||||||||||||||||||||||||||||
Db 61 ADSVKGRFTISRDDSKNTLYLQMNSLKTEDTAVYYCARATGFGTVVFDYWGQGTLVTVSS 120
SEQ ID NO:381
US-16-954-484-2245
(NOTE: this sequence has 1 duplicate in the database searched)
Sequence 2245, US/16954484
Patent No. 11773171
GENERAL INFORMATION
APPLICANT: Surrozen, Inc.
APPLICANT: Li, Yang
APPLICANT: Yuan, Tom Zhiye
APPLICANT: Sato, Aaron Ken
APPLICANT: Yeh, Wen-Chen
APPLICANT: Xie, Liqin
APPLICANT: Brezski, Randall J.
APPLICANT: Lu, Chenggang
TITLE OF INVENTION: WNT SURROGATE MOLECULES AND USES THEREOEOF
FILE REFERENCE: SRZN-006/03WO 328202-2033
CURRENT APPLICATION NUMBER: US/16/954,484
CURRENT FILING DATE: 2020-06-16
PRIOR APPLICATION NUMBER: US 62/607,875
PRIOR FILING DATE: 2017-12-19
PRIOR APPLICATION NUMBER: US 62/641,217
PRIOR FILING DATE: 2018-03-09
PRIOR APPLICATION NUMBER: US 62/680,522
PRIOR FILING DATE: 2018-06-04
NUMBER OF SEQ ID NOS: 2267
SEQ ID NO 2245
LENGTH: 236
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: MAde in Lab - Fab-IgG construct
Query Match 100.0%; Score 547; Length 236;
Best Local Similarity 100.0%;
Matches 107; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 23 DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPS 82
Qy 61 RFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIK 107
|||||||||||||||||||||||||||||||||||||||||||||||
Db 83 RFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIK 129
SEQ ID NO:181
Sequence 6, US/19204342
Publication No. US20250313616A1
GENERAL INFORMATION
APPLICANT: Surrozen Operating, Inc (en)
TITLE OF INVENTION: MODULATION OF WNT SIGNALLING IN OCULAR DISORDERS (en)
FILE REFERENCE: SRZN-013/02US
CURRENT APPLICATION NUMBER: US/19/204,342
CURRENT FILING DATE: 2025-05-09
NUMBER OF SEQ ID NOS: 8
SEQ ID NO 6
LENGTH: 472
TYPE: PRT
FEATURE:
NAME/KEY: REGION
LOCATION: 1..472
QUALIFIERS: note = synthesized WNT agonist
FEATURE:
NAME/KEY: source
LOCATION: 1..472
QUALIFIERS: mol_type = protein
organism = synthetic construct
Query Match 96.5%; Score 601; Length 472;
Best Local Similarity 95.0%;
Matches 114; Conservative 5; Mismatches 1; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLVQPGGSLRLSCAASGFTFTSYAMSWVRQAPGKGLEWVSAISGSGGSTYY 60
||||||||||||:|||||||||||||||||:|||||||||||||||||||||||||||||
Db 23 EVQLVESGGGLVKPGGSLRLSCAASGFTFTNYAMSWVRQAPGKGLEWVSAISGSGGSTYY 82
Qy 61 AESVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARATGFGTVVFDYWGQGTLVTVSS 120
|:|||||||||||:||||||||||||: ||||||||||||||||||||||||||||||||
Db 83 ADSVKGRFTISRDDSKNTLYLQMNSLKTEDTAVYYCARATGFGTVVFDYWGQGTLVTVSS 142
US20240150473 teaches a Wnt surrogate molecule comprising a polypeptide having the amino acid sequence of instant SEQ ID NO:1 an anti-Fzd antibody heavy chain comprising the amino acid sequence of SEQ ID NO:129, which is 96.5% identical to instant SEQ ID NO:181 and an anti-LRP5/6 having the amino acid sequence of SEQ ID NO:2245, which is 100% identical to instant SEQ ID NO:381 (see the sequence alignment below).
SEQ ID NO:1
Sequence 4, US/18281253
Publication No. US20240150473A1
GENERAL INFORMATION
APPLICANT: Surrozen Operating, Inc.
TITLE OF INVENTION: MODULATION OF WNT SIGNALING IN GASTROINTESTINAL DISORDERS
FILE REFERENCE: SRZN-020/03WO 328202-2153
CURRENT APPLICATION NUMBER: US/18/281,253
CURRENT FILING DATE: 2023-09-08
PRIOR APPLICATION NUMBER: US 63/247,151
PRIOR FILING DATE: 2021-09-22
PRIOR APPLICATION NUMBER: US 63/190,535
PRIOR FILING DATE: 2021-05-19
PRIOR APPLICATION NUMBER: US 63/159,010
PRIOR FILING DATE: 2021-03-10
NUMBER OF SEQ ID NOS: 41
SEQ ID NO 4
LENGTH: 336
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: R2M13-03 humanized LALAPG- light chain
Query Match 100.0%; Score 1733; Length 336;
Best Local Similarity 100.0%;
Matches 336; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLVQPGGSLRLSCASSANIQSIETLGWYRQAPGKQRELIANMRGGGYMKYA 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVESGGGLVQPGGSLRLSCASSANIQSIETLGWYRQAPGKQRELIANMRGGGYMKYA 60
Qy 61 DSLKGRFTMSTDNSKNTMYLQMNSLRAEDTAVYYCYVKLRDEDYVYRGQGTQVTVSSGGG 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 DSLKGRFTMSTDNSKNTMYLQMNSLRAEDTAVYYCYVKLRDEDYVYRGQGTQVTVSSGGG 120
Qy 121 GSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGV 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 GSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGV 180
Qy 181 PSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIKRTVAAPSVFIF 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 PSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIKRTVAAPSVFIF 240
Qy 241 PPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSST 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 PPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSST 300
Qy 301 LTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 336
||||||||||||||||||||||||||||||||||||
Db 301 LTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 336
Sequence 6, US/18281253
Publication No. US20240150473A1
GENERAL INFORMATION
APPLICANT: Surrozen Operating, Inc.
TITLE OF INVENTION: MODULATION OF WNT SIGNALING IN GASTROINTESTINAL DISORDERS
FILE REFERENCE: SRZN-020/03WO 328202-2153
CURRENT APPLICATION NUMBER: US/18/281,253
CURRENT FILING DATE: 2023-09-08
PRIOR APPLICATION NUMBER: US 63/247,151
PRIOR FILING DATE: 2021-09-22
PRIOR APPLICATION NUMBER: US 63/190,535
PRIOR FILING DATE: 2021-05-19
PRIOR APPLICATION NUMBER: US 63/159,010
PRIOR FILING DATE: 2021-03-10
NUMBER OF SEQ ID NOS: 41
SEQ ID NO 6
LENGTH: 336
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: R2M13-03 humanized N297G- light chain
Query Match 100.0%; Score 1733; Length 336;
Best Local Similarity 100.0%;
Matches 336; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLVQPGGSLRLSCASSANIQSIETLGWYRQAPGKQRELIANMRGGGYMKYA 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVESGGGLVQPGGSLRLSCASSANIQSIETLGWYRQAPGKQRELIANMRGGGYMKYA 60
Qy 61 DSLKGRFTMSTDNSKNTMYLQMNSLRAEDTAVYYCYVKLRDEDYVYRGQGTQVTVSSGGG 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 DSLKGRFTMSTDNSKNTMYLQMNSLRAEDTAVYYCYVKLRDEDYVYRGQGTQVTVSSGGG 120
Qy 121 GSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGV 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 GSDIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGV 180
Qy 181 PSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIKRTVAAPSVFIF 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 PSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIKRTVAAPSVFIF 240
Qy 241 PPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSST 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 PPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSST 300
Qy 301 LTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 336
||||||||||||||||||||||||||||||||||||
Db 301 LTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 336
SEQ ID NO:321-SEQ ID NO:341-SEQ ID NO:361
Sequence 4, US/18281253
Publication No. US20240150473A1
GENERAL INFORMATION
APPLICANT: Surrozen Operating, Inc.
TITLE OF INVENTION: MODULATION OF WNT SIGNALING IN GASTROINTESTINAL DISORDERS
FILE REFERENCE: SRZN-020/03WO 328202-2153
CURRENT APPLICATION NUMBER: US/18/281,253
CURRENT FILING DATE: 2023-09-08
PRIOR APPLICATION NUMBER: US 63/247,151
PRIOR FILING DATE: 2021-09-22
PRIOR APPLICATION NUMBER: US 63/190,535
PRIOR FILING DATE: 2021-05-19
PRIOR APPLICATION NUMBER: US 63/159,010
PRIOR FILING DATE: 2021-03-10
NUMBER OF SEQ ID NOS: 41
SEQ ID NO 4
LENGTH: 336
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: R2M13-03 humanized LALAPG- light chain
Query Match 82.2%; Score 117.6; Length 336;
Best Local Similarity 33.3%;
Matches 27; Conservative 0; Mismatches 0; Indels 54; Gaps 2;
Qy 1 ANIQSIET----------------NMRGGGYM---------------------------- 16
|||||||| ||||||||
Db 26 ANIQSIETLGWYRQAPGKQRELIANMRGGGYMKYADSLKGRFTMSTDNSKNTMYLQMNSL 85
Qy 17 ----------YVKLRDEDYVY 27
|||||||||||
Db 86 RAEDTAVYYCYVKLRDEDYVY 106
15. 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.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see https://ppair-my.uspto.gov/pair/PrivatePair. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
Chang-Yu Wang
April 27, 2026
/CHANG-YU WANG/Primary Examiner, Art Unit 1675
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