DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s amendment of claims 1 and 17 in the paper of 1/30/2026, is
acknowledged. Applicants' arguments filed on 1/30/2026, have been fully considered
and are deemed to be persuasive to overcome some of the rejections previously
applied. Rejections and/or objections not reiterated from previous office actions are
hereby withdrawn. Claims 1-20 are still at issue and are present for examination.
Election/Restrictions
Applicant's election without traverse of the invention of Group 1, claims 1-19, to a polypeptide, in the paper of 8/18/2025, is acknowledged. Applicant's election without traverse of the following species, Species Group 1: SEQ ID No: 5, Species Group 2: SEQ ID No: 131; Species Group 3: SEQ ID No: 34, Species Group 4: SEQ ID No: 13, in the paper of 8/18/2025, is acknowledged.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609 A(1) states, "the list may not be incorporated into the specification but must be submitted in a separate paper."
There are currently no information disclosure statements in the application file.
Specification
The disclosure is objected to because of the following informalities:
Previously it was stated that Figure 23A comprises 4 sequences, each of which require a sequence identifier either in the figure or in the description of the figure, but the description of Figure 23A only has 3 sequence identifiers.
Applicants amendment of the description of Figure 23A is acknowledged, however, not sufficient to overcome the objection because applicants amendment while adding a SEQ ID NO:, also left part of a SEQ ID NO: out “(i.e. SEQ ID NO:)”.
Appropriate correction is required.
Claim Objections
Claims 9 and 13-18 are objected to because of the following informalities:
Claims 9 and 13-19 are dependent on a rejected claim.
Claims 13-18 are drawn to non-elected subject matter.
Appropriate correction is required.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-3, 6, 7, 11 and 19 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Crine and Elefteriou (US 2013/0323244).
This rejection was stated in the previous office action as it applied to previous claims 1-7, 11 and 19. In response applicants have amended claims 1 and traverse the rejection as it applied to the newly amended claims. For applicants convenience the original rejection is repeated herein.
Crine and Elefteriou (US 2013/0323244) disclose methods, compositions, and kits for the treatment of neurocutaneous syndromes, such as neurofibromatosis type I; disorders associated with overactivation of FGFR3, such as achondroplasia; bone or cartilage disorders; or vascular smooth muscle disorders; or for the elongation of bone (see abstract and whole specification). As a part of the taught embodiments, Crine and Elefteriou teach polypeptides having a soluble alkaline phosphatase fused to an Fc domain of an immunoglobin (see figure 5B and supporting text). The polypeptide taught by Crine and Elefteriou comprises amino acid sequence encoding a secretion signal peptide, an amino acid sequence having at least 90% sequence identity to a SEQ ID NO: 11; an amino acid sequence comprising a linker; an Fc is a Fc domain Immunoglobulin domain), and a 12 amino acid sequence (4 to 6 amino acids plus 1 to 8 amino acids) (see Figure 5B and supporting text). Crine and Elefteriou teach that the with regard to the linker, the C-terminal GPI anchor portion of human TNALP, or homologs or variants or fragments thereof (e.g., residues 503-524 of SEQ ID NO: 1208) may be used as a linker (Claims 1-6 and 19). Crine and Elefteriou teach the above polypeptides wherein the Fc domain comprises the sequence of instant SEQ ID NO:9, which has at least 97% sequence identity to instant SEQ ID NO:130 (see SEQ ID NO:1204 of Crine and Elefteriou) (Claim 6). Crine and Elefteriou teach the above polypeptides wherein the polypeptide has an amino acid sequence having at least 97% sequence identity to instant SEQ ID NO:130 (see SEQ ID NO:1202 of Crine and Elefteriou) (claim 7).
Applicants Response
Applicants traverse the rejection on the basis that applicants submit that they disagree that Crine discloses all of the elements of the claimed invention. Applicants submit that they have amended the claims and applicants review the various teachings of Crine. Following applicants submission of the teachings of Crine, applicants submit that Crine does not disclose a bone tag that comprises units of a -D-S-S- triamino acid such as required by the claimed invention.
Applicants amendment of the claims and applicants complete traversal is acknowledged and has been carefully considered, however, is not found persuasive in overcoming the rejection for the reasons previously stated and for those reasons repeated herein. It is noted that applicants amendment has resulted in claims 4 and 5 being withdrawn from the rejection.
In response to applicants submit that they have amended the claims and applicants review of the various teachings of Crine, it is noted that the rejection is based upon the teachings of Crine, not what Crine does not teach, unless it is a requirement of the claims. By virtue of applicants claim language, the only claims that require the presence of one to six repeat units of a -D-S-S- triamino acid are amended claims 4 and 5. For this reasons claims 4 and 5 are withdrawn from the rejection because they require the presence of the Following applicants submission of the teachings of one to six repeat units of a -D-S-S- triamino acid. Claims 1-3, 6, 7, 11 and 19 remain rejected for the reasons previously stated and repeated above. It is noted that by virtue that each of q, v, w, x, y,and z may be “0”, each of these structural aspects of the claimed polypeptide are not required for claims 1-3, 6, 7, 11 and 19.
Thus claim(s) 1-3, 6, 7, 11 and 19is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Crine and Elefteriou (US 2013/0323244).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 1-3, 6, 7, 11, 12 and 19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Crine and Elefteriou (US 2013/0323244) and Nan Hatch (US 10,822,596).
This rejection was stated in the previous office action as it applied to previous claims 1-7, 11, 12 and 19. In response applicants have amended claims 1 and traverse the rejection as it applied to the newly amended claims. For applicants convenience the original rejection is repeated herein.
As stated above, Crine and Elefteriou (US 2013/0323244) disclose methods, compositions, and kits for the treatment of neurocutaneous syndromes, such as neurofibromatosis type I; disorders associated with overactivation of FGFR3, such as achondroplasia; bone or cartilage disorders; or vascular smooth muscle disorders; or for the elongation of bone (see abstract and whole specification). As a part of the taught embodiments, Crine and Elefteriou teach polypeptides having a soluble alkaline phosphatase to an Fc domain of an immunoglobin ( see figure 5B and supporting text). The polypeptide taught by Crine and Elefteriou comprises amino acid sequence encoding a secretion signal peptide, an amino acid sequence having at least 90% sequence identity to a SEQ ID NO: 11; an amino acid sequence comprising a linker; an Fc is a Fc domain Immunoglobulin domain), and an 12 amino acid sequence (4 to 6 amino acids plus 1 to 8 amino acids) (see Figure 5B and supporting text). Crine and Elefteriou teach that the with regard to the linker, the C-terminal GPI anchor portion of human TNALP, or homologs or variants or fragments thereof (e.g., residues 503-524 of SEQ ID NO: 1208) may be used as a linker. Crine and Elefteriou teach the above polypeptides wherein the Fc domain comprises the sequence of instant SEQ ID NO:9, which has at least 97% sequence identity to instant SEQ ID NO:130 (see SEQ ID NO:1204 of Crine and Elefteriou). Crine and Elefteriou teach the above polypeptides wherein the polypeptide has an amino acid sequence having at least 97% sequence identity to instant SEQ ID NO:130 (see SEQ ID NO:1202 of Crine and Elefteriou).
Like Crine and Elefteriou (US 2013/0323244), Nan Hatch (US 10,822,596) disclose compositions and methods for treating craniosynostosis. In particular, Nan Hatch (US 10,822,596) teach methods of treating and preventing craniosynostosis by administering an isolated TNAP polypeptide or a nucleic acid molecule that encodes a TNAP polypeptide. Nan Hatch (US 10,822,596) disclose a number of soluble alkaline phosphate conjugates including those comprising the amino acid sequence of SEQ ID NO:4 which has at least 98% sequence identity to instant SEQ ID NO:5.
One of skill in the art before the effective filing date would have been motivated to create the polypeptides taught by Crine and Elefteriou (US 2013/0323244), varying all of the various components such as secretion signal sequence, GPI anchor sequence, linker, sequence, alkaline phosphatase sequence, Fc domain sequence using all of the domain sequences taught by Crine and Elefteriou (US 2013/0323244) as a means of creating additional polypeptides for treating neurocutaneous syndromes. One would have been further motivated to additionally substitute the soluble alkaline phosphate conjugates comprising the amino acid sequence of SEQ ID NO:4, as taught by Nan Hatch (US 10,822,596) for the alkaline phosphate sequence taught by Crine and Elefteriou (US 2013/0323244) within the polypeptide constructs taught by Crine and Elefteriou (US 2013/0323244). The expectation of success is high based upon the high level of skill in the art of recombinant polypeptide engineering as exemplified by both Crine and Elefteriou (US 2013/0323244), Nan Hatch (US 10,822,59.
Applicants Response
Applicants traverse the rejection, as above rejection based upon anticipation, on the basis that applicants submit that they disagree that Crine discloses all of the elements of the claimed invention. As above applicants submit that they have amended the claims and applicants review the various teachings of Crine. As above following applicants submission of the teachings of Crine, applicants submit that Crine does not disclose a bone tag that comprises units of a -D-S-S- triamino acid such as required by the claimed invention.
Applicants further submit that both Crine and Nan Hatch teach bone tags including repeating aspartic acid residues or repeating glutamic acid residues and neither disclose or suggest a polypeptide including a bone tag having one to six repeating units of the -D-S-S- triamino acid.
Applicants further submit that [DSS] tags target bone-formation surfaces, while D10 tags target bone-resorption surfaces and the skilled artisan would appreciate the differences as related to physiological conditions of bone formation.
Applicants amendment of the claims and applicants complete traversal is acknowledged and has been carefully considered, however, is not found persuasive in overcoming the rejection for the reasons previously stated and for those reasons repeated herein. It is noted that applicants amendment has resulted in claims 4 and 5 being withdrawn from the rejection.
As above under anticipation. in response to applicants submission that they have amended the claims and applicants review of the various teachings of Crine and Nan Hatch, it is noted that the rejection is based upon the teachings of Crine and Nan Hatch, not what Crine, and Nan Hatch do not teach, unless it is a requirement of the claims. By virtue of applicants claim language, the only claims that require the presence of one to six repeat units of a -D-S-S- triamino acid are amended claims 4 and 5. For this reasons claims 4 and 5 are withdrawn from the rejection because they require the presence of the Following applicants submission of the teachings of one to six repeat units of a -D-S-S- triamino acid. Claims 1-3, 6, 7, 11 and 19 remain rejected for the reasons previously stated and repeated above. It is noted that by virtue that each of q, v, w, x, y,and z may be “0”, each of these structural aspects of the claimed polypeptide are not required for claims 1-3, 6, 7, 11 and 19.
In response to applicants additional argument that both Crine and Nan Hatch teach bone tags including repeating aspartic acid residues or repeating glutamic acid residues and neither disclose or suggest a polypeptide including a bone tag having one to six repeating units of the -D-S-S- triamino acid, this is acknowledged, however, only found persuasive to claims 4 and 5 which are the only claims which require the one to six repeat units of a -D-S-S- triamino acid.
Thus, claim(s) 1-3, 6, 7, 11, 12 and 19 remain rejected under 35 U.S.C. 103 as being unpatentable over Crine and Elefteriou (US 2013/0323244) and Nan Hatch (US 10,822,596).
Claim(s) 1-8, 10, 11 and 19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Crine and Elefteriou (US 2013/0323244) and Saidak et al. (Journal of Biological Chemistry, Vol 290, No. 11, pp 6903-6912, March 2015).
As stated above, Crine and Elefteriou (US 2013/0323244) disclose methods, compositions, and kits for the treatment of neurocutaneous syndromes, such as neurofibromatosis type I; disorders associated with overactivation of FGFR3, such as achondroplasia; bone or cartilage disorders; or vascular smooth muscle disorders; or for the elongation of bone (see abstract and whole specification). As a part of the taught embodiments, Crine and Elefteriou teach polypeptides having a soluble alkaline phosphatase to an Fc domain of an immunoglobin ( see figure 5B and supporting text). The polypeptide taught by Crine and Elefteriou comprises amino acid sequence encoding a secretion signal peptide, an amino acid sequence having at least 90% sequence identity to a SEQ ID NO: 11; an amino acid sequence comprising a linker; an Fc is a Fc domain Immunoglobulin domain), and an 12 aspartic acid sequence (“bone targeting domain”, 4 to 6 amino acids plus 1 to 8 amino acids) (see Figure 5B and supporting text). Crine and Elefteriou teach that the with regard to the linker, the C-terminal GPI anchor portion of human TNALP, or homologs or variants or fragments thereof (e.g., residues 503-524 of SEQ ID NO: 1208) may be used as a linker. Crine and Elefteriou teach the above polypeptides wherein the Fc domain comprises the sequence of instant SEQ ID NO:9, which has at least 97% sequence identity to instant SEQ ID NO:130 (see SEQ ID NO:1204 of Crine and Elefteriou). Crine and Elefteriou teach the above polypeptides wherein the polypeptide has an amino acid sequence having at least 97% sequence identity to instant SEQ ID NO:130 (see SEQ ID NO:1202 of Crine and Elefteriou).
Saidak et al. (Journal of Biological Chemistry, Vol 290, No. 11, pp 6903-6912, March 2015) disclose Wnt/b-catenin signaling mediates osteoblast differentiation triggered by peptide induced a5b1 integrin priming in mesenchymal skeletal cells. Saidak et al. teach the use of a (DSS)6 polypeptide linked to cyclized GACRETAWACGA for in vivo systemic delivery to bone-forming sites and that such increased serum osteocalcin levels and improved bone mass and microarchitecture.
One of skill in the art before the effective filing date would have been motivated to create the polypeptides taught by Crine and Elefteriou (US 2013/0323244), varying all of the various components such as secretion signal sequence, GPI anchor sequence, linker, sequence, alkaline phosphatase sequence, Fc domain sequence using all of the domain sequences taught by Crine and Elefteriou (US 2013/0323244) as a means of creating additional polypeptides for treating neurocutaneous syndromes. One would have been further motivated to substitute the12 aspartic acid sequence (“bone targeting domain”, 4 to 6 amino acids plus 1 to 8 amino acids) taught by Crine and Elefteriou with the (DSS)6 bone targeting domain taught by Saidak et al. within the polypeptide constructs taught by Crine and Elefteriou (US 2013/0323244) as a means of targeting the polypeptides to bone-forming sites . The expectation of success is high based upon the high level of skill in the art of recombinant polypeptide engineering as exemplified by both Crine and Elefteriou (US 2013/0323244), Saidak et al. who teach all the required methodology to create the obvious polypeptides..
Thus claim(s) 1-8, 10, 11 and 19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Crine and Elefteriou (US 2013/0323244) and Saidak et al. (Journal of Biological Chemistry, Vol 290, No. 11, pp 6903-6912, March 2015).
Related Art
Crine and Leonard (WO 2008/128131).disclose methods and compositions and kits for the treatment of matrix mineralization disorders (see abstract and whole specification). As a part of the taught embodiments, Crine and Leonard teach polypeptides having a soluble alkaline phosphatase to an Fc domain of an immunoglobin. Crine and Leonard disclose that the soluble TNALP (herein called sTNALP) so formed contains all amino acids of the native anchored form of TNALP necessary for the formation of the catalytic site but lacks the GPI membrane anchor. Known TNALP include human.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Remarks
No claim is allowed.
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rgh
3/31/2026
/RICHARD G HUTSON/Primary Examiner, Art Unit 1652