The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This office action is in response to Applicants’ amendments/remarks received January 29, 2026.
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.
Claims 2-4 are canceled. Claims 1, 5-10 are under consideration.
Priority: This application is a 371 of PCT/JP2021/017849, filed May 11, 2021, which claims benefit of foreign priority application JP 2020-084916, filed May 14, 2020. A copy of the foreign priority document has been received in the instant application on November 9, 2022, and is not in the English language.
Objections and Rejections
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.
Claims 1, 5-10 are rejected under 35 U.S.C. 103 as being unpatentable over Hamakubo et al. (US 20150299277; IDS 02.14.23, previously cited) in view of Valeria et al. (2017 A New Approach to Drug Therapy: Fc-Fusion Technology. Prim Health Care 7:255, 8 pages; previously cited). Hamakubo et al. disclose a therapeutic or prophylactic agent comprising as an active ingredient a polypeptide containing an amino acid sequence the same or substantially the same as the amino acid sequence of the N-terminal domain of pentraxin 3 (PTX3) capable of binding to histone to form a polypeptide aggregate (at least paragraph 0061). Hamakubo et al. disclose the amino acid sequence of the N-terminal of PTX3 is a partial sequence of not less than 30 amino acids and the N-terminal domain of the PTX3derived from human contains any of the following regions: a region consisting of the 18th-67th amino acids of the amino acid sequence set forth in SEQ ID NO: 2 (a region consisting of the lst-50th amino acids of the amino acid sequence shown in SEQ ID NO: 3) (at least paragraphs 0068-0070). Hamakubo et al. disclose that PTX3 with increased blood concentration plays a defensive role against sepsis (at least paragraph 0005). Hamakubo et al. do not teach fusing the PTX3 to a Fc portion of an immunoglobulin.
Valeria et al. disclose that Fc-fusion technology has been successfully implemented in the treatment of diseases, including prolonging the drug half-life, which in turn allows for longer dosing intervals (at least p. 1). Valeria et al. disclose that the IgG-Fc is commonly used as a fusion partner for extending the half-life of the protein of interest and can further enhance therapeutic effects depending on the disease (at least p. 2). Valeria et al. disclose that Fc-fusion proteins improve pharmacological properties of therapeutic drugs and have low immunogenicity and are able to significantly increase serum half-life and selectively enhance or disable effector functions, all while maintaining drug efficacy (at least p. 5).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the references and arrive at the claimed therapeutic or prophylactic agent comprising as an active ingredient, a fusion protein comprising at least a polypeptide containing an amino acid sequence the same or substantially the same as the amino acid sequence of the N-terminal domain of pentraxin 3 (PTX3) capable of binding to histone to form a polypeptide aggregate and a Fc portion of an immunoglobulin, wherein the amino acid sequence of the N-terminal of PTX3 contains the region consisting of the 18th-67th amino acids of the amino acid sequence set forth in SEQ ID NO: 2 (instant claim 1). The motivation to do so is given by the prior art. Hamakubo et al. disclose a therapeutic agent comprising as an active ingredient a polypeptide containing an amino acid sequence the same or substantially the same as the amino acid sequence of the N-terminal domain of PTX3 capable of binding to histone to form a polypeptide aggregate, wherein the amino acid sequence of the N-terminal of PTX3 contains the region consisting of the 18th-67th amino acids of the amino acid sequence set forth in SEQ ID NO: 2. Hamakubo et al. disclose that PTX3 with increased blood concentration plays a defensive role against sepsis. Valeria et al. disclose that fusion of a therapeutic protein with IgG-Fc significantly increases plasma or serum half-life with low immunogenicity and further maintains drug efficacy. Therefore, one of ordinary skill would have reasonable motivation to incorporate the Fc portion of an immunoglobulin disclosed in Valeria et al. with the therapeutic agent comprising the amino acid sequence of the N-terminal domain of PTX3 capable of binding to histone to form a polypeptide aggregate of Hamakubo et al. to arrive at a PTX3-Fc fusion protein because there was interest in increasing blood concentrations of PTX3. One of ordinary skill would have a reasonable expectation of success because Fc-fusion technology is a recognized technology for prolonging and/or enhancing therapeutic drug half-life and function.
Regarding instant claims 5-7, Hamakubo et al. the 47th, 49th and 103rd cysteine residues of the amino acid sequence shown in SEQ ID NO: 2 are replaced with serine residues to optimize expression (at least paragraph 0166).
Regarding instant claim 8, Valeria et al. disclose examples of Fc-fusion proteins where the Fc portion of the immunoglobin is fused to the C-terminus of the therapeutic protein (at least p. 4-5). Therefore, it would be obvious to one of ordinary skill to fuse the N-terminus of the Fc portion of the immunoglobulin to the C-terminus of the polypeptide containing an amino acid sequence the same or substantially the same as the amino acid sequence of the N-terminal domain of PTX3 capable of binding to histone to form a polypeptide aggregate.
Regarding instant claims 9-10, the claims are still drawn to the PTX3-Fc fusion protein, regardless of the disease treated by the therapeutic agent. As noted above, it would have been obvious to incorporate the Fc portion of an immunoglobulin disclosed in Valeria et al. with the therapeutic agent comprising the amino acid sequence of the N-terminal domain of PTX3 capable of binding to histone to form a polypeptide aggregate of Hamakubo et al. to arrive at a PTX3-Fc fusion protein because there was interest in increasing blood concentrations of PTX3. One of ordinary skill would have a reasonable expectation of success because Fc-fusion technology is a recognized technology for prolonging and/or enhancing therapeutic drug half-life and function.
Reply: Applicants’ amendments/remarks have been considered but they are not persuasive.
Applicants assert that the fusion protein recited in amended claim 1 corresponds to the PTX3-Fc fusion protein in example 1, example 5, and Fig. 6 of the specification. Applicants assert that in example 2, it was demonstrated that the PTX3-Fc fusion protein has an inhibitory effect on histone damage in vascular endothelial cells. Applicants assert that in example 3, it was demonstrated that it actually improves the survival rate of a sepsis mouse model. Applicants assert that even if it was known that an Fc portion to a protein can prolong the drug half-life, it would be impossible to predict this improvement in drug half-life would lead to an increase in survival rate of the sepsis model mice.
Applicants’ remarks are not persuasive. In this instance, Hamakubo et al. also disclose that the PTX3 suppresses vascular endothelial cytotoxic activity of histone and that the mouse administered with the N-terminal PTX3 showed significantly improved mortality due to LPS administration (at least p. 13 paragraphs 0172-0174). Therefore, one of ordinary skill would have a reasonable expectation of success that the N-terminal PTX having a fused Fc portion and a prolonged half-life would lead to an increase in survival rate of a sepsis model mice.
Applicants assert that as shown in Fig. 7 and 9, it was demonstrated that the PTX3-Fc fusion protein can bind to the spike protein of the SARS-CoV-2 virus and can bind to the N protein of the SARS-CoV-2 virus. Applicants assert that these effects are neither described nor suggested in any of the cited references and cannot be predicted from the cited references.
Applicants’ remarks are not persuasive. As noted above in the 103 rejection of instant claims 9-10, the claims are still drawn to the PTX3-Fc fusion protein, regardless of the disease treated by the therapeutic agent. As noted above, it would have been obvious to incorporate the Fc portion of an immunoglobulin disclosed in Valeria et al. with the therapeutic agent comprising the amino acid sequence of the N-terminal domain of PTX3 capable of binding to histone to form a polypeptide aggregate of Hamakubo et al. to arrive at a PTX3-Fc fusion protein because there was interest in increasing blood concentrations of PTX3. One of ordinary skill would have a reasonable expectation of success because Fc-fusion technology is a recognized technology for prolonging and/or enhancing therapeutic drug half-life and function.
The N-terminal PTX3 disclosed in Hamakubo et al. is structurally the same as the recited N-terminal PTX3 in instant claim 1. Hamakubo et al. disclose a therapeutic agent comprising as an active ingredient a N-terminal PTX3 that is structurally the same as the recited N-terminal PTX3 and having the same significantly improved mortality in mouse models. Fc-fusion technology is a recognized technology for prolonging and/or enhancing therapeutic drug half-life and function (Valeria). Therefore, one of ordinary skill would have reasonable motivation to incorporate the Fc portion of an immunoglobulin disclosed in Valeria et al. with the therapeutic agent comprising the amino acid sequence of the N-terminal domain of PTX3 capable of binding to histone to form a polypeptide aggregate of Hamakubo et al. to arrive at a PTX3-Fc fusion protein because there was interest in increasing blood concentrations of PTX3.
No claim is allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/Marsha Tsay/Primary Examiner, Art Unit 1656