DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Claim Status and Formal Matters
This is in response to papers filed 7/23/2026.
Claims 2-3 have been canceled.
Claims 1 and 4 have been amended.
Claims 5-13 have been added by amendment.
Claims 1, 4-13 are being examined.
Priority
The instant application was filed 08/15/2024 and is a continuation of 16549387, filed 08/23/2019 which is a continuation of 13819398 filed 05/09/2013 which is a national stage entry of PCT/JP2011/069734 with international filing date: 08/31/2011and claims foreign priority to JP2010-193213, filed 08/31/2010. There is no English translation of the priority document in the instant file wrapper.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 8/15/2024 is being considered by the examiner.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 4-13 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
MPEP 2163 IB New or amended claims section II
With respect to newly added or amended claims, applicant should show support in the original disclosure for the new or amended claims. See, e.g., Hyatt v. Dudas, 492 F.3d 1365, 1370, n.4 (Fed. Cir. 2007) (citing MPEP § 2163.04 which provides that a "simple statement such as ‘applicant has not pointed out where the new (or amended) claim is supported, nor does there appear to be a written description of the claim limitation ‘___’ in the application as filed’ may be sufficient where the claim is a new or amended claim, the support for the limitation is not apparent, and applicant has not pointed out where the limitation is supported."); see also MPEP §§ 714.02 and 2163.06 ("Applicant should ... specifically point out the support for any amendments made to the disclosure."); and MPEP § 2163.04
Claim 1 has been amended to recite, “wherein the FGF-23 is detected in a concentration ranging from 5 pg/mL to 1,000 pg/mL.”
Claim 4 has been amended to recite, “with a calibration curve prepared using known concentrations of FGF-23 ranging from 5 pg/mL to 1,000 pg/mL.”
Claim 8 has been added by amendment and recites, “wherein the sample comprises FGF-23 in a concentration ranging from 800 pg/mL to 1,000 pg/mL..”
Claim 9 has been added by amendment and recites, “wherein the sample comprises FGF-23 in a concentration ranging from 10 pg/mL to 800 pg/mL”
Claim 10 has been added by amendment and recites, “wherein the sample comprises FGF-23 in a concentration ranging from 10 pg/mL to 500 pg/mL”
Claim 11 has been added by amendment and recites, “wherein the sample comprises FGF-23 in a concentration ranging from 5 pg/mL to 10 pg/mL”
Claim 12 has been added by amendment and recites, “wherein the sample comprises FGF-23 in a concentration ranging from 50 pg/mL to 1,000 pg/mL.”
The response provides no indication where support of the amendments can be found.
The originally filed claims provide a range of 1000pg/ml to 10000 pg/ml.
Review and searching of the specification revealed support for concentration range of 5 pg/mL to 10,000 pg/mL in example 2. Further example 2 provides FGF23 calibration curve of 10,000 pg/mL, 3,000 pg/mL, 1,000 pg/mL, 300 pg/mL, 100 pg/mL, 50 pg/mL, 10 pg/mL, and 5 pg/mL. Thus the response appears to be picking and choosing the ranges as the specification and claims as originally filed do not provide blaze marks to the recited ranges. Thus the amendment has introduced new matter.
Response to Arguments
This is a new ground of rejection necessitated by amendment.
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 1, 5-13 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites, “1) reacting, in an aqueous medium, FGF-23 in a sample with a magnetic particle, a first antibody or a fragment thereof which binds to FGF-23, and a second antibody or a fragment thereof which binds to FGF-23, to form on the magnetic particle an immunocomplex comprising the first antibody or a fragment thereof which binds to FGF-23, FGF-23, and the second antibody or a fragment thereof which binds to FGF-23.” However, claim 6 has been added by amendment and requires, “where the first antibody binds and a site of FGF-23 where the second antibody binds can be same.” Thus the metes and bounds of claim 1 are unclear as to what is required of immunocomplex as antibodies binding to the sample site or epitope will not be able to bind at the same time and thus form an immunocomplex in which both are bound to FGF-23 as appears to be required by the independent claim. Further claim 6 is confusing as it recites, “where the first antibody binds and a site of FGF-23 where the second antibody binds can be same.” It is unclear what is required in view of the “and.”
Claim 5 has been added by amendment and recites, “wherein the first antibody or a fragment thereof comprises a biotinylated first antibody in which biotin is bound to the first antibody can be used.” The claims is vague and unclear as what the recitation, “the first antibody can be used,” requires.
Claim 7 is confusing as it recites, “wherein a site of FGF-23 where the first antibody binds and a site of FGF-23 where the second antibody binds can be different.” It is unclear what is required in view of the “and.” Further it is unclear what different is relative to.
Claim 8 recites, “wherein the sample comprises FGF-23 in a concentration ranging from 800 pg/mL to 1,000 pg/mL.” However, the preamble of claim 1 recites, “A method for measuring fibroblast growth factor-23 (hereinafter indicated as FGF-23) in a sample.” Thus the metes and bounds are confusing and unclear as the wherein clause requires a specific range of FGF-23 concentration for the sample, however the preamble is to just measuring or detecting FGF-23. Thus it is unclear if the wherein clause limits the sample, the antibodies, assay conditions, etc. to provide for the required range.
Claim 9 recites, “wherein the sample comprises FGF-23 in a concentration ranging from 10 pg/mL to 800 pg/mL.” Thus the metes and bounds are confusing and unclear as the wherein clause requires a specific range of FGF-23 concentration for the sample, however the preamble is to just measuring or detecting FGF-23. Thus it is unclear if the wherein clause limits the sample, the antibodies, assay conditions, etc. to provide for the required range.
. Claim 10 recites, “wherein the sample comprises FGF-23 in a concentration ranging from 10 pg/mL to 500 pg/mL.” Thus the metes and bounds are confusing and unclear as the wherein clause requires a specific range of FGF-23 concentration for the sample, however the preamble is to just measuring or detecting FGF-23. Thus it is unclear if the wherein clause limits the sample, the antibodies, assay conditions, etc. to provide for the required range.
Claim 11 recites, “wherein the sample comprises FGF-23 in a concentration ranging from 5 pg/mL to 10 pg/mL.” Thus the metes and bounds are confusing and unclear as the wherein clause requires a specific range of FGF-23 concentration for the sample, however the preamble is to just measuring or detecting FGF-23. Thus it is unclear if the wherein clause limits the sample, the antibodies, assay conditions, etc. to provide for the required range.
Claim 12 recites, “wherein the sample comprises FGF-23 in a concentration ranging from 50 pg/mL to 1,000 pg/mL.” Thus the metes and bounds are confusing and unclear as the wherein clause requires a specific range of FGF-23 concentration for the sample, however the preamble is to just measuring or detecting FGF-23. Thus it is unclear if the wherein clause limits the sample, the antibodies, assay conditions, etc. to provide for the required range.
Response to Arguments
This is a new ground of rejection necessitated by amendment.
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 pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim 1, 4-13 is/are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Luethy (2006/0160181), Ibrahim (Int Urol Nephrol (2009) 41:163–169), Kazama et al (Kidney International Vol. 67, pp 1120-1125, 2005), Pandian (US Patent Number 7,439,026), Seiler (Kidney International (2009) 76 (Suppl 114), S34–S42).
Leuthy teaches, “[0211]The anti-FGF-23 antibodies of the invention may be employed in any known assay method, such as competitive binding assays, direct and indirect sandwich assays, and immunoprecipitation assays (Sola, Monoclonal Antibodies: A Manual of Techniques 147-158 (CRC Press, Inc., 1987)) for the detection and quantitation of FGF-23 polypeptides.”
Leuthy does not specifically teach the use of two antibodies, use of magnetic particles or concentration ranges.
However, Ibrahim teaches detection of FGF-23 in serum in subjects in chronic hemodialysis,(title). Ibrahim teaches, “Serum FGF23 level was markedly elevated in the study patients compared with healthy controls (1525 ± 373 pg/ml vs. 37 ± 9 pg/ml, P\0.0001). Serum FGF23 was markedly elevated in all haemodialysis patients irrespective of serum calcium and phosphate levels” (165, bottom 1st column-2nd column). Ibrahim teaches, “FGF23 (pg/ml) 1525 ± 373 (845–2196)) table 1, bottom)
Kazama teach serum FGF-23 levels can be used to predict the efficacy of calcitrol therapy in dialysis patients. (See abstract). Kazama et al measured FGF-23 levels in serum samples taken from patients who were undergoing hemodialysis, and further indicate that such patients were also treated with anticoagulants. Kazama et al further teach that antibodies to FGF-23 were known in the art. (See page 1121).
As is made clear in the discussion by Pandian et al of other sandwich immunoassay formats, reacting the sample with the two antibodies results in formation of an immunocomplex involving the two antibodies, the magnetic particle, and the antigen. (See column 13, lines 36-56; Example 1). Furthermore, Pandian et al make clear that their sandwich assay formats that use magnetic particles involve washing by exposure to a magnetic field to immobilize the magnetic particles, allowing solution to be removed from the well while antigen remains bound to the magnetic particles that are immobilized by the magnetic field.
Pandian teach of sandwich immunoassay methods using streptavidin-coated magnetic particles and biotinylated antibodies. The methods may be conducted in one of three formats, the first being a simultaneous assay format in which two antibodies (capture and labeled antibody) and the solid phase (magnetic particles) are incubated with the sample at the same time. The antibodies should recognize different epitopes of the antigen being assayed. (See column 13, lines 4-35; column 10, lines 4-54, column 12 line 11 to column 13, line 3; and column 14, line 58 to column 15, line 3). Pandian et al teach measuring antigen (ITA in this case) in biological samples including blood, and further teach providing the immunoassay reagents in liquid solutions such as those containing PBS buffer. (See column 5, line 66 to column 6, line 39; column 9, lines 49-51; column 13, lines 36-38; column 14, lines 61-66; and Example 1). Pandian et al further teach antibodies labeled with alkaline phosphatase. (See column 8, lines 5-18). Pandian teaches the use of a standard curve to determine concentrations (example 1).
Seiler teaches, “FGF-23 is a 251 amino acid protein (MW 26 kDa) synthesized and secreted by bone cells, mainly osteoblasts. It is composed of an amino-terminal signal peptide (residues 1–24), followed by an ‘FGF-like sequence’ (residues 25–180)
and a carboxyl-terminal extended sequence (residues 181–251) that is unique compared with other members of the FGF family.14 The biologically active protein can be cleaved at its RXXR motif by a subtilisin-type proprotein convertase.18–20 The half-life of intact FGF-23 in the circulation of healthy individuals has been estimated to be
58 min.21 Two assays for measurement of human FGF-23 are commercially available. Full-length FGF-23 levels can be determined with a sandwich enzyme-linked immunosorbent assay, in which two kinds of monoclonal antibodies detect the simultaneous presence of both the N-terminal and C-terminal portions of FGF-23. In contrast, the C-terminal assay recognizes both full-length and processed (presumably
inactive) C-terminal fragments of FGF-23 (Figure 1). For the C-terminal FGF-23 assay, intra-assay variability is 5% at 52.7 and 140.0 RU/ml, whereas interassay variability is 5% at 50.9 RU/ml and 7.3% at 153.0 RU/ml, with a lower detection limit of 3.0 RU/ml. For the intact FGF-23 assay, intra-assay variability is 4.4% at 14.6 pg/ml and 2.6% at 148.0 pg/ml, whereas interassay variability is 6.1% at 15.6 pg/ml and 6.5% at 166.0 pg/ml, with a lower detection limit of 1.0 pg/ml (according to the manufacturer’s specifications).” (page 535 1st column bottom-2nd column).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art to adapt the sandwich immunoassay format of Pandian and Seiler to measure serum FGF-23 and a standard curve in the ranges of the claims in hemodialysis patients undergoing anticoagulant treatment and controls in order to predict whether patients are likely to benefit from treatment with calcitriol therapy. More particularly, it would have been obvious to adapt sandwich immunoassay format of Pandian and Seilerl to the detection of FGF-23 as the antigen by providing antibodies specific to FGF-23, which were known in the art as indicated by Kazama, Ibrahim, and Luethy. One of ordinary skill in the art would have had a reasonable expectation of success in measuring serum FGF-23 in such patients using known sandwich immunoassay format of Pandian and Seiler because Kazama, Ibrahim, and Luethy taught that serum FGF-23 can indeed be successfully measured by sandwich immunoassay.
With regards to claim 5, Luethy teaches biotinylated antibodies (0243).
With regards to claim 6-7, Seiler teaches
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Thus Seiler teaches antibodies to the same site or different sites in FGF-23.
With regards to claim 8, Ibrahim teaches, “Serum FGF23 level was markedly elevated in the study patients compared with healthy controls (1525 ± 373 pg/ml vs. 37 ± 9 pg/ml, P\0.0001).
Thus it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claims the cited prior art would allow for detection of FGF-23 at concentrations of 800 pg/ml to 1000 pg/ml as the cited prior art teaches concentrations above and below the range. The artisan would be motivated to detect FGF23 at known concentrations. The artisan would have a reasonable expectation of success as the artisan is merely detecting FGF23 in the range encompassed by the prior art. (Claim 8)
With regards to claims 9-12, Ibrahim teaches, “Serum FGF23 level was markedly elevated in the study patients compared with healthy controls (1525 ± 373 pg/ml vs. 37 ± 9 pg/ml, P\0.0001).
Seiler teaches, “For the intact FGF-23 assay, intra-assay variability is 4.4% at 14.6 pg/ml and 2.6% at 148.0 pg/ml, whereas interassay variability is 6.1% at 15.6 pg/ml and 6.5% at 166.0 pg/ml, with a lower detection limit of 1.0 pg/ml (according to the manufacturer’s specifications).” (page 535 1st column bottom-2nd column).
Therefore it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claims detection of FGF23 in ranges of 1 pg/ml to 1525 ± 373 pg/ml. The artisan would be motivated to detect FGF23 at known concentrations. The artisan would have a reasonable expectation of success as the artisan is merely using known methods.
With regards to claim 13, Ibrahim teaches healthy controls (page 165, 2nd column top)
Response to Arguments
The response traverses the rejection asserting the ranges in the claims do not overlap with the prior art cited. This argument has been thoroughly reviewed but is not considered persuasive as Ibrahim teaches, “Serum FGF23 level was markedly elevated in the study patients compared with healthy controls (1525 ± 373 pg/ml vs. 37 ± 9 pg/ml, P\0.0001).” Seiler teaches, “For the intact FGF-23 assay, intra-assay variability is 4.4% at 14.6 pg/ml and 2.6% at 148.0 pg/ml, whereas interassay variability is 6.1% at 15.6 pg/ml and 6.5% at 166.0 pg/ml, with a lower detection limit of 1.0 pg/ml (according to the manufacturer’s specifications).” (page 535 1st column bottom-2nd column).
Thus the arguments are not consistent with the teachings of the cited prior art.
1The response continues traversing the rejection by asserting Ibrahim does not teach all the limitations of the claims. This argument has been thoroughly reviewed but is not considered persuasive as Luethy, Kazama, Pandian , Seiler render the limitations not taught by Ibrahim obvious.
The response further alleges the prior art of record does not teach the immunocomplex of the claims. This argument has been thoroughly reviewed but is not considered persuasive as Seiler teaches, “FGF-23 is a 251 amino acid protein (MW 26 kDa) synthesized and secreted by bone cells, mainly osteoblasts. It is composed of an amino-terminal signal peptide (residues 1–24), followed by an ‘FGF-like sequence’ (residues 25–180) and a carboxyl-terminal extended sequence (residues 181–251) that is unique compared with other members of the FGF family.14 The biologically active protein can be cleaved at its RXXR motif by a subtilisin-type proprotein convertase.18–20 The half-life of intact FGF-23 in the circulation of healthy individuals has been estimated to be 58 min.21 Two assays for measurement of human FGF-23 are commercially available. Full-length FGF-23 levels can be determined with a sandwich enzyme-linked immunosorbent assay, in which two kinds of monoclonal antibodies detect the simultaneous presence of both the N-terminal and C-terminal portions of FGF-23. In contrast, the C-terminal assay recognizes both full-length and processed (presumably inactive) C-terminal fragments of FGF-23 (Figure 1). For the C-terminal FGF-23 assay, intra-assay variability is 5% at 52.7 and 140.0 RU/ml, whereas interassay variability is 5% at 50.9 RU/ml and 7.3% at 153.0 RU/ml, with a lower detection limit of 3.0 RU/ml. For the intact FGF-23 assay, intra-assay variability is 4.4% at 14.6 pg/ml and 2.6% at 148.0 pg/ml, whereas interassay variability is 6.1% at 15.6 pg/ml and 6.5% at 166.0 pg/ml, with a lower detection limit of 1.0 pg/ml (according to the manufacturer’s specifications).” (page 535 1st column bottom-2nd column).
Double Patenting
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, 4 -13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No12,498,366 in view of Ibrahim (Int Urol Nephrol (2009) 41:163–169), Kazama et al (Kidney International Vol. 67, pp 1120-1125, 2005), Pandian (US Patent Number 7,439,026), Seiler (Kidney International (2009) 76 (Suppl 114), S34–S42. Although the claims at issue are not identical, they are not patentably distinct from each other because they are coextensive in scope.
Instant claims are drawn to a method for measuring fibroblast growth factor-23 (hereinafter indicated as FGF-23) in a sample, wherein the method comprises the steps of:(1) reacting, in an aqueous medium, FGF-23 in a sample with a magnetic particle, a first antibody or a fragment thereof which binds to FGF-23, and a second antibody or a fragment thereof which binds to FGF-23, to form on the magnetic particle an immunocomplex comprising the first antibody or a fragment thereof which binds to FGF-23, FGF-23, and the second antibody or a fragment thereof which binds to FGF-23 wherein the FGF-23 is detected in a concentration ranging from 5 pg/mL to 1,000 pg/mL.
The claims of 366 are drawn to A method for measuring fibroblast growth factor-23 (FGF-23) in a sample, which comprises the steps of: (1) reacting in a first aqueous medium, a sample and a first antibody produced by FERM BP-7838 hybridoma or an antibody fragment thereof which binds to FGF-23 to produce Immunocomplex 1 consisting of FGF-23 and the first antibody or the antibody fragment thereof which binds to FGF-23; (2) reacting in a second aqueous medium, a second antibody produced by FERM BP-7839 hybridoma or an antibody fragment thereof which binds to FGF-23 with Immunocomplex 1 produced in the aforementioned step (1) to produce Immunocomplex 2 consisting of the first antibody or the antibody fragment thereof which binds to FGF-23, FGF-23, and the second antibody or the antibody fragment thereof which binds to FGF-23; and (3) measuring Immunocomplex 2 produced in the aforementioned step (2); wherein the first aqueous medium comprises at least one type of surfactant selected from the group consisting of NONION E-230, NONION K-220, PLONON 208, and NEWCOL 740, or the first aqueous medium comprises at least one type of surfactant selected from the group consisting of NONION E-230, NONION K-220, PLONON 208, and NEWCOL 740 and the second aqueous medium is the same as first aqueous medium.
The claims do not specifically teach the use of magnetic particles or concentration ranges.
However, Ibrahim teaches detection of FGF-23 in serum in subjects in chronic hemodialysis,(title). Ibrahim teaches, “Serum FGF23 level was markedly elevated in the study patients compared with healthy controls (1525 ± 373 pg/ml vs. 37 ± 9 pg/ml, P\0.0001). Serum FGF23 was markedly elevated in all haemodialysis patients irrespective of serum calcium and phosphate levels” (165, bottom 1st column-2nd column). Ibrahim teaches, “FGF23 (pg/ml) 1525 ± 373 (845–2196)) table 1, bottom)
Kazama teach serum FGF-23 levels can be used to predict the efficacy of calcitrol therapy in dialysis patients. (See abstract). Kazama et al measured FGF-23 levels in serum samples taken from patients who were undergoing hemodialysis, and further indicate that such patients were also treated with anticoagulants. Kazama et al further teach that antibodies to FGF-23 were known in the art. (See page 1121).
As is made clear in the discussion by Pandian et al of other sandwich immunoassay formats, reacting the sample with the two antibodies results in formation of an immunocomplex involving the two antibodies, the magnetic particle, and the antigen. (See column 13, lines 36-56; Example 1). Furthermore, Pandian et al make clear that their sandwich assay formats that use magnetic particles involve washing by exposure to a magnetic field to immobilize the magnetic particles, allowing solution to be removed from the well while antigen remains bound to the magnetic particles that are immobilized by the magnetic field.
Pandian teach of sandwich immunoassay methods using streptavidin-coated magnetic particles and biotinylated antibodies. The methods may be conducted in one of three formats, the first being a simultaneous assay format in which two antibodies (capture and labeled antibody) and the solid phase (magnetic particles) are incubated with the sample at the same time. The antibodies should recognize different epitopes of the antigen being assayed. (See column 13, lines 4-35; column 10, lines 4-54, column 12 line 11 to column 13, line 3; and column 14, line 58 to column 15, line 3). Pandian et al teach measuring antigen (ITA in this case) in biological samples including blood, and further teach providing the immunoassay reagents in liquid solutions such as those containing PBS buffer. (See column 5, line 66 to column 6, line 39; column 9, lines 49-51; column 13, lines 36-38; column 14, lines 61-66; and Example 1). Pandian et al further teach antibodies labeled with alkaline phosphatase. (See column 8, lines 5-18). Pandian teaches the use of a standard curve to determine concentrations (example 1).
Seiler teaches, “FGF-23 is a 251 amino acid protein (MW 26 kDa) synthesized and secreted by bone cells, mainly osteoblasts. It is composed of an amino-terminal signal peptide (residues 1–24), followed by an ‘FGF-like sequence’ (residues 25–180)
and a carboxyl-terminal extended sequence (residues 181–251) that is unique compared with other members of the FGF family.14 The biologically active protein can be cleaved at its RXXR motif by a subtilisin-type proprotein convertase.18–20 The half-life of intact FGF-23 in the circulation of healthy individuals has been estimated to be
58 min.21 Two assays for measurement of human FGF-23 are commercially available. Full-length FGF-23 levels can be determined with a sandwich enzyme-linked immunosorbent assay, in which two kinds of monoclonal antibodies detect the simultaneous presence of both the N-terminal and C-terminal portions of FGF-23. In contrast, the C-terminal assay recognizes both full-length and processed (presumably
inactive) C-terminal fragments of FGF-23 (Figure 1). For the C-terminal FGF-23 assay, intra-assay variability is 5% at 52.7 and 140.0 RU/ml, whereas interassay variability is 5% at 50.9 RU/ml and 7.3% at 153.0 RU/ml, with a lower detection limit of 3.0 RU/ml. For the intact FGF-23 assay, intra-assay variability is 4.4% at 14.6 pg/ml and 2.6% at 148.0 pg/ml, whereas interassay variability is 6.1% at 15.6 pg/ml and 6.5% at 166.0 pg/ml, with a lower detection limit of 1.0 pg/ml (according to the manufacturer’s specifications).” (page 535 1st column bottom-2nd column).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art to adapt the sandwich immunoassay format of Pandian and Seiler to measure serum FGF-23 and a standard curve in the ranges of the claims in hemodialysis patients undergoing anticoagulant treatment and controls in order to predict whether patients are likely to benefit from treatment with calcitriol therapy. More particularly, it would have been obvious to adapt sandwich immunoassay format of Pandian and Seilerl to the detection of FGF-23 as the antigen by providing antibodies specific to FGF-23, which were known in the art as indicated by Kazama, Ibrahim, and Luethy. One of ordinary skill in the art would have had a reasonable expectation of success in measuring serum FGF-23 in such patients using known sandwich immunoassay format of Pandian and Seiler because Kazama, Ibrahim, and Luethy taught that serum FGF-23 can indeed be successfully measured by sandwich immunoassay.
With regards to claim 5, Luethy teaches biotinylated antibodies (0243).
With regards to claim 6-7, Seiler teaches
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Thus Seiler teaches antibodies to the same site or different sites in FGF-23.
With regards to claim 8, Ibrahim teaches, “Serum FGF23 level was markedly elevated in the study patients compared with healthy controls (1525 ± 373 pg/ml vs. 37 ± 9 pg/ml, P\0.0001).
Thus it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claims the cited prior art would allow for detection of FGF-23 at concentrations of 800 pg/ml to 1000 pg/ml as the cited prior art teaches concentrations above and below the range. The artisan would be motivated to detect FGF23 at known concentrations. The artisan would have a reasonable expectation of success as the artisan is merely detecting FGF23 in the range encompassed by the prior art. (Claim 8)
With regards to claims 9-12, Ibrahim teaches, “Serum FGF23 level was markedly elevated in the study patients compared with healthy controls (1525 ± 373 pg/ml vs. 37 ± 9 pg/ml, P\0.0001).
Seiler teaches, “For the intact FGF-23 assay, intra-assay variability is 4.4% at 14.6 pg/ml and 2.6% at 148.0 pg/ml, whereas interassay variability is 6.1% at 15.6 pg/ml and 6.5% at 166.0 pg/ml, with a lower detection limit of 1.0 pg/ml (according to the manufacturer’s specifications).” (page 535 1st column bottom-2nd column).
Therefore it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claims detection of FGF23 in ranges of 1 pg/ml to 1525 ± 373 pg/ml. The artisan would be motivated to detect FGF23 at known concentrations. The artisan would have a reasonable expectation of success as the artisan is merely using known methods.
With regards to claim 13, Ibrahim teaches healthy controls (page 165, 2nd column top)
Response to Arguments
The response traverses the rejection in view of the amendment. This argument is not persuasive for the reasons of record.
Claims 1, 4-13 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of U.S. Patent No. 10,422,796. Although the claims at issue are not identical, they are not patentably distinct from each other because they are coextensive in scope.
Instant claims are drawn to a method for measuring fibroblast growth factor-23 (hereinafter indicated as FGF-23) in a sample, wherein the method comprises the steps of:(1) reacting, in an aqueous medium, FGF-23 in a sample with a magnetic particle, a first antibody or a fragment thereof which binds to FGF-23, and a second antibody or a fragment thereof which binds to FGF-23, to form on the magnetic particle an immunocomplex comprising the first antibody or a fragment thereof which binds to FGF-23, FGF-23, and the second antibody or a fragment thereof which binds to FGF-23 wherein the FGF-23 is detected in a concentration ranging from 5 pg/mL to 1,000 pg/mL.
The claims of 796 are drawn A method for measuring fibroblast growth factor-23 (FGF23) in a serum or plasma sample, comprising: (1) simultaneously reacting, in an aqueous medium, FGF23 in the sample with (i) a magnetic particle, (ii) a first antibody which binds to FGF23, and (iii) a second antibody which binds to FGF23, to form on the magnetic particle an immunocomplex comprising the first antibody, FGF23, and the second antibody in a reaction mixture, wherein the first antibody is an anti-FGF-23 monoclonal antibody produced by hybridoma deposited as FERM BP-7838, and the second antibody is an anti-FGF-23 monoclonal antibody Fab or Fab′ fragment produced by digesting anti-FGF23 monoclonal antibody produced by the hybridoma deposited as FERM BP-7839, the magnetic particle does not directly immobilize the first antibody; and one of two substances with affinity to each other is fixed to the magnetic particle and the other of the two substances with affinity to each other is bound to the first antibody, (2) collecting the magnetic particle after step (1) by magnetic force, and separating the magnetic particle collected by magnetic force from the other components; and (3) measuring the immunocomplex on the magnetic particle separated in step (2).
Claim 8 draws the invention to wherein the method detects FGF23 concentrations of 5 pg/mL to 10,000 pg/m L.
Therefore it would have been prima facie obvious to one of ordinary skill in the art at the time of the invention the claims of 796 were a species which renders the instant claims.
Dependent claims are rejected as they are commensurate in scope.
Response to Arguments
The response alleges the rejection has been overcome by the filing of a terminal disclaimer. This argument is not persuasive because no terminal disclaimer has been filed.
Claims 1, 4-13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No12,092,637. Although the claims at issue are not identical, they are not patentably distinct from each other because they are coextensive in scope.
Instant claims are drawn to a method for measuring fibroblast growth factor-23 (hereinafter indicated as FGF-23) in a sample, wherein the method comprises the steps of:(1) reacting, in an aqueous medium, FGF-23 in a sample with a magnetic particle, a first antibody or a fragment thereof which binds to FGF-23, and a second antibody or a fragment thereof which binds to FGF-23, to form on the magnetic particle an immunocomplex comprising the first antibody or a fragment thereof which binds to FGF-23, FGF-23, and the second antibody or a fragment thereof which binds to FGF-23 wherein the FGF-23 is detected in a concentration ranging from 5 pg/mL to 1,000 pg/mL
The claims of 637 are drawn A method for measuring fibroblast growth factor-23 (FGF-23) in a sample, wherein the method comprises the steps of: (1) reacting, in an aqueous medium, FGF-23 in a sample with a magnetic particle bonded with a first antibody or a fragment thereof which binds to FGF-23, and a second antibody or a fragment thereof which binds to FGF-23, to form on the magnetic particle an immunocomplex comprising the first antibody or a fragment thereof which binds to FGF-23, FGF-23, and the second antibody or a fragment thereof which binds to FGF-23, wherein the sample comprises FGF-23 in a concentration ranging from 5 pg/mL to 10,000 pg/mL; (2) collecting the magnetic particle in the reaction mixture after step (1) by magnetic force, and separating the magnetic particle collected by magnetic force from the other components; and (3) measuring the immunocomplex on the magnetic particle separated in step (2)..
Therefore it would have been prima facie obvious to one of ordinary skill in the art at the time of the invention the claims of 637 were a species which anticipates the instant claims.
Dependent claims are rejected as they are commensurate in scope.
Response to Arguments
The response alleges the rejection has been overcome by the filing of a terminal disclaimer. This argument is not persuasive because no terminal disclaimer has been filed.
Summary
No claims are allowed.
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.
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/Steven Pohnert/Primary Examiner, Art Unit 1683
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