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 .
Response to Amendment
Claims 1, 4, 11, 13, 15-16, 26-27, 29-30, and 39 have been amended and claims 39-71 have been newly added as requested in the amendment filed on 10 July 2026. Following the amendment, claims 1-5, 7, 9, 11-16, 26-30, 33-34, and 39-71 are pending in the instant application, and are under examination in the instant office action.
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.
As currently amended, Claims 1-5, 7, 9, 11-12, 34, 39-43, 59-65, and 70-71 are rejected under 35 U.S.C. 103 as being unpatentable over WO2012080518, publication 21 June 2012 (hereafter the ‘518 reference).
Regarding Claim 1, the ‘518 reference teaches the exact antibody comprising all 6 CDRs set forth in the claim (see search results). Further the prior art teaches methods comprising detecting misfolded SOD1 (see pg. 8, Figure 4) in a body fluid (pg. 29, line 21), and specifically teaches ELISA (pg. 6, lines 14-19; pg. 7, legends for Figs. 2 and 3).
Regarding Claim 2 and newly added Claim 70, the ‘518 reference teaches samples include cerebrospinal fluid (pg. 29, line 21).
Regarding Claim 3, the ‘518 reference teaches presence of the mSOD1 indicates ALS (pg. 1, lines 15-28; pg. 6, lines 14-19).
Regarding Claim 4, as stated above, the prior art teaches an antibody comprising all six CDRs of the claim, and teaches a detection antibody that is different than the capture antibody.
Regarding Claim 5, the prior art teaches aberrant SOD1 species can be found in both sALS and fALS (pg. 11, lines 4-9).
Regarding Claim 7 and newly added Claim 71, the ‘518 reference teaches the antibodies are monoclonal (pg. 8, Fig. 4).
Regarding Claim 9, the ‘518 reference discloses an antibody that is 100% identical to SEQ ID NOs: 2 and 7.
Regarding Claim 11, the ‘518 reference discloses direct labeled assay (pg. 36, lines 3, 8 and 10; and pg. 67, lines 10-14).
Regarding Claim 12, the ‘518 reference teaches antibodies can be labelled by enzymes, fluorescent markers or radioactives (pg. 66, lines 20-23).
Regarding Claim 34, the ‘518 reference teaches the capture antibody comprising a VH sequence of SEQ ID NO: 2 and a VL sequence of SEQ ID NO: 7. Applicant should note that a capture antibody comprising the VH of the capture antibody comprises the amino acid sequence of SEQ ID NO: 1; and the VL of the capture antibody comprises the amino acid sequence of SEQ ID NO: 6, is free of the prior art (claim 33).
Regarding Claims 39-43 and newly added claims 59-61, the prior art teaches a capture antibody that has all six CDRs of instant claim 1, therefore it is assumed that the same antibody binds to the same epitopes within human SOD1 as recited instant claims 39-41, since a chemical composition cannot be separated from its physical properties. The ‘518 reference discloses antibodies that bind epitopes covering amino acids 85-107 and 93-99 (see pg. 9, at Fig. 7). Additionally, the prior art discloses antibodies by the following names: NI-204.10Dl2; NI-204-12G7; NI-204.11F11; NI-204.10A8; NI-204.67El2; NI.204.6H1; NI.204.12G3; NI.204.7G5; NI.204.25H3; NI.204.34A3; NI.204.7B3 (see pg. 9, Fig. 9). The prior art does not refer to antibodies by their Abcam names. However, since the prior art teaches the six CDRs of instant claim 1, it is assumed that NI-204.12G of the instant claims corresponds to one of the “NI-204-12G” antibodies listed above, which must go by the synonyms of “EPR1726,Abcam ab52950, Abcam ab79390” listed in the instant claims.
Regarding Claims 43 and 44 and newly added claims 62-64, the prior art teaches a detection antibody comprising the CDRs of SEQ ID NO:16-18 and 20-22 of instant claims 44 and 64 (see attached search strategies). While the prior art teaches the exact same antibody it does not teach, “the detection antibody competes with EPR1726, Abcam ab52950, Abcam ab79390, or NI-204.12G for binding SOD1 in a sandwich ELISA assay”. However, since a chemical substance cannot be separated from its properties, then it has the same claimed properties, which includes having the same synonyms in the art.
Regarding Claim 45 and newly added Claim 65, the prior art teaches the antibody comprising SEQ ID NO: 15 and 19 of the instant claims, which the prior art calls “NI-204.12G3 that binds to 121-HEKADDLGKGGNEES-135 within SOD1. The prior art teaches that it was known these antibodies bind to different epitopes within SOD1 (see pg. 96 line10 through pg. 97 line 22 including Table IV) and explicitly teaches methods comprising two or more monoclonal antibodies with different binding specificities (ex. pg. 76, line 23). Thus, the prior art teaches detection antibodies that bind to an epitope of SOD1 that is different from an epitope within SOD1 than the capture antibody.
Regarding Claim 47, the prior art teaches aberrant SOD1 species can be found in both sALS and fALS (pg. 11, lines 4-9).
Regarding Claims 48 and 50, the prior art teaches the identical antibody comprising SEQ ID NOs: 2 and 7.
Regarding Claims 51 and 52, the ‘518 reference discloses antibodies conjugated to a detectable label and specifically teaches several embodiments within instant claim 52 including enzymes, fluorescent markers or radioactives (pg. 66, lines 20-23).
Claim(s) 13-15, 26-28, 46, 53-57, and 66-69 are rejected under 35 U.S.C. 103 as being unpatentable over WO2012080518, publication 21 June 2012 (the ‘518 reference) as applied to Claims 1-5, 7, 9, 11-12, 34, 39-43, 59-65, and 70-71 above, and further in view of WO 2012/129610 (2012) (the ‘610 publication; also of record in the previous action).
While the ‘518 reference teaches the limitations of 1-5, 7, 9, 11-12, 34, 39-43, 59-65, and 70-71, it fails to teach the limitations of 13-15, 26-28, 46, 53-57, and 66-69. The ‘610 publication remedy these deficiencies.
The ‘610 publication remedies these deficiencies.
Regarding Claim 13, the ‘610 publication teaches direct immunoassay methods wherein the assay platform is a multi-well plate (“microplate” as required of the instant claims). The immobilization (“spotted” of the instant claims) agent is an antibody (“capture antibody” of the claims). The sample (sample of the instant claims) and the solid substrate are contacted before contacting with the capture agent and/or the detectable agent. The sample and the solid substrate are first contacted in the reaction vessel (teaches “allowing capturing” of instant claims). The sample and the solid substrate are not substantially incubated before contacting with the capture agent and/or the detectable agent (“detection antibody” of the instant claims). The capture agent and the detectable agent are contacted before contacting with either or both of the sample and the solid substrate (see Equivalent Abstract). The ‘610 publication further teaches: “The immobilization agent and the ligand (“ligand” of the instant claim) comprise a binding pair comprising an anti-peptide tag antibody and a peptide tag (“ligand binding tag” and “detectable label” of the instant claims). The peptide tag comprises amino acid sequence of SEQ ID NO: 1 (Asp-Tyr-Lys-Asp-Asp-Asp-Asp-Lys). The antibody capture agent comprises several ligands. The concentration of the capture agent is 10-1000 ng/ml or 50-500 ng/ml. The detectable agent comprises an antibody and a detectable tag. The tag comprises an enzyme, a fluorophore (“chemiluminescent” of the instant claims), or a lanthanide. The reaction vessel comprises the solid substrate. The immobilization agent and the ligand comprise a binding pair comprising avidin, streptavidin, biotin and/or their derivatives” (Summary starting on page 2).
Regarding Claim 14, the ‘610 publication teaches ligand binding pairs comprise biotin, of the instant claim, and the ligand tag is streptavidin or derivative thereof (see paragraphs [00119] and [00120]), and the detectable label is an enzyme capable of catalyzing a chemiluminescent substrate (see paragraph [00153]). The ‘610 publication further teaches the substrate is TMB (paragraph [00302]), as claimed, further comprises washing (paragraph [00301]) the microplate is covered with a lid (the prior art teaches “foil” see paragraph [00302]).
Regarding Claim 15, the ‘610 publication discloses detection at 100 pg/ml or less (see paragraph [0080]).
Regarding Claim 26, the ‘610 publication teaches the incubation is performed for 2 h (see claim 15, pg. 89) at room temperature (paragraph [0025]) on a plate shaker (paragraph [00300]) at a speed of ~300 rpm (see paragraphs [00300] and [00302]), and further teaches the incubation in step is performed for 30 min (claim 16 of the prior art). While this does not teach the 600 rmp of the instant claims, the Court has stated that, generally, such differences amount to mere optimization and will not support patentability unless there is evidence indicating the claimed feature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Laboratories Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997). In KSR International Co. v. Teleflex Inc., 550 U.S. 398 (2007), the Supreme Court held that "obvious to try" was a valid rationale for an obviousness finding, for example, when there is a "design need" or "market demand" and there are a "finite number" of solutions. 550 U.S. at 421. MPEP 2144 sets forth Applicant' s burden for rebuttal of a prima facie case of obviousness based upon routine optimization. Applicant must provide either a showing that the particular amount or range recited within the claims is critical; and/or a showing that the prior art reference teaches away from the claimed amount. In the instant case, the specification as filed provides no evidence that the 600 rpm recited within the claims is critical because throughout the specification it states “preferably set to 600 rpm” (see pg. 15).
Regarding Claim 27, the ‘610 publication teaches method comprising a single incubation, single-wash ELISA (equivalent to the “singleplex immunoassay” of instant claim 26) and comparing to a similar assay run with a buffer-only control for the analyte (paragraph [0020]).
Regarding Claim 28, the ‘610 prior art publications teaches the enzyme is horseradish peroxidase, as claimed, (see paragraph [00302]).
It would have been obvious to a person having ordinary skill in the art that the antibodies, as taught by the ‘518 reference, could be used in the method disclosed in the ‘610 publication. A person having ordinary skill in the art would recognize that these antibodies would predictably yield a direct assay of mSOD1 in CSF samples because the ‘518 reference teaches successful detection of mSOD1 in said samples. In KSR International Co. v. Teleflex, Inc., the Supreme Court has stated that combining prior art elements according to known method to yield predictable results is prima facie obvious if the following rationale can be applied:
(1) the prior art includes each element claimed though not necessarily in the same reference.
(2) it was within the technical grasp of one of ordinary skill in the art to combine the elements as claimed by known methods, and that in combination, each element merely would have performed the same function as it did separately.
(3) one of ordinary skill in the art would have recognized that the results of such combination were predictable.
(KSR International Co. v. Teleflex, Inc. 127 S. Ct. 1727, 82 USPQ2d 1385, Supreme Court, April 30, 2007). All of the three elements can be applied: each element is disclosed. Based on the guidance and direction within the prior art, such combination would have been well within the technical grasp of a skilled artisan since it is a simple substitution of antibodies into a known method. Since each of the elements in combination are merely performing the same function as they did separately, then one of ordinary skill in the art would have been able to predictably combine the elements with a reasonable expectation of success. Therefore, the invention as a whole is prima facie obvious, if not actually anticipated by the reference.
Allowable Subject Matter
Claims 16, 29-30, 33, and newly added claims 46, 53-57, and 66-69 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims. There is no disclosure in the prior art pertaining to digital ELISA or the imaging methods recited in these claims.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to STACEY NEE MACFARLANE whose telephone number is (571)270-3057. The examiner can normally be reached M-F 7:30-5 (EST) & Sat. A.M..
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/STACEY N MACFARLANE/ Examiner, Art Unit 1675
