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 Amendments
Claims 6, 8, and 17-25 have been cancelled. Claims 1-5, 7, and 9-16 have been amended and claims 26-39 have been newly added as requested in the amendment filed on 15 January 2026. Following the amendment, claims 1-5, 7, 9-16 and 26-39 are pending in the instant application, and are under examination in the instant office action.
Claim Rejections - 35 USC § 112(b) (New, 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.
As currently amended, Claims 1-5, 7, 9-16 and 26-39 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.
On page 16 of Remarks filed 15 January 2026, Applicant asserts that the amendments to remove trademarks/trade names have overcome all issues. The new amendments raise the following new issues under 112(b).
Claims 1-5, 7, 9-16 and 26-39 recite a capture antibody comprising six specific CDR sequences or a variant thereof comprising one or two amino acid substitutions. The variants of the claims fail to further limit the scope of the CDRs. The transitional term "comprising", which is synonymous with "including" or "containing", while it is open-ended language providing for additional elements, an antibody comprising a CDR sequence must comprise at a minimum those amino acids within the sequence. While variants having additional amino acids outside of those sequences are encompassed, substitutions within the recited sequences are not because the antibody requires, de minimis, those amino acids set forth in the sequences. See MPEP2111.03(I). Therefore, the scope of an antibody comprising a specific sequence and further reciting “comprises one or two amino acid substitutions”, is entirely indefinite. This affects all depending claims.
Claim Rejections - 35 USC § 112(a) (New, Necessitated by Amendment)
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.
As currently amended to recite variants comprising one or two amino acid substitutions and sequences having at least 90% identity, Claims 1-5, 7, 9-16 and 26-39 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.
On pages 15-16 of Remarks (Id), Applicant asserts the amendments to recite the six CDR sequences have overcome the rejection of record. This is not persuasive for the following reasons.
As currently amended, all of the independent claims read upon variants comprising one or two amino acid substitutions within the claimed CDR sequences (SEQ ID NOs 3-5 and 8-10). However, the specification provides no adequate written description of which one or two amino acid substitutions could be made within the complementarity determining regions that would also provide for the functional requirement of the claim – namely, binding “to an epitope of SOD1 within the amino acid sequence of SEQ ID NO: 11” (claim 1). Claims 9 and 36 further read upon antibodies that may not only comprise one or two substitutions within the CDRs, but also comprise up to 10% alteration of residues within the VH or VL chains. Thus, the claims encompass genera of variants (for each of the six CDRs) and VH/VL chains having at least 90% identity, and there is not adequate written description of all, the variants claimed.
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice (see MPEP 2163(II)(3)(a)(i)(A), reduction to drawings MPEP 2163(II)(3)(a)(i)(B), or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus MPEP 2163(II)(3)(a)(i)(C). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
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. 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. MacCallum et al. J. Mol. Biol. (1996) 262, 732-745, analyzed many different antibodies for interactions with an antigen and conclude that non-contacting residues within the CDRs are as important in defining antigen binding as contacting residues (see page 735, left col.). Casset et al. also states that 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., Casset et al. Biochem and Biophys Res Comms, 307: 198-205, 2003) 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.). Vajdos et al. (2002) 320, 415-428, additionally state that antigen binding is primarily mediated by residues supporting the CDR loop conformations and in some cases framework residues, within the larger VH or VL chains, that also contact antigen (page 416, left col.). Taken together the references indicate much unpredictability remains with respect to un-described variations within the CDRs or within both the CDRs and the larger VH or VL chains.
The references demonstrate that an antibody must comprise all 6 CDRs, and largely the associated framework regions, in order to maintain the antigen binding specificity and affinity which is characteristic of the antibody. Without adequate written description of which residues within the CDRs can be altered, which up to 10% of residues within the VH or VL chain can be altered, yet antigen binding retained, the specification does not provide adequate written description of the claimed variants. Lastly, the specification fails to provide a representative number of species within the genera of the claims, therefore, the specification does not provide adequate written description of the claimed antibody variants. Claims 1-5, 7, 9-16 and 26-39 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.
Claims 1-5, 7, 9-16 and 26-39 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. rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for making and using the two discrete antibodies comprising the CDR sequences set forth in claims 1 and 10, does not reasonably provide enablement for the method comprising any variant, wherein the variant of each of the VH-CDR1, VH-CDR2, VH-CDR3, VL-CDR1,VL-CDR2, and VL-CDR3 of the capture antibody comprises one or two amino acid substitutions; nor for the method comprising an antibody that has an amino acid sequence which is at least 90% identical to the sequences claimed. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
On page 17 of Remarks (Id), Applicant asserts that the claims have been amended to incorporate the six CDR sequences and this overcomes the rejection of record. This is not persuasive for toe following reasons.
As stated in the rejection above, the claims encompass a genus of antibodies that contain one or two undescribed amino acid substitutions within the six CDR sequences listed; and depending claims further comprise antibodies that can have up to 10% altered amino acid residues within the larger VH or VL chains. Yet, the claims recite functional language that these antibodies must meet: “an anti-SOD1 antibody that binds to an epitope of SOD1 within the amino acids sequence of SEQ ID NO: 11”.
In AMGEN INC. ET AL. v. SANOFI ET AL. (No. 21-757, decided May 18, 2023), the Supreme Court held that Amgen was not enabled for “the entire genus” of antibodies that (1) “bind to specific amino acid residues on PCSK9,” and (2) “block PCSK9 from binding to [LDL receptors]” (872 F. 3d 1367, 1372) even though Amgen identified the amino acid sequences of 26 antibodies that perform these two functions.
In Amgen, the Supreme Court has stated:
“An antibody’s structure does much to dictate its function—its ability to bind to an antigen and, in some instances, to block other molecules in the body from doing the same. ‘For an antibody to bind to an antigen, the two surfaces have to fit together and contact each other at multiple points.’ Id., at 11. But just because an antibody can bind to an antigen does not mean that it can also block. To bind and block, the antibody must establish a sufficiently broad, strong, and stable bond to the antigen. See ibid. Different antibodies have different binding and blocking capacities based on the amino acids that compose them and their three-dimensional shapes. See id., at 11–12.
Despite recent advances, aspects of antibody science remain unpredictable. For example, scientists understand that changing even one amino acid in the sequence can alter an antibody’s structure and function. See id., at 14. But scientists cannot always accurately predict exactly how trading one amino acid for another will affect an antibody’s structure and function. Ibid.”
Given that structure is essential to function; and given that the Supreme Court has said unpredictability remains within the state of the art with respect to creating antibodies with specific function, a person having ordinary skill in the art would have to perform further experimentation in order to make the variants encompassed by the claims and use them in the method with a reasonable expectation of success. Given the nature of the invention, a skilled artisan would have to make multiple variants comprising at least one or two amino acid substitutions, and antibodies comprising an amino acid sequence at least 90% identical to the claimed sequences, and then validate each of these antibodies for their function as an anti-SOD1 antibody that binds to an epitope of SOD1 within the amino acids sequence of SEQ ID NO: 11. Similar to the scenario in Amgen, this amount of experimentation goes beyond what is considered “a reasonable degree of experimentation” and constitutes undue further experimentation in order to enable the method for the breadth of what is claimed.
For all of these reasons, the specification does not enable the claims, and Claims 1-5, 7, 9-16 and 26-39 are rejected under 35 U.S.C. 112(a).
Claim Rejections - 35 USC § 102 (New, Necessitated by Amendment)
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 1-5, 7, 9-12, 15, 31-32, 34-37 and 38-39 are rejected under 35 U.S.C. 102(a)(1), or in the alternative under 35 U.S.C. 102(a)(2), as being anticipated by Neurimmune Holding, US Patent 9,283,271, issued 15 March 2016, effectively filed 17 December 2010 (hereafter “the Neurimmune patent”).
Applicant’s arguments (pgs. 17-18 of Remarks) pertaining to the Montrasio art of record are moot in view of the current claim amendments, which now recite a particular capture antibody. New prior art has been applied in view of the current claim amendments.
Regarding Claims 1, 9 and 31, the Neurimmune patent teaches assays for the detection of misfolded SOD1 (col. 5, lines 4-12) in biological fluid samples (col. 21, lines 20-27). The prior art discloses an antibody comprising a VH chain that is 100% identical to SEQ ID NO: 2 of the instant claims (see first alignment below). In this VH chain CDRs 1-3, corresponding to the instantly claimed SEQ ID NOs: 3 (AYYIH), SEQ ID NO: 4 (VINPSTGTTFYAQNFPD) and SEQ ID NO: 5 (AISEHGSGSYSPYY), are highlighted (note VH-CDR2 spans across two alignment lines). The Neurimmune patent further teaches this antibody has a VL chain that is 100% identical to SEQ ID NO: 7 (see second alignment below), in which VL chain CDRs corresponding to SEQ ID NOs: 8-10 of the instant claims, respectively, are highlighted. Thus, the prior art teaches methods of assaying misfolded SOD1 in body fluid samples comprising the identical capture antibody of the instant claims 1, 9 and 31.
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Regarding Claim 2, the Neurimmune prior art patent teaches the sample comprises cerebrospinal fluid (CSF) (col. 21, line 13).
Regarding Claim 3, the Neurimmune prior art patent teaches the antibodies can be used as a diagnostic tool to identify misfolded SOD1 in CSF, and teaches disorders related to misfolded SOD1 includes amyotrophic lateral sclerosis (ALS) (col. 1, lines 35-40).
Regarding Claim 4 and 32, the Neurimmune prior art teaches immunodiagnostic methods (col. 4, lines 37-46) for “disorders related to misfolded/aggregated SOD1, such as ALS” and, as stated above, teaches the antibody that is 100% identical to the claimed sequences: VH-CDR1 of SEQ ID NO 3, VH-CDR2 of SEQ ID NO: 4 and VH-CDR3 of SEQ ID NO: 5; and VL-CDR1 of SEQ ID NO: 8, VL-CDR2 of SEQ ID NO: 9, and VL-CDR3 of SEQ ID NO: 10, of instant claims 4 and 32.
Regarding Claim 5, the Neurimmune prior art teaches both sporadic and familial ALS show aberrant SOD1 species suggesting misfolded SOD1 is a common origin (col. 8, lines 19-27).
Regarding Claim 7, the Neurimmune patent discloses the antibodies as monoclonal (col. 4, lines 6-13 and Figure 4 and legend at col. 6, lines 22-28).
Regarding Claim 9 and 34, the antibody disclosed in the Neurimmune patent is 100% identical to a VH of SEQ ID NO: 2 (see alignments provided above) and a VL of SEQ ID NO: 7. Thus, the prior art teaches an antibody comprising an amino acid sequence at least 90% identical to these claimed sequences, as recited by instant claim 9, and comprises the amino acid sequence of SEQ ID NOs: 2 and 7, as recited by instant claim 34.
Regarding Claims 10, 35 and 36-37, the Neurimmune patent discloses another antibody comprising sequences identical to SEQ ID NOs: 16-18 and SEQ ID NOs: 20-22. The first alignment below corresponds to the VH chain of claimed SEQ ID NO: 15 aligned to the VH sequence disclosed in the prior art, and SEQ ID NOs: 16-18 are highlighted; and the second alignment below corresponds to the VL chain of SEQ ID NO: 19 and the VL chain disclosed in the prior art, in which SEQ ID NOs: 20-22 are highlighted. This teaches the antibody of instant claims 35-37.
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Regarding Claim 11, the Neurimmune patent discloses assay methods in which the detection antibody is labelled. Specifically, the prior art patent teaches competition assays comprising two antibodies that share a common antigen within SOD1, in which the SOD1 or aggregates are bound to a solid surface and an unlabelled test immunoglobulin and a labeled reference immunoglobulin are used to determine the presence or amount of SOD1 (col. 25, line 36 through col. 26, line 9). Thus, the prior art teaches labelled detection antibodies, as claimed.
Regarding Claim 12, the prior art patent discloses label moieties include “fluorescent, radioactive, enzyme, nuclear magnetic, heavy metal and the like” (col. 49, lines 15-16).
Regarding Claim 15, while the Neurimmune patent discloses detection of mSOD1 at a dilution of 3.3 µg/mL (see Example 1, col. 65), it does not disclose a lower limit of quantification of < 22.32 pg/mL, as claimed. However, the MPEP § 2112 makes clear that “[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer.” Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Additionally, the court has held that there is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of invention, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003); see also Toro Co. v. Deere & Co., 355 F.3d 1313, 1320, 69 USPQ2d 1584, 1590 (Fed. Cir. 2004) (“[T]he fact that a characteristic is a necessary feature or result of a prior-art embodiment (that is itself sufficiently described and enabled) is enough for inherent anticipation, even if that fact was unknown at the time of the prior invention.”); Abbott Labs v. Geneva Pharms., Inc., 182 F.3d 1315, 1319, 51 USPQ2d 1307, 1310 (Fed.Cir.1999).
Since the examiner has applied prior art which discloses the identical antibodies of the claims, and a composition is not severable from its properties, then the antibodies of the prior art must also have a lower limit of quantification for mSOD1 of < 20.32 pg/mL. The examiner’s assertion of inherency is based upon the structural similarity between the patented composition and the claimed composition.
Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established and the burden of proof rests upon the Applicant to demonstrate that the prior art does not necessarily or inherently possess the characteristics of Applicant’s claimed product. In re Fitzgerald, 619 F.2d 67, 70, 205 USPQ 594, 596 (CCPA 1980) (quoting In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977)). “When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).
Regarding Claims 38-39, the Neurimmune prior art teaches assay methods comprising anti-SOD1 antibodies that bind to different epitopes within SOD1. Specifically, the legend of Figure 4 states: “(4) FIG. 4: EC50 analysis at increasing coating concentrations of human SOD1 that favors the formation of conformational epitopes. Human antibodies NI-204.10D12 (A), NI-204.10A8 (B), NI-204-9F6 (C) and NI-204.12G7 (D) EC50 determination and murine monoclonal antibody SOD-1 72B1 binding affinity (E) for recombinant human SOD1 at increasing coating concentration (.Math.30 μg/ml; .box-tangle-solidup.10 μg/ml; .square-solid.1 μg/ml; .circle-solid.0.1 μg/ml; coating concentration of recombinant human SOD1) using direct ELISA. Determined EC50 values are indicated in Table (F) below. NI-204.10D12 antibody (A) and NI-204.12G7 antibody (D) preferentially target an epitope of human SOD1 that is most probably exposed or formed at high coating concentrations and concomitant misfolding or aggregation of recombinant human SOD1. Both NI-204.10A8 (B) and the NI-204.9F6 antibody (C) recognize an epitope of human SOD1 that is present both in the physiological protein conformation as well as in the misfolded/aggregated SOD1.” The legend for Figure 7 states: “NI.204.10D12 binds to the central domain of human SOD1 as assessed by pepscan analysis. Antibody binding occurs at peptides covering amino acids 85-107. The NI.204.10D12 binding epitope comprises accordingly amino acids 93-99 with the sequence DGVADVS (SEQ ID NO: 2).” Thus, the prior art discloses direct immunoassays comprising antibodies that bind different epitopes and specifically one, NI.204.10D12, that binds an epitope within 100-105, as claimed.
For all of these reasons, the invention of the claims fails to distinguish over the methods and elements disclosed in the prior art, and Claims 1-5, 7, 9-12, 15, 31-32, 34-37 and 38-39 are rejected.
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 factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 13-14, and 26-28 are rejected under 35 U.S.C. 103 as being unpatentable over Neurimmune Holding, US Patent 9,283,271 (2016) but effectively filed 17 December 2010 as applied to Claims 1-5, 7, 9-12, 15, 31-32, 34-37 and 38-39 above, and further in view of WO 2012/129610 A1 published 4 October 2012 (hereafter the ‘610 publication).
The teachings of the Neurimmune patent as they pertain to Claims 1-5, 7, 9-12, 15, 31-32, 34-37 and 38-39 are set forth in the rejection above.
The Neurimmune patent does not teach:
The method of claim 13 comprising “(i) providing a microplate to the wells of which the capture antibody is spotted; (ii) adding the body fluid sample to the wells followed by incubation, thereby allowing capturing of mSOD1 present in the body fluid sample by the capture antibody; (iii) adding the detection antibody, followed by incubation, thereby allowing binding of the detection antibody to the captured mSOD1; (iv) adding a conjugate comprising a ligand-binding tag and a detectable label followed by incubation; (v) adding a chromogenic or chemiluminescent substrate solution; and (vi) imaging the signal”; wherein (1) the incubation in step (ii) is performed for 2 h at room temperature on a plate shaker set to a speed of 600 rpm;(2) the incubation in step (iii) is performed for 30 min at room temperature on a plate shaker set to a speed of 600 rpm;(3) the incubation in step (iv) is performed for 30 min at room temperature on a plate shaker set to a speed of 600 rpm;(4) the method further comprises a step of comparing the assayed level of mSOD1 to a reference standard and/or a control; and/or (5) the method is a singleplex immunoassay (claim 26); the method according to claim 26, wherein the method further comprises a step of comparing the assayed level of mSOD1 to a reference standard and/or a control and wherein the reference standard and/or the control is added to different wells of the same microplate from the wells containing the sample (claim 27).
The method of claim 14 “wherein (a) the microplate is a 96-well plate; (b) the body fluid sample is a (CSF) sample; (c) the ligand is biotin, or a biotin analog or derivative thereof; (d) the ligand-binding tag is streptavidin or a functional analog or derivative thereof, and wherein the detectable label is an enzyme capable of catalyzing the conversion of the chromogenic or chemiluminescent substrate, (e) the chromogenic or chemiluminescent substrate is 3,3',5,5'-tetramethylbenzidine (TMB) or a luminol substrate;(f) imaging is performed by imaging system; (g) a washing step is performed after steps (ii), (iii) and/or (iv); and/or (h) the microplate is covered with a lid; the method according to claim 14, wherein:(1) the enzyme is horseradish peroxidase; and/or (2) the lid has a fluid-absorbing matrix filled with a fluid during the incubation (claim 28).
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 Neurimmune methods utilize a 96-well microplate and disclose the body fluid sample is a (CSF) sample. The ‘610 publication teaches ligand binding pairs comprise biotin, of the instant claim, and the ligand tag is streptavidin or 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 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 Neurimmune patent, 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 Neurimmune patent 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 and 33 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.
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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/STACEY N MACFARLANE/ Examiner, Art Unit 1675
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