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 .
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.
DETAILED ACTION
Election/Restrictions
Applicant's election with traverse of Group I in the reply filed on 3/6/26 is acknowledged. The traversal is on the ground(s) that there is no undue burden. This is not found persuasive because this is a general allegation that does not point to any specific deficiency in the Restriction requirement. The Restriction set forth the reasons that an undue burden exists and Applicant has not attempted to rebut any of the conclusions set forth therein.
The requirement is still deemed proper and is therefore made FINAL.
Claims 1-20 are pending.
Claims 19-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 3/6/26.
Claims 1-18 are under examination.
Claim Objections
Claim 1 is objected to because of the following informalities: the semicolon in line 3 should be replaced with “, and wherein” to maintain consistency with the other “wherein” clauses used throughout the claims. Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 3-7 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.
Claims 3-7 include the limitation of the microsphere being an “A” microsphere, where the “A” microsphere is A1, A2, A3, A4, and A5. Considering the specification as filed and the state of the art, it is unclear what an “A” microsphere is, nor is it clear what distinguishes, e.g., an A1 microsphere from an A5 microsphere.
In one interpretation, these are merely administrative labels to distinguish and reference the five microspheres but do not impart any structural requirements or differences. However, this interpretation is inconsistent with the specification as filed, which lists specific model and fluorescence intensities for the microspheres in table 4. It is unclear if this is meant to act as a definition for these microspheres or not.
Further, in considering table 4, it is unclear which limitations are required. Claim 4 requires the fluorescence intensity of each of A1-A5 to be different; however, according to table 4, the fluorescence is necessarily different, e.g., A1 must have a fluorescence of 4000, A2 must have a fluorescence intensity of 20000, etc. Thus, the claim suggests this is a further limitation, which in turn would indicate that Table 4 is not a definition. If table 4 is not a definition, then there is no apparent definition of what qualities, properties, structure, or function is required of, e.g., an A1 microsphere. It is noted that fluorescence intensity is generally reported in relative or arbitrary units, i.e., the intensity of the fluorescence is dependent on factors such as concentration of the various reagents, detection settings, etc.
Further, table 4 lists these microspheres as constructed by Biolegend; it is unclear if the recitation of, e.g., A1 requires that this microsphere is constructed in the same factory as disclosed in the specification or if any microsphere with the same properties would infringe the claim. Where a trademark or trade name—such as Biolegend—is used as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name.
Table 4 also lists model numbers. However, these model numbers directly contradict the Biolegend model numbers. According to Biolegend A5 (form 892), their “A5” bead is catalog number 740168, which is the model number of “A2” in the specification. This Biolegend document teaches that the “A” series of beads is 5 µm. This is the same as the instant limitation in claim 3 (an A microsphere which is a 5 µm carboxyl microsphere) but it is unclear if the size of the bead is the only limitation of the claimed “A” microsphere and, if so, how the recitation of A1, A2, etc. is meant to be interpreted.
Reading the specification and taking into account the state of the art, the skilled artisan is not fairly warned as to when a microsphere is an “A1” microsphere or any other microsphere as there does not appear to be any particular requirements for the microspheres other than a size, where each of A1-A5 is the same size (5µm).
Finally, the claim clearly requires a single bead (an A microsphere) to comprise five different microspheres (comprises an A1 …and A5 microsphere). It is unclear what this limitation is meant to convey. It is possible that A1-A5 microspheres are all defined as “5 µm” and so a single 5µm bead is simultaneously all five of A1-A5. However, this is not supported by claim 4 that requires each of A1-A5 to be different. Alternately, there is meant to be at least five microspheres in claim 3, but this is not supported by the claim’s use of “the antibody-conjugated microsphere” (singular) or “is an A microsphere” (singular). It is also possible that the A1-A5 is meant as a Markush group, but the claim lacks the “selected from the group consisting of” language and instead clearly recites that the A microsphere comprises all five options.
Therefore, claims 3-7 are indefinite.
Claims 1-18 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 “a biotin conjugated an antibody”. This is not a grammatically correct phrase and leads to confusion over the intent of the scope. In one interpretation, the article is accidental and the phrase should be “a biotin-conjugated antibody”. In another interpretation, there is an omitted comma and the phrase should be “an antibody-conjugated microsphere, biotin conjugated” to indicate that the microsphere is also biotin conjugated. It is noted in this case the phrase would be better written as “a microsphere conjugated to both an antibody and biotin”. In a third interpretation, there is an omitted word or phrase, such that the biotin is meant to be conjugated to something other than the microsphere or second antibody, and there is also another antibody as a separate element.
Dependent claims do not clarify this deficiency.
Further, claim 1 also uses the phrase “the antibody is selected” at line 3-4. However, there are two earlier references to an antibody: the one conjugated to the microsphere and the “an antibody” that may or may not be biotin-conjugated. Where “the antibody” may refer to more than one antibody, there is insufficient antecedent basis for this limitation in the claim; see MPEP §2173.05(e) and the “two lever” example.
Therefore, claims 1-18 are indefinite.
Claim 4 is 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 4 is directed to the fluorescence intensity of the microspheres. This claim specifically requires the microspheres to possess (or have possessed) a different fluorescence intensity and is not directed to where the microsphere-antibody-analyte-antibody-reporter has a different intensity. In other words, the claim requires the microsphere itself to have a different fluorescence intensity independent of any additional elements.
Claim 4 requires the fluorescence intensity of the microspheres “was different”.
It is unclear how to interpret this phrase with respect to the claim scope. First, the instant claims are directed to a composition of matter, not a method. While microspheres such as the ones disclosed are capable of fluorescence, there is no inherent fluorescence intensity and only occurs when excited by a laser (Saporita figure 1). Further, the use of “was” rather than “is” suggests that there has been some unclaimed step where the fluorescence intensity is manifested or measured; however, a composition of matter cannot contain method steps as adding process steps to a product claim creates confusion as to when direct infringement occurs; MPEP §2173.05(p)(II).
Alternately, the use of “was” suggests that, to infringe, the fluorescence intensity might be identical when in possession of the microspheres, but would still infringe if at any point in the past the intensities were different. This does not fairly warn others as to when infringement occurs because there is no means of determining what fluorescence intensities a bead might have had in the past but no longer has.
Therefore, claim 4 is indefinite.
Claim 11 is 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 11 recites “the tris…”. There is no antecedent basis for this phrase.
Therefore, claim 11 is indefinite.
Claim 13 is 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 13 recites “the buffer” in line 2. This could refer to the Tris buffer, the washing buffer, or the reaction buffer. There is insufficient antecedent basis for this phrase.
Therefore, claim 13 is indefinite.
Claim 10 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 10 contains the trademark/trade name Proclin®. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe an element of the dilution solution and, accordingly, the identification/description is indefinite.
Therefore, claim 10 is indefinite.
Claim Rejections - 35 USC § 103
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.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-2 is/are rejected under 35 U.S.C. 103 as being unpatentable over Saporita (form 892) in view of Dasgupta (form 892), Waterboer (form 892), and Dias (form 892).
Regarding claim 1, it is initially noted that there is no special definition of a “kit”. As this recitation occurs only in the preamble and the body of the claim stands without it, the “kit” as well as the intended use in the preamble do not distinguish the claim from the individual components existing separately in the body of the claim.
Saporita teaches a multiplex assay for the detection of Alzheimer’s disease (AD) biomarkers in human plasma and serum. Plasma and serum are components of blood and so meet the limitations of “in blood”. Further, the preamble of instant claim 1 is an intended use that does not alter the structure of the kit. Saporita quantifies Aß40, Aß42, total tau, pTau181, and α-synuclein (figures 3A and 3B). This is performed using a Luminex bead (a microsphere) conjugated to a capture antibody (an antibody-conjugated microsphere) which is specific to the analyte (figures 1 and 2). This meets the limitations of the antibody-conjugated microsphere where the antibody is Aß1-40, Aß1-42, pTau181, T-tau (total tau), and α-synuclein. The captured analyte was then contacted with a biotin-conjugated antibody (biotinylated; figures 1 and 2); while the phrase is indefinite, the phrase “a biotin-conjugated an antibody” is reasonably interpreted as “a biotin-conjugated antibody”. The beads were mixed with liquid samples, meeting the limitations of the beads in “a solution”.
While Saporita teaches mixing the beads with a sample to incubate (allow for binding), Saporita does not teach a specific incubating agent.
Dasgupta teaches sorbitol stabilizes the proteins in blood and reduces aggregation (abstract).
Waterboer teaches a solution comprising the polymer polyvinylpyrrolidone (PVP) reduces detrimental non-specific binding when incubated with serum samples (abstract). This was demonstrated using the Luminex assay (abstract).
Dias teaches a blocking solution comprising the nonionic surfactant Triton X-100 for use in multiplex assays (title; table 1; p.960 C2).
It would have been obvious to combine known prior art elements according to known methods to yield predictable results. The prior art included each element instantly claimed:
Saporita teaches a solution of antibody-conjugated microspheres and biotin-conjugated microspheres.
Saporita teaches the antibody conjugated to the microspheres is an antibody against Aß1-40, Aß1-42, p-tau-181, T-tau, and α-synuclein.
Dasgupta teaches a polyol
Waterboer teaches a polymer
Dias teaches a nonionic surfactant
One of ordinary skill in the art could have combined the elements as claimed by known methods and in that combination each element merely performs the same function as it does separately:
Saporita teaches a multiplex assay using antibody-conjugated microspheres and biotin-conjugated antibodies to detect the levels of certain proteins in serum. In the combination, these microspheres continue to perform this known function.
Dasgupta teaches sorbitol will stabilize proteins and reduce aggregation. In the combination, the sorbitol will stabilize the antibodies (proteins) and biomarkers (proteins) and reduce aggregation in Saporita Luminex assay (which contains antibodies and biomarkers) the same way.
Waterboer teaches PVP reduces non-specific binding in serum samples when using Luminex. Including PVP in the combination will also reduce the non-specific binding of the Saporita antibodies in the Saporita Luminex assay.
Dias teaches a nonionic surfactant is useful for blocking solutions in multiplex assays. Including a nonionic surfactant will be useful in blocking solutions for the Saporita Luminex assay (multiplex assay) for the same reasons.
Additionally, Saporita, Waterboer, and Dias are all concerned specifically with multiplex/Luminex assays, further suggesting the combination of the individual components. Dasgupta is not used specifically for a multiplex assay, but the teaching that protein aggregation is reduced in blood samples when using sorbitol would have made obvious the inclusion of sorbitol in a kit that comprises proteins and is intended for blood and/or blood component analysis.
As the identity and function of each element was known as well as teachings that the elements were useful in multiplex and/or blood sample assays, one of ordinary skill in the art would have recognized the results as predictable. Further, as a composition of matter, including the individually known elements does not require interaction of those elements in any way. This further emphasizes that each known element is performing the same functions as they do individually. The antibody-conjugated microspheres are separate from the biotin-conjugated microspheres which are separate from the incubating agent. While the incubating agent contains the polyol, polymer, and nonionic surfactant, there is no evidence nor rationale to suggest that combining these three components behaves in any unpredictable manner.
As such, claim 1 would have been obvious.
Regarding claim 2, Dasgupta teaches the polyol is sorbitol, Waterboer teaches the polymer is PVP, and Dias teaches the nonionic surfactant is Triton X-100.
Therefore, claims 1-2 would have been obvious.
Claim(s) 3-5 is/are rejected under 35 U.S.C. 103 as being unpatentable over Saporita, Dasgupta, Waterboer, and Dias as applied to claims 1-2 above, and further in view of Biolegend A4, Biolegend A5, Biolegend A6, Biolegend A7, and Biolegend A8 (form 892). Note that the Biolegend documents are numbered according to the bead they disclose.
Claims 1-2 would have been obvious as above and incorporated herein. While the antibody-conjugated microspheres are disclosed as above, the art cited does not disclose the size of the microsphere or the fluorescence intensity of the microspheres.
Regarding claim 3, nevertheless it would have been obvious to use a 5µm carboxyl microsphere. First, it is noted that the instant specification states that the microspheres were purchased, suggesting their commercial availability at the time of filing. Further, Saporita discloses using commercially available microspheres and using them according to the product instruction manuals (p.1 C2). Biolegend discloses the A4-A8 beads as being 5 µm carboxyl beads designed for multiple assay development, with the application disclosed as “multiplex”, which is the same type of assay in Saporita. Claim 3 is indefinite as above; it is unclear how a single microsphere can comprise five microspheres. Under the interpretation that 1) this was meant to be a Markush group (the A microsphere is A1…or A5) or 2) that there was meant to be five different microspheres, it would have been obvious to use the commercially available microspheres designed for this purpose. As there are at least five biomarkers measured in Saporita, it would have been obvious to select at least five different microspheres, which are provided by Biolegend A4-A8.
With respect to the claim limitation of being an “A” microsphere, it is unclear what attributes such a microsphere has. Biolegend teaches their “A” microspheres are also 5µm and is the same company as the one in instant table 4, supporting the conclusion that the Biolegend “A” microspheres meet the limitations of the instantly claimed “A” microspheres.
With respect to the A1-A5 designation, it is also unclear what structural requirements differentiate one from the others. The A4-A8 Biolegend microspheres are the same company, same size, and sold under the same model/product number as the instant table 4 discloses. Thus, while not having the “A1-A5” label, the “A4-A8” microspheres appear to meet the limitations of the instantly claimed microspheres.
Regarding claim 4, Biolegend discloses that each bead set has a different level of APC fluorescence (p.1; figure on p.1). Since the beads would have been obvious, the fluorescence intensity being different would have been obvious. Further, Saporita figure 1 demonstrates that the assay functions in part by exciting the microsphere to fluoresce, where that fluorescence is a “unique fluorescent signature” to identify the bead and thereby distinguish the biomarkers, which also renders the difference in intensity obvious.
Regarding claim 5, the five biomarkers and five beads would have been obvious as above. Further, using a separate bead type for each of the biomarkers would have been obvious as 1) that is what Saporita does and 2) the art discloses that this allows the biomarkers to be separated and categorized from a single sample/assay. Choosing the “A1” (A4) bead for a specific biomarker, such as Aß40, is a matter of rearrangement of parts or a finite choice with predictable results. MPEP §2144.04 notes that rearranging parts such that the function is unaffected is prima facie obvious. MPEP §2143 notes that an “obvious to try” rationale is choosing from a finite number of identified, predictable solutions with a reasonable expectation of success.
Saporita lists a finite number of biomarkers. Each is attached to a different microsphere as the assay of Saporita requires this arrangement in order to measure the individual biomarkers from the single sample/assay. Further, there is no technical difference in the manner of operation nor in the results obtained in choosing any specific microsphere for a particular biomarker. Biolegend teaches all of the microspheres are for “do-it-yourself conjugations”, providing a reasonable expectation that any of the five beads could be conjugated to any of the five biomarkers and the result—detecting the biomarker—would be unchanged.
Therefore, claims 1-5 would have been obvious.
Claim(s) 6 is/are rejected under 35 U.S.C. 103 as being unpatentable over Saporita, Dasgupta, Waterboer, and Dias as applied to claims 1-2 above, and further in view of Todd (form 892), Qi (form 892), Zhang (form 892), and Elfarrash (form 892).
Claims 1-2 would have been obvious as above and incorporated herein. While the antibody-conjugated microspheres are disclosed as above, the art cited does not disclose that the antibodies are rabbit antibodies.
First, it is noted the antibodies were purchased according to the specification, suggesting their commercial availability at the time of filing. Further, each of the biomarkers was known to be detectable by rabbit monoclonal antibodies.
Todd teaches the anti-Aß42 antibody D9A3A for detecting Aß42 in an immunoassay (p.5 C1), which the Examiner notes is inherently a monoclonal rabbit antibody.
Qi teaches the antibody D8Q7I is a rabbit monoclonal antibody that detects Aß40 in an immunoassay (p.3 C1).
Stefanoska teaches the antibody D5D8N for detecting total tau (p.11 C2), which the Examiner notes is inherently a monoclonal rabbit antibody.
Zhang teaches the antibody D9F4G is a pTau181 antibody (p.3 C1), which the Examiner notes is inherently a monoclonal rabbit antibody.
Elfarrash teaches the antibody D1R1R and MJFR1, which are both rabbit monoclonal antibodies that bind alpha-synuclein.
Given the teachings of Saporita to measure these five biomarkers using antibody-conjugated microspheres, it would have been obvious at the time of filing to select a known, commercially available antibody for conjugation to the microspheres. At the time of filing, the art contained many rabbit monoclonal antibodies that were effective in immunoassays and selecting a known antibody with a known target in a known assay would have provided a reasonable expectation of success. Thus, the selection of rabbit monoclonal antibodies would have been obvious.
Therefore, claims 1-2 and 6 would have been obvious.
Claim(s) 7 is/are rejected under 35 U.S.C. 103 as being unpatentable over Saporita, Dasgupta, Waterboer, and Dias as applied to claims 1-2 above, and further in view of Bilan (form 892).
Claims 1-2 would have been obvious as above and incorporated herein. While the antibody-conjugated microspheres are disclosed as above, the art cited does not disclose that the antibodies conjugated to the beads lack an Fc region.
Regarding claim 7, nevertheless it would have been a predictable substitution to use antibodies lacking an Fc fragment, such as a Fab, instead of the full-length antibodies of Saporita. Conjugating Fab antibodies to luminescent beads was a known, predictable technique in multiplex immunoassays as taught by Bilan (p.4, Development and technical validation of the xMAP® bead-based 3-plex sandwich immunoassay).
Therefore, claims 1-2 and 7 would have been obvious.
Claim(s) 9 is/are rejected under 35 U.S.C. 103 as being unpatentable over Saporita, Dasgupta, Waterboer, and Dias as applied to claims 1-2 above, and further in view of Reinsberg (form 892) and Andersen (form 892).
Claims 1-2 would have been obvious as above and incorporated herein. While the art teaches the components as useful for detecting biomarkers in biological samples, and also includes suggestions of blocking agents, the art cited does not teach the blocking agent comprising inactivated murine IgG and an anti-HAMA polyclonal antibody.
Regarding claim 9, Reinsberg teaches blocking with IIR, which is a formulation of immunoglobulins (polyclonal antibodies) targeted against HAMA (anti-HAMA). Reinsberg teaches that this blocking agent should be included when testing serum samples (such as those in Saporita) because murine IgG blocking is effective but incomplete. This would have made obvious the addition of anti-HAMA polyclonal antibodies to the kit. Further, it would have made obvious the inclusion of murine IgG in the blocking reagent as the combination was known to be effective.
However, Reinsberg does not teach the IgG was inactivated. Andersen teaches blocking with heat-inactivated mouse serum, which inherently comprises mouse IgGs. This is further supported by Andersen teaches the serum as an alternative to mouse IgGs. (abstract). Thus, it would have been obvious to use both the anti-HAMA blocking reagent of Reinsberg and the heat-inactivated mouse serum/IgG blocking reagent of Andersen as they are both taught as being beneficial as blocking agents in immunoassays.
Therefore, claims 1-2 and 9 would have been obvious.
Allowable Subject Matter
Claim 8 contains allowable subject matter. None of the art of record nor any art the Examiner discovered utilized a biotin-BSA-SA-PE complex. Saporita is the closest prior art, which discloses a biotin-SA-PE complex, but does not include BSA. In general, the art of record (see above) uses BSA as a separate blocking agent but using BSA in this manner would not create the rectangular structure of the instantly claimed complex (see figure 1A and 1B). Moreover, the specification notes that this structure has the surprising property of amplifying the detection signal by effectively attaching more of the PE reporter per biotin-labeled secondary antibody (paragraph 169). While this is certainly one outcome the ordinary artisan might have expected, it would also have been reasonable to expect a failure of the technique as the necessary biotin binding sites on the avidin could have been occupied such that the reporter complex failed to bind the secondary antibody. As noted in the specification, neither was this a commercially available product as Applicant took the step of complexing the BSA-biotin (paragraph 91). Taking the evidence as a whole, the complex of claim 8 appears to be non-obvious.
Claim 10 contains allowable subject matter. Saporita teaches a sample diluting solution (“diluted samples”; p.1 C2) but is silent regarding the composition of the dilution solution. Saporita also teaches using control samples (see figure 4 “normal”), which meets the limitations of a quality control.
Dias teaches washing the microspheres with phosphate buffer (p.960 C1) as part of the protocol, which would have made it obvious to include a washing buffer. Dias also includes a reference standard (po.960 C2), which meets the limitations of a quality control and/or calibration product. Dias teaches the microspheres are added to histidine buffer, which is then included in the final reaction with the sample (p.960 C2), which would have made it obvious to include a reaction buffer.
Nifong (wo2013016226; form 892) is also concerned with fluorescent multiplex assays (claims 18 and 20), where such assays measure quality control (claim 12) and analyze calibration standards (claim 13). As these are desired results in a multiplex assay, it would have been obvious to provide the quality control and calibration product necessary to obtain those results.
While the samples were diluted as above, the cited art does not teach that the diluting solution contains the claimed elements. Further, the examiner did not discover any art that combined these three elements into a single solution which would be compatible with the other elements of claim 1. Such solutions exist—see Shaoxiong (form 892) at 2.2—but is used for column chromatography elution. There is no elution step in the conjugation/multiplex assay of the cited art nor any rationale for diluting samples, microspheres, or any other element of the assays of the cited art with the elution solution of Shaoxiong. The mere existence of the solution is insufficient to support a proper obviousness rationale as, unlike the other existing compositions discussed, there is no known relationship between the claimed diluting solution and an antibody/bead-based assay.
Claims 11-18 depend from claim 10 and so would have been non-obvious for the same reasons.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Harma (form 892): teaches incubating multiplex beads in a solution comprising sorbitol (p.87 C1).
Baier (form 892): teaches sorbitol is protective in aqueous samples containing proteins and was specifically tested on BSA, a serum protein (abstract).
Nicoud (form 892) teaches polyols reduce antibody aggregation by stabilizing antibodies (highlights). Nicoud teaches sorbitol is widely used as an excipient for this purpose (p.41 C1) and that sorbitol specifically reduces “monomer depletion” (p.41 C2), i.e., reduces aggregation.
Antonian (NZ19920241889; form 892): teaches inclusion of the polymer polyvinylpyrrolidone (PVP) in microparticle (microsphere) based immunoassays (antibodies) when sampling body fluids to increase the sensitivity and signal of the immunoassay (claim 1).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ADAM M WEIDNER whose telephone number is (571)272-3045. The examiner can normally be reached M-T 9-18; W-R 9-15.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Stucker can be reached at 571-272-0911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Adam Weidner/Primary Examiner, Art Unit 1675
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