Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Claim Rejections - 35 USC § 103
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 134 is rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over US 5,976,896 (“Kumar”).
The following disclosure by Kumar is considered relevant to Applicant’s claims.
Kumar teaches an assay system that can be automated.
More specifically, Kumar in column 17, line 2 to column 18, line 10 discloses the following.
“Capillary tubes prepared by the methods described above can be used individually or in combination for an immunoassay in accordance with the method discussed above. The assay can be performed manually or automatically, as discussed hereinafter. One end of a single capillary tube can be introduced into a sample and sample drawn up by any convenient means, e.g. capillary action or active pumping, to provide an appropriately sized sample in the capillary tube. Alternatively, a plurality of capillary tubes coated with appropriate binding members can be used to permit a plurality of immunoassays on one sample or a single immunoassay on multiple samples to screen for one or multiple analytes. The capillary tubes can be held in a cartridge that permits sequential or simultaneous use and/or that permits interaction with other devices and/or apparatus to effectuate an immunoassay of this invention.” Column 17, line 2 to column 18, line 10. (Emphasis added.)
Moreover, column 18, lines 41-46 of Kumar discloses the following.
“Capillary tubes as prepared above can be used with commercially available containers suitable for independently housing the reagents and waste of immunoassays, such as microtiter wells or plates. Alternatively, the capillary tubes can be used with a sample tray designed to contain a reagent and means to mix fluid held within the wells.” Column 18, lines 41-46. (Emphasis added).
Thus Kumar teaches that reagents can be provided in wells of a microtiter plate or wells of a sample tray. Moreover, Kumar teaches that the reagents can be provided in the wells or plates, as an alternative to reagents being contained and mixed in a sample tray. [The microtiter plate or the sample tray is equivalent to Applicant’s cartridge. The wells of the microtiter wells or sample tray are equivalent to Applicant’s sample well and reagent well wherein the capillary is used to transfer the sample and reagents from the wells.]
Kumar teaches capillary tubes used individually or in combination for an immunoassay. One end of the capillary tube can be introduced into a sample. The capillary tubes are coated with binding members to permit a plurality of immunoassay on one sample or multiple samples to screen for one or multiple analytes. The capillary tubes can be held in a cartridge that permits sequential or simultaneous use and/or that permits interaction with other devices and/or apparatus to effectuate an immunoassay (col. 17, lines 62 to col. 18, line 10.)
The capillary tubes can be used with a sample tray designed to contain a reagent and means to mix the fluid within the wells [of the sample tray.] Column 18, lines 41-46.
The apparatus has the ability to manipulate one or more capillary tubes and a sample tray, to control the flow of and house fluids, to carry out a substantial portion of the steps of a plurality of immunoassays for efficiency, including the step of detecting and analyzing the signal. Column 19,lines 6-19.
In figure 12 there is shown an apparatus 200 that comprises prep station 201, capillary tubes 2, and detection station 203. Column 29, lines 55-67. The prep station 201 comprises syringe 210, a first section for containing the cartridge 1 (which holds capillaries, see for example col. 21, lines 19-22), and a second section comprising a tray holder 212 for holding the sample tray 3. See column 30, lines 1-10.
The capillary tubes are spaced apart along the outside of the longitudinal side of a cylinder or by a disc or plurality of discs, containing openings to hold a plurality of spaced apart capillary tubes in a circular manner. The cylinder can rotate to present a particular tube to a sample source or to a fluid source for washing, adding reagent, or other desired fluid to each tube. The cylinder can also rotate to present a capillary tube to a signal generation and detection means. Column 35, line 66-column 36, line 16.
See also figure 1, disclosing cartridge (1), capillary tube 92) where reaction takes place, sample tray (3) for containing sample, reagents, and other fluids.
The Kumar capillary is equivalent to Applicant’s assay unit. The capillaries having an interior reaction site having thereon an immobilized binding reagent such that a reaction occurs within the assay unit (see col. 17, lines 62 to col. 18, line 10, disclosing that the capillaries are coated with binding members to screen analytes.)
Kumar’s syringe is equivalent to the claimed fluid transfer device configured to direct transfer of the sample and the cartridge reagents from the plurality of reagent units into the assay unit such that a reaction occurs within the assay unit.
The microtiter plate or the sample tray is equivalent to Applicant’s cartridge. The wells of the microtiter wells or sample tray are equivalent to Applicant’s sample well and reagent well wherein the capillary is used to transfer the sample and reagents from the wells.
See also column 18, lines 44-46, disclosing that the sample tray is designed to contain a reagent and means to mix fluid held within the wells, and column 19, lines 35-36 disclosing that the sample is added to one or more wells in the sample tray). Examiner emphasizes that since Applicant’s claims are directed to a device, rather than a method, the prior art meets the claims if it is capable of performing the intended use. In this case the intended use of containing a reagent in one well and a sample in a separate well for sequentially being introduced into the capillary separately from the sample.
See also column 18, lines 41-46 disclosing another example in which the capillary tubes can be used with commercially available containers suitable for independently housing the reagents and waste of immunoassays, such as microtiter wells or plates, or alternatively a sample tray can contain a reagent and means to mix fluid held within the wells.” Column 18, lines 41-46. Thus Kumar teaches microtiter well plates as alternatives to a sample tray. Microtiter well plates are thus alternatively considered equivalent to Applicant’s cartridge comprising a sample well and a reagent well since the wells of microtiter plates are capable of containing a sample in one well and a reagent in another well.
Moreover, Kumar discloses a method for use with the disclosed system, wherein the sample is added to the capillary with free antibody and an enzyme linked antibody, and free antibody is washed away before enzyme substrate is added to the complex, following with detection. Column 33, line 63 to column 34, line 8.
Thus, Kumar shows an example of use of the disclosed capillary wherein sample is added to the capillary, and then subsequently another reagent (e.g., enzyme substrate) is added to the capillary. While Kumar does not give details as to the container holding the sample and reagent in the disclosure of this assay format, it is understood that the sample and reagent can be provided in a container generally disclosed elsewhere by Kumar in the patent, that is, commercially available microtiter well plates or a sample tray (col. 18, lines 41-46.) See also disclosure of wells in the sample tray (column 19, lines 35-36; and col. 32, lines 20-24 and see figures 4 and 9). [Examiner advises that, as an alternative grounds for rejection, providing the sample and reagents in separate wells in the same microtiter well plate or the same sample well plate requires only ordinary skills in the art since it leads to a predictable outcome of providing the materials necessary for performing the assay.]
Kumar also discloses that the apparatus positions the sample tray under the cartridge [the cartridge contains capillary tube(s), which are equivalent to Applicant’s assay unit] located thereon and draws the mixture into one or more capillary tubes, e.g., via suction. Column 19, lines 42-56. See also column 30, lines 47-49 disclosing a motor for moving the sample tray under the cartridge [which holds the capillary, equivalent to Applicant’s assay unit.]
A syringe or suctioning means (column 30, lines 1-10) is equivalent to the claimed fluid transfer device configured to direct transfer of the sample and the cartridge reagents from the cartridge into the assay unit such that a reaction occurs within the assay unit.
Kumar also teaches that the sample tray holder, and thereby the sample tray, is lifted by a lift motor 309 so that the tips of the capillary tubes 2 contact each sample and fluorescently-labeled conjugate reagent mixture in the wells 57 (col. 32, lines 20-24 and see figures 4 and 9).
[The Kumar sample holder 212 and lift motor together are equivalent to Applicant’s translational stage, and they are configured to move the sample tray 3 (equivalent to Applicant’s claimed cartridge)].
Examiner notes that therefore the sample tray is capable of being moved relative to the assay unit to place one of the wells of the sample tray into fluid communication with the capillary [equivalent to Applicant’s assay unit]. Examiner also notes that while Kumar is silent as to moving a microtiter plate to the capillary, Kumar discloses that a microtiter plate can be used alternatively to the sample tray (column 18, lines 41-46), and thus it is understood that if a microtiter is used in place of the sample tray, the microtiter can be moved in the same manner as the sample tray. In any case, Kumar discloses that the sample tray, and therefore the wells of the sample tray (column 18, lines 41-46), are capable of being moved relative to the cartridge containing capillaries [a capillary being equivalent to an assay unit] for fluid communication (column 19, lines 42-56; see also column 30, lines 47-49). Examiner notes that Kumar teaches that fluid in the wells of the sample tray are moved in and out of the wells (see column 36, lines 50-67), and that the sample tray [and thus wells of the sample tray] are moved by a motor for positioning into fluid communication with the capillary tubes (column 19, lines 42-56; and see column 30, lines 47-49.) Moreover, Examiner again emphasizes that since Applicant’s claims are directed to a device, rather than a method, the prior art meets the claims if it is capable of performing the intended use, in this case the intended use of containing a reagent in one well and a sample in a separate well, of a sample tray or microtiter plate, for sequentially being introduced into the capillary separately from the sample. Kumar teaches that wells of the sample tray are moved into fluid communication with the capillary, and thus the wells of the sample tray are capable of moving sequentially into fluid communication with the capillary.
Clai 134 further recites that the fluid transfer device is automated to transfer the sample form the sample well and the reagent from the reagent well into the assay unit according to a protocol for performing an assay to detect the analyte.
However, column 31, lines 40-44 of Kumar discloses that "[t]he automated non-operator dependent portion of the apparatus 200 system software is provided by an erasable programmable read only memory (EPROM) module 348 connected to the control PCA 300 via a 30 position edge connector 349." (Emphasis added).
Moreover, column 36, lines 50-67 of Kumar discloses the following: "An important aspect of an alternative embodiment of the apparatus for use with a preferred embodiment of the cartridge and sample tray is that embodiments of the apparatus are able to communicate with the cartridge and sample tray, that the apparatus is equipped with appropriate electronics and/or optics for a given, immunoassay, and that the apparatus is capable of performing or interfaced with an instrument capable of performing an automated immunoassay and of computing qualitative, semi-quantitative, and/or quantitative results. Another aspect of the apparatus for use with a preferred embodiment of the cartridge and sample tray combination is that the apparatus house or control a suitably substantial portion of the means to move fluid in and out of the wells, capillary tubes, and chambers." (Emphasis added.)
Column 37, lines 56-67 discloses the following: "Alternative embodiments of the apparatus of the present invention can also include various levels of automation. One embodiment of the apparatus of the present invention can be designed such that only instrument control is possible with the stand alone apparatus and all data reduction and analysis is performed by a computer connected or networked to the apparatus via a port, such as RS-232, IEEE-488 (HP-IB), contact closure, and the like. Similarly, control of the apparatus can be automated by a connection to a computer as previously described where all control inputs are directed by the computer and initiated by an operator or alternatively by a computer program." (Emphasis added).
Moreover, Kumar in column 3, lines 1-18: "Additionally, a preferred embodiment of the apparatus of the present invention or variations of it can be interfaced with laboratory robots, such as cylindrical, cartesian, and articulated robots and the like; to enable complete automation of the immunoassay. The robotics device can be programmed to remove sample from a central container and add it to each well and alternatively to perform any pre-assay sample processing and preparation necessary, such as filtration, extraction, dilution, removal of certain components, and other manipulations depending on the sample. The robotics device can also place the sample tray and cartridge on the apparatus and subsequently move the cartridge to the centrifuge or other device and dispose of the sample tray. The robotics device can be integrated into an alternative embodiment of the apparatus of the present invention or it can be a commercially available robot for use in the laboratory and known to those of ordinary skill in the art of the present invention." Thus Kumar discloses use of laboratory robots to enable complete automation of an immunoassay, including adding a sample to a container and performing dilution [which Examiner notes is addition of a reagent].
Thus Kumar teaches the disclosed system can be automated and programed for automating an assay (column 31, lines 40-44), including controlling the means to move fluid in and out of wells of a sample tray (column 36, lines 50-67), and that the control inputs can be directed by the computer or initiated by an operator (column 37, lines 56-67). Again, a syringe or suctioning means as disclosed by Kumar (column 30, lines 1-10) is equivalent to the claimed fluid transfer device configured to direct transfer of the sample and the cartridge reagents from the cartridge into the assay unit such that a reaction occurs within the assay unit. Thus, regarding Applicant’s claim 109, the automated fluid transfer device is configured to direct transfer (capable of transferring) sample from a well (sample well) and a reagent from a well (reagent) of the sample tray (Applicant’s cartridge) according to a protocol (via a program or control initiated by an operator). [Examiner advises that providing a computer program with instructions that direct transfer of a sample from one well and a reagent from another well, such as from a microtiter plate, would have been obvious to one skilled in the art given the teachings of Kumar to achieve a predictable outcome of contacting a sample and reagent as would be desirable for performing an assay.]
Claim 134 further recites that the assay unit comprises a tapered tip which has an opening at a first end and a second end that is enlarged relative to the first end, wherein the assay unit further comprises a reaction site having thereon an immobilized binding reagent.
However, such limitations regarding the shape of the assay unit is merely a design choice that produces a predictable outcome, and therefore would have been obvious to one skilled in the art.
It would have been obvious or predictable to one skilled in the art that the recited configuration of the assay unit is a design choice that would provide an alternative configuration that also results in an element that works in the same general manner as disclosed by Kumar.
Thus, modifying Kumar such that the capillary has a tapered tip as recited by Applicant requires only routine skills in the art since it is a mere change in shape that is a design choice with a predictable outcome, in using the capillary as taught by Kumar.
Examiner notes that new claim 134 has limitations recited in allowable independent claim 109 (and independent claim 118), with exception that claim 134 does not recite that the assay unit further comprises a reaction site having thereon an immobilized binding reagent, and that the assay unit is engaged with the automated fluid transfer device such that the detection assembly is configured to detect the signal withing the assay unit.
Thus, while Kumar (US 5,976,896), does not disclose or suggest in one embodiment wells or containers (equivalent to sample or reagent units) that move to the capillary tubes (equivalent to assay units) and a detector that is arranged proximate to the assay unit to detect a signal within the assay unit when the assay unit is engaged with the automated fluid transfer device, Applicant’s claim 134 (unlike claims 109 and 118) also does not recite that the assay unit further comprises a reaction site having thereon an immobilized binding reagent, and that the assay unit is engaged with the automated fluid transfer device such that the detection assembly is configured to detect the signal withing the assay unit. Thus, the limitations of Applicant’s claim 134 are met by Kumar, for the reasons set forth above.
Response to Arguments
Applicant’s amendment have overcome the rejection under 35 USC 112 in the last Office action. However, newly added claim 134 is rejected under Kumar, as mentioned above.
Allowable Subject Matter
Claims 109-115, 117-120, and 125-133 are allowed.
The following is an examiner’s statement of reasons for allowance.
Regarding independent claims 109 and 118, it was not found in the prior art search a teaching or suggestion for a system comprising:
the combination of a cartridge comprising wells (i.e., a sample well and reagent well); an assay unit comprising immobilized binding reagent, wherein the cartridge is movable independent of the assay unit;
a translational stage configured to move the cartridge relative to the assay unit to place the sample well into fluid communication with the assay unit, and to place the reagent well into fluid communication with the assay unit;
an automated fluid transfer device configured to engage the enlarged second end of the assay unit and to direct transfer of the sample from the sample well and the reagent from the reagent well into the assay unit
such that a reaction occurs within the assay unit that yields a signal indicative of a presence of the analyte;
and a detection assembly arranged proximate to the assay unit when the assay unit is engaged with the automated fluid transfer device such that the detection assembly is configured to detect the signal within the assay unit.
Examiner notes that the previously cited reference, Kumar (US 5,976,896), does not disclose or suggest in one embodiment wells or containers (equivalent to sample or reagent units) that move to the capillary tubes (equivalent to assay units) nor a detector that is arranged proximate to the assay unit to detect a signal within the assay unit when the assay unit is engaged with the automated fluid transfer device.
For example, the embodiment in Kumar in column 35, line 66 to column 36, line 16, does not have wells or sample tray that move to the capillaries (assay unit). Kumar discloses that the capillary tubes are provided in a circular manner around a cylinder and rotated to present a particular tube to a sample source or to a fluid source for washing or adding reagent, and the cylinder can also rotate to present a capillary tube to a signal generation and detection means. “Alternatively, the cylinder can cooperate with a multiwelled circular sample tray for serial or simultaneous sample removal and/or washing and expelling of fluid and even multiple signal generation and detection means. The circularly spaced apart capillary tubes can encircle a central syringe that is in fluid communication with the capillary tubes and draws fluid into the capillary tubes and/or advances fluid from the capillary tubes into any chambers and/or reaction sites on the surface of the capillary tubes.” (Kumar, in col. 35, line 66 to col. 36, line 16). Thus there is no teaching or suggestion in this embodiment for moving the wells or reagent/sample containers to the capillary tubes in Kumar.
In the embodiment in column 32, lines 20-46 wherein the sample tray (equivalent to Applicant’s cartridge with sample or reagent units) are moved to the cartridge of capillaries, the detector is not arranged to detect a signal within the assay unit when the assay unit is engaged with the fluid transfer device, since the syringe (210) (equivalent to a fluid transfer device) is provided at a separate location from the detection station (203) (see fig. 13, for example.)
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Ann Montgomery whose telephone number is (571)272-0894. The examiner can normally be reached Mon-Fri, 9-5:30 PM PST.
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/Ann Montgomery/Primary Examiner, Art Unit 1678
