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 .
Status of the Claims
Claims 3, 6, 8-9, 11-15, 18, 20-22, 24-28, and 51 are pending in the application.
Claims 12-15, 18, 20, 24-28 are withdrawn.
Claims 3, 6, 8-9, 11, 21-22, and 51 are the subject of this office action.
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.
Claims 3, 6, 8-9, 21-22 are rejected under 35 U.S.C. 103 as being unpatentable over Anteo Diagnostics Limited (AU 2016100182 A4, IDS entered), hereinafter Anteo, in view of Hornes et al (US 2010/0006509 A1).
Regarding claims 3 and 6, Anteo teaches a method for removing an interference from a biological sample (Pg. 2, Ln. 22-27: a method to remove or decrease interference in an analyte. In some embodiments, the analyte is a bodily fluid or biological sample), the method comprising:
Combining the sample with a lyophilized particle, said particle being from 0.050 micrometers to 3 micrometers in diameter, comprising a capture moiety that binds the interference to provide a mixture (Pg. 3: invention comprises an apparatus for use in removing or decreasing interference in an analyte. The apparatus may be a magnetic bead which comprises an immobilized member of a binding pair, wherein the member of the binding pair is an antibody, antigen, Fab, SdAb, immunoglobulin, etc. that specifically binds the interfering substance; Pg. 14-15: “Uniform size, 1.0 to 3.0 micron, paramagnetic microparticles, functionalized with Mix&GoTM and coated with HAAA and/or MASI specific blocker(s)…This approach is the addition, mixing, and removal of the magnetic particles can easily be automated…With magnets to pull the magnetic beads to the sides of the sample tube as only the targeted interference will be captured and bound (sequestered) to the sample tube’s wall via the magnetic particles and magnets, while the supernatant in the sample tube will now be depleted and free of such interreference as well as depleted and free of the magnetic particles which could interfere in the assay if still present in the sample.”; Pg. 15, Ln. 27:, “magnetic beads dried/lyophilized in the primary sample tube”; Pg. 14, Ln. 6: uniform size 1.0 to 3.0 micron paramagnetic particles);
wherein the capture moiety is mouse IgG, sheep IgG, goat IgG, rabbit IgG, cow IgG, pig IgG or horse IgG (Pg. 18, Ln. 3-5: beads used in the method may be mouse IgG beads, goat IgG beads, sheep IgG beads, etc);
Mixing the mixture to provide particle complexes to the interference (Pg. 19, Ln. 8-10: Mix&Go Secondary tube + Mix&Go beads pretreatment- sample is transferred (aspirated and dispensed) into the Mix&Go specific secondary tube, and Mix&Go bead(s) are added to the sample, mixed, and removed with magnet”); and
Removing or eliminating the particle complexes to provide a depleted solution, thereby decreasing or reducing the amount of the interference (Pg. 14-15:, “Uniform size, 1.0 to 3.0 micron, paramagnetic microparticles, functionalized with Mix&GoTM and coated with HAAA and/or MASI specific blocker(s)…This approach is the addition, mixing, and removal of the magnetic particles can easily be automated…With magnets to pull the magnetic beads to the sides of the sample tube as only the targeted interference will be captured and bound (sequestered) to the sample tube’s wall via the magnetic particles and magnets, while the supernatant in the sample tube will now be depleted and free of such interreference as well as depleted and free of the magnetic particles which could interfere in the assay if still present in the sample”); and
Anteo further teaches the method as a process of creating a depleted sample for providing increased accuracy in downstream diagnostic testing (Pg. 16, Ln. 8-14: The Anteo Mix&GoTM technology can be used to prepare functionalized sample tubes, as well as paramagnetic particles for subsequent binding of functionally active blocking reagents for sample pre-treatment to mitigate, remove, and/or eliminate heterophiles and/or manufacture assay-specific interferences from patient specimens prior to testing these specimens on a given analyzer; Pg. 11, Ln. 1-6: the serum depletion approach can be used to develop new solid phase extraction products to support the LC-MS/MS diagnostic market for simple, inexpensive, and automatable serum depletion of target analytes for subsequent elution and analysis by LC-MS/MS, as well as the molecular diagnostics market for sample preanalytical processing and nucleic acid purification and concentration for accurate, reproducible, clinically relevant molecular diagnostics for precision medicine).
Although Anteo does not explicitly recite the step of subjecting the depleted solution to a diagnostic test, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Anteo to include a step of subjecting the depleted solution to diagnostic testing, because preparation of depleted samples for improved performance in diagnostic testing is an explicitly stated purpose of the method of Anteo, and one of ordinary skill in the art would be motivated to remove interferences using the method of Anteo for the purpose of improving the accuracy of downstream diagnostic testing. One of ordinary skill in the art would have a reasonable expectation of success in making this modification because Anteo explicitly teaches that sample depletion can be performed to prepare a sample for downstream diagnostic testing.
Regarding claims 3, 6, and 8-9 Anteo further teaches that the at least 90% of the interference is removed (claims 3 and 6); that a sufficient amount of interference is removed to provide less than 100 ppm interference in the biological sample (claim 8); and that a sufficient amount of interference is removed to provide a less than detectable amount of the interference in a diagnostic test (claim 9) (Pg. 14 Ln. 1-Pg. 15, Ln. 2: The approach requires magnetic particles with excellent magnetic susceptibility and size uniformity for 100% removal after addition, and good colloidal stability (slow settling rate) to maximize binding kinetics and minimize incubation time needed. Magnets are used to restrain the magnetic beads which have bound to the interference, such that only the targeted interference will be captured by the magnetic sequestration of the magnetic beads, while the supernatant in the sample tube will now be depleted and free of such interference as well as depleted and free of the magnetic particles which could interfere in the assay if still present in the sample), wherein the teaching that the sample is free of interference requires that enough of the interference is removed to meet the limitations of claims 3, 6, 8, and 9.
Additionally, Anteo is understood to meet these limitations because they are understood to be a result of the recited active method steps and reagents of the instant claim. That is, because Anteo teaches the same reagents and the same steps as the instantly claimed method, it is assumed herein to achieve the same claimed results.
Regarding claims 3 and 21-22, Anteo teaches the method of claim 3, and further teaches the method wherein the removing or eliminating is a separation (Pg. 3, Ln. 7-23: the apparatus is exposed to the analyte, and when the apparatus is separated from the analyte, one or more interfering substances are removed from the analyte without adulterating the analyte or changing its form). Anteo further teaches the method wherein the separation comprises physical separation such as magnetic separation, and wherein the magnetic separation uses a strong magnet to provide a pellet and a supernatant (Pg. 14-15:, “Uniform size, 1.0 to 3.0 micron, paramagnetic microparticles, functionalized with Mix&GoTM and coated with HAAA and/or MASI specific blocker(s)…This approach is the addition, mixing, and removal of the magnetic particles can easily be automated…With magnets to pull the magnetic beads to the sides of the sample tube as only the targeted interference will be captured and bound (sequestered) to the sample tube’s wall via the magnetic particles and magnets, while the supernatant in the sample tube will now be depleted and free of such interreference as well as depleted and free of the magnetic particles which could interfere in the assay if still present in the sample”). The disclosure of Anteo is understood to read on the instantly claimed pellet and supernatant insofar as the solid particles which have captured the interference are understood to read on pellets which are separated from the supernatant in the sample tube.
Anteo does not specifically teach the method wherein the magnet is a magnet within a disposable pipette tip cover or sheath.
Regarding claims 3 and 6, Hornes teaches a magnetic separation device provided for separating magnetic particles from a liquid in which they are suspended (Abstract). Hornes teaches that the magnetic separation device may comprise a pipette tip and a magnet within the pipette tip, wherein the magnet is removable from the pipette tip or capable of being deactivated (Abstract; Par. 63-64: the pipette tip comprises a tube 36 having an opening 40 in the downward facing end. A plurality of magnetizable sphere 37 are provided within tube 36 and form a uniform matrix. The magnetizable spheres 37 are magnetized as desired by magnet 38. A suction device in the pipette or liquid handling apparatus will draw in and expel liquid from the pipette tip through the opening 40. Magnetic beads suspended in the liquid will be retained by magnetizable spheres 37; Par. 55, 23, 33, 40, 42). The pipette tip of Hornes is understood to be disposable in so far as it may be thrown away (i.e. disposed of).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the invention of Anteo to use the pipette tips for magnetic separation as taught by Hornes (which comprise a magnet within the pipette tip which is capable of being deactivated) for the magnetic separation. One would be motivated to make this modification because the magnetic separation pipette tips taught by Hornes allow for liquid handling and isolation of magnetic particles in a single step within a single pipette tip, allowing for efficient and effective separation of magnetic particles from supernatant. Use of the pipette tips provides the advantage of allowing a user to easily manipulate or physically remove the magnetic particles from the sample solution. Further, Hornes teaches that the matrix of magnetizable particles within the pipette tip is advantageous because it allows for application of a stronger magnetic field inside the pipette tip as compare to the use of external magnets, thereby allowing and ensuring separation of magnetic particles even when the particles are smaller and more weakly magnetic. One of ordinary skill in the art would have a reasonable expectation of success in making this modification because both Anteo and Hornes disclose means of isolating magnetic particles from a liquid.
Regarding claim 51, Anteo differs from the instant claim in that it does not teach the method wherein the particle is from 0.200 micrometers to 0.600 micrometers in diameter. Anteo does teach that advantageous features for separating magnetic particles from a solution include magnetic susceptibility, size uniformity, and good colloidal stability (slow settling rate) to maximize binding kinetics (Pg. 14, Ln. 23-26).
Hornes teaches a magnetic separation device for separating magnetic particle from a liquid in which they are suspended (Abstract). Hornes teaches that the disclosed magnetic separation device is advantageous in allowing for separation of smaller and more weakly magnetic particles from a solution (Par. 13), and teaches that the use of smaller particles, such as those with a diameter of less than 1 micron is preferable and advantageous in separating a target substance from a liquid solution (Par. 13, 16, 18: smaller beads have a larger relative surface are and therefore provide a more efficient binding of the target substance because a greater amount of the substance can be bound per gram of the particles. Furthermore, smaller particles stay in solution longer).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Anteo to use smaller diameter particles (i.e. particles of less than 1 micron in diameter, which overlaps the instantly claimed range of 0.200 to 0.600 microns) as taught by Hornes. One would be motivated to make this modification because Hornes teaches that smaller particles have an advantageous surface area to volume ratio which allows for more efficient binding of the target substance, and further teaches that smaller particles stay in solution longer (i.e. have a slower settling time) which Anteo teaches is desirable for maximizing binding kinetics. One of ordinary skill in the art would have a reasonable expectation of success in making this modification because Anteo and Hornes are both directed to methods of separating magnetic particles from a liquid solution.
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Anteo Diagnostics Limited (AU 2016100182 A4, IDS entered), hereinafter Anteo, in view of Hornes et al (US 2010/0006509 A1), as applied to claim 3 above, and further in view of Gorman et al (WO 91/06559; previously cited).
Regarding claim 11, Anteo in view of Hornes teaches the method of claim 3, as described above. Anteo teaches that the capture moiety may be IgG, but does not specifically teach that the capture moiety is any of the species recited in claim 11.
Regarding claim 11, Gorman teaches a method of reducing false positive results in an immunoassay using polymerized IgG to overcome non-specific binding (Abstract). Gorman teaches that the polymerized IgG can be useful and advantageous in reducing false positive results by limiting nonspecific binding caused by a variety of interferences (RF, heterophilic antibodies, etc.) (Pg. 4, Ln. 16-19; Pg. 5, Ln. 17-20; Pg. 12-13, Example III.2).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Anteo in view of Hornes such that the capture moiety comprises polymerized IgG as taught by Gorman. Though Anteo does not specifically teach the use of polymerized IgG, one of ordinary skill in the art would be motivated to use polymerized IgG because Gorman teaches that the polymerized IgG is effective in removing interferences and reducing false positive results, and can be advantageous over prior art methods employing monomeric IgG (Table 2). One of ordinary skill in the art would have a reasonable expectation of success in making this modification because both Anteo and Gorman teach methods of reducing false positive results in an immunoassay by removing an interference, and both Anteo and Gorman teach that IgG may be used as a capture moiety in this context.
Response to Arguments
Applicant’s arguments filed 2 August 2026 have been fully considered.
Applicant’s arguments regarding the previous 103 rejection are persuasive in view of the amendments to the claims, wherein OPS Diagnostics does not teach the amended limitation that the magnet is removable from the disposable pipette tip, cover, or sheath, or capable of being deactivated. The previous 103 rejections are withdrawn, and new 103 rejections which address the amended claims are presented above.
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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/ELLIS FOLLETT LUSI/Examiner, Art Unit 1677
/CHRISTOPHER L CHIN/Primary Examiner, Art Unit 1677
