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 .
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-3, 5-12, 14, 17-18, 20-23) in the reply filed on 6/15/26 is acknowledged.
Claims 24 and 25 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 6/15/26.
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.
Claim(s) 1-3, 5, 7, 9, 11, 14, 17, 18, 20 and 21 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hu et al., “The on-bead digestion of protein corona on nanoparticles by trypsin immobilized on the magnetic nanoparticle”, Journal of Chromatography A, vol. 1334, 5 February 2014, pp.55-63)
in view of US 20110251094 (hereinafter “Kas”).
Regarding Applicant’s claim 1, Hu discloses the claimed limitations as follows:
a method, comprising:
providing a sample reagent, the sample reagent comprising
a buffer,
and magnetic beads or magnetic particles
[see p. 56, section 2.4 disclosing Fe3O4 nanoparticles (i.e., magnetic beads) suspension in PBS (i.e., a buffer); see also p. 56, section 2.2 disclosing PBS buffer being used to preserve the Fe3O4 nanoparticles],
wherein a hydrolysis enzyme is conjugated to the magnetic beads or magnetic particles [see p. 56, section 2.2 disclosing immobilization of tryps (which is a hydrolysis enzyme) to the Fe3O4 nanoparticles],
incubating the sample reagent with a liquid sample to prepare a hydrolysate suspension [see p. 56, section 2.4 disclosing incubating BS (bovine serum; equivalent to the claimed liquid sample) with Fe3O4 nanoparticles suspension in PBS],
and purifying the hydrolysate suspension with magnetic based purification [see p. 56, section 2.4, disclosing the digested peptides of the BS protein corona on the nanoparticle were collected by removing the residual Fe3O4 nanoparticles as well as the magnetic immobilized trypsin by a magnetic].
Hu however is silent as to providing a internal standard with the sample reagent. Examiner notes however that Hu discloses that 173 BS proteins were identified from the protein on the Fe3O4 nanoparticles (p. 59, left col.) Mass spectrometry was used for the protein analysis [see p. 57, section 2.5, disclosing MS/MS analysis; see also p. 62, disclosing mass spectrometry (MS) for detection of proteins].
However use of an internal standard [such as a labeled agent in which the agent is the same type as the analyte] is well-known in the prior art for analysis such as mass spectrometry as a means for comparison for use such as in quantitation of the analyte. This is also exemplified by Kas (see paras. 0432-0437, disclosing use of a labeled internal standard in mass spectrometry to determine concentration of a peptide). Providing such an internal standard in the Hu invention would have required ordinary skills in the art as it uses a well-known technique in a familiar manner, as shown by Kas.
As to claim 2, which claims that the magnetic based purification comprises magnetically separating the magnetic beads or magnetic particles from the hydrolysate suspension to produce a supernatant, see Hu on page 56, section 2.4, disclosing the digested peptides of the BS protein corona on the nanoparticle were collected by removing the residual Fe3O4 nanoparticles as well as the magnetic immobilized trypsin by a magnetic.
As to claim 3 which claims that the liquid sample comprises a biological sample selected from the group consisting of urine, blood, oral fluid, and plasma, see Hu on page 57, section 2.5, disclosing analysis of protein corona of human plasma on Fe3O4 nanoparticles by the immobilized trypsin.
As to claim 5, which claims that the sample reagent is incubated with the liquid sample for at least about 5 minutes, Examiner notes that the incubation step has been discussed above regarding claim 1. Regarding incubation for at least about 5 minutes, this range falls within a workable or optimum range, and its discovery requires routine skills in the art, given the general disclosures of the claimed invention as taught by the prior art (as discussed above).
As to claim 7, it would have been understood by one skilled in the art that the internal standard is assay dependent [i.e., dependent on the analyte of choice; see discussion of claim 1 above.]
Claim 9 recites that the concentration of the at least one internal standard is between about 50 ng/mL to about 4800 ng/mL. This range falls within a workable or optimum range, and its discovery requires routine skills in the art, given the general disclosures of the claimed invention as taught by the prior art (as discussed above).
As to claim 11, the hydrolysis enzyme is trypsin (see discussion of claim 1 above regarding the Hu disclosure.)
As to claim 14, the magnetic separation discussed above regarding claim 1 is equivalent to the claimed solid phase extraction.
As to claims 17, 18, 20 and 21, these steps are well-known steps in mass spectrometry analysis, which are disclosed in general by Hu (see for example page 57, section 2.5 disclosing RPLC-MS/MS analysis; or page 62, left column, first 2 paras.) Use of well-known techniques in a familiar manner requires ordinary skills in the art and results in a predictable outcome, and thus would have been obvious.
Claim(s) 6 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hu et al., “The on-bead digestion of protein corona on nanoparticles by trypsin immobilized on the magnetic nanoparticle”, Journal of Chromatography A, vol. 1334, 5 February 2014, pp.55-63)
in view of US 20110251094 (hereinafter “Kas”),
and further in view of US 20110137002 (hereinafter “Hauer”).
Hu and Kas have been discussed above.
Applicant’s claim 6 recites that the magnetic beads or magnetic particles comprise streptavidin and the hydrolysis enzyme comprises biotin.
Hu and Kas are silent as to how the trypsin is immobilized to the particles/beads.
However using streptavidin and biotin to immobilize an agent onto a substrate is well-known in the art, and Hauer exemplifies this (see para. 0098 disclosing a noncovalent binding of the enzyme can be achieved by labeling the enzyme with biotin and immobilization on a support provided with avidin or streptavidin). Utilizing streptavidin and biotin to immobilize the trypsin to the beads in the modified Hu invention would have been obvious to one skilled in the art as it merely uses well-known immobilization techniques using well-known binding partners.
Claim(s) 8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hu et al., “The on-bead digestion of protein corona on nanoparticles by trypsin immobilized on the magnetic nanoparticle”, Journal of Chromatography A, vol. 1334, 5 February 2014, pp.55-63)
in view of US 20110251094 (hereinafter “Kas”),
and furter in view of US 20170189902 (hereinafter “Moran”).
Hu and Kas are silent as to the internal standard being codeine-d6.
However, one skilled in the art would have understood that the modified Hu invention can be used to detect various analytes as desired, including codeine-d6, which is a known substance (as shown by Moran, see para. 0083), and thus using codeine-d6 as the internal standard according to the modified Hu invention discussed above would have been obvious to one skilled in the art.
Claims 10 and 12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hu et al., “The on-bead digestion of protein corona on nanoparticles by trypsin immobilized on the magnetic nanoparticle”, Journal of Chromatography A, vol. 1334, 5 February 2014, pp.55-63),
in view of US 20110251094 (hereinafter “Kas”),
in view of US 20180067116 (hereinafter “Rozas”).
Regarding claims 10 and 12, Hu and Kas are silent as to hydrolyzing glycosidic linkages (claim 10), or hydrolyzing codeine-6-glucuronide (claim12).
However, Rozas teaches β-glucuronidase enzyme which hydrolyzes codeine-6-glucuronide (claim12) (see Rozas in para. 0052) as useful in mass spectrometry (para. 0017). Examiner notes that β-glucuronidase enzyme hydrolyzes glycosidic linkages (meeting claim 10).
Claim(s) 22 and 23 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hu et al., “The on-bead digestion of protein corona on nanoparticles by trypsin immobilized on the magnetic nanoparticle”, Journal of Chromatography A, vol. 1334, 5 February 2014, pp.55-63),
in view of US 20110251094 (hereinafter “Kas”),
in view of US 20160195502 (hereinafter “Mansani”).
As to claim 22, using clinical analysis to screen for drugs of abuse requires ordinary skills in the art given that it would have been predictable to utilize the modified Hu invention to analyze the analyte of choice, such as drugs to determine drug abuse. Mansani also exemplies this (see para. 0009).
As to claim 23, Mansani specifically gives an example of detecting amphetamines, including by mass spectrometry, to determine drug abuse (see para. 0009).
Conclusion
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/Ann Montgomery/Primary Examiner, Art Unit 1678
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