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 .
DETAILED ACTION
Election/Restrictions
1. Applicant's election of Species A: immunopurification or affinity purification and Species B: ion exchange, without traverse, filed April 14, 2026 is acknowledged and has been entered. Upon further consideration, all the species have been rejoined for prosecution on the merits. Accordingly, claims 1, 9, 10, 12, 15-17, 23, 28, 30, 31, 33, and 35-42 are pending and are under examination.
Priority
2. Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. This application is a 371 National Stage application of PCT/IB2022/052566 filed 03/21/2022, which claims the benefit of Provisional Application Number 63/164,870 filed 03/23/2021. Based on the filing receipt, the effective filing date of this application is March 23, 2021 which is the filing date of Provisional Application Number 63/164,870 from which the benefit of domestic priority is claimed.
Drawings
3. The drawings are objected to because many of the text in Figures 1A to E are indecipherable. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
4. 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, requires the specification to be written in “full, clear, concise, and exact terms.” The specification is replete with grammatical errors and terms which are not clear, concise and exact. The specification should be revised carefully in order to comply with 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112. An example of some unclear, inexact or verbose terms used in the specification is in paragraph [0002]: “resulting in complexes that may prove challeding the analyze directly.”
5. The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code in paragraph [0052]. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Objections
6. Claim 37 is objected to in reciting “The hydrolysis enzyme is 3- glucuronidase, trypsin, chymotrypsin, a protease, LysC, LysN, AspN, GluC, ArgC, pronase, pepsin, prolidase.” It should recite “The hydrolysis enzyme is 3- glucuronidase, trypsin, chymotrypsin, a protease, LysC, LysN, AspN, GluC, ArgC, pronase, pepsin, or prolidase.” Appropriate correction is required.
7 Claim 38 is objected to in reciting “the hydrolysis enzyme is capable of hydrolyzing glycosidic linkages or glycosidic linkages of a glucuronide.’ It should recite “the hydrolysis enzyme is capable of hydrolyzing glycosidic linkages of a glucuronide.’
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.
8. Claims 1, 9, 10, 12, 15-17, 23, 28, 30, 31, 33, and 35-42 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.
Claim 1 is vague and indefinite in reciting, “treating the liquid sample with a hydrolysis enzyme” and “hydrolyzing the liquid sample to prepare a hydrolysate” because it is unclear how the “hydrolyzing” step is distinct from the “treating” step since the treating step with the hydrolysis enzyme appears to have already contacted or exposed the enzyme with the liquid sample to cause hydrolysis.
Claim 1 is further ambiguous in reciting “liquid sample” in all its occurrences in the claim because it is unclear what is encompassed in the recitation of “liquid sample” in a manner that is prepared by treatment with a hydrolysis enzyme, since liquid samples encompass marine samples, tap water samples, or intravenous fluid samples. Paragraph [0032] provides that the “liquid sample may be a biological sample” in an exemplary statement and lists what is encompassed in “biological sample” which may be “biological fluids” such as ”blood, plasma, serum, oral fluid, or other bodily fluids or excretions….” Perhaps, Applicant intends “a biological fluid” as set forth in paragraph [0032]. See also claim 31.
Claim 1 is confusing in reciting, “purifying the hydrolysate with magnetic based purification” because it is unclear what components are being purified (i.e. isolated) within the resultant hydrolysate using the magnetic beads having bound thereto, the hydrolysis enzyme. Claim 1 appears to imply that the “purifying” step intends that a magnetic field is applied to the treated liquid sample so that the hydrolysis enzyme capable of hydrolyzing glycosidic linkages that is bound to the magnetic beads is simply separated from the sample; thereby, producing the hydrolysate which may contain products (carbohydrates) that may have been produced as a result of hydrolysis of glycosidic linkages. However, claim 1 fails to clearly define what is encompassed in this “magnetic-based purification” in a manner that “purifies” the hydrolysate resulting from the liquid sample in the claimed method and what component in the liquid sample mixture is being purified. See also claim 9.
Claim 9 is confusing, especially relative to claim 1 from which it depends, in reciting “the magnetic-based purification is based on … ion-exchange” because it is unclear, as recited, how “ion-exchange” can be performed on the basis of magnetic bead-based purification. See also claim 12.
Claim 10 is vague and indefinite in reciting “The magnetic particle comprises a monoclonal antibody, a polyclonal antibody, …” because it is unclear how the monoclonal antibody or polyclonal antibody should be comprised in the magnetic particles specifically having bound thereto the hydrolysis enzyme. Should the monoclonal antibody, polyclonal antibody, or aptamer, etc. be bound as well, and coated or immobilized directly on the surface of the magnetic particle alongside the hydrolysis enzyme?
Claim 10 is further confusing, especially relative to claim 1 from which it ultimately depends, in reciting “The magnetic particle comprises a monoclonal antibody, a polyclonal antibody, … or peptides that bind to specific targets with high affinity” because it is unclear what essential structural and/or functional cooperative relationships exist between these recited antibodies and peptides and the specific targets to which they bind with high affinity in the instant claim, and the hydrolysis enzyme and glycosidic linkages recited in claim 1.
Claim 10 is indefinite in reciting, “DARPins”. Acronyms or abbreviations should be fully defined and recited at least one time in a given set of claims.
Claim 35 is vague and indefinite in reciting, “treating the liquid sample with a hydrolysis enzyme” and “hydrolyzing the liquid sample to prepare a hydrolysate” because it is unclear how the “hydrolyzing” step is distinct from the “treating” step since the treating step with the hydrolysis enzyme appears to have already contacted or exposed the enzyme with the liquid sample to cause hydrolysis.
Claim 35 is further ambiguous in reciting “liquid sample” in all its occurrences in the claim because it is unclear what is encompassed in the recitation of “liquid sample” in a manner that is prepared by treatment with a hydrolysis enzyme, since liquid samples encompass marine samples, tap water samples, or intravenous fluid samples. Paragraph [0032] provides that the “liquid sample may be a biological sample” in an exemplary statement and lists what is encompassed in “biological sample” which may be “biological fluids” such as ”blood, plasma, serum, oral fluid, or other bodily fluids or excretions….” Perhaps, Applicant intends “a biological fluid” as set forth in paragraph [0032].
Claim 35 is indefinite in reciting, “purifying the hydrolysate with magnetic based purification to produce a hydrolysate” because it is unclear how “magnetic based purification” is performed absent magnetic beads. Claim 35 is further unclear as to what components are being purified (i.e. isolated) within the resultant hydrolysate and how they are being purified, as claimed. Claim 35 appears to imply that the “purifying” step intends that a magnetic field is applied to the treated liquid sample so that the hydrolysis enzyme is simply separated from the sample; thereby, producing the supernatant which may contain products (carbohydrates) that may have been produced as a result of hydrolysis. However, claim 35 fails to clearly define what is encompassed in this “magnetic-based purification” in a manner that “purifies” the hydrolysate resulting from the liquid sample in the claimed method and what component in the liquid sample mixture is being purified. See also claims 40 and 42.
Claim 40 lacks clear antecedent basis in reciting “proteins … in the hydrolysate.”
Claim 40 lacks clear antecedent basis in reciting “magnetic beads or magnetic particles….”
Claim 40 is further confusing, especially relative to claim 35 from which it depends, in reciting “precipitating proteins … in the hydrolysate” because it is unclear what these proteins are and what essential structural and/or functional cooperative relationships exist between these proteins and the “liquid sample” and the “hydrolysis enzyme” in recited in claim 35.
Claim 42 is vague and indefinite in reciting “the magnetic beads or magnetic particles comprise a monoclonal antibody, a polyclonal antibody, …” because it is unclear how the monoclonal antibody or polyclonal antibody should be comprised in the magnetic particles specifically having bound thereto the hydrolysis enzyme recited in claim 36 and claim 35 from which the instant claim ultimately depends. Should the monoclonal antibody, polyclonal antibody, or aptamer, etc. be bound as well, and coated or immobilized directly on the surface of the magnetic particle alongside the hydrolysis enzyme?
Claim 42 is further confusing, especially relative to claim 35 from which it depends, in reciting “the magnetic beads or magnetic particles comprise a monoclonal antibody, a polyclonal antibody, … or peptides that bind to specific targets with high affinity” because it is unclear what essential structural and/or functional cooperative relationships exist between these recited antibodies and peptides and the specific targets to which they bind with high affinity in the instant claim, and the glycosidic linkages and glucuronide recited in claim 38, and the hydrolysis enzyme in claim 35.
Claim 42 is indefinite in reciting, “DARPins”. Acronyms or abbreviations should be fully defined and recited at least one time in a given set of claims.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
9. Claims 1, 9, 15-17, 23, 28, 30, 31, 33, and 35-39 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 10-12, 14, 17, 18, and 20-25 of copending Application No. 18/562,090 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because both inventions recite a method of preparing a liquid sample, comprising: treating the liquid sample with a hydrolysis enzyme, wherein the hydrolysis enzyme is beta glucuronidase capable of hydrolyzing glycosidic linkages of a glucuronide and wherein the hydrolysis enzyme is bound to a magnetic bead or a magnetic particle; hydrolyzing the liquid sample to prepare a hydrolysate, the hydrolysis enzyme hydrolyzing codeine-6-glucuronide linkages and morphine-6-glucuronide linkages, and purifying the hydrolysate with magnetic based purification. The method is used to prepare a liquid sample for clinical analysis, wherein the clinical analysis is used to screen for drugs of abuse such as opioids or opiates (codeine, morphine). The magnetic based purification is based on immunopurification, affinity purification, or ion-exchange.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
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 th0e 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.
10. Claims 1, 9, 10, 15-17, 23, 28, 30, 31, 33, and 35-39 are rejected under 35 U.S.C. 103 as being unpatentable over Miao et al. (Liquid-chromatographic and mass-spectrometric identification of lens proteins using microwave-assisted digestion with trypsin-immobilized magnetic nanoparticles. Biochemical and Biophysical Research Communications 380: 603-608 (2009) IDS) in view of Lakshmi Narayanan et al. (US 2016/0231341) and Correa et al. (Stabilization of b-Glucuronidase by Immobilization in Magnetic-Silica Hybrid Supports. Catalysis 10 (6): 669 (13 June 2020) IDS).
Miao et al. teach preparing a liquid sample for by treating the liquid sample (lens solution) with a hydrolysis enzyme bound (immobilized) to a magnetic bead or particle (magnetic nanoparticle: TIMNs); wherein the hydrolysis enzyme is trypsin (Abstract; p. 603, left & right cols.; p. 605, left & right cols.: Immobilization of trypsin on magnetic nanoparticles). Miao et al. teach hydrolyzing (digesting) proteins into denatured and reduced digestion products in the liquid sample to prepare a hydrolysate (supernatant) and the magnetic beads were held with a magnet; thus, separating and purifying the hydrolysate by magnetic based purification. The hydrolysate or supernatant was injected (deposited) into matrix-assisted laser desorption/ionization (MALDI) plate (ionization source) and the digested products were identified using liquid chromatography and mass spectrometry (LC-MS). Miao et al. teach that the magnetic bead surface is coated and functionalized with polyethylenimine (PEI: silica) (Abstract; pp. 605-606).
Miao et al. differ from the instant invention in failing to teach that the hydrolysis enzyme is capable of hydrolyzing glycosidic linkages.
Lakshmi Narayanan et al. disclose a method for determining multiple drug abuse substances (Abstract). Lakshmi Narayanan et al. teach hydrolyzing the drug metabolites with a hydrolysis enzyme capable of hydrolyzing glycosidic linkages; wherein the hydrolysis enzyme is beta- glucuronidase which hydrolyzes glycosidic linkages of a glucuronide. Lakshmi Narayanan et al. teach that the liquid sample may contain glucuronide: codeine-6-glucuronide or morphine-6-glucuronide [0026-0029, 0049] and the liquid sample is screened for clinical analysis of drugs of abuse including opioid or opiates (narcotics) [0029, 0032]. After centrifugation, the supernatant portion of the sample is injected into liquid chromatography tandem mass spectrometer (LC-MS-MS) or matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) MS analysis to determine the concentration of the drug metabolites [0032, 0049, 0050].
Although glucuronidase enzyme as taught by Lakshmi Narayanan et al. is not bound to a magnetic particle; Correa et al. teach that beta glucuronidase can be stabilized by immobilization into magnetic-silica particles (Abstract). Correa et al. teach that integration and immobilization of beta glucuronidase enzyme into the magnetic-silica particles provided advantage in allowing reuse of the catalyst via magnetic separation while maintaining residual activity (Abstract).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to substitute the magnetic bead bound hydrolysis enzyme trypsin of Miao with beta glucuronidase as taught Lakshmi Narayanan that is immobilized on magnetic beads as taught by Correa because beta glucuronidase enzyme hydrolyzes glycosidic linkages of codeine-6-glucuronide or morphine-6-glucuronide to prepare liquid biological samples into a hydrolysate for clinical analysis of drugs of abuse using LC-MS. One of ordinary skill would have had reasonable expectation of success in combining the teaching of Lakshmi Narayanan and Correa into the method of Miao because all of Miao, Lakshmi Narayanan, and Correa teach analogous art in preparing samples for LC-MS analysis.
11. Claims 12 and 42 are rejected under 35 U.S.C. 103 as being unpatentable over Miao et al. (Biochemical and Biophysical Research Communications 380: 603-608 (2009) IDS) in view of Lakshmi Narayanan et al. (US 2016/0231341) and Correa et al. (Catalysis 10 (6): 669 (13 June 2020) IDS) as applied to claims 9 and 35, and in further view of Pont et al (Comparison of magnetic bead surface functionalities for the immunopurification for growth hormone-releasing hormones prior to liquid chromatography-high resolution mass spectrometry. Journal of Chromatography A. Vol. 1631 (17 September 2020)).
Miao et al., Lakshmi Narayanan et al., and Correa et al. are discussed supra. Miao et al., Lakshmi Narayanan et al., and Correa et al. differ from the instant invention in failing to teach immobilizing affinity antibodies and peptide into the magnetic particles.
Pont et al. teach a method for preparing a biological liquid sample for use in clinical analysis and for screening the presence of drugs (sermorelin, tesamorelin, CJC-1295) in the biological liquid sample (Abstract). Pont et al teach using functionalized immunopurification-based magnetic particles to extract drug substances by magnetic field separation for further analysis of the remaining supernatant for drug metabolites by LC-MS (Abstract). The magnetic particles are coated with antibody or peptides that bind to specific targets with high affinity for immunopurification of the biological liquid sample (pp 1-3; p. 4, right col.: 3.1.2 Immunopurification with magnetic beads).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to coat the magnetic beads of Miao and Correa with affinity antibodies as taught by Pont because it enables selective immunopurification of biological samples to prepare liquid samples for further analysis using LC-MS. One of ordinary skill would have had reasonable expectation of success in combining the teaching of Pont into the method of Miao and Correa as modified by Lakshmi Narayanan because all of Miao, Lakshmi Narayanan, Correa, and Pont teach analogous art in preparing samples for LC-MS analysis.
Prior Art
12. Claims 40-41 are free of the prior art of record.
13. No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GAILENE R. GABEL whose telephone number is (571)272-0820. The examiner can normally be reached Monday, Tuesday, and Thursday 5:30 AM to 4:00 PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Gregory S. Emch can be reached at (571) 272-8149. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/GAILENE GABEL/Primary Examiner, Art Unit 1678
May 30, 2026
Prosecution Insights