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 .
NON-FINAL ACTION
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 9/25/25 has been entered.
Amendment Entry
2. Applicant’s response to the Office Action dated 3/26/25 is acknowledged (reply filed 9/25/25). In the amendment filed therein claims 30, 33, 35, 37, 38, and 39 were modified. While new claims 50-59 were added. Claims 1-29, 34, 36, and 42-49 were previously canceled without prejudice or disclaimer.
3. Currently, claims 30-33, 35, 37-41, and 50-59 are pending and under consideration.
4. Rejections and/or objections of record not reiterated herein have been withdrawn.
Priority
5. This application claims priority, through a series of applications, to provisional application number 62/435,409- filed December 16, 2016.
Terminal Disclaimer
6. The terminal disclaimer filed on 7/6/24 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of US Patent No. 10,866,242 has been reviewed and is accepted. The terminal disclaimer has been recorded.
NEW GROUNDS OF REJECTIONS NECSSITATED BY AMENDMENTS
Claim Rejections - 35 USC § 112
7. 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 30-33, 35, 37-41, and 50-59 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.
A. The term “exceeding a dynamic range detectable by a mass spectrometer” in claim 30 is a relative term which renders the claim indefinite. The term “exceeding” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is not clear how the parameter is going to be assessed because the mass spectrometer for comparison reads on an plethora of instruments with no configured boundaries for measurement.
In other words the instrument employed for mass spectrometry in the method is unclear. Therein making the “exceeding a dynamic range” ambiguous. It is suggested that the actual detection parameter is included in order to obviate the rejection.
9. Claim limitation “mass spectrometer used for performing liquid chromatography-tandem mass spectrometry” invokes 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. See claim 30 step c. However, the written description fails to disclose the corresponding structure, material, or acts for performing the entire claimed function and to clearly link the structure, material, or acts to the function. Claims 30-33, 35, 37-41, and 50-59 are directed to measuring concentration that exceeds a dynamic range measurable by a mass spectrometer utilized in the assay. This wording does not set forth a measurable detection parameter. The actual instrument that is employed is not recited. The actual detection units or range is not provided. As such the comparison for observation (exceeding what range?) is unclear. Therefore, the claim is indefinite and is rejected under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph.
Applicant may:
(a) Amend the claim so that the claim limitation will no longer be interpreted as a limitation under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph;
(b) Amend the written description of the specification such that it expressly recites what structure, material, or acts perform the entire claimed function, without introducing any new matter (35 U.S.C. 132(a)); or
(c) Amend the written description of the specification such that it clearly links the structure, material, or acts disclosed therein to the function recited in the claim, without introducing any new matter (35 U.S.C. 132(a)).
If applicant is of the opinion that the written description of the specification already implicitly or inherently discloses the corresponding structure, material, or acts and clearly links them to the function so that one of ordinary skill in the art would recognize what structure, material, or acts perform the claimed function, applicant should clarify the record by either:
(a) Amending the written description of the specification such that it expressly recites the corresponding structure, material, or acts for performing the claimed function and clearly links or associates the structure, material, or acts to the claimed function, without introducing any new matter (35 U.S.C. 132(a)); or
(b) Stating on the record what the corresponding structure, material, or acts, which are implicitly or inherently set forth in the written description of the specification, perform the claimed function. For more information, see 37 CFR 1.75(d) and MPEP §§ 608.01(o) and 2181.
Please Note: The ODP rejection of claims 30-33, 35, 37-41, and 50-59 over US Patent No. 12,000,827 in view of US Patent No. 11,435,360 is made because the safe harbor provision of 35 U.S.C. § 121 against double patenting does not apply in this case because the instantly presented claims were not restricted or presented in the cited patents.
Double Patenting
10. 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.
11. Claims 30-33, 35, 37, 41, 50, and 53-59 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 12,00827 in view of claims 1-29 of U.S. Patent No. 11,435,360 and further in view of Hajipour et al. (Biomater. Sci., 2014, 2, 1210-1221).
The claims in the instant method a directed in part to determining a biological state in a mammalian subject by assaying a biological sample obtained from the mammalian subject, comprising: (a) incubating a plurality of sensor elements in a sample volume of the biological sample, wherein the plurality of sensor elements comprises different physicochemical properties to adsorb a plurality of biomolecules on respective surfaces of the plurality of sensor elements, wherein at least a first subset of the plurality of sensor elements differs from at least a second subset of the plurality of sensor elements based on a physicochemical property; (b) separating at least a portion of the plurality of biomolecules from the plurality of sensor elements to provide a plurality of separated biomolecules; and (c) performing mass spectrometry on the plurality of separated biomolecules to detect a plurality of separated detected biomolecules, wherein the detected biomolecules correspond to biomolecules present in the biological sample at concentrations across a dynamic range exceeding a dynamic range detectable by a mass spectrometer used for performing liquid chromatography-tandem mass spectrometry; and (d) determining the biological state in the mammalian subject based on the plurality of detected biomolecules.
Although the claims in U.S. Patent No. 12,000,827 and U.S. Patent No. 11,435,360 do not recited verbatim embodiments of the instantly claimed method, the methods are not patentably distinct from the claimed methods for the following reasons:
The method of claims 1-19 of U.S. Patent No. 12,000,827 are drawn to distinguishing states of complex biological samples utilizing a plurality of particles that differ by different physicochemical properties. Analyzing the binding pattern to produce a biomolecule fingerprint relating to the biological state of the subject.
For example, see claims 1 and 2. The method is performed by mass spectrometry – See claims 9 and 10. The biological state includes assessments of diseases such as cancer, See claims 11-14. While the claims do not specifically recite the measurement of a sample volume, the claims read on fluid samples that encompass volume measurements (blood, cell lysates, urine, tears, saliva, etc.) See claim 18.
U.S. Patent No. 12,000,827 differs from the instant invention in not including first and second subset particle analysis wherein the concentration is measured across a dynamic range exceeding a dynamic range detected by a mass spectrometer.
The claims in U.S. Patent No. 11,408,898 are directed to a method of assaying a biological sample with a plurality of different particle types. The particles are separated in subsets and analyzed across a dynamic range of at least 6 orders of magnitude. See claims 1, 4, 5, and 6. The particles differ by physiochemical properties. See claims 25 and 26. The method measures protein concentrations greater than 1mg/ml and less than 10ng/ml – Claim 2. And concentrations of 100ng/ml or less – Claim 6. Additionally, the method measures a dynamic range that exceeds the detection limit of the assay – Claim 5. The patent measures a sample volume in claim 18.
It would have been prima facie obvious to one of ordinary skill in the art at the effective filing date of the instant invention to include subset particles and measure proteins across a dynamic range as claimed in U.S. Patent No. 11,435,360 as a means for optimizing the method claimed in U.S. Patent No. 12,000,827. Automating a method to improve protein detection capabilities across a dynamic range is deemed obvious. Absent evidence to the contrary broadly claiming an automated means to replace a manual function to accomplish the same result does not distinguish over the prior art.
Furthermore, implementing a known function on a computer has been deemed obvious to one of ordinary skill in the art if the automation of the known function on a general purpose computer is nothing more than the predictable use of prior art elements according to their established functions. KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 417, 82 USPQ2d 1385, 1396 (2007).
The claims of U.S. Patent No. 11,435,360 in view of the claims in U.S. Patent No. 12,000,827 differ from the instant invention in not specifically reciting sensor elements.
However, Hajipour incubated two different nanoparticles (“NPs”) (polystyrene and silica — having surfaces with different physicochemical properties – sensor elements) with plasma from human subjects with different diseases and determined a pattern of binding proteins that varied in a “personalized protein corona’ (“PPC) manner correlated with the type of disease (abstract).
Hajipour teaches that “we found that changes in plasma protein concentrations and structures (mediated by different disease states) affect the formation of the protein corona on a NP” (p. 1219) or sensor elements.
Hajipour defines a biomolecule fingerprint representative of the proteins that bind to the NPs (sensor elements) and associates the fingerprint with the biological state — i.e. Fig. 2 SDS-PAGE of plasma proteins obtained from polystyrene and silica associated with breast cancer vs. healthy (the proteins are separated from the particles). Hajipour teaches identification of the proteins at 3.1.3 (page 1214) including albumin.
It would have been prima facie obvious to one of ordinary skill in the art at the effective filing date of the instant invention to include sensor elements as exemplified by Hajipour et al. in the claimed method of U.S. Patent No. 12,000,827 in view of U.S. Patent No. 11,435,360 because Hajipour et al. taught that that changes in plasma protein concentrations and structures (mediated by different disease states) affect the formation of the protein corona on a NP” (p. 1219) or sensor elements.
And these biomolecule fingerprints are representative of the proteins that bind to the NPs (sensor elements) and associated with the biological state — i.e. Fig. 2 SDS-PAGE of plasma proteins obtained from polystyrene and silica associated with breast cancer vs. healthy (the proteins are separated from the particles). One skilled in the art would have been motivated to analyze the sensors to evaluate diseases for identification and treatment.
One of ordinary skill in the art would have a reasonable expectation of success in combining the references and arriving at the claimed invention because the prior art references both relate to the application of protein corona analysis in biological systems. Therefore, claims 30, 31, 32, 40, and 41 are prima facie obvious.
The Supreme Court stated in KSR "if a technique has been used to improve one device, and a person of ordinary skill in the art would recognize that it would improve similar devices in the same way, using the technique is obvious unless its actual application is beyond that person's skill." KSR Intern. Co. v. Teleflex Inc., 127 S.Ct. 1727, 1731 (2007).
Because utilizing well-known mass spectrometry, NPs (sensor elements), and classification techniques is routinely used in methods similar to those claimed here, the application of the same technique would be obvious.
Regarding claim 30 – see claim 1 of US Patent No.12,000,827 and claim 1 of US Patent No. 11,435,360.
Regarding claim 31 – see claim 17 of US Patent No.12,000,827 and claim 12 of US Patent No. 11,435,360.
Regarding claim 32 – see claim 14 of US Patent No. 11,435,360.
Regarding claim 33 – see claim 11 of US Patent No. 11,435,360.
Regarding claim 35 – see claims 15 and 16 of US Patent No.12,000,827.
Regarding claim 37 – see claim 26 of US Patent No. 11,435,360.
Regarding claim 41 – see claim 1 of US Patent No.12,000,827 and claim 1 of US Patent No. 11,435,360.
Regarding claim 50 – see claim 3 of US Patent No. 11,435,360.
Regarding claim 53 – see claim 29 of US Patent No. 11,435,360.
Regarding claim 54 – see claim 10 of US Patent No. 11,435,360.
Regarding claim 55 – see claim 1 of US Patent No. 11,435,360.
Regarding claim 56 – see claim 18 of US Patent No. 11,435,360.
Regarding claim 57 – see claims 2 and 6 of US Patent No. 11,435,360.
Regarding claim 58 – see claim 18 of US Patent No.12,000,827 and claim 22 of US Patent No. 11,435,360.
Regarding claim 59 – see claims 11-13 of US Patent No.12,000,827.
Regarding claims 38-40 and 51-52, it would have been obvious to one of ordinary skill in the art at the effective filing date of the instant invention to optimize the particle sensors as taught in claims 1-19 of U.S. Patent No. 12,00827 in view of claims 1-29 of U.S. Patent No. 11,435,360 and further in view of Hajipour et al. (Biomater. Sci., 2014, 2, 1210-1221). Claims 38-40 and 51-52 are drawn to known particle types (claim 40 and 51-52) and coatings (claims 38-39) that were previously known in the prior art. Modifying the type and coating of the particles is routinely performed in the art to optimize the intended result. Therefore the claims are deemed obvious.
KSR forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness. See recent Board decision Ex parte Smith,— USPQ2d—, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007)(citing KSR, 82 USPQ2d at 1396).
Response to Argument
Applicant arguments have been carefully considered but are MOOT in light of the newly cited references.
13. For reasons aforementioned, no claims are allowed.
14. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LISA V COOK whose telephone number is (571)272-0816. The examiner works a flexible schedule but can normally be reached on Monday-Friday from 9am to 5pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis, can be reached at telephone number 571-270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Lisa V. Cook
Patent Examiner
Art Unit 1642
571-272-0816
11/1/25
/LISA V COOK/Primary Examiner, Art Unit 1642