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
Applicant’s response and affidavit filed October 28, 2025 are acknowledged. Claims 1-28 are pending and further considered on the merits. In light of applicant’s response, the examiner maintains the grounds of rejection set forth in the office action filed May 2, 2025.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-3, 5, 7-10, 12-15, 17-20, 22-23, and 27-28 is/are rejected under 35 U.S.C. 102(a1/a2) as being anticipated by Khoja et al., US 2017/0283788 (Khoja).
Regarding claim 1, Khoja discloses a method of analyzing proteins and/or metabolites in a sample (abstract, ¶ 0007) comprising:
Providing a sample (see “blood”, ¶ 0007) including a plurality of different types of protein (i.e. immunoglobulin, albumin, fibrinogen, complement components, etc.), at least two of the types of protein forming a plurality of complexes in which a first protein is bound to a second protein (i.e. albumin/protein complexes, various complement factor complexes, etc.); and
Exposing the sample to focused acoustic energy to disrupt the plurality of complexes and disassociate the first protein from the second protein in each of the complexes (¶ 0006-0007).
Regarding claim 2, Khoja discloses a method wherein the second protein (i.e. immunoglobulin) has a higher molecular weight than the first protein (i.e. albumin).
Regarding claim 3, Khoja discloses a method wherein the first protein is sequestered at least partially within the second protein prior to dissociation from the second protein (i.e. IgG-albumin complexes).
Regarding claim 5, Khoja discloses a method further comprising depleting the sample of the second protein (¶ 0023).
Regarding claim 7, Khoja discloses a method wherein the sample includes blood plasma, and the first protein (i.e. IgG) is present in the sample at a first concentration that is at least an order of magnitude lower than a second concentration at which the second protein (i.e. albumin) is present in the sample (¶ 0023).
Regarding claim 8, Khoja discloses a method wherein the first protein (free complement component) is present in the sample free of any complex with the first protein (¶ 0007, 0023).
Regarding claim 9, Khoja discloses a method wherein type of proteins other than the first and second types of proteins (i.e. histones) are present in the sample (¶ 0023).
Regarding claim 10, Khoja discloses a method wherein the plurality of protein complexes include HSA-bilirubin (¶ 0007, 0023).
Regarding claim 12, Khoja discloses a method wherein disassociation of the first and second proteins from the complexes by exposing the sample to focused acoustic energy increases a measurable concentration of the first protein in the sample (implicitly disclosed).
Regarding claim 13, Khoja discloses a method of analyzing proteins and/or metabolites in a sample (abstract, ¶ 0007, 0023) comprising:
Providing a sample (see “plasma”, ¶ 0023) including at least one protein (i.e. histone) and a metabolite (i.e. cfDNA), the at least one protein and the metabolite forming a plurality of complexes in which the metabolite is bound to a protein; and
Exposing the sample to focused acoustic energy to disrupt the plurality of complexes and disassociate the metabolite from the protein of each of the complexes (¶ 0023).
Regarding claim 14, Khoja discloses a method wherein the protein (i.e. histone) has a higher molecular weight than the metabolite (i.e. cfDNA).
Regarding claim 15, Khoja discloses a method wherein the metabolite (cfDNA) is at least partially sequestered within the protein prior to disassociation of the metabolite from the protein (implicitly disclosed).
Regarding claim 17, Khoja discloses a method further comprising depleting the sample of the protein (¶ 0023).
Regarding claim 18, Khoja discloses a method further comprising recovering the metabolite from the sample after depletion of the protein from the sample (¶ 0023).
Regarding claim 19, Khoja discloses a method wherein the sample includes blood plasma (¶ 0023), and the metabolite is present in the sample at a first concentration that is at least an order of magnitude lower than a second concentration at which the protein is present in the sample (implicitly disclosed).
Regarding claim 20, Khoja discloses a method wherein the metabolite (cfDNA) is present in the sample free of any complex with the protein (i.e. after focused acoustic energy).
Regarding claim 22, Khoja discloses a method wherein disassociation of the plurality of complexes by exposing the sample to focused acoustic energy increases a measurable concentration of the metabolite in the sample (implicitly disclosed).
Regarding claim 23, Khoja discloses a method that does not use a solvent for disassociation (¶ 0023).
Regarding claim 27, Khoja discloses a method wherein the first protein includes heparin cofactor-2 (implicitly disclosed).
Regarding claim 28, Khoja discloses a method wherein the step of exposing the sample to focused acoustic energy incudes adjusting a total amount of acoustic energy applied to the sample to adjust a level or rate of disassociation of selected ones of the plurality of complexes (¶ 0023).
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.
Claim(s) 4, 6, 11, 16, 21, and 24-26 is/are rejected under 35 U.S.C. 103 as being unpatentable over Khoja.
Regarding claims 4 and 16, Khoja does not disclose a method wherein disassociation is achieved at temperatures below 60°C. However, it can be envisaged that Khoja would treat the sample at temperatures below 60°C since Khoja does not disclose the temperature as being significant, the method is conducted independent of temperature, and since it is widely known that higher temperatures would denature and/or destroy components of the sample thereby diminishing the possibility of downstream analysis.
Regarding claims 11 and 21, Khoja discloses a method wherein the focused acoustic energy has PIP between 10-500W, duty factor of 5%, and 50 cycles per second (¶ 0023). While Khoja does not disclose the recited duty factor or cycles per second, Khoja recognizes that other PIP settings may be successfully employed, as well as higher duty factor settings, and/or shorter time periods of treatment (¶ 0023).
Therefore, it would have been obvious to one having ordinary skill in the art to modify the method of Khoja to have the recited duty factor and cycles per second as recited, since it has been held that where the general conditions of a claim are recited in the prior art, discovering the optimum or workable ranges involves only routine skill in the art absent a showing of criticality or unexpected results (MPEP 2144.05, Section II, Part A).
Regarding claim 6, Khoja does not disclose a method further comprising recovering and identifying the first protein from the sample after depletion of the second protein from the sample. However, Khoja contemplates determining relative concentrations and profiles of specific metabolites in samples (¶ 0004), extracting proteins and metabolites from a sample (¶ 0007), and molecule specific binding and separation to increase the concentration of a desired molecule (¶ 0023).
Taking the disclosure of Khoja as a whole, it can be envisaged in alternate disclosed embodiments (i.e. protein, metabolite extraction, ¶ 0007) that when the desired component is a single protein of a protein complex, after focused acoustic energy treatment, molecule-specific extraction will occur of the desired protein via similar methods disclosed in Khoja (¶ 0023).
Regarding claim 24, Khoja does not disclose exposing the sample to focused acoustic energy while the sample includes a protein depletion medium to bind specific proteins. However, in alternate disclosed embodiments (i.e. protein, metabolite extraction, ¶ 0007), it can be envisaged that the desired component will be extracted via similar methods as cfDNA (i.e. magnetic beads, ¶ 0023), where component-specific magnetic beads are used to extract cfDNA after exposure to focused acoustic energy treatment.
While Khoja does not disclose performing acoustic energy treatment with the protein depletion medium in the sample, it would have been obvious to one having ordinary skill in the art to try, since performing the two steps concurrently would provide no more than predictable and reliable results, i.e. simultaneous separation of protein bound complexes and binding of protein to component-specific magnetic beads.
Regarding claim 25, Khoja discloses the protein depletion medium includes magnetic beads (¶ 0023).
Regarding claim 26, while Khoja does not disclose albumin or immunoglobulin as the targeted proteins, it would have been a matter of obvious design choice to target albumin and immunoglobulin, since Khoja contemplates extracting a variety of components found in blood serum/plasma including proteins and metabolites (¶ 0007), where albumin and immunoglobulin are widely known to provide a significant concentration of the protein mass within a blood sample.
Response to Arguments
Applicant's arguments and affidavit filed October 28, 2025 have been fully considered but they are not persuasive.
As an initial matter, the affidavit filed October 28, 2025 contains statements which mischaracterize the rejection filed May 2, 2025. The current rejection (repeated above) relies on elements of Khoja drawn to providing whole blood as a sample (¶ 0004) and subjecting the whole blood to focused acoustic energy (abstract, ¶ 0006). The rejection notes whole blood contains a plurality of protein complexes, where one having ordinary skill in the art would readily understand whole blood comprising serum, plasma, a variety of cells (erythrocytes, lymphocytes, platelets, etc.) in addition to all those proteins and factors circulating within the serum and/or plasma. One having ordinary skill in the art recognizes whole blood and all those components recited above as synonymous.
As seen in the claims, the method comprises two manipulative steps: providing a sample including different types of protein; exposing the sample to focused acoustic energy. Claim 1 is silent with respect to associated metabolites, a degree of dissociation, or an actual manipulation of separation and/or analysis. Therefore, so long as the prior art discloses providing a sample having protein complexes, and subjecting said sample to focused acoustic energy, the examiner considers the prior art to anticipate the recited claim elements. The examiner does not rely on cfDNA since that element is not recited in the claim. The examiner does not consider the affidavit persuasive.
Applicant’s arguments are similarly not considered persuasive. The examiner notes the prior art providing whole blood (containing those protein complexes recited in the rejection) and subjecting those components to focused acoustic energy whereby said complexes dissociate. The claims are silent with respect to any other manipulation or limitation beyond those two method steps. Therefore, so long as the prior art teaches what follows the preamble of the claim, it is considered to teach the preamble. In this case, applicant’s method of analysis merely involves subjecting protein complexes to focused acoustic energy to dissociate at least one of said protein complexes. The examiner maintains the prior art teaches these elements.
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 DIRK R BASS whose telephone number is (571)270-7370. The examiner can normally be reached 8-4:30 EST Monday-Friday.
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, Bobby Ramdhanie can be reached at (571) 270-3240. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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DIRK R. BASS
Primary Examiner
Art Unit 1779
/DIRK R BASS/ Primary Examiner, Art Unit 1779