DETAILED ACTION
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 Applications, Amendments and/or Claims
It is noted that the examiner of record has changed. Please address all future correspondence to Examiner Olayinka Oyeyemi, whose correspondence information is provided at the conclusion of the office action.
This action is written in response to applicant's correspondence submitted 07/21/2025. In the paper of 07/21/2025, Applicant amended claims 3-4 and 6 and 7 and newly canceled claims 1-2 and 7.
Accordingly, Claims 3-6 are pending and under review.
This paper contains new rejections that are necessitated by claim amendments.
Response to Arguments
Moot and/or Withdrawn Rejection(s)
The rejection of claim 7 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is moot based on the cancellation of this claim.
The rejections of claims 1-2 under 35 U.S.C. 101 are moot based on the cancellation of these claims.
The rejection of claims 1-2 and 7 under 35 U.S.C. 102(a)(1) as being anticipated by RayBiotech (Quantibody® Human Cytokine Antibody Array 1200 User Manual) are moot based on the cancellation of these claims.
Maintained Rejection(s)
The rejection of claim 6 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is maintained.
The rejection of claims 3-6 under 35 U.S.C. 102(a)(1) as being anticipated by RayBiotech (Quantibody® Human Cytokine Antibody Array 1200 User Manual) are maintained.
Maintained Rejection(s)
Applicant's arguments filed 07/21/2025 have been fully considered but they are not persuasive because of the following.
Applicant argues that RayBiotech Quantibody® Human Cytokine Antibody Array 1200 User Manual discloses a generalized protein array platform that includes individual antibodies for FCAR, MBL, and MMP-9 among hundreds of other cytokines, but does not disclose a reagent for combined detection of FCAR, MBL, and MMP-9 in the context of IgAN (see Remarks of 07/21/2025, pg 5, 1st para).
Applicant argues that the specification at paragraph [0047] discloses that the combined detection of blood biomarkers FCAR, MBL, and MMP-9 demonstrates significantly improved diagnostic value for IgAN, especially severe IgAN, with a combined score calculated using a specific regression formula yielding an AUC of 0.9902, and sensitivity and specificity values of 93.75% and 96.88%, respectively. This performance far surpasses that of each biomarker alone (with individual AUCs of only 0.6865, 0.9473, and 0.9199, respectively), demonstrating that the claimed combination provides unexpected and superior diagnostic results (see Remarks of 07/21/2025, pg 5, 1st para).
Applicant argues that RayBiotech Quantibody® Human Cytokine Antibody Array 1200 User Manual do not teach or suggest the combined detection of these three specific biomarkers, the use of a diagnostic scoring formula, or any application specifically directed to the diagnosis or prognosis of IgAN.
Accordingly, the cited art, RayBiotech User Manual, fails to disclose or suggest at least the disease-specific diagnostic application, combined biomarker use, or clinical performance characteristics of the claimed invention.
For claims 3-5, Applicant’s argument of superior performance are not commensurate in scope with these claims as these claims are broadly drawn to a reagent for detecting expression level of biomarkers consisting FCAR, MBL and MMP-9. There is no limiting structure that is applied to the instant reagent of claims 3-5.
Concerning claim 6, Applicant’s argument is also not found to persuasive. Applicant’s claim of superior performance for detecting IgAN using the expression values from measuring only FCAR, MBL and MMP-9 biomarkers in the blood from a subject has not been supported by comparative evidence shown by presentation of an adequate numbers of tests so as to provide an adequate basis for concluding that these biomarkers possesses superior and unexpected properties relative to other known prognostic IgAN blood/non-invasive biomarkers.
Claim Objections
Claim 3 is objected to because of the following informalities: Specifically, claims 3-4 and 6 each recite the abbreviations FCAR (IgA-Fc fragment receptor or CD89), MBL (Mannose binding lectin) and MMP-9 (Matrix metalloproteinase 9). The abbreviations should be spelt out in their initial use for clarity. 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.
Claims 3-6 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 3 is drawn to a reagent/product that has a functional limitation of detecting expression level of FCAR (IgA-Fc fragment receptor or CD89), MBL (Mannose binding lectin) and MMP-9 (Matrix metalloproteinase 9) in a blood sample of a subject. Claim 3 is found lacking of clarity of scope because it is not known if the claim requires a single reagent with the ability to detect all three biomarkers or whether more than one product is intended to meet the functional limitation. Claims 4-5 are further rejected as they depend from claim 3 and are so broadly drawn that they also do not make clear any limiting structure(s) for the claimed reagent(s) for providing the claimed functional ability.
Claim 6 is drawn to an application of a reagent for detecting a combination of the blood biomarkers. The limitation of “an application of a reagent” renders claim 6 confusing and thus indefinite as the limitation fails to clearly recite a claim within one of the statutory classes. It is unclear whether the preamble requires a process, an article of manufacture, or composition of matter.
Furthermore, there is insufficient antecedent basis for the preamble limitation, “the blood biomarkers” as claimed by the preamble of claim 6.
Finally, claim 6 omits essential limitations. The preamble of claim 6 is found to be lacking in clarity. However, because claim 6 currently recites the limitations, “using the calculated score for assisting diagnosis of the IgAN” and “assessing the prognosis of the IgAN, wherein a score boundary value of 0.025 indicates severe IgAN”, the Office construes that claim 6 is intended as being drawn to a method for diagnosing and evaluating prognosis of immunoglobulin A nephropathy (IgAN) in a subject.
Claim 6 is again rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for reciting the limitations, “using the following formula” and “using the calculated score for assisting diagnosis of the IgAN”. The words “using” renders claim 6 indefinite as it is unclear how the combined diagnostic score of the combination of blood markers provides a diagnosis of immunoglobulin A nephropathy (IgAN) and evaluation of prognosis of IgAN.
Claim 6 fails to make clear how the “score boundary value” and the “combined diagnostic score of the combination of blood markers” are related, or what values of the combined diagnostic score of the combination of blood markers promotes diagnosis of immunoglobulin A nephropathy (IgAN) and/or evaluation of prognosis of IgAN.
Claim Interpretation
Prior to analysis of the art, the claims must be construed. As noted in MPEP 2111, citing Phillips v. AWH Corp., 415 F.3d l303, 75 USPQ2d l321 (Fed. Cir. 2005), "During patent examination, the pending claims must be 'given their broadest reasonable interpretation consistent with the specification.' ".
For the purpose of search and examination:
Claim 3 is construed as being drawn to a product for diagnosing and evaluating prognosis of immunoglobulin A nephropathy (IgAN),
the product comprising:
a reagent for detecting expression level of a combination of blood biomarkers consisting of FCAR, MBL, and MMP-9 in a blood sample.
Claim 4 is construed as being drawn to a product,
wherein a score of the combination of blood biomarkers with a measure of picogram/milliliter (pg/mL) is calculated as m:
wherein m = 0.17 * FCAR - 4.684 * MBL - 0.162 * MMP-9 + 8.834,
wherein FCAR, MBL and MMP-9 are the respective concentrations or expression level, with a measure of pg/mL; and 8.834 is a constant in the formula calculated by a logistic regression model.
Claim 6 is construed as being drawn to a method comprising:
providing a reagent for detecting a combination of the blood biomarkers for diagnosing and evaluating prognosis of immunoglobulin A nephropathy (IgAN);
detecting expression level of a combination of the blood biomarkers consisting of FCAR, MBL, and MMP-9 in a blood sample from a subject;
calculating a combined diagnostic score of the combination of blood biomarkers using the following formula:
m = 0.17 x FCAR - 4.684 x MBL - 0.162 x MMP-9 + 8.834,
wherein FCAR, MBL, and MMP-9 represent concentrations of the respective combination of the blood biomarkers in pg/mL or ng/mL; and
using the calculated score for assisting diagnosis of the IgAN and
assessing the prognosis of the IgAN, wherein a score boundary value of 0.025 indicates severe IgAN.
Claim Rejections – 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
The claimed invention is not directed to patent eligible subject matter. Based upon an analysis with respect to the claim as a whole, claim(s) 3-5 do not recite something significantly different than a judicial exception.
The rationale for this determination is explained below:
The instant claims have been considered with respect to these three inquiries.
Are the claims directed to one of the four statutory categories as explained in MPEP 2106(I)? Are the claims directed to a process, machine, manufacture or composition of matter?
In this case, claims 3-4 are directed to a product/reagent or a composition of matter, having a functional limitation associated thereto, i.e. a functional capability to detect expression level of a combination of blood biomarkers consisting of FCAR, MBL, and MMP-9 in a blood sample.
Claim 5 is directed to a kit comprising the composition of matter of claim 3, or to a protein microarray comprising the composition of matter of claim 3.
Claim(s) 3-5 are broadly drawn and encompasses naturally occurring polynucleotides and/or naturally occurring cytokines (for claim 5, these polynucleotides/cytokines are in a container or on a substrate and the kit or microarray of claim 5 do not alter the characteristics of the reagents so that they are markedly different relative to the naturally occurring counterparts).
As a whole, none of claims 3-5 establish any functional differences for the claimed reagent relative to the naturally occurring counterparts.
Are there any elements, or combination of elements in the claim that is sufficient to ensure that the claim as a whole is significantly more than the judicial exception?
No. Claims 3-5 encompass naturally-occurring proteins or polynucleotides for hybridizing FCAR, MBL and MMP-9 per se, which represent natural products, and are thus not patent eligible.
MPEP 2106.04(b)(i) identifies nucleic acid sequence(s) having no structural or functional differences from naturally occurring nucleic acids as an example of a patent-ineligible natural product.
In addition, as discussed in MPEP 2016.04(b)(II), “[P]roduct of nature exceptions include both naturally occurring products and non-naturally occurring products that lack markedly different characteristics from any naturally occurring counterpart.” See Ambry Genetics, 774 F.3d at 760, 113 USPQ2d at 1244.
Are the claim as a whole integrate the recited judicial exception into a practical application of the exception?
In the instant case, the claims do not appear to recite any additional elements beyond those that may reasonably be consider part of a naturally occurring elements. There are no additional claim elements recited beyond the nucleotide probes/cytokines FCAR, MBL, and MMP-9.
Claims 3-5 do not include additional elements that are sufficient to amount to significantly more than the judicial exception or that are able to integrate the claims into a practical application of the exception.
Claim 6 is rejected under 35 U.S.C. §101 because these claims are not directed to patent eligible subject matter. Based upon an analysis with respect to the claims as a whole, claim(s) 20-21 do not recite something significantly more than a judicial exception. The rationale for this determination is explained below:
According to the Manual of Patent Examination Procedure (MPEP) sections 2103 through 2106.07(c), which now incorporates the 2019 Revised Patent Subject Matter Eligibility Guidance (2019 PEG), October 2019 Patent Eligibility Guidance Update (October 2019 Update), and the Berkheimer Memo, an initial two step analysis is required for determining statutory eligibility.
Step 1
Step 1 requires a determination of whether the claims are directed to a process, machine, manufacture, or a composition of matter. In the instant case, the Step 1 requirement is satisfied as the claims are directed towards a process.
Step 2
The Step 2 analysis is a two-part analysis, Step 2A and Step 2B.
Step 2A, prong 1
Step 2A, prong 1 requires a determination of whether the claims are directed towards a judicial exception, i.e. a law of nature, natural phenomenon, or an abstract idea, while step 2A, prong 2 requires an analysis of whether the judicial exception integrated into a practical application if the claim recites a judicial exception under Prong 1.
Step 2A, prong 2
Step 2A, prong 2 requires an analysis of whether the judicial exception integrated into a practical application if the claim recites a judicial exception under Prong 1.
Step 2B
The second part, Step 2B of the two step analysis is drawn to determining whether any element or combination of elements, in the instant claims is/are sufficient to ensure that the claims as a whole amounts to significantly more than the judicial exception.
Following the analysis below the claims are not patent eligible under 35 U.S.C. 101.
Concerning Step 1: YES. Claim 6 is directed to methods, therefore the claims are directed to a process, which is a statutory category.
Concerning Step 2A: YES. Claim 6 recite a method for diagnosing and evaluating prognosis of immunoglobulin A nephropathy (IgAN). Claim 6 rely on a naturally-occurring correlation i.e. the naturally occurring expression of FCAR (IgA-Fc fragment receptor or CD89), MBL (Mannose binding lectin) and MMP-9 (Matrix metalloproteinase 9) in a blood sample of a subject is assessed to diagnose and/or prognose immunoglobulin A nephropathy (IgAN).
Concerning Step 2A, prong 1, claim 6 is directed towards a judicial exception, i.e. a law of nature, as noted above. Claim 6 also recite abstract ideas of comparing and parsing data, as these claims recite steps of calculating a combined diagnostic score of the combination of blood biomarkers and determining severe IgAN disease based on a score boundary value of 0.025.
The calculating and indicating severe IgAN are steps fall within the “Mental processes” grouping of abstract ideas and as they merely instruct a user to analyze the expression quantities of MBL, MMP-9 and CD89/FCAR (analyze the natural law) and to draw a conclusion based on a mathematical representation of these expression quantities.
Concerning Step 2A, prong 2, the judicial exception of claim 6 is not integrated into a practical application because of the following.
A claim that integrates a judicial exception into a practical application will apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception, such that the claim is more than a drafting effort designed to monopolize the judicial exception. When the exception is so integrated, then the claim is not directed to a judicial exception.
Claim 6 do not recite any additional process steps beyond the step of concluding the presence or severity of IgAN. Every process step of the instant claim 6 as presently recited is for establishing judicially excluded subject matter (law of nature). Claim 6 do not recite steps/elements that are construed to be a practical application that apply, rely on, or use the judicial exceptions (e.g. a practical application can be treating IgAN after its diagnosis/prognosis with an effective amount of a therapy).
Concerning Step 2B, claim 6 do not recite any additional elements that ensure that the claims as a whole amount to significantly more than the judicial exception(s).
There is no inventive concept in claim 6, and thus they are rejected as being ineligible under 35 U.S.C. 101.
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.
Claims 3-6 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by RayBiotech (Quantibody® Human Cytokine Antibody Array 1200 User Manual: previously cited) as evidenced by Moresco et al. (2015, Autoimmunity reviews, 14(10), pp.847-853) and Maixnerova et al., (2016, Journal of nephrology, 29(4), pp.535-541) and Endo et al. (2006, Clinical and experimental nephrology, 10(4), pp.253-261).
RayBiotech sold a protein microarray kit called Quantibody® Human Cytokine Antibody Array 1200 at least as early as November 16, 2021 (see User Manual, page 1, included with this Office action).
The kit comprised a combination of 30 non-overlapping arrays to measure 1200 human cytokines (id.). MMP-9 antibody was present on array QAH-CYT-5 (page 13 of User Manual). MBL antibody was present on array QAH-CYT-6 (page 12 of User Manual). FCAR antibody was present on array QAH-CYT-14 (page 15 of User Manual).
Note that in disclosing arrays measuring these cytokines (meeting the product of claims 3-5), the User Manual disclosed the cytokines per se (meeting the biomarkers of claims 3-6), as well as a method (“an application”) of using the arrays to measure them (meeting the application of claim 6; see “Protocol” on pages 8-12).
Regarding the language “related to diagnosis and prognosis of…IgAN” in claim 1, the language “for diagnosing and evaluating prognosis of IgAN” in claim 3, and the language “for assisting diagnosis of IgAN and assessing the prognosis of IgAN” in claim 6, these are statements of intended use that do not distinguish the reagent products of claims 3-5 over the cited prior art. The limitations regarding calculating a score in claims 4 and 6 and the formula “m” recited by these claims does not distinguish over the product of claims 4 and 6, as claim 4 is drawn to a product and not a process and for claim 6, the cytokines FCAR, MBL and MMP-9 of RayBiotech inherently would yield the combined diagnostic score.
Morever, the following prior art are cited to establish that the cytokines of the array of RayBiotech possess the claimed functional limitations of diagnosing and prognosing of IgAN.
Specifically, Moresco et al. teach that high serum expression levels of IgA-soluble CD89 (sCD89) complexes in the serum of patients was already associated with IgAN in contrast to the low serum levels of sCD89–IgA complexes in the disease progression group (pg 850, Table 1) and that urinary MBL, a reliable non-invasive biomarker for evaluation of disease severity (pg 850, Table 1 and pg 850, below Table 1, 1st para of left col.).
Maixnerova et al. teach CD89 or i.e. FCAR was a known marker for the progression of IgAN (pg 4, last 2 paragraphs). Maixnerova et al. teach serum MBL was a known marker for the progression of IgAN (abstract).
Endo et al. teach that in IgAN, patients with a relatively poor prognosis associated with a widening of the mesangial matrix (MM) were found to have high levels of both plasma MMP-9. Endo further teach MMP-9 and MMP-2 in the peripheral blood are associated with glomerular pathologies (pg 260, right col., 2nd para).
Accordingly, the instant claims 3-6 are still anticipated by RayBiotech.
Conclusion
No claims are currently allowed.
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.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to OLAYINKA A OYEYEMI whose telephone number is (571)270-5956. The examiner can normally be reached Monday -Thursday: 9:00 am - 5:00 pm, EST.
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, GARY Benzion can be reached at 571-272-0782. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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OLAYINKA A. OYEYEMI
Examiner
Art Unit 1681
/OLAYINKA A OYEYEMI/Examiner, Art Unit 1681
/GARY BENZION/Supervisory Patent Examiner, Art Unit 1681
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