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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 March 27, 2026 has been entered.
Status of Claims
Claims 18-31 were pending. Claims 21-23 and 27-29 are canceled. Claims 18-20, 24-26, and 30-31 are amended.
Claims 18-20, 24-26, and 30-31 are examined herein.
Withdrawn Rejections
The rejection of claims 18, 20, and 24 under 35 U.S.C. §102 is withdrawn in view of claims amendments. The amendments necessitated a new prior art search and new grounds of rejection have been found in view of newly found prior art reference of De Kleijn. Therefore, claims 18, 20, and 24 are rejected under 35 U.S.C. § 103 as unpatentable over Sailaja, De Kleijn, and as evidenced by Balshaw.
The rejection of claim 25 under 35 U.S.C. §103 is withdrawn in view of claim amendments. The amendments necessitated a new prior art search and new grounds of rejection have been found in view of newly found prior art reference of De Kleijn. Therefore, claim 25 is rejected under 35 U.S.C. § 103 as unpatentable over Sailaja, De Kleijn, and Blume, and as evidenced by Balshaw.
The rejection of claims 19, 26, 30, and 31 under 35 U.S.C. §103 is withdrawn in view of claims amendments. The amendments necessitated a new prior art search and new grounds of rejection have been found in view of newly found prior art reference of De Kleijn. Therefore, claims 19, 26, and 30 are rejected under 35 U.S.C. § 103 as unpatentable over Sailaja, De Kleijn, and Balshaw. Claim 31 is rejected under 35 U.S.C. § 103 as unpatentable over Sailaja, De Kleijn, and Balshaw, and further in view of Blume.
The rejections of claims 21-23 and 27-29 are withdrawn in view of claims cancellation.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL. —The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 20, 24-26, and 30-31 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 20 and 26 are directed to methods for providing information required for determining a therapy for antibody-mediated rejection after kidney transplantation based on the measured level of cystatin C.
The specification provides only general statements linking a therapy for antibody-mediated rejection with the measurements of present invention. For example, “the present invention provides a method for providing information required for diagnosing antibody-mediated rejection after kidney transplantation or predicting the prognosis of a patient after kidney transplantation, including measuring the expression level of any one or more proteins selected from the group consisting of LBP and CST3, or mRNA of a gene encoding the same in a sample isolated from a subject” (pg. 4, lines 20-25).
There is no specific therapy for antibody-mediated rejection. Applicant discloses several art recognized treatments: steroid, plasmapheresis, intravenous immunoglobulin, an anti-CD20 antibody (rituximab), a lymphocyte-depleting antibody, a proteasome inhibitor, a Cl-inhibitor, and a monoclonal antibody against complement factor 5 (pg. 6, lines 19-23).
The specification is silent on information linking the treatments listed in the specification (pg. 6, lines 19-23) and recited in claims 25 and 31 to specific biomarker measurement results. Claims 20 and 26 recite “providing information required for determining a therapy” but the specification fails to disclose what information is provided, how this information or the measurement results are interpreted, and what therapy options are chosen based on the provided information.
The following examples are disclosed:
Example 1 - Selection of patients and preparation of urine samples (pg. 24);
Example 2 - Processing of urine samples and separation of exosomes (pg. 25);
Example 3 - LC-MS analysis and protein identification (pg. 26);
Example 4 - Selection of biomarker candidates (pg. 26-34).
However, no examples are provided on how to interpret biomarker assay information for the treatment purposes and how to select an appropriate treatment from the list of treatments known in the art.
The specification lacks direction or guidance with regard to how to use information obtained by the methods of claim 20 and 26 for determining a therapy.
Claims 24-25 and 30-31 are rejected to as being dependent upon rejected base claims 20 and 26.
Therefore, based on the above findings, one of ordinary skill in the art would conclude that Applicant did not have possession of the claimed invention.
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 18-19 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.
Claims 18-19 recite compositions of a material. It is unclear what is actually claimed because a composition of a material is essentially a composition of matter, which is one of the four categories of patent eligible subject matter. The claims do not recite any composition by its structure, kinds of materials, or chemical compositions. The claims recite the compositions only by their desired properties.
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
Determining the scope and contents of the prior art.
Ascertaining the differences between the prior art and the claims at issue.
Resolving the level of ordinary skill in the pertinent art.
Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 18, 20, and 24 are rejected under 35 U.S.C. 103 as being unpatentable over Sailaja et al. (Indian Journal of Transplantation, Vol. 9, Issue 2, 2015, 65-66) in view of De Kleijn et al. (PGPub 20140024046) and as evidenced by Balshaw et al. (IDS; WO2009143624).
Regarding claims 18, 20, and 24, Sailaja teaches measuring cystatin C biomarker in urine samples using a commercially available kit (pg. 65, col. 2, section “Methodology”) for predicting acute rejection and graft survival following renal transplantation (pg. 65, col. 2, section “Aim”). Therefore, the reference teaches the kit comprising a composition of a material for measuring an expression level of cystatin C protein.
Balshaw provides evidence that acute rejection is also known as acute antibody-mediated rejection ([0007]). Therefore, Sailaja teaches the kit for diagnosing antibody-mediated rejection after kidney transplantation.
Sailaja does not specifically teach a composition of the material suitable for measuring the expression level of cystatin C in exosomes.
Regarding claim 18, De Kleijn teaches exosomal biomarkers for cardiovascular events (Title). De Kleijn also teaches cystatin C detection in exosomes. Specifically, the reference teaches cystatin C as one of the biomarkers that can be isolated from serum, plasma, blood, urine, amniotic fluid, malignant ascites, bronchoalveolar lavage fluid, synovial fluid, breast milk, and saliva (Abstract). As such, De Kleijn’s teaching is reasonably pertinent to the particular problem with which the inventor is concerned: biomarkers, specifically, cystatin C biomarker, and urine as a sample fluid.
Additionally, De Kleijn teaches “The invention further relates to a kit for performing any one of the methods disclosed herein, wherein the kit comprises means for detecting the presence of a biomarker as defined above. The means for detecting the presence of the biomarker are preferably antibodies, antibody fragments or antibody derivates” ([0055]).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have modified the composition of a material for measuring an expression level of cystatin C of Sailaja and employing purification of exosomes from urine as taught by De Kleijn, in order to diagnose antibody-mediated rejection after kidney transplantation. One having ordinary skill in the art would have been motivated to make such a change because the purification of exosomes from urine removes contaminating molecules present in urine that are not bound to the exosomes. The use of such combination would have been desirable to those of ordinary skill in the art because exosomes purification can reduce assay interference from molecules present in urine.
One having ordinary skill in the art would have had a reasonable expectation of success in combining the prior art references because both Sailaja and De Kleijn teach the same biomarker - cystatin C, and De Kleijn has demonstrated successful detection of cystatin C in exosomes purified from urine.
Regarding claim 20, Sailaja and De Kleijn teach measuring levels of cystatin C in urine samples using a commercially available kit (pg. 65, col. 2, section “Methodology”). The reference also teaches that “Occurrence of acute cellular rejection (AR) increased the levels of both KIM-1 and Cystatin C” (Sailaja, pg. 66, col. 1, par. 1); therefore, Sailaja and De Kleijn teach a method for providing information required for determining a therapy for antibody-mediated rejection after kidney transplantation.
Regarding claim 24, Sailaja and De Kleijn teach measuring levels of cystatin C in urine samples collected from patients following renal transplantation and from healthy controls (pg. 65, col. 2, section “Methodology”), which indicates that the results from the transplant patients and healthy controls were compared. The conclusion that “Occurrence of acute cellular rejection (AR) increased the levels of both KIM-1 and Cystatin C” (Sailaja, pg. 66, col. 1, par. 1) indicates the increased levels of Cystatin C, meeting the limitation of claim 24 reciting “upregulation of CST3 protein in the patient sample.
Claims 19, 26, and 30 are rejected under 35 U.S.C. 103 as being unpatentable over Sailaja, De Kleijn, and as evidenced by Balshaw, as applied to claims 18 and 20 above, in view of Balshaw.
The teachings of Sailaja and De Kleijn, as evidenced by Balshaw have been set forth above.
Sailaja and De Kleijn do not specifically teach the kit further comprising a composition of a material for measuring an expression level of lipopolysaccharide-binding protein in exosomes derived from urine isolated from a kidney transplanted subject.
Regarding claims 19, Balshaw teaches a kit for use in assessing or diagnosing a subject's rejection status, the kit comprising reagents for specific and quantitative detection of LBP ([00230]). Balshaw teaches a method of diagnosing rejection of a kidney allograph (Title), where an allograft is a tissue graft taken from one person and transplanted into another person's body. Therefore, Balshaw teaches kidney transplantation.
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have combined in one kit the composition of a material for measuring an expression level of cystatin C of Sailaja and De Kleijn with the composition of a material for measuring an expression level of LBP as taught by Balshaw, in order to measure expression levels of cystatin C and LBP after kidney transplantation. It is prima facie obvious to combine elements, each of which is taught by the prior art to be useful for the same purpose, MPEP 2144.06.
One skilled in the art would have a reasonable expectation of success of combining both compositions in a kit because kits are known in the art as a form of reagent organization.
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have combined the composition of a material for measuring an expression level of cystatin C of Sailaja and De Kleijn with the composition of a material for measuring an expression level of LBP as taught by Balshaw, in order to measure expression levels of cystatin C and LBP after kidney transplantation by assaying the biomarkers contained in exosomes, as an obvious matter of simple substitution of one known element (LBP biomarker in exosomes) for another (LBP biomarker) to obtain predictable results.
One skilled in the art would have a reasonable expectation of success by assaying the biomarkers contained in exosomes because Sailaja and De Kleijn teach successful measurement of expression levels of cystatin C after kidney transplantation by assaying the biomarkers contained in exosomes, and measuring expression levels of LBP in exosomes is a matter of routine additional assay of already purified exosomes (for cystatin C assays) with LBP-specific components.
Regarding claim 26, Sailaja and De Kleijn teach measuring levels of cystatin C in urine samples using a commercially available kit (pg. 65, col. 2, section “Methodology”). The reference also teaches that “Occurrence of acute cellular rejection (AR) increased the levels of both KIM-1 and Cystatin C” (Sailaja, pg. 66, col. 1, par. 1); therefore, Sailaja and De Kleijn teach a method for providing information required for determining a therapy for antibody-mediated rejection after kidney transplantation.
Sailaja and De Kleijn do not specifically teach measuring the expression levels of both cystatin C and LBP proteins in the sample.
Regarding claim 26, Balshaw teaches a method of diagnosing rejection of a kidney allograft (Title) using proteomic expression profiling of one or more biological samples obtained from a subject ([0022]). Specifically, measuring LBP protein levels in samples from subjects who received a renal transplant ([00235]).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Sailaja and De Kleijn by measuring an expression level of LBP as taught by Balshaw, in order to diagnose antibody-mediated rejection after kidney transplantation using two independent biomarkers. It is prima facie obvious to combine elements, each of which is taught by the prior art to be useful for the same purpose, MPEP 2144.06.
One having ordinary skill in the art would have had a reasonable expectation of success of detecting both cystatin C and LBP biomarkers, because each assay is run independently without affecting the other.
Regarding claim 30, Sailaja teaches measuring levels of cystatin C in urine samples collected from patients following renal transplantation and from healthy controls (pg. 65, col. 2, section “Methodology”), which indicates that the results from the transplant patients and healthy controls were compared. The conclusion that “Occurrence of acute cellular rejection (AR) increased the levels of both KIM-1 and Cystatin C” (pg. 66, col. 1, par. 1) indicates the increased levels of cystatin C, meeting the limitation of claim 30 reciting increased levels of cystatin C protein in the patient sample.
Regarding claim 30, Balshaw does not specifically teach urine levels of LBP, but one having ordinary skill in the art would have expected urine levels of LBP to increase following the increase in LBP levels in plasma because the acute kidney rejection results in a loss of kidney function. The acute kidney rejection diagnosis follows from measuring levels of cystatin C in urine samples taught by Sailaja (pg. 65, col. 2, section “Methodology”).
Claim 25 is rejected under 35 U.S.C. 103 as being unpatentable over Sailaja, De Kleijn, and as evidenced by Balshaw, as applied to claim 24 above, in view of Blume et al. (J Transplant. 2012; 2012:201754).
The teachings of Sailaja, De Kleijn, and Balshaw have been set forth above.
Sailaja, De Kleijn, and Balshaw do not specifically to teach therapy selected from the group consisting of steroid, plasmapheresis (PP), intravenous immunoglobulin (IVIG), an anti-CD20 antibody (rituximab), a lymphocyte-depleting antibody, a proteasome inhibitor, a Cl-inhibitor, and a monoclonal antibody against complement factor 5.
Regarding claim 25, Blume teaches “Antibody-mediated rejection: pathogenesis, prevention, treatment, and outcomes” (Title). Blume teaches specific treatments for antibody-mediated rejection: plasmapheresis (pg. 4, col. 1, par. 2), intravenous immunoglobulin (IVIG) (pg. 4, col. 1, par. 4), and rituximab (pg. 5, col. 2, par. 3).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have combined the method for diagnosing antibody-mediated rejection of Sailaja, De Kleijn, and Balshaw with specific treatments as taught by Blume, in order to provide comprehensive health care to the patients, as an obvious matter of combining prior art elements according to known methods to yield predictable results.
One having ordinary skill in the art would have had a reasonable expectation of success of combining the teachings of Sailaja, De Kleijn, Balshaw, and Blume, because diagnostics and therapy are independent methods and their combination is expected to yield predictable results.
Claim 31 is rejected under 35 U.S.C. 103 as being unpatentable over Sailaja, De Kleijn, and as evidenced by Balshaw, as applied to claim 30 above, further in view of Blume.
The teachings of Sailaja, De Kleijn, and Balshaw have been set forth above.
Sailaja, De Kleijn, and Balshaw do not specifically to teach therapy selected from the group consisting of steroid, plasmapheresis (PP), intravenous immunoglobulin (IVIG), an anti-CD20 antibody (rituximab), a lymphocyte-depleting antibody, a proteasome inhibitor, a Cl-inhibitor, and a monoclonal antibody against complement factor 5.
Regarding claim 31, Blume teaches “Antibody-mediated rejection: pathogenesis, prevention, treatment, and outcomes” (Title). Blume teaches specific treatments for antibody-mediated rejection: plasmapheresis (pg. 4, col. 1, par. 2), intravenous immunoglobulin (IVIG) (pg. 4, col. 1, par. 4), and rituximab (pg. 5, col. 2, par. 3).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have combined the method for diagnosing antibody-mediated rejection of Sailaja, De Kleijn, and Balshaw with specific treatments as taught by Blume, in order to provide comprehensive health care to the patients, as an obvious matter of combining prior art elements according to known methods to yield predictable results.
One having ordinary skill in the art would have had a reasonable expectation of success of combining the teachings of Sailaja, De Kleijn, Balshaw, and Blume, because diagnostics and therapy are independent methods and their combination is expected to yield predictable results.
Response to Arguments
Applicant’s arguments filed March 27, 2026 have been fully considered.
Applicant argues about rejection of claims 18, 20, and 24 under 35 U.S.C. § 102(a)(l) in view of the amended claims (pg. 5-6, section 35 U.S.C. § 102). The argument is persuasive; therefore, the rejection of claims 18, 20, and 24 under 102 is withdrawn. However, the amendments necessitated a new prior art search and new grounds of rejection have been found in view of newly found prior art references. Therefore, claims 18, 20, and 24 are rejected under 35 U.S.C. § 103 as unpatentable over Sailaja, De Kleijn, and as evidenced by Balshaw (see § 103 rejection above for details).
Briefly, De Kleijn teaches cystatin C detection in exosomes. Specifically, the reference teaches cystatin C as one of the biomarkers that can be isolated from serum, plasma, blood, urine, amniotic fluid, malignant ascites, bronchoalveolar lavage fluid, synovial fluid, breast milk, and saliva (Abstract).
Applicant argues about rejection of claims 19, 20, and 24 under 35 U.S.C. § 102(a)(l) in view of the amended claims (pg. 6, section 35 U.S.C. § 103 and pg. 7, par. 1-2). The argument is persuasive; therefore, the rejection of claims 18, 20, and 24 under 102 is withdrawn. However, the amendments necessitated a new prior art search and new grounds of rejection have been found in view of newly found prior art reference of De Kleijn. Therefore, claims 18, 20, and 24 are rejected under 35 U.S.C. § 103 as unpatentable over Sailaja, De Kleijn, and as evidenced by Balshaw (see § 103 rejection above for details). Briefly, the rejection is updated with De Kleijn’s teaching of cystatin C detection in exosomes.
Applicant argues that “Sailaja merely discloses CysC as a biomarker for acute cellular rejection, and does not disclose CysC as a biomarker for antibody-mediated rejection” (pg. 7, par. 3). The argument is not persuasive because although Sailaja does not explicitly teach CysC as a biomarker for antibody-mediated rejection, Balshaw provides evidence that acute rejection taught by Sailaja is also known as acute antibody-mediated rejection ([0007]). Therefore, Sailaja teaches diagnosing antibody-mediated rejection after kidney transplantation.
Applicant argues that “Balshaw does not disclose CysC or the use of urine-derived exosomes as a sample, and Blume does not disclose LBP or CysC as biomarkers at all” (pg. 7, last par. – pg. 8, par. 1). The argument is not persuasive because while Balshaw does not teach CysC or the use of urine-derived exosomes as a sample, it is not relied upon for that since CysC as a biomarker is taught by Sailaja and the use of urine-derived exosomes as a sample is taught by new prior art reference of De Kleijn (see § 103 rejection above for details). Balshaw is cited of its teaching of quantitative detection of LBP ([00230]). While Blume does not disclose LBP or CysC as biomarkers it is not relied upon for that and it is cited of its teaching of specific treatments for antibody-mediated rejection: plasmapheresis (pg. 4, col. 1, par. 2), intravenous immunoglobulin (IVIG) (pg. 4, col. 1, par. 4), and rituximab (pg. 5, col. 2, par. 3). LBP or CysC as biomarkers are taught by Sailaja, De Kleijn, and Balshaw (see § 103 rejection above for details).
Applicant argues about hindsight knowledge of Applicant's claimed invention (pg. 8, par. 5 - pg. 10, par. 1). Specifically, “the assertions and conclusion in the Office Action do not simply "take[] into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made” (pg. 8, par. 5), and “impermissible hindsight must be avoided and the legal conclusion must be reached on the basis of the facts gleaned from the prior art” (pg. 10, par. 1).
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
The arguments are not persuasive because Applicant fails to present specific evidence, demonstrate improper benefit of hindsight knowledge, and explain what facts were gleaned from the disclosure, but could not be gleaned from the prior art.
Applicant also argues that “the person of ordinary skill in the art would not have considered the Examiner's asserted combination of these references in the first place unless such a person had the impermissible benefit of hindsight knowledge of Applicant's claimed invention” (pg. 8, last par.). It is unclear what combinations of references Applicant is talking about. An example of a proper combination of references in 103 rejection is rejection of claim 25 in view of Sailaja, De Kleijn, and Balshaw and further in view of Blume. Sailaja, De Kleijn, and Balshaw do not specifically to teach therapy selected from the group consisting of steroid, plasmapheresis (PP), intravenous immunoglobulin (IVIG), an anti-CD20 antibody (rituximab), a lymphocyte-depleting antibody, a proteasome inhibitor, a Cl-inhibitor, and a monoclonal antibody against complement factor 5. Blume teaches specific treatments for antibody-mediated rejection: plasmapheresis (pg. 4, col. 1, par. 2), intravenous immunoglobulin (IVIG) (pg. 4, col. 1, par. 4), and rituximab (pg. 5, col. 2, par. 3).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have combined the method for diagnosing antibody-mediated rejection of Sailaja, De Kleijn, and Balshaw with specific treatments as taught by Blume, in order to provide comprehensive health care to the patients, as an obvious matter of combining prior art elements according to known methods to yield predictable results.
Applicant argues that “there is nothing that would have made the asserted modifications predictable” (pg. 9, par. 2). The argument is not persuasive because it is unclear what modifications of references Applicant is talking about. The rejection of claim 25 used as an example above provides a clear predictability of the modification because Blume already teaches specific treatments for antibody-mediated rejection: plasmapheresis (pg. 4, col. 1, par. 2), intravenous immunoglobulin (IVIG) (pg. 4, col. 1, par. 4), and rituximab (pg. 5, col. 2, par. 3).
Applicant argues that “modifying a reference to fill in gaps in the disclosure of one or more cited references is based on the results of the Examiner's prior art search, such results having been identified from a baseline of knowledge of that matter constituting the claimed invention. But such baseline knowledge was not available to the person of ordinary skill in the art at the time of the claimed invention” (pg. 9, last par.). The argument is not persuasive because it is unclear what gaps in the disclosure Applicant is talking about.
The rejection of claim 25 will be used as an example. Sailaja, De Kleijn, and Balshaw teach measuring cystatin C biomarker in urine exosomes using a commercially available kit for predicting antibody-mediated rejection (see § 103 rejection above for details). Sailaja, De Kleijn, and Balshaw do not teach rejection therapy. This gap of knowledge is filled by Blume teaching plasmapheresis, intravenous immunoglobulin, and rituximab as specific treatments for antibody-mediated rejection. The teaching of Blume is sufficient to complement the teaching of Sailaja, De Kleijn, and Balshaw without the need to read instant disclosure.
Applicant is pointing out that “collectively, the deficiencies among these references such that even their combination still does not provide a teaching or suggestion of each and every element recited in Applicant's claim language” (pg. 10, par. 2). The argument is not persuasive because it is unclear what deficiencies among what references Applicant is talking about. Please, see § 103 rejection updated with new prior art of De Kleijn for details.
Applicant argues that “the collective deficiencies of these references still fail to produce a teaching or suggestion of each and every element recited in at least Applicant's independent claim 16” (pg. 10, par. 3). The argument is not persuasive because the final OA mailed November 28, 2025 addressed claims 18-31, while claim 16 was canceled August 29, 2025.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Alexander Volkov whose telephone number is (571) 272-1899. The examiner can normally be reached M-F 9:00AM-5:00PM (EST).
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bao-Thuy Nguyen can be reached on (571) 272-0824. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ALEXANDER ALEXANDROVIC VOLKOV/
Examiner, Art Unit 1677
/REBECCA M GIERE/Primary Examiner, Art Unit 1677
