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 Claims
Claims 17-18, 20-25, 27-48 are pending in the application.
Claims 23, and 28-35 are withdrawn.
Claims 17-18, 20-22, 24-25, 27, and 36-48 are the subject of this office action.
Claim Rejections - 35 USC § 112(a)
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 17-18, 20-22, 24-25, 27, and 36-48 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being partially enabling for a method of therapeutic treatment of fibrosis, does not reasonably provide enablement for a method of prevention of fibrosis progression. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
In In re Wands the Court set forth a non-exhaustive list of factors to be considered in determining whether undue experimentation would be involved in making and/or using the claimed invention. These factors include, but are not limited to:
(a) The breadth of the claims; (b) the nature of the invention; (c) the state of the prior art; (d) the level of one of ordinary skill; (e) the level of predictability in the art; (f) the amount of direction provided by the inventor; (g) the existence of working examples; and (h) the quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Breadth of the claims and nature of the invention: the independent claims recite a method for “prevention of fibrosis progression” in a subject wherein the subject has been identified as having low (or low or moderate) kidney fibrosis. The method of identification includes determining VTN protein levels in a urine sample; comparing the VTN protein levels with a reference value, wherein decreased VTN with respect to the reference value is indicative of low (or low or moderate) kidney fibrosis; and administering an antifibrotic treatment or agent to the identified subject.
Thus, the claims encompass prevention of progression of fibrosis, and comparison of VTN protein levels to any reference value to determine severity of kidney fibrosis.
State of the prior art/level of one of ordinary skill/level of predictability in the art: The state of the prior art does not support the full breadth of the claims, as there are no examples in the prior art which indicate that it is possible to prevent the progression of fibrosis in a patient with low of moderate kidney fibrosis. The prior art indicates that antifibrotic agents can be used for the therapeutic treatment of kidney fibrosis, and that these may slow the progression of fibrosis, but no treatment is demonstrated in the prior art that is known to reliably prevent any progression of fibrosis. See, for example, Chen et al (Decoding organ fibrosis: mechanistic insights and emerging therapeutic strategies. Signal Transduct Target Ther. 2026 Mar 6;11(1):82.), (Pg. 20, Col. 2, Par. 3: Despite substantial advances in understanding renal fibrosis, key molecular mechanisms remain incompletely elucidated, and no effective antifibrotic therapies currently exist to halt or reverse disease progression). See also, Vanhove et al ("Kidney Fibrosis: Origins and Interventions," Transplantation 101:713- 726, 2017.; IDS entered).
Regarding determination of fibrosis severity from VTN protein levels and reference values: The prior art indicates some known relationship between VTN levels and kidney fibrosis. Anderberg et al (WO 2013/078253 A1; IDS entered) teaches that increased VTN in urine as compared to a healthy control is associated with kidney injury (see, e.g., the VTN (UO) section of Table 1 on Pg. 60; the VTN (UO) section on Pg. 76; the VTN (UO) section of Table 4 on Pg. 93). Reilly et al (“Vitronectin (serum spreading factor): its localization in normal and fibrotic tissue”, JClin Pathol 41:1269-1272, 1988; IDS entered) teaches that VTN levels are increased in fibrotic kidney tissues as compared to healthy controls (Abstract). However, Anderberg does not teach that VTN levels are associated specifically with kidney fibrosis (as opposed to other factors associated with kidney injury and renal dysfunction), and Reilly does not teach measurement of VTN in urine or define a predictable relationship between VTN levels measured in tissues and VTN levels measured in urine samples. Further, neither Anderberg nor Reilly teaches that decreased VTN levels with respect to a reference value is indicative of any particular level of kidney fibrosis. Thus, the prior art does not indicate a known or predictable relationship between decreased VTN levels in the urine and low or moderate kidney fibrosis, and instead indicates that kidney fibrosis is generally associated with an increase in VTN levels as compared to healthy controls.
Amount of direction provided by the inventor/existence of working examples: The specification indicates that a reference value is generally a mean value of preferably a statistically significant number of sample obtained from a reference control population and indicates that a person of ordinary skill in the art will know how to determine an appropriate reference value depending on the diagnostic or prognostic goals (Pg. 28, Ln. 34-36; Pg. 21, Ln. 37-Pg. 22, Ln. 3). It is noted that while this context provides exemplary guidelines for what a reference value may comprise, it does not specifically limit the scope of the reference value recited in the claim. The most relevant working examples are shown in Figs. 4-5 and discussed in Example 3-4. The results shown in Fig. 5 indicate that the distribution of VTN values was useful in discriminating patients with low and moderate fibrosis from those with severe fibrosis.
Thus, this provides a working example of a method wherein a VTN level lower than a particular reference value may indicate low or moderate kidney fibrosis, however, it is insufficient to support or enable the full scope of the method as claimed. That is, a single example which relies on a single particular reference value, does not enable the full scope of the claim in which the reference value is not defined or limited. The claimed method performed with a reference value taken from a healthy control population will yield different results from the method performed with a reference value taken from a population with severe fibrosis, and the specification does not enable both of these embodiments.
Further, the specification provides no working examples which support the prevention of progression of kidney fibrosis in the subject. The specification provides no data on the treatment of any particular subject using the claimed method, does not explicitly recite the prevention of progression of kidney fibrosis, and therefore provides no reduction to practice or evidentiary support to enable this recitation in the claim.
As such, the quantity of experimentation needed to make or use the invention based on the content of the disclosure is considered undue because the disclosure does not support that one can reliably or consistently evaluate the severity of kidney fibrosis in a subject (i.e. determine that a subject has low or moderate fibrosis) and cannot reliably or consistently prevent the progression of fibrosis based only on the limitations and steps of the method as claimed.
Claim Rejections - 35 USC § 112(b)
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 17-18, 20-22, 24-25, 27, and 36-48 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.
Independent claims 17 and 37 are both rejected as indefinite because the construction of the claims is unclear and because they both recite a method of prevention and/or treatment without reciting any active steps of those methods. That is, the claims recite a method of prevention of fibrosis progression or treatment of fibrosis and then recite “wherein the subject has been identified…according to a method comprising”. Wherein all actively recited method steps in the claims are recited as steps of the method of identification and not as steps of the method of prevention or treatment, such that what the instantly claimed method of treatment or prevention of progression actually comprises is unclear. Clarification is required.
Dependent claims 18, 20-22, 24-25, 27, 36, and 38-48 are rejected as indefinite because they depend from an indefinite claim and fail to remedy its deficiencies.
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.
Claims 17-18, 20-22, 24-25, 27, and 36-48 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more.
The claims recited determining that a subject has low or moderate kidney fibrosis based on VTN protein levels in a urine sample from the subject. This constitutes both an abstract idea (i.e. determining that VTN protein levels in a sample from a subject are decreased with respect to a reference value encompasses, for example, a practitioner interpreting data to draw a conclusion, which is a mental process/abstract idea; drawing a diagnostic conclusion about kidney fibrosis also constitutes a mental process/abstract idea) and a law of nature (i.e. the relationship between levels of a particular protein and a particular disease state is a law of nature).
The claims do not integrate the recited judicial exceptions into a practical application. As it applies to the instant claims, the most relevant practical application would be applying or using a judicial exception to effect a particular treatment for a disease, as discussed in MPEP 2106.04(d)(2), however the treatment step of the instant claims is insufficient to comprise a “particular treatment” and is therefore insufficient to integrate the judicial exception into a practical application.
Regarding whether integration of the judicial exception into a method of treatment comprises integration of the judicial exception into a practical application, MPEP 2106.04(d)(2) provides the following: “One way to demonstrate such integration is when the additional elements apply or use the recited judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition. The application or use of the judicial exception in this manner meaningfully limits the claim by going beyond generally linking the use of the judicial exception to a particular technological environment, and thus transforms a claim into patent-eligible subject matter. Such claims are eligible at Step 2A, because they are not “directed to” the recited judicial exception”. Regarding the particularity of the treatment step, the MPEP indicates that recitation of an abstract idea in conjunction with a step of, for example, “administering a suitable medication to a patient” does not integrate the judicial exception into a practical application because the treatment step is general (not particular) and is merely instruction to “apply” the judicial exception in a generic way.
As it applies to the instant case, the claimed treatment step recites administering to the subject “an antifibrotic treatment or agent” wherein the instant specification describes an antifibrotic treatment or agents at Pg. 32-33: a treatment or agent for the preventive and/or therapeutic treatment of fibrosis can be generally referred to as antifibrotic treatment or agent; this treatment may be any known treatment suitable for the preventive and/or therapeutic treatment of fibrosis. As such, the recited treatment step comprises administration of any treatment or agent that is known to be suitable for the identified disease, and is thus similar to the example discussed in the MPEP wherein “administering a suitable medication to a patient” is not sufficiently particular to integrate a judicial exception into a practical application.
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exceptions.
The step of determining how VTN protein levels compare to a reference value is itself a judicial exception since it encompasses embodiment wherein VTN protein levels are compared to a reference value in the mind as part of a mental process.
Additional elements of the claim which are directed to measuring VTN protein levels in a urine sample are insufficient to provide significantly more than the judicial exceptions because they pertain to necessary data gathering activities required for implementing the judicial exceptions. That is, a practitioner must measure and determine levels of VTN protein in a sample in order to compare them to a reference value and draw a diagnostic conclusion. Steps which amount to data gathering in conjunction with a judicial exception are considered to be adding insignificant extra-solution activity to the judicial exception, and are not considered enough to qualify as significantly more when recited in a claim with a judicial exception. See MPEP 2106.05(g).
Additionally, the determination of a biomarker level in a patient sample has been identified in the MPEP as routine and conventional activity in the life sciences arts. See MPEP 2106.05(d)(II).
Further, the particular detection of VTN protein levels in a urine sample from a subject is known to be routine and conventional in the art, as evidenced by Anderberg et al (WO 2013/078253 A1; IDS entered), Takahashi et al (Vitronectin in children with renal disease--2. Examination of urinary vitronectin excretion. Nihon Jinzo Gakkai Shi. 1995 Apr;37(4):224-30. Japanese. PMID: 7541481.), and Caterino et al (Urine Proteomics Revealed a Significant Correlation Between Urine-Fibronectin Abundance and Estimated-GFR Decline in Patients with Bardet-Biedl Syndrome. Kidney Blood Press Res. 2018;43(2):389-405. Epub 2018 Mar 8.) which all teach detection of VTN in urine, indicating that such detection had been performed by multiple different practitioners using well-known methods of measurement prior to the effective filing date of the instant application.
The only further additional elements of the claims which are not themselves judicial exceptions are regarding the recitation of treatment administration. These elements are not sufficient to amount to significantly more than the judicial exceptions because the administration of such antifibrotic treatments to patients known to have kidney fibrosis is routine and conventional in the art, as evidenced by Klinkhammer et al (Treatment of Renal Fibrosis-Turning Challenges into Opportunities. Adv Chronic Kidney Dis. 2017 Mar;24(2):117-129.; IDS entered) and Vanhove et al ("Kidney Fibrosis: Origins and Interventions," Transplantation 101:713- 726, 2017.; IDS entered) which teach that the standard therapy for patients with kidney fibrosis is the administration of antifibrotic treatments.
For all these reasons, the claimed elements, when taken alone or in combination, fail to include additional elements that are sufficient to either integrate the judicial exceptions into a practical application or amount to significantly more than the judicial exceptions.
Subject Matter Free of Prior Art
Claims 17-18, 20-22, 24-25, 27, and 36-48 are rejected, as described above, but appear to be free of the prior art.
The closest prior art is Anderberg et al (WO 2013/078253 A1; IDS entered) and Reilly et al ("Vitronectin (serum spreading factor): its localization in normal and fibrotic tissue," JClin Pathol 41:1269-1272, 1988.; IDS entered).
Anderberg discloses methods and compositions for monitoring, diagnosis, prognosis, and determination of treatment regimens in subjects suffering for or suspected of having a renal injury (Abstract). Anderberg further teaches the method comprising determining the level of VTN protein in a urine sample from a subject, and comparing it to a reference value to make a diagnosis or prognosis of kidney injury (Abstract; Par. 24).
Anderberg differs from the instant claim in that it does not teach the method wherein decreased VTN protein levels in the urine sample with respect to the reference value is indicative that said subject has low or low-moderate kidney fibrosis. Anderberg instead teaches that increased levels of VTN are generally associated with kidney injury (see, e.g., the VTN (UO) section of Table 1 on Pg. 60; the VTN (UO) section on Pg. 76; the VTN (UO) section of Table 4 on Pg. 93).
Reilly teaches method of measuring VTN in tissue samples and concludes that VTN is significantly increased in reactive and fibrotic tissue (Abstract). Thus, Reilly teaches a correlation between kidney fibrosis and VTN levels, but differs from the instant claim in that it measures VTN in tissue samples rather than in urine samples and in that it teaches that increased VTN is associated with kidney fibrosis and therefore does not teach that decreased VTN protein levels in a urine sample with respect to a reference value is indicative that the subject has low or low-moderate kidney fibrosis.
Response to Arguments
Applicant’s arguments filed 19 February 2026 have been fully considered.
The previous 112(b) rejections are withdrawn in view of the amendments to the claims, and new grounds of 112(b) rejection which address the amended claims are presented above.
The previous 101 rejection is withdrawn in view of the amendments to the claims. Regarding subject matter eligibility, Applicant argues that the amended claims integrate the recited judicial exceptions into a practical application via a particular treatment step. This argument is not persuasive for the reasons outlined in the new grounds of 101 rejection above which address the amended claims.
The previous 112(a) rejection is withdrawn in view of the amendments to the claims, and new grounds of 112(a) rejection which address the amended claims are presented above.
Regarding the 112(a) rejection, Applicant argues that the amended claims are fully enabled by the disclosure, as demonstrated by the examples and data discussed in the remarks (i.e. Figs. 4-5, 11-12; Examples 3-4). These arguments are not persuasive. As discussed above, the full scope of the amended claims are not enabled by the disclosure because the disclosure does not support prevention of progression of fibrosis and does not support determining whether a subject has low or moderate fibrosis by comparing VTN levels to any reference value.
Conclusion
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.
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/ELLIS FOLLETT LUSI/Examiner, Art Unit 1677
/BAO-THUY L NGUYEN/Supervisory Patent Examiner, Art Unit 1677 April 14, 2026
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