DETAILED ACTION
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 2, 13-16 and 24 have been canceled.
Claims 1, 3-12, 17-23, and 25-27 are currently pending.
Election/Restrictions
Applicant’s election with traverse of Group I, Claims 1, 5-12 and 25-27, and without traverse of species PTPs comprising at least PTPN2, PTPRF, PTPRK, PTPN12, PTPN7, PTPN1, and PTPN6, and hepatocellular carcinoma, in the reply filed on 2/6/2026 is acknowledged. The traversal is on the ground(s) that the cited reference fails to teach or suggest the special technical feature. This is not found persuasive because as indicated by the rejections below, the groups do not share the special technical feature which contributes over the prior art at the time the invention was made.
The requirement is still deemed proper and is therefore made FINAL.
Claims 3-4, 7-12, 17-23, and 25 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions and species, there being no allowable generic or linking claims.
Claims 1, 5-6 and 26-27 are being examined in this application, insofar as they read on the elected species of PTPs comprising at least PTPN2, PTPRF, PTPRK, PTPN12, PTPN7, PTPN1, and PTPN6, and hepatocellular carcinoma.
Claim Rejections – 35 USC § 112(a)
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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 1, 5-6 and 26-27 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 claims contain 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 pre-AIA the inventor(s), before the effective filing date of the claimed invention, had possession of the claimed invention.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include “level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient” (MPEP 2163).
A claimed genus may be satisfied through sufficient description of a representative number of species or disclosure of relevant, identifying characteristics such as functional characteristics coupled with a known or disclosed correlation between function and structure (MPEP 2163(3)a(II)). The number of species that describe the genus must be adequate to describe the entire genus; if there is substantial variability, a large number of species must be described.
Claim 1 recites “measuring the aggregate expression level of PTPs in a sample of the subject, and measuring the aggregate oxidation level of PTPs in a sample of the subject, wherein the aggregate expression level and the aggregate oxidation level correspond to a reference value or threshold value that is characteristic of a subject with a known diagnosis, prognosis and/or disease status of cancer, and wherein a deviation or no deviation is indicative for the diagnosis, prognosis and/or disease status of cancer in the subject”. The claim is considered a genus claim that encompasses a wide array of protein tyrosine phosphatases (PTPs) as well as a very diverse types of cancer. The instant specification fails to set forth a representative number of examples in order to reasonably verify possession of such a potentially enormous number of PTPs and cancer types.
The MPEP states that written description for a genus can be achieved by a representative number of species within a broad generic. It is unquestionable that the claim is broad generics, with respect to all PTPs and all cancer types.
This lack of ability to predict if a given expression level and/or oxidation level of PTP(s) is indicative for the diagnosis, prognosis and/or disease status of any cancer types in a subject. Diamandis (J Natl Cancer Inst. 2010;102:1462-1467.) teaches in the last decade, many reports have described new cancer biomarkers that promised to revolutionize the diagnosis of cancer and the management of cancer patients, however, many initially promising biomarkers have not been validated for clinical use (Abstract). Diamandis also teaches most cancer biomarkers in clinical use are not suitable for population screening or for early diagnosis (p.1462 col right – para 2), and one requirement among many requirements is that the biomarker should be highly specific for the tissue of origin because if other tissues also produce this biomarker, then its background level in normal healthy individuals will likely be high (p.1463 col left – para 1). Therefore, cancer biomarker predictability is difficult because of significant biological tumor heterogeneity, and the high rate of failure in validating findings across different clinical trials.
A patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that the inventor invented the claimed invention. Thus, an applicant complies with the written description requirement “by describing the invention, with all its claimed limitations, no that which makes it obvious,” and by using “such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention.” The instant specification lacks sufficient variety of measured expression level and oxidized level of PTPs using samples from sufficient variety of cancer types to reflect this variance in the genus since the instant specification does not provide any examples of such a genus of PTPs and cancer types. Accordingly, the instant specification fails to provide adequate written description for the genus of PTPs and cancer types, and does not reasonably convey to one skilled in the relevant art that the inventors, at the time the application was filed had possession of the entire scope of the claimed invention. Moreover, the specification neither describes the complete structure of a representative number of PTPs, nor describes a representative number of PTPs in terms of partial structure and relevant identifying characteristics. Absent of such teachings and guidance as to the structure and function of these PTPs and cancer types, the instant specification does not describe the claimed PTPs and cancer types in such full, clear, concise and exact terms so as to indicate that applicant had possession of these PTPs and cancer types at the time of filing of the present application. Thus, the written description requirement has not been satisfied.
Claims 1, 5-6 and 26-27 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for an in vitro method for measuring protein tyrosine phosphatases (PTPs) in a subject, comprising: measuring the expression level of PTPs in a sample of the subject, and measuring the oxidation level of PTPs in a sample of the subject, wherein individual expression level of PTPRF, PTPRK, PTPN7, PTPN12, PTPN2, PTPN1, and oxidized level of PTPN1 are indictive for the diagnosis and/or prognosis of hepatocellular carcinoma in the subject, does not reasonably provide enablement for an in vitro method for measuring the aggregate expression level of all PTPs in a sample of a subject, and measuring the aggregate oxidation level of all PTPs in a sample of the subject, wherein the aggregate expression level and the aggregate oxidation level of all PTPs correspond to a reference value or threshold value that is characteristic of a subject with a known diagnosis, prognosis and/or disease status of cancers other than hepatocellular carcinoma, and wherein a deviation or no deviation is indicative for the diagnosis, prognosis and/or disease status of cancers other than hepatocellular carcinoma in the subject instantly claimed. 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 use the invention commensurate in scope with these claims.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is undue. These factors include, but are not limited to: (a) breadth of the claims; (b) nature of the invention; (c) state of the prior art; (d) level of one of ordinary skill in the art; (e) level of predictability in the art; (f) amount of direction provided by the inventor; (g) existence of working examples; and (h) quantity of experimentation needed to make or use the invention based on the content of the disclosure. (See Ex parte Forman 230 USPQ 546 (Bd. Pat. App. & Inter. 1986) and In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988).
The above factors, regarding the present invention, are summarized as follows:
The breadth of the claims – The breadth of the claims is drawn to a method for measuring the expression level and the oxidation level of PTPs in a sample of a subject, wherein individual expression level of PTPRF, PTPRK, PTPN7, PTPN12, PTPN2, PTPN1, and oxidized level of PTPN1 are indictive for the diagnosis and/or prognosis of hepatocellular carcinoma in the subject.
The Nature of the invention – The nature of the invention is drawn to measuring the expression level and the oxidation level of PTPs in a sample of a subject, wherein individual expression level of PTPRF, PTPRK, PTPN7, PTPN12, PTPN2, PTPN1, and oxidized level of PTPN1 are indictive for the diagnosis and/or prognosis of hepatocellular carcinoma in the subject.
The state of the prior art / The predictability or lack thereof in the art – Predicting cancer biomarker utility is difficult due to the vast diversity of cancer cells within a single tumor or between tumors of the same type, spanning genetic, phenotypic, and environmental differences, and the evolution of cancer cells over time. Diamandis (J Natl Cancer Inst. 2010;102:1462-1467.) teaches in the last decade, many reports have described new cancer biomarkers that promised to revolutionize the diagnosis of cancer and the management of cancer patients, however, many initially promising biomarkers have not been validated for clinical use (Abstract). In addition, Diamandis teaches most cancer biomarkers in clinical use are not suitable for population screening or for early diagnosis (p.1462 col right – para 2), and one requirement among many requirements is that the biomarker should be highly specific for the tissue of origin because if other tissues also produce this biomarker, then its background level in normal healthy individuals will likely be high (p.1463 col left – para 1). Therefore, cancer biomarker predictability is difficult because of significant biological tumor heterogeneity, and the high rate of failure in validating findings across different clinical trials.
The relative skill of those in the art – The relative skill of those in the art is high, with a typical practitioner possessing commensurate degree level, as well as several years of professional experience.
The amount of direction or guidance present – There is no direction or guidance present for measuring the aggregate expression level and the aggregate oxidation level of all PTPs in a sample of a subject, wherein the aggregate expression level and the aggregate oxidation level of all PTPs correspond to a reference value or threshold value that is characteristic of a subject with a known diagnosis, prognosis and/or disease status of cancers other than hepatocellular carcinoma, and wherein a deviation or no deviation is indicative for the diagnosis, prognosis and/or disease status of cancers other than hepatocellular carcinoma in the subject.
Examples provided in the instant specification demonstrate that individual expression level of PTPRF, PTPRK, PTPN7, PTPN12, PTPN2, PTPN1, and oxidized level of PTPN1 are indictive for the diagnosis and/or prognosis of hepatocellular carcinoma in a subject.
The presence or absence of working examples – The working examples present in the instant specification demonstrate that individual expression level of PTPRF, PTPRK, PTPN7, PTPN12, PTPN2, PTPN1, and oxidized level of PTPN1 are indictive for the diagnosis and/or prognosis of hepatocellular carcinoma in a subject. There are no working examples present for measuring the aggregate expression level and the aggregate oxidation level of all PTPs in a sample of a subject, wherein a deviation or no deviation between the aggregate expression level / the aggregate oxidation level of all PTPs and a reference value or threshold value is indicative for the diagnosis, prognosis and/or disease status of cancers other than hepatocellular carcinoma in the subject.
The quantity of experimentation needed – The quantity of experimentation needed is undue experimentation. Diamandis teaches many requirements must be fulfilled before a cancer biomarker can be approved for clinical use (p.1462 col right – para 3), problems can develop at many stages of biomarker discovery and validation that contribute to the short life span of many “newly discovered” biomarkers, these problems can occur during preanalytical, analytical, and postanalytical phases of cancer biomarker discovery and validation (p.1463 col left – para 2). Such a task has yet to be accomplished in the art and the instant specification provides no particular guidance on how to accomplish such a task.
A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. {In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)}.
Genetech, 108 F.3d at 1366, states that, “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion.” And “patent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable.”
Therefore, in view of the Wands factors discussed above, to practice the claimed invention herein, a person of skill in the art would have to engage in undue experimentation to measure aggregate expression level and aggregate oxidation level of all PTPs using samples from sufficient variety of cancer types encompassed in the instant claims, with no assurance of success.
Claim Rejections - 35 USC § 103
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 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 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 of this title, 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.
Claims 1, 5-6 and 26-27 are rejected under 35 U.S.C. 103 as being unpatentable over Golub et al (US 2011/0263441 A1; 10/27/2011.) in view of Karisch et al (Cell. 2011;146(5):826-840. Cited on IDS) and Hussein et al (BMC Cancer. 2018;18:836. Cited on IDS).
The instant claims recite an in vitro method for measuring protein tyrosine phosphatases (PTPs) in a subject, the method comprising: measuring the aggregate expression level of PTPs in a sample of the subject, and measuring the aggregate oxidation level of PTPs in a sample of the subject, wherein the aggregate expression level and the aggregate oxidation level correspond to a reference value or threshold value that is characteristic of a subject with a known diagnosis, prognosis and/or disease status of cancer, and wherein a deviation or no deviation is indicative for the diagnosis, prognosis and/or disease status of cancer in the subject.
Golub teaches a method for detecting, characterizing, preventing, and treating hepatic disorders such as hepatocellular carcinoma (Abstract, para 0009) and determining if a subject is at risk for developing a hepatic disorder (para 0007), comprising comparing the level of expression of a marker or a plurality of markers in a subject sample and the level of expression of the marker or plurality of markers in a control sample (para 0007), wherein the marker or plurality of markers include PTPN2, PTPRF, PTPRK, PTPN12, PTPN7, and PTPN6 (Fig. 19), determination of the level of expression of the marker or plurality of markers involves in vitro methods (para 0011), a significant difference between the level of expression of the marker or plurality of markers in the subject sample and the control sample is an indication that the subject is at risk for developing the hepatic disorder (para 0007), any marker or combination of markers may be used (para 0114), and said markers are useful in the diagnosis and/or prognosis of hepatic disorders (para 0074, 0095, 0270). In one embodiment, the marker or plurality of markers have increased expression relative to a control. In another embodiment, the marker or plurality of markers have decreased expression relative to a control. In still another embodiment, at least one marker has increased expression and at least one marker has decreased expression relative to a control (para 0008). The subject sample is fresh tissue, fresh frozen tissue, needle biopsy tissue, and fixed embedded tissue (para 0011). Samples are blood, plasma, lymph, urine, tissue, mucus, sputum, or saliva (para 0114).
Golub does not teach the method comprises measuring the aggregate oxidation level of PTPs in a sample of the subject, wherein the aggregate oxidation level corresponds to a reference value or threshold value that is characteristic of a subject with a known diagnosis, prognosis and/or disease status of cancer (claim 1), and said PTPs comprise PTPN1 (claim 6).
However, Golub does teach the method comprises measuring the aggregate expression level of PTPs in a sample of a subject, wherein the aggregate expression level corresponds to a reference value or threshold value that is characteristic of a subject with a known diagnosis, prognosis and/or disease status of cancer. Karisch teaches reversible PTP oxidation is emerging as an important cellular regulatory mechanism and might contribute to diseases such as cancer, mouse and human cells and tissues, including cancer cells, display distinctive expressed classical PTPs (PTPome) and the oxidized subset of the PTPome (oxPTPome), revealing additional levels of complexity in the regulation of protein-tyrosine phosphorylation in normal and malignant cells (Summary). Karisch teaches cancer cells often produce high levels of reactive oxygen species (ROS), PTPs were proposed as important ROS targets, oxidation of specific PTPs, including PTPN1 and PTPN2 in insulin signaling and PTPN6 in B cell receptor signaling, is required for optimal responses to various stimuli (p.2 para 3-4), and each cancer line contained a unique profile of oxidized PTPs (p.7 para 1). Karisch teaches measuring all PTP oxidation states (p.10 para 4), and comparing PTP oxidation (p.6 para 6-7).
In addition, Hussein teaches detection of oxidized-PTP might be indicative of consecutive exposure to oxidative stresses, oxidation of PTPs is common in human cancers and influences tumorigenesis, oncogenic mutation induces ROS production and that enhances mitogenic and mutogenic signaling to contribute to tumor development (p.2 col left – para 1). Hussein teaches evaluation of the expression of oxidized-PTP might be indicative for evaluation of cells under oxidative stress-mediated cellular damage (p.2 col left – last para), and the expression of oxidized-PTP is predictive for the prognosis of gastric carcinoma patients (p.6 col right – para 2).
Thus, before the effective filing date of the claimed invention, it would have been obvious to one of ordinary skill in the art to measure the aggregate oxidation level of PTPs in a sample of a subject, and to evaluate the aggregate oxidation level of PTPs in cancer prognosis, since Golub discloses that the aggregate expression level of PTPs are useful for cancer prognosis, Karisch discloses that each cancer line contains a unique profile of oxidized PTPs, and Hussein discloses that the expression of oxidized-PTP is prognostic indicator for cancer. In other words, a skill in the art would measure the aggregate oxidation level of PTPs in a sample of a subject, wherein the aggregate oxidation level corresponds to a reference value or threshold value that is characteristic of a subject with a known diagnosis, prognosis and/or disease status of cancer, since normal cells and various cancer types contain a unique profile of oxidized PTPs, oxidized PTPs indicate high levels of intracellular oxidative stress, high levels of intracellular oxidative stress are a hallmark of cancer, and oxidized PTPs have been successfully identified as effective prognostic marker for indicating poor prognosis in cancer, as evidenced by the cited references. Moreover, before the effective filing date of the claimed invention, one of ordinary skill in the art would have been motivated by the cited references to measure the aggregate oxidation level of PTPs in a sample of a subject, and to evaluate the aggregate oxidation level of PTPs in cancer prognosis with a reasonable expectation of success.
Conclusion
No claims are allowed.
Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LYNN Y FAN whose telephone number is (571)270-3541. The examiner can normally be reached on M-F 7am-4pm.
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/Lynn Y Fan/
Primary Examiner, Art Unit 1759
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