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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 12/22/25 has been entered.
Amendment Entry
2. Applicant’s response to the Final action mailed 9/5/25 is acknowledged (Reply filed 12/22/25). In the amendment filed therein claims 2-9 and 17-24 have been canceled without prejudice or disclaimer. Claims 1, 15, and 16 have been modified. Currently, claims 1 and 10-16 are pending and under consideration.
3. Objections and/or rejections of record not reiterated herein have been withdrawn.
Priority
4. This application has a priority date of 12/14/20 : This application is a 371 of PCT/IB2021/061690 filed 12/14/2021 and foreign application filed in the UNITED KINGDOM, application number 2019682.0 filed on 12/14/2020.
WITHDRAWN REJECTIONS
5. Applicants Amendment on 12/22/25 has changed the scope of the invention. The claims previously required testing a blood sample for the presence of Ipo5 along with at least one other marker (Ran, KpnB1, Kpna2, CRM1, CAS, Transportin 1, etc.), determining that the subject has cancer; and administering cancer treatment to the subject or performing surgery on the subject.
Currently the invention involves the measurement of all seven biomarkers (Ipo5, Ran, KpnB1, Kpna2, CRM1, CAS, and Transportin 1). Therein making the previous rejections under 35 USC 112(b), 101, and 103 MOOT.
REJECTONS MAINTAINED
Claim Interpretation
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
6. Claims 15 and 16 in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art.
The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
7. Accordingly, the recitation of “means for obtaining or receiving a blood sample” in claims 15 and 16; has been interpreted to read on any loading or receiving area for sample placement as defined on page 10 of the disclosure.
Response to Arguments
Applicant has not addressed the rejection. Accordingly, it is maintained.
NEW GROUNDS OF REJECTIONS NECESSITATED BY AMENDMENTS
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.
8. Claims 1 and 10-16 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.
A. Claim 1 is vague and indefinite in utilizing the following relatives terms: “threshold level” and “higher than the threshold level”. The terms are not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
On page 9 of the disclosure “threshold” is generally defined as “values [that] can be determined based on levels of biomarkers which are typically found in patients without cancer, and the levels of the biomarkers detected in the sample can be compared to the cut-off [or threshold] levels when making the determination of whether or not the subject has cancer. In other words, the method will detect whether the biomarkers in the panels are under- or over-expressed relative to a subject who does not have cancer”. However, this general description of the threshold levels does not remove ambiguity from the measured parameters because it is not clear what the cut-off or threshold value is or what will be considered “higher than” said threshold value. As such it appears that the indicators are variable with no set standard for evaluation. This leads to ambiguity in the claims.
Page 19 and Table 2 of the specification identifies the mean, median and range concentrations of serum KPNß1, CRM1, KPNa2, CAS, RAN, IPO5 and TNPO1 in non-cancer control subjects, cervical cancer and oesophageal cancer patients. Yet, the results do not appear to support the method as claimed because merely determining serum levels higher than a threshold will not distinguish controls from cancer. For example, the results for Ip05 and Tnp01 in Table 2 demonstrate that specific biomarker values are necessary for the claimed method. The median values for these biomarkers are: Ip05 control 0.2ng/ml compared to 7.2ng/ml in cervical cancer. Therefore a mere higher than value of 1.0ng/ml (higher than control of 0.2ng/ml) would not appear to be sufficient to be indicative of cervical cancer. TnP01 median control values were 10pg/ml compared to 810pg/ml in oesophageal cancer. Therefore a mere higher than value of 50pg/ml (higher than 10pg/ml) would not appear to be sufficient to be indicative of oesophageal cancer.
Additionally, the western block analysis in various cancer cell types also demonstrates that a mere higher than value as compared to control is not indicative of the presence of cancer. For example, in figure 6 – RAN and CAS do appear to not have higher than bands as compared to control in all the cell types (see CaSKi, MCF7, and HepaRG).
It is suggested that the claim includes the actual measured values associated with cancer detection in order to obviate the rejection (i.e. Ip05 of 7.2ng/ml in cervical cancer and 4.7ng/ml in oesophageal cancer). Appropriate correction is required.
B. In claim 15, “the biomarkers” in line 6 lacks antecedent bases because biomarker is not previously recited in the claim. There is insufficient antecedent basis for this limitation in the claim. Appropriate correction is required.
C. Claim 16 is vague and indefinite because it is not clear as to what the kit will include. As recited the claim is drawn to one or more of the listed components. It is not clear if the kit comprises all of the listed components or only one. For example, will the kit comprise only the capture agents, only instructions, only the device of claim 15, or only a means for collecting the sample. It is suggested that “one or more of” is omitted in order to remove ambiguity. Please clarify the contents of the kit.
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.
9. Claims 1 and 10-15 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 methods of detecting a biomarker combination that includes KPNß1, CRM1, KPNa2, CAS, RAN, IPO5 and TNPO1 in patient bloods samples and allowing for the differential expression in non-cancer control subjects, cervical cancer and oesophageal cancer patients, it does not provide enablement for any and all cancers wherein a mere higher than threshold value is obtained.
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 or use the invention commensurate in scope with the instant claims.
Claims 1 and 10-15 are drawn to a method of diagnosing and treating cancer in a subject, comprising the step of: a) contacting a blood sample from a subject with capture agents which bind to the following biomarkers: Ipo5 (Importin 5), Ran (Ras-related nuclear protein), Kpnß1 (Karyopherin beta 1), Kpnα2 (Karyopherin alpha 2), CRM1 (XP01 / Chromosome Region Maintenance 1 Protein Homolog), CAS (Cellular apoptosis- susceptibility protein) and Transportin 1; b) detecting binding of the capture agents to each of the biomarkers; c) measuring the levels of the detected biomarkers; d) comparing the level of each of the detected biomarkers with a threshold level of the same biomarker associated with subjects without cancer; e) determining that the subject has cancer if the level of each of the biomarkers in the blood sample is higher than the threshold level of the same biomarker associated with subjects without cancer; and f) administering an effective amount of cancer treatment to the subject determined to have cancer or performing surgery on the subject determined to have cancer.
However, the specification does not teach methods to measure any and all cancers wherein of serum KPNß1, CRM1, KPNa2, CAS, RAN, IPO5 and TNPO1 in any and all cancers are determined to be simply higher that the levels found in non-cancer control subjects.
On page 9 of the disclosure “threshold” is generally defined as “values [that] can be determined based on levels of biomarkers which are typically found in patients without cancer, and the levels of the biomarkers detected in the sample can be compared to the cut-off [or threshold] levels when making the determination of whether or not the subject has cancer.
In other words, the method will detect whether the biomarkers in the panels are under- or over-expressed relative to a subject who does not have cancer”. However, this general description of the threshold levels does not remove ambiguity from the measured parameters because it is not clear what the cut-off or threshold value is or what will be considered “higher than” said threshold value. As such it appears that the indicators are variable with no set standard for evaluation. This leads to ambiguity in the claims.
Page 19 and Table 2 of the specification identifies the mean, median and range concentrations of serum KPNß1, CRM1, KPNa2, CAS, RAN, IPO5 and TNPO1 in non-cancer control subjects, cervical cancer and oesophageal cancer patients. Yet, the results do not appear to support the method as claimed because merely determining serum levels higher than a threshold will not distinguish controls from cancer. For example, the results for Ip05 and Tnp01 in Table 2 demonstrate that specific biomarker values are necessary for the claimed method.
The median values for these biomarkers are: Ip05 control 0.2ng/ml compared to 7.2ng/ml in cervical cancer. Therefore a mere higher than value of 1.0ng/ml (higher than control of 0.2ng/ml) would not appear to be sufficient to be indicative of cervical cancer.
TnP01 median control values were 10pg/ml compared to 810pg/ml in oesophageal cancer. Therefore a mere higher than value of 50pg/ml (higher than 10pg/ml) would not appear to be sufficient to be indicative of oesophageal cancer.
Additionally, the western block analysis in various cancer cell types also demonstrates that a mere higher than value as compared to control is not indicative of the presence of cancer. For example, in figure 6 – RAN and CAS do appear to not have higher than bands as compared to control in all the cell types (see CaSKi, MCF7, and HepaRG).
The nature of the invention is an in vivo method of treatment.
The level of skill of one skilled in this art is high.
Upon further review of the claims and specification, it is clear that, in light of the specification, the claims as broadly recited, as interpreted are not enabled to their full scope.
In view of the lack of the predictability of the art to which the invention pertains, the lack of guidance and direction provided by applicant, and the absence of working examples, undue experimentation would be required to practice the methods claimed with a reasonable expectation of success, absent a specific and detailed description in applicant’s specification of how to effectively practice this and absent working examples providing evidence which is reasonably predictive that the claimed serum biomarkers are functional/operable, commensurate in scope with the claimed invention.
It is recommended that Applicant amend the claims to recite specific biomarker detection levels that provide for cervical and oesophageal cancer assessments as taught by the disclosure.
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.
10. Claims 1 and 10-14 are rejected under 35 U.S.C. 101 because the claimed invention is not directed to patent eligible subject matter. Based upon an analysis with respect to the claims as a whole, the claims are determined to be directed to a law of nature/natural principle and abstract ideas (testing of natural compositions without wet steps that broadly read on mental processes). The claimed invention is directed to a natural phenomenon and/or abstract ideas without significantly more.
The rationale for this determination is explained below: A claim that focuses on the use of a natural principle (such as testing of a natural phenomenon or biomarkers Ipo5, Ran, KpnB1, Kpna2, CRM1, CAS and Transportin 1), must also include additional elements or steps to show that the inventor has been practically applied, or added something significant to, the natural principle itself. See Mayo, 101 USPQ2d at 1966.
To show integration, the additional elements or steps must relate to the natural principle in a significant way to impose a meaningful limit on the claim scope.
The analysis turns on whether the claim has added enough to show a practical application. See id. at 1968. In other words, the claim cannot cover the natural principle itself such that it is effectively standing alone. A bare statement of a naturally occurring correlation, albeit a newly discovered natural correlation or very narrowly confined correlation, would fail this inquiry. See id. at 1965, 1971.
It is not necessary that every recited element or step integrate or relate to the natural principle as long as it is applied in some practical manner.
However, there must be at least one additional element or step that applies, relies on or uses the natural principle so that the claim amounts to significantly more than the natural principle itself.
Along with integration, the additional steps must be sufficient to ensure that the claim amounts to significantly more than the natural principle itself by including one or more elements or steps that limit the scope of the claim and do more than generally describe the natural principle with generalized instructions to “apply it.” See id. at 1965,
1968. The additional elements or steps must narrow the scope of the claim such that others are not foreclosed from using the natural principle (a basic tool of scientific and technological work) for future innovation.
Elements or steps that are well-understood, purely conventional, and routinely taken by others in order to apply the natural principle, or that only limit the use to a particular technological environment (field-of-use), would not be sufficiently specific. See id. at 1968.
Claim(s) 1 and 10-14 recite(s): methods, which comprises testing a blood sample for the presence of Ipo5, Ran, KpnB1, Kpna2, CRM1, CAS, Transportin 1.
detecting, comparing, and determining that the subject has cancer; and administering cancer treatment to the subject or performing surgery on the subject.
The methods “detecting, comparing, and determining that the subject has cancer” reads on mental processed as it is not related to the presence of a biomarkers and does not include any method of measurement (units of concentration, nonmental comparison to a normal control, or commercially available techniques, such as laboratory- based techniques including ELISA, micro-array or multiplex bead array technology as defined on page 9 of the disclosure). See claims 1 and 10-14. This wording reads on mental processes or an abstract idea wherein the detecting, comparing, and determination can be conducted mentally or by a visual signal (without a wet step). Therein, reading on a mental analysis (JE) that is not integrated.
Additionally, the judicial exception is not integrated into a practical application because all the listed biomarkers may not be higher than the threshold value. Claim 1 step e includes an “if clause” that only necessitates treatment when all of the biomarkers are present above their respective threshold values. As written, in some embodiments, the treatment step does not occur.
The invention appears to be the measurement of all 7 biomarkers for sensitivity/specificity in cervical and esophageal cancer. The cutoff values, sensitivity, and specificity varies for each individually measured biomarker but the combined measurements demonstrated improved detection limitations. See Table 3 and Table 4.
In the instant case the claims are directed to the measurement of a naturally occurring protein (Ipo5, Ran, KpnB1, Kpna2, CRM1, CAS and Transportin 1). The prior art teaches that the measurement of these biomarkers in cancer is known. For example, see van der Watt et al. (Cancer Cell Biology, Vol.124, Issue 8, pages 1829-1840, 4/15/09).Therefore the assays are routinely conducted in the prior art.
Further “detecting, determining presence and comparing” data is information regarding a sample or test subject to a control or target data that reads on “An Idea ‘Of Itself’” as when given its broadest reasonable interpretation, such a comparison would read on a mental process that could be performed in the human mind, or by a human using pen and paper. (detecting is cited at a high degree of generality, while determining and comparing the presence or a signal could conceivably involve a visual analysis for color indication without any additional hand of man requirement) See July 2015 Update, Quick Reference Guide.
Similar mental processes have been held by the courts to be abstract ideas, e.g., collecting and comparing known information in Classen, or comparing information regarding a sample or test subject to a control or target data in Ambry and Myriad CAFC.
The specific information that is being compared the presence of “(Ipo5, Ran, KpnB1, Kpna2, CRM1, CAS and Transportin 1” merely narrows the abstract idea, which does not make the determining/comparison step less abstract and is not sufficient to provide eligibility on its own.
In particular, the “detecting, determining, and administering” step is recited at a high level of generality and is not sufficient to ensure that the claims amount to significantly more than the naturally occurring correlation itself.
This is because every application of the correlation would require detecting the of the biomarker; because the “determining or detecting” step does not relate to the natural principle in a significant way to impose a meaningful limit on the claim scope (for example, see claims 1 and 10-14).
Limitations that are necessary for all practical applications of the natural principle, such that everyone practicing the natural principle would be required to perform those steps or every product embodying that natural principle would be required to include those features, would not be sufficient to confer patent eligibility.
In addition, appending conventional steps, specified at a high level of generality, to a natural principle does not make the claim patent-eligible. Steps that amount to instructions that are well-understood, routine, conventional activity, previously engaged in by those in the field add nothing specific to the natural principle that would render it patent-eligible.
The claims do not include additional elements/steps or a combination of elements/steps that are sufficient to ensure that the claims amount to significantly more than a natural principle itself. This is because (1) the claims would cover every substantial practical application of the correlation and (2) the additional steps recited in the claim were previously taken by those in the field. When the claims are considered as a whole, the steps taken together amount to no more than recognizing the law of nature itself.
The claimed invention is directed to non-statutory subject matter because the claims are drawn to mental analyses that are not integrated into a practical application. Therefore, the claimed invention is not directed to patent eligible subject matter.
Based upon consideration of all of the relevant factors with respect to the claims as a whole, the “detecting, determining and comparing” step in claim(s) 1 and 10-14 is determined to be directed to an abstract idea. The rationale for this determination is explained below:
Mental determinations of possible effects are not patentable. Simply reciting “detecting, comparing, and determining cancer” does not provide proper patentable limitations. The judicial exceptions, reading on mental processes have not been integrated into the claimed method.
The active method steps of the present claims; detecting, determining and administering in a cancer patient are conventional, well understood and routine. See Zhang et al. (Journal of Experimental & Clinical Cancer Research, July 2019, 38:296, pages 1-14, https://doi.org/10.1186/s13046-019-1290-0) and van der Watt et al. (Cancer Cell Biology, Vol.124, Issue 8, pages 1829-1840, 4/15/09). These steps are the activities that a scientist would have relied upon to achieve the goals of the invention. The steps are interpreted as being drawn to mental steps and/or computer-implemented abstract ideas and are insufficient to make an otherwise ineligible claims patent eligible, the claims are ineligible subject matter under 35 U.S.C. 101. (Alice Corporation Pty. Ltd. v. CLS Bank International, et al). In the present claims there are no other active method steps that transform the process into an inventive application of the detected biomarker(s).
The analysis is to be used for evaluating whether a claim is drawn to patent-eligible subject matter.
Step 1 determines whether the claim is directed to a process, machine, manufacture, or composition of matter. If the claim is directed to a statutory category, proceed to Step 2.
Step 2 is the two-part analysis from Alice Corp. (also called the Mayo test) for claims directed to laws of nature, natural phenomena, and abstract ideas (the judicially recognized exceptions).
In Step 2A, Prong 1 determine whether the claim is directed to a law of nature, a natural phenomenon, or an abstract idea enumerated in the 2019 PEG (judicial exceptions) and
Step 2A, Prong 2 determine whether the claim recites additional elements that integrate the exception into a practical application of the exception
If the exception is not integrated into a practical application, then proceed to Step 2B determines whether the claim as a whole, amounts to significantly more than the exception.Analysis of Claim 1:
I. The present claims are directed to a process so Step 1 is satisfied.
II. The present claims are directed to judicial exceptions? Wherein mental processes are utilized at least in claim 1 (detecting, comparing, and determining biomarkers in a patient sample); for a diagnosis of cancer (cervical, esophageal, liver, or breast) and administering a treatment to a cancer patient. The methods are drawn to a natural phenomenon (JE). And this judicial exception includes mental processes - concepts performed in the human mind (including an observation, evaluation, judgment, opinion). Therefore, step 2A Prong 1 and Prong 2 is satisfied.
Claims 1 and 10-14 are directed to an abstract idea that is not integrated into a practical application (the JE is not integrated into a practical application).
The scope of claim 1 encompasses embodiments where the biomarker are not present at higher than threshold values. Therein making the method in operable and further not integrating the JE (mental comparison) into to the claimed methods. (determining and comparing for presence can result in detection or non-detection of the biomarker).
The recited abstract ideas are insufficient to make an otherwise ineligible claim patent eligible without significantly more recited in the claim. The detecting/determining/comparing step can be done by merely reviewing the data mentally and mentally making a determination. See Bilski V. Kappos 95 USPQ2d 1001 (2010). Additionally, see Mayo Collaborative Services v. Prometheus Laboratories Inc. 101 USPQ2d 1961 (2012) at 1965, quoting Gottschalkv. Benson, 409 U.S. 63, 67 [175 USPQ 673] (1972).
("Phenomena of nature, though just discovered, mental processes, and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work."). Furthermore, the method of “detecting, comparing, and determining” does not actually require an active step of treatment but encompasses abstract ideas and are insufficient to make an otherwise ineligible claims patent eligible, the claims are ineligible subject matter under 35 U.S.C. 101. (Alice Corporation Pty. Ltd. v. CLS Bank International, et al.).
III. Step 2B, is to determine whether the claim as a whole amount to significantly more than the exception. The active method steps of claim 1 are detecting, comparing, determining and administering.
All of the additional claim elements listed are well-understood, routine, and conventional in this art. The active method steps of the present claims are conventional, well understood and routine.
These steps are the activities that a scientist would have relied upon to achieve the goals of the invention. The steps are interpreted as being drawn to mental steps and/or computer-implemented abstract ideas and are insufficient to make an otherwise ineligible claims patent eligible, the claims are ineligible subject matter under 35 U.S.C. 101. (Alice Corporation Pty. Ltd. v. CLS Bank International, et al).
In the present claims there are no other active method steps that transform the process into an inventive application.
In sum, when the relevant factors are analyzed, they weigh against the present claim amounting to significantly more than the judicial exceptions themselves. Accordingly, the claims do not qualify as eligible subject matter.
The subject matter which courts have found to be outside of, or exceptions to, the four statutory categories of invention is limited to abstract ideas, laws of nature and physical phenomena. Bilski v. Kappos, 561 U.S. ___, ___, 130 S. Ct. 3218, 3225, 95 USPQ2d 1001, ___ (2010) (citing Diamond v. Chakrabarty, 447 U.S. 303, 309, 206 USPQ 193, 197 (1980)). While this is easily stated, determining whether an applicant is seeking to patent an abstract idea, a law of nature or a physical phenomenon has proven to be challenging.
These three exclusions recognize that subject matter that is not a practical application of an idea, a law of nature or a physical phenomenon is not patentable. See, e.g., Rubber-Tip Pencil Co. v. Howard, 87 U.S. (20 Wall.) 498, 507 (1874) (“idea of itself is not patentable, but a new device by which it may be made practically useful is”);
Mackay Radio & Telegraph Co. v. Radio Corp. of America, 306 U.S. 86, 94, 40 USPQ 199, 202 (1939) (“While a scientific truth, or the mathematical expression of it, is not patentable invention, a novel and useful structure created with the aid of knowledge of scientific truth may be.”).
The courts have also held that a claim may not preempt abstract ideas, laws of nature or physical phenomena; i.e., one may not patent every “substantial practical application” of an abstract idea, law of nature or physical phenomenon. This is because such a patent would “in practical effect be a patent on the [abstract idea, law of nature or physical phenomenon] itself. ”Gottschalk v. Benson, 409 U.S. 63, 71-72, 175 USPQ 673, 676 (1972).
The concern over preemption was expressed as early as 1852. See Le Roy v. Tatham, 55 U.S. 156, 175 (1852) (“A principle, in the abstract, is a fundamental truth; an original cause; a motive; these cannot be patented, as no one can claim in either of them an exclusive right.”).
Examiners are reminded that 35 U.S.C. 101 is not the sole tool for determining patentability; where a claim encompasses an abstract idea, 35 U.S.C. 112, 35 U.S.C. 102 , and 35 U.S.C. 103 will provide additional tools for ensuring that the claim meets the conditions for patentability. As the Court made clear in Bilski:
Accordingly, to the reasons set forth above, claims 1 and 10-14 are ineligible. Also, see Alice v. CLS Bank.
Response to Arguments
Applicant argues that the amended claims recite the detection, comparing, and determining Ipo5, Ran, Kpnß1, Kpna2, CRM1, CAS and Transportin 1 in blood. And the method was not previously taken/taught by those in the field, nor were they conventional, well understood and routine, as alleged by the Examiner. In particular, Applicant contends that the seven antibody combination in blood was not contemplated for cancer analysis. This argument was carefully considered but was not found persuasive because the rejection under 35 USC 101 is directed to mental processes and/or abstract ideas. The cited prior art under 35 USC 101 is to establish routine assays in general. The assessment of the specific method embodiment with respect to judicial exceptions is what is at issue. The steps of “detecting, comparing, and determining that the subject has cancer is an abstract idea reading on mental processes that is a judicial exception that has not been integrated into the process. Additionally, the claims include an “if clause” wherein the treatment is not conducted or integrated into the method. Therefore the rejection is maintained.
Claim Rejections - 35 USC § 103
11. 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.
It is noted that the kit as claimed merely requires one of the listed components, therefore the prior art does not have to teach blood samples to read on the invention. The cited prior art teaches at least kits including instructions for biomarker analysis in cancer.
12. Claim(s) 16 is/are rejected under 35 U.S.C. 103 as being unpatentable over van der Watt et al. (Cancer Cell Biology, Vol.124, Issue 8, pages 1829-1840, 4/15/09) in view of Stelma et al. (IUBMB Life, 68(4):268–280, 2016) and Li et al. (European Review for Medical and Pharmacological Sciences, April 24, 2020, 24, pages 4246-4254) and further in view of Vashist & Luong (Point of Care Technologies Enabling Next Generation Healthcare Monitoring and Management, Springer, 2019, pages 1-232, ISBN 978-3-030-11416-9) and Foster (4,444,879).
Van der Watt et al. teach methods for measuring increased expression of members of the nuclear transport protein family in cancer cells. Nuclear transport proteins have been reported to be secreted by cells and found in the serum. In this study, mass spectrometry identified 10 nuclear transport proteins in the secretome and exosomes of cultured cancer cells, and Western blot analysis confirmed increased secreted levels in cancer cells compared to normal.
To investigate their presence in patient serum, enzyme-linked immunosorbent assays were performed and revealed significantly increased levels of KPNβ1, CRM1, CAS, IPO5 and TNPO1 in cervical and oesophageal cancer patient serum compared to non-cancer controls. See abstract.
Van der Watt et al. differ from the instant invention in not specifically disclosing all of the biomarkers listed in the claims and their relationship to other cancers including liver cancer and breast cancer.
However, Stelma et al. disclose that in cancer cells, the altered expression or localization of nuclear transporters as well as the disruption of endogenous nuclear transport inhibitors may result in Karyopherin protein dysregulated.
And the value of nuclear transporters in the diagnosis, prognosis and treatment of cancer is currently being elucidated with recent studies highlighting their potential as biomarkers and therapeutic targets. See abstract.
The elevated expression of the Karyopherin proteins associates with the global dysregulation of protein transport and this has been observed in various types of cancer. Amongst all members of the Karyopherin family, XPO1, KPNB1, KPNA2 and CSE1L are the most frequently reported to be overexpressed in cancer (Table 1). See page 272. Table 1 outlines several biomarkers including the ones recited in the claims. And also identifies them as indicators in various cancers including liver and breast.
The upregulation of nuclear transporters and their association with poor prognosis in cancer highlights their potential as therapeutic targets. Page 275. Nuclear transport proteins play an essential role in cellular functioning.
The increased reliance, of transformed and cancer cells, on the nuclear transport proteins for their increased metabolic demands warrants their usefulness as chemotherapeutic targets.
More recently, the potential of nuclear transporters as cancer biomarkers has been investigated. For example, the secretion of certain Karyopherin proteins into the urine or serum of cancer patients shows diagnostic potential, while the differential expression of Karyopherin proteins in cancer tissue in comparison to normal tissue suggests that these proteins have potential as prognostic markers as well. See conclusion and perspectives.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include the biomarkers taught by the prior art reference to Stelma et al. in the multiple biomarker cancer diagnosis method of van der Watts et al. because Stelma et al. taught that certain members of the Karyopherin family, XPO1, KPNB1, KPNA2 and CSE1L are the most frequently reported to be overexpressed in cancer (Table 1).
Absent evidence to the contrary combining biomarkers previously taught in the prior art (references to van der Watts and Stelma et al.) in order to detect cancers previously identified (liver and breast cancer) in the prior art is an obvious selection of design choice that is routinely conducted in the art.
Van der Watts in view of Stelma et al. differ from the instant invention in not specifically teaching a nexus between Ipo5 and cancer. However, Li et al. disclose that IPO5 expression significantly increased in esophageal cancer tissues, which was associated with pathological staging and poor prognosis of esophageal cancer patients. IPO5 may promote malignant progression of esophageal cancer through the regulation of MMP7. See abstract – Conclusion.
The researchers taught that their findings undoubtedly provide a new direction in the treatment of esophageal cancer. [As the] IPO5/MMP7 axis may be utilized as effective markers for screening and treating esophageal cancer. See page 4253.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to employ Ipo5 as a marker for cancer because Li et al. taught that the IPO5/MMP7 axis may be utilized as effective markers for screening and treating esophageal cancer. See page 4253.
A change in physical form is not patentable unless it is more efficacious or possess new properties by a combination with other ingredients and not merely a change of form which has the advantages which one skilled in the art would expect from the change. Glue Co. v. Upton (USSC 1878) 97 US 3, 24 L. Ed. 985.
KSR forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness. See recent Board decision Ex parte Smith,— USPQ2d—, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007)(citing KSR, 82 USPQ2d at 1396).
While the prior art references to van der Watt et al. in view of Stelma et al., Li et al. and further in view of Vashist & Luong teach the reagents required by the claims; they do not specifically teach the reagents in kit configurations. In other words, the reference fails to teach the reagents as a kit.
However, kits are well known embodiments for assay reagents. Foster et al.
(U.S. Patent #4,444,879) describe one example. In their patent kits including the reactant reagents, a microplate, positive controls, negative controls, standards, and instructions are taught. The reagents are compartmentalized or packaged separately for utility. See figure 6, and column 15, lines 10-34.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to take the detection reagent taught by the prior art (van der Watt et al. in view of Stelma et al., Li et al. and further in view of Vashist & Luong) and format it into a kit because Foster et al. teach that it is convenient to do so and one can enhance sensitivity of a method by providing reagents as a kit. Further, the reagents in a kit are available in pre-measured amounts, which eliminates the variability that can occur when performing the assay. Kits are also economically beneficial in reagent distribution.
It is also worth noting that the printed matter on instructions merely teaches the use of an existing product, and thus cannot impart patentability. See In re Ngai, 5/13/04, Michel, Gajarsa, Linn, per curiam.
In other words the printed matter on the instructions in a kit cannot serve to define the kit over the prior art. See In re Gulack, 217 USPQ (CAFC 1983).
Response to Arguments
13. Applicant contends that van der Watt (2009) does not teach or suggest that Ipo5, Ran, Kpnß1, Kpnα2, CRM1, CAS and Transportin 1 are a suitable combination for diagnosing cancer in blood, and Stelma, Li and Vashist & Luong do not remedy the deficiencies of van der Watt (2009). Applicant respectfully submits that Foster also does not remedy the deficiencies of van der Watt (2009), Stelma, Liand Vashist & Luong, as Foster does not refer to cancer biomarkers, much less teach or suggest that Ipo5, Ran, Kpnß1, Kpnα2, CRM1, CAS and Transportin 1 are a suitable combination for diagnosing cancer in blood.
This argument was carefully considered but not found persuasive because the kit of claim 16 is not limited to the blood sample measurements of Ipo5, Ran, Kpnß1, Kpnα2, CRM1, CAS and Transportin 1. The claim reads on “one or more of the following.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
In response to applicant's argument that the references do not teach Ipo5 in combination with only Ran or Kpnβ1, the test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references.
Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981).
14. For reasons aforementioned, no claims are allowed.
15. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LISA V COOK whose telephone number is (571)272-0816. The examiner works a flexible schedule but can normally be reached on Monday-Friday from 9am to 5pm.
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Lisa V. Cook
Patent Examiner
Art Unit 1642
Hoteling
2/20/26
/LISA V COOK/Primary Examiner, Art Unit 1642