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 .
1. Claims 1-8 as amended on July 12, 2023 are pending and under consideration.
Priority
2. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
It is noted that the Examiner has established a priority date of January 13, 2022 for claims 1-8 of the instant application because the priority of the instantly claimed inventions is based on the prior filed application JP2021-0036671 which is written in Japanese. The prior filed application has not been translated and the Examiner is unable to determine the information in the document.
If Applicant disagrees with any rejection set forth in this action based on examiner's establishment of a priority date of January 13, 2022 for claims 1-8, then Applicant is invited to submit a proper translation of the priority document and to point to page and line where support can be found establishing an earlier priority date. If Applicant chooses to file a translation, then the translation must be filed together with a statement that the translation of the certified copy is accurate. See 35 U.S.C. 119 (b)(3), 37 C.F.R. 1.55(g)(3)(4), 37 C.F.R. 1.78(d)(7), and MPEP 1895.01.
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.
3. Claims 6-8 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 6 is drawn to a method for predicting efficacy determination of an antiplatelet agent in a method for assessing a risk of cancer-associated thrombosis in a perioperative period of a cancer patient, by providing samples derived from the cancer patient from preoperative period to 30 days postoperatively over time, and monitoring risk assessment continuously.
Given that method is drawn to both predicting efficacy determination of an antiplatelet agent and a method for assessing a risk of cancer-associated thrombosis, it is unclear what the objective of the claimed method is given that the method steps are only drawn to providing samples and monitoring risk assessment. Thus this lack of clarity renders the claim and its dependent claims indefinite. The claim will be interpreted to be drawn to either objective alternatively.
Additionally, it is unclear what steps are required to be performed and for how long to meet the limitation of “monitoring risk assessment continuously”. Does the cancer patient need to be monitored over the entire perioperative period to meet the limitation or can the monitoring be intermittent? How often do samples need to be obtained to allow for monitoring risk continuously? Thus this lack of clarity renders the claim indefinite and its dependent claims.
Regarding claim 7, the parenthetical phrase "(lung, esophageal, cervix, and the like)" renders the claim indefinite because it is unclear whether the limitation(s) the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
4. Claim 5 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 5 is drawn to the method according to claim 1, wherein a value obtained by dividing the soluble CLEC2 concentration by a platelet count is used instead of the soluble CLEC2 concentration. Claim 5 switches the measure of soluble CLEC2 from its concentration in claim 1 to a value obtained by dividing the soluble CLEC2 concentration by a platelet count. Thus claim 5 fails to include all the limitations of the claim upon which it depends.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
5. Claims 6-8 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 a method for predicting efficacy determination of an antiplatelet agent in a method for assessing a risk of cancer-associated thrombosis in a perioperative period of a cancer patient, by measuring a concentration of soluble CLEC2 in blood samples derived from the cancer patient from preoperative period to 30 days postoperatively over time, and monitoring risk assessment continuously, does not reasonably provide enablement for a method for predicting efficacy determination of an antiplatelet agent in a method for assessing a risk of cancer-associated thrombosis in a perioperative period of a cancer patient, by providing samples derived from the cancer patient from preoperative period to 30 days postoperatively over time, and monitoring risk assessment continuously. 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.
The factors to be considered in determining whether undue experimentation is required are summarized in In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988). The court in Wands states: "Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations." (Wands, 8 USPQ2d 1404). The factors to be considered in determining whether undue experimentation is required include: (1) the quantity of experimentation necessary, (2) the amount or direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims.
The claims are broadly drawn to a method for predicting efficacy determination of an antiplatelet agent in a method for assessing a risk of cancer-associated thrombosis in a perioperative period of a cancer patient, by providing samples derived from the cancer patient from preoperative period to 30 days postoperatively over time, and monitoring risk assessment continuously. Thus, the claims encompass method for predicting efficacy determination of an antiplatelet agent or assessing a risk of cancer-associated thrombosis in a perioperative period of a cancer patient by simply providing samples derived from the cancer patient in the perioperative period.
The specification teaches that if the sCLEC2 concentration is higher than that of normal persons or a non-thrombotic and hemostatic disease group, it can be said that the possibility of having a CAT thrombotic and hemostatic disease or the risk of contracting such a disease is high. Based on such a comparison, the sCLEC2 concentration can be compared between pre- and postoperative periods and used as a risk prediction for thrombosis. See p. 8-¶ 0040.
The specification teaches that if the sCLEC2 concentration is measured in patients with pancreatic cancer or brain tumors, and the ratio of sCLEC2 concentration is high, it can be judged that platelet activation in vivo is occurring, and may be used to administer antiplatelet agents such as aspirin as primary prophylaxis. See p. 8-¶ 0041.
The specification teaches that sCLEC2 is elevated in the plasma of pancreatic cancer patients and elevated levels of were found in patients with high thrombosis risk. See Example 2.
The specification teaches that sCLEC2 is elevated in the plasma of brain tumor patients and elevated levels of were found in patients with deep vein thrombosis (DVT) and pulmonary artery embolism (PE). See Example 3 and Fig. 5-7.
The specification teaches that sCLEC2 concentration is sensitive to therapy. See p. 15-¶ 0067.
One of skill in the art cannot extrapolate the teachings of the specification to enable the scope of the claims because the specification discloses measuring the concentration of sCLEC2 in blood to predict efficacy of an antiplatelet agent or for assessing a risk of cancer-associated thrombosis in a perioperative period of a cancer patient. However, the specification does not teach how simply providing samples derived from the cancer patient in the perioperative period can be used to predict efficacy of an antiplatelet agent or for assessing a risk of cancer-associated thrombosis. Thus, given the breadth of the claims in absence of sufficient guidance in the specification as filed undue experimentation would be required to make and use the method as broadly claimed.
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.
6. Claims 1-8 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract, mental correlation of a natural law/phenomenon without significantly more without significantly more. The claims recite assessing a risk of cancer-associated thrombosis in a perioperative period of a cancer patient or predicting efficacy determination of an antiplatelet agent by measuring a concentration of soluble CLEC2 in blood collected from the cancer patient or providing samples from the cancer patient. This judicial exception is not integrated into a practical application because the claims generally link the natural soluble CLEC2 concentration or providing samples with assessing a risk of cancer-associated thrombosis. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because claims determine the level of soluble CLEC2 concentration or provides samples a high level of generality and that were well-understood, purely conventional or routine in art
A claim that focuses on use of a natural principle must also include additional elements or steps to show that the inventor has practically applied, and added something significant to, the natural principle itself. See Mayo, 101 USPQ2d at 1966. Patents cannot be obtained on subject matter identified by the courts as being exempted from eligibility (i.e., laws of nature, natural phenomenon, and abstract ideas).
The Mayo framework provides that first whether the claims at issue are directed to a patent-ineligible concept is determined. If the answer is yes, then the elements of each claim both individually and “as an ordered combination” are considered to determine whether additional elements “transform the nature of the claim” into a patent-eligible application. The second step—known as the “inventive concept”—requires that claims include elements which would render the method both new and useful.
The recent Eligibility Guidance (2014 Interim Guidance on Patent Subject Matter Eligibility (Interim Eligibility Guidance and 2018 Revised Patent Subject Matter Eligibility Guidance published in the Federal Register (84 FR 50) on January 7, 2019) address the subject matter eligibility analysis for all claims (i.e., machine, composition of matter, manufacture and process claims). 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 for claims directed to laws of nature, natural phenomena, and abstract ideas (the judicially recognized exceptions).
In Step 2A, determine whether the claim is directed to a law of nature, a natural phenomenon, or an abstract idea (judicial exceptions). “Directed to” means the exception is recited in the claim, i.e., the claim sets forth or describes the exception.
In Prong One of Step 2A it is determined if the claim recites a judicial exception. If the claim recites a judicial exception then Prong Two of Step 2A determines whether the claims recites additional elements that integrate the exception into a practical application.
If the answer to Prong Two of Step 2A is no, Step 2B is used to determine whether the claim as a whole amounts to significantly more than the exception by the recitation of additional elements.
The present claims are directed to processes so Step 1 is satisfied.
For Prong One of Step 2A the claims recite a judicial exception. In particular, the claims recite assessing a risk of cancer-associated thrombosis in a perioperative period of a cancer patient or predicting efficacy determination of an antiplatelet agent by measuring a concentration of soluble CLEC2 in blood collected from the cancer patient or providing samples from the cancer patient. This is an abstract, mental correlation of the soluble CLEC2 concentration or the provided samples with assessing a risk of cancer-associated thrombosis or predicting efficacy determination of an antiplatelet agent. So the answer to Prong One of Step 2A is yes the claims do recite a judicial exception.
For Prong Two of Step 2A the claims do not integrate the exception into a practical application. This judicial exception is not integrated into a practical application because the claims generally link the natural soluble CLEC2 concentration or providing samples with assessing a risk of cancer-associated thrombosis or predicting efficacy determination of an antiplatelet agent. So the answer to Prong Two of Step 2A is no.
With respect to Step 2B MPEP 2106.05 (I) teaches that
While abstract ideas, natural phenomena, and laws of nature are not eligible for patenting by themselves, claims that integrate these exceptions into an inventive concept are thereby transformed into patent-eligible inventions. Alice Corp. Pty. Ltd. v. CLS Bank Int'l, 134 S. Ct. 2347, 2354, 110 USPQ2d 1976, 1981 (2014) (citing Mayo Collaborative Servs. v. Prometheus Labs., Inc., 566 U.S. 66, 71-72, 101 USPQ2d 1961, 1966 (2012)). Thus, the second part of the Alice/Mayo test is often referred to as a search for an inventive concept. Id.
An inventive concept "cannot be furnished by the unpatentable law of nature (or natural
phenomenon or abstract idea) itself." Genetic Techs. v. Merial LLC, 818 F.3d 1369, 1376, 118 USPQ2d 1541, 1546 (Fed. Cir. 2016). See also Alice Corp., 134 S. Ct. at 2355, 110 USPQ2d at 1981 (citing Mayo, 566 U.S. at 78, 101 USPQ2d at 1968 (after determining that a claim is directed to a judicial exception, "we then ask, ‘[w]hat else is there in the claims before us?") (emphasis added)); RecogniCorp, LLC v. Nintendo Co., 855 F.3d 1322, 1327, 122 USPQ2d 1377 (Fed. Cir. 2017) ("Adding one abstract idea (math) to another abstract idea (encoding and decoding) does not render the claim non-abstract"). Instead, an "inventive concept" is furnished by an element or combination of elements that is recited in the claim in addition to (beyond) the judicial exception, and is sufficient to ensure that the claim as a whole amounts to significantly more than the judicial exception itself. Alice Corp., 134 S. Ct. at 2355, 110 USPQ2d at 1981 (citing Mayo, 566 U.S. at 72-73, 101 USPQ2d at 1966
With respect to Step 2B MPEP 2106.05 (d) teaches that:
Another consideration when determining whether a claim recites significantly more than a judicial exception is whether the additional element(s) are well-understood, routine, conventional activities previously known to the industry. If the additional element (or combination of elements) is a specific limitation other than what is well-understood, routine and conventional in the field, for instance because it is an unconventional step that confines the claim to a particular useful application of the judicial exception, then this consideration favors eligibility. If, however, the additional element (or combination of elements) is no more than well-understood, routine, conventional activities previously known to the industry, which is recited at a high level of generality, then this consideration does not favor eligibility.
On the other hand, Mayo Collaborative Servs. v. Prometheus Labs., Inc., 566 U.S. 66, 67, 101 USPQ2d 1961, 1964 (2010) provides an example of additional elements that were not an inventive concept because they were merely well-understood, routine, conventional activity previously known to the industry, which were not by themselves sufficient to transform a judicial exception into a patent eligible invention. Mayo Collaborative Servs. v. Prometheus Labs., Inc., 566 U.S. 66, 79-80, 101 USPQ2d 1969 (2012) (citing Parker v. Flook, 437 U.S. 584, 590, 198 USPQ 193, 199 (1978) (the additional elements were "well known" and, thus, did not amount to a patentable application of the mathematical formula)). In Mayo, the claims at issue recited naturally occurring correlations (the relationships between the concentration in the blood of certain thiopurine metabolites and the likelihood that a drug dosage will be ineffective or induce harmful side effects) along with additional elements including telling a doctor to measure thiopurine metabolite levels in the blood using any known process. 566 U.S. at 77-79, 101 USPQ2d at 1967-68. The Court found this additional step of measuring metabolite levels to be well-understood, routine, conventional activity already engaged in by the scientific community because scientists "routinely measured metabolites as part of their investigations into the relationships between metabolite levels and efficacy and toxicity of thiopurine compounds." 566 U.S. at 79, 101 USPQ2d at 1968. Even when considered in combination with the other additional elements, the step of measuring metabolite levels did not amount to an inventive concept, and thus the claims in Mayo were not eligible. 566 U.S. at 79-80, 101 USPQ2d at 1968-69.
Additionally MPEP 2106.05 (d) II teaches that:
The courts have recognized the following laboratory techniques as well-understood, routine, conventional activity in the life science arts when they are claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity.
i. Determining the level of a biomarker in blood by any means, Mayo, 566 U.S. at 79, 101 USPQ2d at 1968; Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1362, 123 USPQ2d 1081, 1088 (Fed. Cir. 2017);
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ii. Using polymerase chain reaction to amplify and detect DNA, Genetic Techs. v. Merial LLC, 818 F.3d 1369, 1376, 118 USPQ2d 1541, 1546 (Fed. Cir. 2016); Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d 1371, 1377, 115 USPQ2d 1152, 1157 (Fed. Cir. 2015);
iii. Detecting DNA or enzymes in a sample, Sequenom, 788 F.3d at 1377-78, 115 USPQ2d at 1157); Cleveland Clinic Foundation 859 F.3d at 1362, 123 USPQ2d at 1088 (Fed. Cir. 2017);
iv. Immunizing a patient against a disease, Classen Immunotherapies, Inc. v. Biogen IDEC, 659 F.3d 1057, 1063, 100 USPQ2d 1492, 1497 (Fed. Cir. 2011);
v. Analyzing DNA to provide sequence information or detect allelic variants, Genetic Techs., 818 F.3d at 1377; 118 USPQ2d at 1546;
vi. Freezing and thawing cells, Rapid Litig. Mgmt. 827 F.3d at 1051, 119 USPQ2d at 1375;
vii. Amplifying and sequencing nucleic acid sequences, University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 764, 113 USPQ2d 1241, 1247 (Fed. Cir. 2014); and
viii. Hybridizing a gene probe, Ambry Genetics, 774 F.3d at 764, 113 USPQ2d at 1247.
With respect to the instant claims the claims perform the well-understood, routine, conventional activity of determining the concentration of soluble CLEC2 in blood or providing samples from a cancer patients at high level of generality and the Federal Circuit court has determined this to be well-understood, routine, and conventional activity. Additionally, Kazama et al. (Platelets 2015 26(8): 711-719) teaches routinely determining the levels of soluble CLEC2 in blood. See abstract and Figures 1-6.
Thus, given the above, the instant claims do not "practically apply" the naturally occurring phenomena of the concentration of soluble CLEC2 in and its correlation with the risk of cancer associated thrombosis or predicting efficacy determination of an antiplatelet agent; rather, the claims "simply inform" to one performing routine active method steps of the phenomena of soluble CLEC2 in the blood or other markers in the blood or sample and their correlation with the cancer associated thrombosis. The claims do not amount to significantly more than the abstract correlation of natural phenomena and thus, as a whole, the claims do not recite something significantly different than a judicial exception(s) and are not patent eligible.
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 for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
7. Claim(s) 1-8 are rejected under 35 U.S.C. 103 as being unpatentable over JP 2014/070942 (Ozaki et al. April 21, 2014, IDS), “Ozaki” in view of Suzuki-Inoue (Blood Nov. 28, 2019, 134(22): 1912-1918), “Suzuki-Inoue”.
Ozaki teaches a method for examining a hemostatic disease, comprising a step of measuring the amount of soluble CLEC-2 in plasma, wherein the hemostatic disease is thrombosis, myocardial infarction or angina. See p. 2-emodiment [5] and [6| of the translation.
Ozaki teaches the plasma sample can be obtained by centrifuging collected blood. See p. 3-4th paragraph of the translation.
Ozaki teaches when the patient's plasma is analyzed using the above-described method, and the presence of soluble CLEC-2 in the sample is detected more than that in a healthy person, the patient may have abnormal platelet activation, etc. It can be determined that the patient may have a disease. See p. 5-11th paragraph of the translation.
Ozaki teaches if the amount of soluble CLEC-2 is large compared to healthy individuals or non-hemostatic disease groups, then it can be said that there is a high possibility of having or a risk of suffering from hemostatic disease. See p. 3-lines 13-14 from the bottom of the page.
Ozaki teaches tumors can activate platelets, which can increase soluble CLEC-2 in the blood. Therefore, soluble CLEC-2 may be used as a cancer metastasis marker. See p. 3-last paragraph of the translation.
Ozaki teaches that an increased concentration of soluble CLEC-2 was found in the plasma of patients with acute coronary syndrome and not in the non-stenotic group. See p. 7 last paragraph.
Ozaki teaches as set forth above, but does not teach measuring the concentration of soluble CLEC2 in blood collected from a cancer patient in a perioperative period to assess the risk of cancer associated thrombosis or predict efficacy of an efficacy of an antiplatelet agent.
Suzuki-Inoue teaches patients with cancer have an increased risk of thromboembolism, which is the second leading cause of death in these patients. See abstract and p. 1912-left column.
Suzuki-Inoue teaches CLEC-2 is a platelet activation receptor and its ligand is podoplanin. See abstract and Figs. 1 and 2
Suzuki-Inoue teaches a membrane protein, podoplanin is expressed in certain types of cancer cells, including squamous cell carcinoma, brain tumor, and osteosarcoma, in addition to several normal tissues, including kidney podocytes and lymphatic endothelial cells but not vascular endothelial cells. In the bloodstream, podoplanin induces platelet activation by binding to CLEC-2 and facilitates hematogenous cancer metastasis and cancer associated thrombosis. See abstract, table 1 and Figure 2.
Suzuki-Inoue teaches CLEC-2 depletion in cancer-bearing mice resulted in reduced cancer associated thrombosis. See abstract.
Suzuki-Inoue teaches that surgery and immobility after surgery are risk factor for thrombosis. Suzuki-Inoue teaches Thus, patients with cancer are prone to develop a prothrombotic state, owing to both cancer pathology–related factors and cancer therapy–related factors. See p. 1913-left column, 2nd paragraph.
Suzuki-Inoue teaches venous thromboembolism (VTE) has been reported to be 10% to 20% of patients with cancer and this relationship between cancer and thromboembolism has been recognized as Trousseau syndrome for 150 years. See p. 1912-left column.
Suzuki-Inoue teaches tumor cells directly activate the coagulation cascade. Pancreatic cancer cells upregulate the tissue factor (TF) and release TF-positive macrovesicles, which results in the direct initiation of the coagulation cascade. See p. 1912-left column.
Suzuki-Inoue teaches plasminogen activator inhibitor (PAI)-1 inhibits fibrinolysis; therefore, increased levels of PAI-1 are associated with thrombosis and increased levels have been reported in pancreatic cancer and brain tumors. See p. 1912-paragtrph bridging columns.
Suzuki-Inoue teaches CLEC-2 is found on platelets in the blood stream. See Fig 2 A.
Suzuki-Inoue teaches that drugs that block the association between CLEC-2 and podoplanin are good candidates for anticancer metastasis and anticancer-associated thrombosis treatments. In theory, these drugs would decrease hematogenous cancer metastasis and cancer associated thrombus formation. See p. 1916-left column.
Suzuki-Inoue teaches targeting CLEC-2 may have advantages in these viewpoints, because anti–CLEC-2 drugs would inhibit cancer-related thrombosis by blocking the association between CLEC-2 and podoplanin, both in cancer cells and in various normal cells,
where podoplanin expression is pathologically induced. Moreover, CLEC-2 expression is highly restricted to platelets and megakaryocytes. See p. 1916-right column.
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of Ozaki and Suzuki-Inoue and measure the concentration of soluble CLEC2 in blood collected from a cancer patient with Trousseau syndrome in a perioperative period to asses and monitor the risk of cancer associated thrombosis because Ozaki teaches measuring the concentration of soluble CLEC2 in blood plasma samples to determine the risk of thrombotic disease and increased amounts soluble CLEC2 indicate high risk a hemostatic disease like thrombosis, Ozaki teaches tumors can activate platelets, which can increase soluble CLEC-2 in the blood, Suzuki-Inoue teaches patients with cancer have an increased risk of thromboembolism, podoplanin binding to CLEC-2 induces platelet activation and facilitates hematogenous cancer metastasis and cancer associated thrombosis, CLEC-2 depletion in cancer- resulted in reduced cancer associated thrombosis and Suzuki-Inoue teaches that surgery and immobility after surgery are risk factor for thrombosis. Thus, one would have been motivated to determine the soluble CLEC2 concentration or levels or other thrombosis markers, like TF and PAI-1, to assess and monitor the risk of cancer associated thrombosis in a perioperative period, such as around the time of cancer surgery, because Ozaki teaches measuring the concentration of soluble CLEC2 to determine the risk of thrombosis and Suzuki-Inoue teaches that the level of CLEC2 correlates with the risk of thrombosis and surgery and immobility after surgery are risk factor for thrombosis.
Additionally, one would have been motivated to use a platelet count as an internal measurement control to compare the concentration of soluble CLEC2 to obtain a standardized value (i.e. dividing the soluble CLEC2 concentration by the platelet count) because Suzuki-Inoue teaches CLEC2 is associated with platelets.
Further, one would have been motivated to predict that an anti-CLEC2/ anti-platelet agent would be effective when the level of soluble CLEC2 is increased because Suzuki-Inoue teaches that increased CLEC2 activity is associated with cancer associated thrombosis and teaches targeting increased CLEC2 to treat cancer associated thrombosis.
8a. Claim(s) 1-8 are rejected under 35 U.S.C. 103 as being unpatentable over WO/2021/172493 (Ishikura et al. Sep 2, 2021, filed Feb. 26, 2021, IDS), “Ishikura-493” in view of Suzuki-Inoue (Blood Nov. 28, 2019, 134(22): 1912-1918), “Suzuki-Inoue”.
8b. Claim(s) 1-8 are rejected under 35 U.S.C. 103 as being unpatentable over US 2023/0168260 A1 (Ishikura et al. June, 2021, filed Feb. 26, 2021, IDS), “Ishikura-260” in view of Suzuki-Inoue (Blood Nov. 28, 2019, 134(22): 1912-1918), “Suzuki-Inoue”.
Ishikura-260 is the publication USC § 371 filing of Ishikura-493, thus the documents have the same disclosure. Ishikura-260 will be cited for both Ishikura-260 and Ishikura-493 disclosures .
Ishikura-260 teaches a method for assisting in grasping the status of platelet activation comprises (1) measuring the concentration of soluble CLEC-2 and a platelet count in a sample obtained from a subject, and (2) calculating a value of [soluble CLEC-2 concentration]/[platelet count] by dividing the soluble CLEC-2 concentration by the platelet count. If desired, the method may further comprise (3) comparing the value with a value of [soluble CLEC-2 concentration]/[platelet count] obtained by using samples from healthy persons. See abstract and ¶¶ 0012-0022.
I Ishikura-260 teaches the value of [soluble CLEC-2 concentration]/[platelet count] is a marker that reflects clinical conditions of thrombotic hemostatic diseases, including thrombosis. See ¶¶ 0020-0021 and 0048.
Ishikura-260 teaches when the value of [sCLEC-2 concentration]/[platelet count] is higher than that of healthy persons or a non-thrombotic hemostatic disease group, it can be said that the patient is likely to have a thrombotic hemostatic disease or is at high risk of developing a thrombotic hemostatic disease. See ¶ 0049.
Ishikura-260 teaches using blood as a sample. See ¶¶ 0012 and 0055-0058.
Ishikura-260 teaches that the above methods can be used as a method for monitoring a prognosis or treatment progress of a thrombotic hemostatic disease in a patient with the thrombotic hemostatic disease. See ¶¶ 0022 and 0062
Ishikura-260 teaches CLEC-2 binds to podoplanin, a membrane protein expressed in certain tumor cells, in vivo, and promotes its metastasis. In patients with podoplanin-expressing tumors, there is a possibility that tumors in the blood may activate platelets and [sCLEC-2 concentration]/[platelet count] may increase, and therefore, [sCLEC-2 concentration]/[platelet count] may be used as a cancer metastasis marker.
Ishikura teaches as set forth above, but does not teach measuring the concentration of soluble CLEC2 in blood collected from a cancer patient in a perioperative period to assess the risk of cancer associated thrombosis.
Suzuki-Inoue teaches as set forth above.
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of Ishikura and Suzuki-Inoue and measure the concentration of soluble CLEC2 in blood collected from a cancer patient with Trousseau syndrome in a perioperative period to asses and monitor the risk of cancer associated thrombosis to obtain a value of [soluble CLEC-2 concentration]/[platelet count] by dividing the soluble CLEC-2 concentration by the platelet count because Ishikura teaches the value of [soluble CLEC-2 concentration]/[platelet count] is a marker that reflects clinical conditions of thrombotic hemostatic diseases, including thrombosis and when the value of [sCLEC-2 concentration]/[platelet count] is higher than that of healthy persons and that indicates a high risk of developing a thrombotic hemostatic disease, Suzuki-Inoue teaches patients with cancer have an increased risk of thromboembolism, podoplanin binding to CLEC-2 induces platelet activation and facilitates hematogenous cancer metastasis and cancer associated thrombosis, CLEC-2 depletion in cancer- resulted in reduced cancer associated thrombosis, and Suzuki-Inoue teaches that surgery and immobility after surgery are risk factor for thrombosis. Thus, one would have been motivated to determine a value of [soluble CLEC-2 concentration]/[platelet count] or levels or other thrombosis markers, like TF and PAI-1, to assess and monitor the risk of cancer associated thrombosis in a perioperative period, such as around the time of cancer surgery, because Ishikura teaches measuring the value of [soluble CLEC-2 concentration]/[platelet count] to determine or monitor the risk of thrombosis and Suzuki-Inoue teaches that the level of CLEC2 correlates with the risk of thrombosis and surgery and immobility after surgery are risk factor for thrombosis.
Further, one would have been motivated to predict that an anti-CLEC2/ anti-platelet agent would be effective when the level of soluble CLEC2 is increased because Suzuki-Inoue teaches that increased CLEC2 activity is associated with cancer associated thrombosis and teaches targeting increased CLEC2 to treat cancer associated thrombosis.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
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9. Claims 1-8 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2 and 6 of co-pending Application No.17/904,966 (published as US 2023/0168260 A1) in view of Suzuki-Inoue (Blood Nov. 28, 2019, 134(22): 1912-1918), “Suzuki-Inoue”..
The ‘966 claims are drawn to:
2. A method for grasping a status of platelet activation, comprising: obtaining or having obtained one or more samples from a human subject, wherein the one or more samples are plasma and/or whole blood: measuring a concentration of soluble CLEC-2 and a platelet count in the one or more samples, wherein the platelet count is measured from a whole blood sample and the concentration of soluble CLEC-2 is measured from a plasma sample or the whole blood sample; calculating a ratio of the concentration of soluble CLEC-2 to the platelet count in the one or more samples to identify the human subject as having or at risk of having a thrombotic hemostatic disease; and administering a treatment to the human subject, wherein the treatment is an antiplatelet agent capable of treating the thrombotic hemostatic disease.
6. The method according to claim 2, further comprising monitoring a prognosis or treatment progress of a thrombotic hemostatic disease in the human subject, wherein monitoring comprises: obtaining or having obtained one or more additional samples from the human subject measuring a concentration of soluble CLEC-2 and a platelet count in the one or more additional samples; calculating a ratio of the concentration of soluble CLEC-2 to the platelet count in the one or more additional samples: and comparing the ratio of the concentration of soluble CLEC-2 to the platelet count in the one or more additional samples to the ratio of the concentration of soluble CLEC-2 to the platelet count in the one or more samples.
The ‘966 claims teach as set forth above, but do not teach measuring the concentration of soluble CLEC2 in blood collected from a cancer patient in a perioperative period to assess the risk of cancer associated thrombosis.
Suzuki-Inoue teaches as set forth above.
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of the ‘966 claims and Suzuki-Inoue and measure the concentration of soluble CLEC2 in blood collected from a cancer patient with Trousseau syndrome in a perioperative period to asses and monitor the risk of cancer associated thrombosis to calculate a ratio of the concentration of soluble CLEC-2 to the platelet count in the plasma or blood samples to identify the human subject as having or at risk of having a cancer associated thrombotic hemostatic disease like thrombosis because Suzuki-Inoue teaches patients with cancer have an increased risk of thromboembolism, podoplanin binding to CLEC-2 induces platelet activation and facilitates hematogenous cancer metastasis and cancer associated thrombosis, CLEC-2 depletion in cancer- resulted in reduced cancer associated thrombosis, and Suzuki-Inoue teaches that surgery and immobility after surgery are risk factor for thrombosis. Thus, one would have been motivated to determine calculate a ratio of the concentration of soluble CLEC-2 to the platelet count in the plasma or blood samples or levels or other thrombosis markers, like TF and PAI-1, to assess and monitor the risk of cancer associated thrombosis in a perioperative period, such as around the time of cancer surgery, because Suzuki-Inoue teaches that the level of CLEC2 correlates with the risk of thrombosis and surgery and immobility after surgery are risk factor for thrombosis.
Further, one would have been motivated to predict that an anti-CLEC2/ anti-platelet agent would be effective when the level of soluble CLEC2 is increased because Suzuki-Inoue teaches that increased CLEC2 activity is associated with cancer associated thrombosis and teaches targeting increased CLEC2 to treat cancer associated thrombosis.
This is a provisional nonstatutory double patenting rejection.
Conclusion
10. No claims are allowed.
11. Any inquiry concerning this communication or earlier communications from the examiner should be directed to PETER J REDDIG whose telephone number is (571)272-9031. The examiner can normally be reached M-F 8:30-5:30 Eastern Time.
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/PETER J REDDIG/Primary Examiner, Art Unit 1646