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 .
Applicant’s response filed 5/1/2026 has been received and entered into the case. Claims 1-20 are pending and have been considered on the merits. All arguments and amendments have been considered.
Claim Interpretation
The claims are drawn to methods (for determining a patient’s likelihood of experiencing a thromboembolic event when receiving an implantable blood contacting medical device) comprising exposing blood samples to metal, metal alloy or ceramic, specifically titanium or zirconia, measuring a thromboembolic marker and determining that if the marker is higher than a threshold, one can determine that the patient is likely to experience a thromboembolic event when receiving an implantable blood contacting medical device. Neither the Specification or the claims disclose the threshold, thus, the threshold is interpreted to be any amount. Further, the Specification does not disclose a particular thromboembolic event and thus, under a broadest reasonable interpretation the term is given its plain meaning by those of ordinary skill in the art and is therefore interpreted to be the formation of a blood clots (thrombi). Thus, for examination purposes, the claimed invention is interpreted as, when a thromboembolic marker in blood, for example TAT complex, is higher than a baseline/threshold when exposed to metal (representative of an implantable blood device composed of metal, metal alloy, or ceramics), it is determined that the patient is likely to experience a thromboembolic event. For examination purposes and when given its broadest reasonable interpretation consistent with the specification, the connection of the metal to the device/pump is interpreted as the implantable medical device/pump would comprise a metal, metal alloy or ceramic tested and thus is representative of a device, and a marker concentration higher than any threshold is indicative of a thromboembolic event.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-14, 18-20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more. The claim(s) recite(s) method for determining the likelihood of experiencing a thromboembolic event comprising exposing a blood sample to metal, metal alloy or ceramic, measuring a thromboembolic marker in the sample and determining the marker to be higher than a threshold and based upon said determining, determining the patient is likely to experience a thromboembolic event. The claimed invention is directed to a naturally occurring correlation between the marker level and determining the likelihood of a thromboembolic event, i.e., a law of nature or natural phenomenon with an abstract idea which are themselves the judicial exception. The method sets forth a judicial exception, because this type of correlation is a consequence of natural processes, similar to the naturally occurring correlation found to be a law of nature by the Supreme Court in Mayo. The correlation is based upon levels of the naturally occurring markers in the blood and therefore includes a natural principle which exists in principle apart from any human action and thus simply describes a relation set forth by a natural law and the likelihood of an event. Additionally, the determining steps could be performed by a human using mental steps or basic critical thinking, which are types of activities that have been found by the courts to represent abstract ideas (e.g., the mental comparison in Ambry Genetics, or the diagnosing an abnormal condition by performing clinical tests and thinking about the results in Grams). Thus, the claim is directed to at least one exception (Step 2A: YES), which may be termed a law of nature, an abstract idea, or both.
The detected level does nothing more than inform the audience about the law of nature. Additionally, the steps of determining can be performed by a human using mental steps or critical thinking, which are themselves abstract ideas. This judicial exception is not integrated into a practical application because the claims do nothing more than inform the audience of the law of nature and does not require any particular application other than to “apply it”. The Court has made clear that to transform an unpatentable law of nature into a patent-eligible application of such a law, one must do more than simply state the law of nature while adding the words "apply it." Essentially, appending conventional steps such as assaying a sample and c) determining, specified at a high level of generality, i.e., determining levels of markers, to laws of nature, natural phenomena, and abstract ideas cannot make those laws, phenomena, and ideas patent-eligible.
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because step of determining a patient has a likelihood of experiencing a thromboembolic event based upon the measured marker levels does not require any particular application other than “apply it” to the judicial exception. Mere instruction to apply an exception cannot provide an inventive concept. Assaying levels of markers in a bodily fluid from a patient is routine and conventional in art (see Thor and Cattaneo below). As claimed, one merely determines whether a marker in the sample is above a threshold value, which is not defined. Determining the level of markers in the sample merely instructs scientists to use a well-known detecting technique at a high level of generality and therefore there is no meaningful limitation which is unconventional to detect the marker. The steps of determining levels in a sample having a threshold value and determining based upon said value does nothing more than instruct to “apply the natural law”. In order to integrate the exception into a practical application, one must add additional elements in which the judicial exception.
Next, one must evaluate whether the claims as a whole integrate the judicial exception into a practical application, thereby imposing a meaningful limit on the judicial exception. Thus, one must identify whether there are any additional elements recited in the claim beyond the judicial exception. The Supreme Court’s decisions make it clear that judicial exceptions need not be old or long-prevalent, and that even newly discovered or novel judicial exceptions are still exceptions. For example, the mathematical formula in Flook, the laws of nature in Mayo, and the isolated DNA in Myriad were all novel or newly discovered, but nonetheless were considered by the Supreme Court to be judicial exceptions because they were "‘basic tools of scientific and technological work’ that lie beyond the domain of patent protection." Myriad, 569 U.S. 576, 589, 106 USPQ2d at 1976, 1978 (noting that Myriad discovered the BRCA1 and BRCA1 genes and quoting Mayo, 566 U.S. 71, 101 USPQ2d at 1965); Flook, 437 U.S. at 591-92, 198 USPQ2d at 198 ("the novelty of the mathematical algorithm is not a determining factor at all"); Mayo, 566 U.S. 73-74, 78, 101 USPQ2d 1966, 1968 (noting that the claims embody the researcher's discoveries of laws of nature). The Supreme Court’s cited rationale for considering even "just discovered" judicial exceptions as exceptions stems from the concern that "without this exception, there would be considerable danger that the grant of patents would ‘tie up’ the use of such tools and thereby ‘inhibit future innovation premised upon them.’" Myriad, 569 U.S. at 589, 106 USPQ2d at 1978-79 (quoting Mayo, 566 U.S. at 86, 101 USPQ2d at 1971). See also Myriad, 569 U.S. at 591, 106 USPQ2d at 1979 ("Groundbreaking, innovative, or even brilliant discovery does not by itself satisfy the §101 inquiry.").
Besides the law of nature, the claim recites additional steps of exposing a blood sample to metal, agitating the sample and measuring a marker in said sample. Exposing the blood to metal does not change the blood sample to a different state or thing according to MPEP 2106.05(c).
Obtaining a sample in order to perform tests is well-understood, routine and conventional activity for those in the field of diagnostics. Further, the step is recited at a high level of generality such that it amounts to insignificant presolution activity, e.g., a mere data gathering step necessary to use the correlation. Detecting a marker level in the blood sample merely instructs a scientist to use any detection technique and when recited at this high level of generality, there is no meaningful limitation, such as a particular or unconventional machine or a transformation of a particular article, in this step that distinguishes it from well-understood, routine, and conventional data gathering activity engaged in by scientists prior to applicant’s invention, and at the time the application was filed, e.g., the routine and conventional techniques of measuring a marker. Further, it is well established that the mere physical or tangible nature of additional elements does not automatically confer eligibility on a claim directed to an abstract idea (see, e.g., Alice Corp. v. CLS Bank Int’l, 134 S.Ct. 2347, 2358-59 (2014)). Consideration of the additional elements as a combination also adds no other meaningful limitations to the exception not already present when the elements are considered separately. Unlike the eligible claim in Diehr in which the elements limiting the exception are individually conventional, but taken together act in concert to improve a technical field, the claim here does not invoke any of the considerations that courts have identified as providing significantly more than an exception. Even when viewed as a combination, the additional elements fail to transform the exception into a patent eligible application of that exception. Thus, the claim as a whole does not amount to significantly more than the exception itself (Step 2B: NO).
In this case, the claims to do not integrate the exception because it does not rely on, use or act on the judicial exception, i.e., the claim does not do anything after arriving at the relevant information, for example a treatment step. Thus, there is not practical application beyond the judicial exception.
The claimed invention is not directed to patent eligible subject matter. Based upon an analysis with respect to the claim as a whole, claim(s) 1-14, 18-20 is/are determined to be directed to a judicial exception.
Claim Rejections - 35 USC § 102
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 (i.e., changing from AIA to pre-AIA ) 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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1-5, 7, 8 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Thor et al. (Biomaterials, vol. 28, p. 966-974, 2007).
Regarding claim 1, Thor teaches a method for determining a thrombotic response comprising exposing a blood sample from a patient to titanium, i.e. a metal, in a container, agitating on a rotator, and measuring the generation of the thrombin-antithrombin (TAT) complex, i.e. a thromboembolic marker. Thor find that whole blood samples in contact with the titanium showed a 1000-fold increase in the TAT complex (abstract). Thor teaches that blood in contact with titanium and titanium alloy surfaces triggers the coagulation cascade thereby having a thrombogenic effect as well as platelet activation (p. 971, 1st , 3rd-6th parag., p. 972, 2nd col., 1st full parag.). Titanium is used for surgical implants and it shown to be more thrombogenic than other biomaterials used for medical implants (introduction).
Regarding claim 2, Thor teaches using 1.5 mL of blood for tests (p. 968, section 2.5).
Regarding claims 3 and 4, the blood is agitated by rotating for a predetermined period of time, i.e. 60 min.
Regarding claim 5, the blood is extracted before receiving an implantable medical device (p. 968, section 2.4).
Regarding claim 7, blood is taken from 4 volunteers and TAT complex is measured before exposure to titanium and after exposure to titanium (Fig. 1). The reference teaches that the activation of the coagulation cascade system, reflected in the generation of the TAT complex seen in whole blood, is increased 3000-fold from baseline values (p. 968, Results section 3.1, Fig. 1, p. 969 section 3.3, 3rd parag., Fig. 3).
Regarding claim 8, the metal is titanium (p. 967, section 2.1).
Thus, the reference anticipates the claimed subject matter.
Claim(s) 1, 5, 7, 8, 11 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Cattaneo et al. (J. Mat. Sci.:Mat. In Med, vol. 30, p. 1-12, 2019).
Regarding claims 1, 11, Cattaneo teach a method of determining thrombogenicity and hemocompatibility of implantable medical devices, i.e. neurovascular titanium (Nitinol) stents/blood flow diverter (intro., section 2.1 test specimens) comprising exposing a blood sample to Nitinol discs and electropolished discs containing a layer of titanium oxynitride or titanium oxide + titanium nitride (abstract, p. 3, 2nd col, 1st full parag., p. 4, section 2.8) in tubes simulating blood circulation. Before and after blood circulation in the tubes containing the titanium discs, TAT complex and Sc5b-9 concentrations were measured (p. 4, section 2.8 and 2.10). Cattaneo teaches that when stents are implanted and in contact with blood, different biochemical and hemostatic reactions may occur thus activating the coagulation cascade and complement system (p. 7-8, section 3.6) and may include ischaemic complications including distal embolism, in-stent thrombosis and stenosis (p. 10, 1st parag.). Compared to baseline and control blood samples not treated with the metal, TAT concentrations and SC5b-9 significantly increased in native stents (not electropolished) and electropolished stents (p. 7-8, section 3.6, Fig. 6B and C). Those samples exposed to the electropolished stents showed some improvement in thrombogenicity and may improve thrombo-ischaemic complications including distal embolism, in-stent thrombosis and occlusion (p. 10, 2nd col, 1st full parag., p. 11, last 2 parag.).
Regarding claim 5, the blood is extracted before the patient receives an implantable device, i.e. volunteers having not received an implantable device (p. 4, section 2.6).
Regarding claim 7, the reference teaches establishing baseline values from 5 donors (section 2.8).
Regarding claim 8, the metal is titanium and electropolished titanium containing titanium nitride (p. 3, section 2.1).
Thus, the reference anticipates the claimed subject matter.
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 (i.e., changing from AIA to pre-AIA ) 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, 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 6, 9, 10, 15-18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Thor et al. (Biomaterials, vol. 28, p. 966-974, 2007) as applied to claims 1-5, 7, 8 above.
The teachings of Thor are found above.
Thor does not teach the blood to be extracted from a patient after receiving an implantable blood contacting medical device according to claim 6; however as stated above, the connection of the metal (tested in the claim) to the device/pump is interpreted as the implantable medical device/pump (if implanted, which is not required by the claims) would comprise a metal, metal alloy or ceramic tested. Before the effective filing date of the claimed invention, blood tests comprising exposing blood samples to metal materials used in or as implantable devices to test their thrombogenicity were known and disclosed by Thor and thus, it would have been obvious to test blood from a patient exposed to an implantable medical device comprising a metal or metal alloy according to the method of Thor because the reference teaches that blood samples in contact with the titanium showed a 1000-fold increase in the TAT complex and that blood in contact with titanium and titanium alloy surfaces triggers the coagulation cascade thereby having a thrombogenic effect as well as platelet activation. Titanium is used for surgical implants and it shown to be more thrombogenic than other biomaterials used for medical implants, therefore, one would have been motivated by the teachings of Thor to test blood (and markers therein) which has been exposed to an implantable medical device which may trigger a thrombogenic effect in said patient to determine the likelihood of experiencing a thromboembolic event when receiving said device. Additionally, regarding claims 9, 10, it would also be obvious to compare blood exposed to an implantable blood contacting medical device with a plurality of samples exposed to a device which is used to establish the threshold levels to determine if the marker value is higher than a threshold, which is indicative of the likelihood of a thromboembolic event to determine if the patient whose blood has been exposed to the device is also likely to experience a thromboembolic event based upon said comparison.
Regarding claim 16, Thor teaches the container to comprise an anticoagulant, i.e. heparin, at a concentration of 1.0 U/mL ((section 2.4).
Regarding claims 15, 17, 18, while Thor teaches blood collected into anticoagulant containing test tubes, i.e. heparinized Falcon® tubes and an additional coupon test in a container (slide chamber) containing at least one metal, metal alloy or ceramic, wherein the metal is 25 mm x 25 mm flat squares which are 2-3 mm thick and circular test discs of 25 mm diameter made of titanium for blood evaluations with 1.3 mL of blood (25 mm equal 6.25 cm2), thus greater than 1cm2/1mL according to claim 15 (p. 967, section 2.1, p. 968, 2.5), they do not specifically teach the coupon test to be in a test tube or the container to be a test tube; however test tubes are routinely used in the art for blood collection and testing and thus it would have been well within the purview of the skilled artisan to pursue known options within his or her technical grasp.
Claim(s) 11-14, 19, 20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Thor et al. (Biomaterials, vol. 28, p. 966-974, 2007) as applied to claims 1-10, 15-18 above, and further in view of Cattaneo et al. (J. Mat. Sci. Mat. In Med, vol. 30, p. 1-12, 2019).
The teachings of Thor are found above.
Thor does not teach exposing the blood separately to titanium and titanium nitride according to claim 11.
Cattaneo teach a method of determining thrombogenicity and hemocompatibility of implantable medical devices, i.e. neurovascular titanium (Nitinol) stents/blood flow diverter (intro., section 2.1 test specimens) comprising exposing a blood sample to Nitinol discs and electropolished discs containing a layer of titanium oxynitride or titanium oxide + titanium nitride (abstract, p. 3, 2nd col, 1st full parag., p. 4, section 2.8) in tubes simulating blood circulation. Before and after blood circulation in the tubes containing the titanium discs, TAT complex and Sc5b-9 concentrations were measured (p. 4, section 2.8 and 2.10). Cattaneo teaches that when stents are implanted and in contact with blood, different biochemical and hemostatic reactions may occur thus activating the coagulation cascade and complement system (p. 7-8, section 3.6) and may include ischaemic complications including distal embolism, in-stent thrombosis and stenosis (p. 10, 1st parag.). Compared to baseline and control blood samples not treated with the metal, TAT concentrations and SC5b-9 significantly increased in native stents (not electropolished) and electropolished stents (p. 7-8, section 3.6, Fig. 6B and C). Those samples exposed to the electropolished stents showed some improvement in thrombogenicity and may improve thrombo-ischaemic complications including distal embolism, in-stent thrombosis and occlusion (p. 10, 2nd col, 1st full parag., p. 11, last 2 parag.). Cattaneo teaches a container containing a metal or metal alloy disc having a diameter of 10 mm and thickness of 0.2 mm (p. 3, 2nd col, 1st full parag., p. 4, section 2.8),wherein the container contains the anticoagulant heparin in an amount of 1.5 U/mL (section 2.8).
Thus, before the effective filing date of the claimed invention, it would have been obvious to expose blood separately to both titanium and titanium nitride in the method of Thor because Cattaneo teaches that the samples exposed to the electropolished stents showed some improvement in thrombogenicity and may improve thrombo-ischaemic complications including distal embolism, in-stent thrombosis and occlusion compared to native titanium implants not containing titanium nitride. Therefore, a posita would have been motivated by the teachings of Cattaneo to test both titanium and titanium nitride in a method to determine the likelihood of a patient experiencing a thromboembolic event because both biomaterials are taught to cause increased TAT complex levels and thrombo-ischaemic complications, with titanium nitride providing some improvements over native titanium. Further, regarding claims 19, 20, it would also be obvious to compare blood exposed to an implantable blood contacting medical device with a plurality of samples exposed to a device which is used to establish the threshold levels to determine if the marker value is higher than the threshold, which is indicative of the likelihood of a thromboembolic event to determine if the patient whose blood has been exposed to the device is also likely to experience a thromboembolic event based upon said comparison.
Claim(s) 6, 9, 10, 15-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Cattaneo et al. (J. Mat. Sci.:Mat. In Med, vol. 30, p. 1-12, 2019) as applied to claims 1, 5, 7, 8, 11 above.
The teachings of Cattaneo are found above.
Cattaneo does not teach the blood to be extracted from a patient after receiving an implantable blood contacting medical device according to claim 6; however as stated above, the connection of the metal (tested in the claim) to the device/pump is interpreted as the implantable medical device/pump (if implanted, which is not required by the claims) would comprise a metal, metal alloy or ceramic tested. Before the effective filing date of the claimed invention, blood tests comprising exposing blood samples to metal materials used in or as implantable devices to test their thrombogenicity were known and disclosed by Cattaneo and thus, it would have been obvious to test blood from a patient exposed to an implantable medical device comprising a metal or metal alloy according to the method of Cattaneo because the reference teaches that before and after blood circulation in the tubes containing the titanium discs, TAT complex and Sc5b-9 concentrations were measured and compared to baseline and control blood samples not treated with the metal, TAT concentrations and SC5b-9 significantly increased in native stents (not electropolished) and electropolished stents. Cattaneo teaches that when stents are implanted and in contact with blood, different biochemical and hemostatic reactions may occur thus activating the coagulation cascade and may include ischaemic complications including distal embolism, in-stent thrombosis and stenosis. Therefore, one would have been motivated by the teachings of Cattaneo to test blood (and markers therein) which has been exposed to an implantable medical device which may trigger a thrombogenic effect in said patient to determine the likelihood of experiencing a thromboembolic event when receiving said device. Additionally, regarding claims 9, 10, 19 and 20, it would also be obvious to compare blood exposed to an implantable blood contacting medical device with a plurality of samples exposed to a device which is used to establish the threshold levels to determine if the marker value is higher than a threshold, which is indicative of the likelihood of a thromboembolic event to determine if the patient whose blood has been exposed to the device is also likely to experience a thromboembolic event based upon said comparison.
Regarding claim 16, Cattaneo teaches the container to comprise an anticoagulant, i.e. heparin, at a concentration of 1.5 U/mL (section 2.8).
Regarding claims 15, 17, 18, while the reference teaches blood collected into a container (polyvinyl chloride tubes) containing a metal or metal alloy disc having a diameter of 10 mm and thickness of 0.2 mm in 6 mL of blood (p. 3, 2nd col, 1st full parag., p. 4, section 2.8), they do not specifically teach the coupon test to be in a test tube or the container to be a test tube; however test tubes are routinely used in the art for blood collection and testing and thus it would have been well within the purview of the skilled artisan to pursue known options within his or her technical grasp.
Response to Arguments
Applicant's arguments filed 5/1/2026 have been fully considered but they are not persuasive. Regarding the 101 rejection of record, applicants argue that the claims are not drawn to a law of nature, but instead recites determining a thromboembolic marker for the sample of blood for a specific patient, and the marker is not universal for all patients, and thus, not based on a law of nature. Applicants cite the MPEP
The courts have also noted, however, that not every claim describing a natural ability or quality of a product, or describing a natural process, necessarily recites a law of nature or natural phenomenon. See Rapid Litig. Mgmt. v. CellzDirect, Inc., 827 F.3d 1042, 1048-49, 119 USPQ2d 1370, 1374 (Fed. Cir. 2016) (claims reciting process steps of fractionating, recovering, and cryopreserving hepatocytes held to be eligible, because they are not focused on merely observing or detecting the ability of hepatocytes to survive multiple freeze-thaw cycles). Thus, in a claimed method of treating cancer with chemotherapy, the cancer cells' inability to survive chemotherapy is not considered to be a law of nature. Similarly, in a claimed method of treating headaches with aspirin, the human body's natural response to aspirin is not considered to be a law of nature. These claims are accordingly eligible at Prong One unless they recite another exception, in which case they require further analysis in Prong Two (and Step 2B, if needed) to determine their eligibility.
Similar to the holding regarding the human body's natural response to aspirin not considered to be a law of nature, in the method of claim 1 the reaction of a blood sample taken from a particular patient to a metal, metal alloy, or ceramic as recited claim 1 cannot be characterized as referring to a law of nature based in view of the guidance provided by the MPEP and the courts. As such, the method of claim 1 does not recite a law of nature, and therefore does not recite a judicial exception comprising a law of nature.
Regarding applicants argument directed at the “particular patient”, the patient is not claimed to be a particular patient, but rather one from which a sample of blood is taken and exposed to metal.
In response to applicants’ citation of above MPEP section, it is important to note that “the analysis of a process claim should focus on the active steps of the process rather than the products used in those steps. For example, when evaluating a claimed process of cryopreserving hepatocyte cells comprising performing density gradient fractionation to separate viable and non-viable hepatocytes, recovering the viable hepatocytes, and cryopreserving the recovered viable hepatocytes, the court did not subject the claim to the markedly different characteristics analysis for the nature-based products (the hepatocytes) used in the process. Rapid Litig. Mgmt. v. CellzDirect, Inc., 827 F.3d 1042, 1049, 119 USPQ2d 1370, 1374 (Fed. Cir. 2016) (claims are directed to a process of creating a preparation of multi-cryopreserved hepatocytes, not to the preparation itself)” MPEP2106.04(b) and (c).
The process steps of the methods referred to involve treatment steps and active process steps of fractionating, recovering and cryopreserving. In the instant claims the method involves measuring a marker in a sample and determining that if the marker levels is higher than a threshold, determining that the patient is likely to experience a thromboembolic event.
It is the Examiners position that applicants claims recite an exception at the determining steps, which describes the law of nature, i.e., the detected level indicating the likelihood of experiencing a thromboembolic event. The claims are comparable to Ex. 29, claim 2, which is ineligible (see below).
2. A method of diagnosing julitis in a patient, said method comprising:
a. obtaining a plasma sample from a human patient;
b. detecting whether JUL-1 is present in the plasma sample by contacting the plasma sample with an anti-JUL-1 antibody and detecting binding between JUL-1 and the antibody; and
c. diagnosing the patient with julitis when the presence of JUL-1 in the plasma sample is detected.
The guideline states that this claim is determined to be ineligible because in step c, the claim recites diagnosing the patient with julitis when the presence of JUL-1 in the plasma sample is detected, which describes a correlation or relationship between the presence of JUL-1 in a patient’s plasma and the presence of julitis in the patient (this is similar to applicants claimed determining steps). This limitation sets forth a judicial exception, the claimed invention is directed to a naturally occurring correlation between the marker level and determining the likelihood of a thromboembolic event, similar to the naturally occurring correlation found to be a law of nature by the Supreme Court in Mayo). Additionally, the determining step could be performed by a human using mental steps or basic critical thinking, which are types of activities that have been found by the courts to represent abstract ideas (e.g., the mental comparison in Ambry Genetics, or the diagnosing an abnormal condition by performing clinical tests and thinking about the results in Grams). Thus, the claim is directed to at least one exception (Step 2A: YES), which may be termed a law of nature, an abstract idea, or both. Note that although the claim recites several nature-based product limitations (e.g., the plasma sample and JUL-1), the claim as a whole is focused on a process of detecting whether JUL-1 is present in a plasma sample, and is not focused on the products per se. Thus, there is no need to perform the markedly different characteristics analysis on the recited nature-based product limitations. Next, the claim as a whole is analyzed to determine whether any element, or combination of elements, is sufficient to ensure that the claim amounts to significantly more than the exception. Besides the law of nature, the claim recites additional steps of obtaining a plasma sample from a human patient (step a), and detecting whether JUL-1 is present in the plasma sample by contacting the plasma sample with an anti-JUL-1 antibody and detecting resultant binding between JUL-1 and the antibody (step b) (similar to applicants exposing a sample to a metal, measuring a marker and determining based on the measured level). Obtaining a sample in order to perform tests is well-understood, routine and conventional activity for those in the field of diagnostics. Further, the step is recited at a high level of generality such that it amounts to insignificant presolution activity, e.g., a mere data gathering step necessary to use the correlation. Detecting whether JUL-1 is present in the plasma sample merely instructs a scientist to use any detection technique with any generic anti-JUL-1 antibody. When recited at this high level of generality, there is no meaningful limitation, such as a particular or unconventional machine or a transformation of a particular article, in this step that distinguishes it from well-understood, routine, and conventional data gathering activity engaged in by scientists prior to applicant’s invention, and at the time the application was filed, e.g., the routine and conventional techniques of detecting a protein using an antibody to that protein. Further, it is well established that the mere physical or tangible nature of additional elements such as the obtaining and detecting steps does not automatically confer eligibility on a claim directed to an abstract idea (see, e.g., Alice Corp. v. CLS Bank Int’l, 134 S.Ct. 2347, 2358-59 (2014)). Consideration of the additional elements as a combination also adds no other meaningful limitations to the exception not already present when the elements are considered separately. Unlike the eligible claim in Diehr in which the elements limiting the exception are individually conventional, but taken together act in concert to improve a technical field, the claim here does not invoke any of the considerations that courts have identified as providing significantly more than an exception. Even when viewed as a combination, the additional elements fail to transform the exception into a patent eligible application of that exception. Thus, the claim as a whole does not amount to significantly more than the exception itself (Step 2B: NO). The claim is not eligible.
Thus, applicants claims, like claim 2, includes steps which recite a law of nature.
In response to the section of the 101 rejection which states “Besides the law of nature, the claim recites additional steps of exposing a blood sample to metal, agitating the sample and measuring a marker in said sample. Exposing the blood to metal does not change the blood sample to a different state or thing according to MPEP 2106.05(c)”, applicants argue that the specification describes placing samples in test tubes to determine how blood reacts to each of the metals and that samples may be centrifuged, and plasma extracted and markers are measure in each blood sample, thus it is clear that the steps of claim 1 are intended to determine a level of change in the state of the blood sample.
It is the Examiners position that, exposing the blood samples to metal and measuring markers, does not change the blood itself, and applicants’ claims do not include the limitations of, for example, after the predetermined time period, centrifuging and extracting plasma, thus applicants’ arguments are not commensurate in scope with the claimed invention.
Regarding Thor, applicant argues that the claimed method recites determining a specific patients likelihood of experiencing a thromboembolic event by exposing a blood sample from the patient to metal, metal alloy or ceramics, measuring a marker and determining based upon the measure level whether the patient has a likelihood of experiencing a thromboembolic event. Applicant’s argue that the reference is drawn to testing whether titanium as a material is thrombogenic, which it is determined to be more thrombogenic that other biomaterials. The reference teaches using blood from healthy volunteers, but does not assess a specific patients elevated risk, apply test results to predict outcomes for that individual patient, or classify patients into risk categories. Applicants argue that a “thrombotic response” to a material is different from determining the likelihood of experiencing a thromboembolic event when receiving an implantable device. While Thor teaches that TAT levels increase 3000-fold in response to titanium contact in the samples tested, they are testing the material and not the individual patient.
It is the Examiners position that Thor teaches exposing blood samples to titanium, agitating the sample, and measuring TAT, i.e. the activation of the coagulation system. The exposure of blood to the metal triggers a thrombogenic effect and the low-grade generation of thrombin, and the studying of the thrombogenic properties of titanium is important for understanding responses to implant materials (Discussion section, p. 971-973) in patients and indicating that whole blood is necessary for sufficient thrombin generation and platelet activation during placement of implants in patients (p. 974, last 2 parag.). Therefore, when practicing the method of Thor, one determines if the patients blood exposure to the metal triggers a thromboembolic event, which can be applied to any patient’s blood to determine if that particular patient will respond to the exposure, which is important in when placing implantable devices as shown by Thor. Thor measures TAT before metal exposure and after metal exposure, thus enabling one to determine that TAT levels are higher than a threshold (starting) level, and thus, that the patient is likely to experience a thromboembolic event when receiving an implantable device based upon the increased TAT levels.
Regarding Cattaneo, applicants also argue that the reference is studying the thrombogenicity of metal surfaces, but not diagnosing individual patient risk. Applicants argue the reference does not use donor blood to characterize surfaces, does not evaluate risk, does not use predetermined thresholds and does not make patient specific diagnostic determinations.
It is the Examiners position that Cattaneo teaches an in vitro thrombogenicity models using donor blood, from which baseline values were obtained and measured after blood sampling, which is contacted with metal stents (section 2.8). Cattaneo teaches that after implantation, implantable blood contacting devices can lead to biochemical reaction affecting the haemostatic system. Cattaneo measure TAT and SC5b-9 levels were measured at baseline and after metal stent exposure (section 3.6) to evaluate thrombogenecity. The treated groups showed significant increases compared to control (section 3.6, Fig. 6). TAT is a sensitive coagulation marker and thus can be used to determine a patients thrombotic response to implantable blood contacting devices. Therefore, as with Thor, a person of ordinary skill in the art when practicing the method of Cattaneo would have a reasonable expectation of successfully determining a patients risk of experiencing a thromboembolic event because the reference teaches exposing blood to a metal used in implantable devices and measuring the thromboembolic marker TAT, for example, to determine a thrombotic response to said device materials. Therefore, when testing an individual patients blood, one would be able to determine based upon said TAT levels if the patient is at risk for a thrombotic risk when receiving the device. Additionally, regarding claims 9, 10, 19 and 20, it would also be obvious to compare blood exposed to an implantable blood contacting medical device with a plurality of samples exposed to a device which is used to establish the threshold levels to determine if the marker value is higher than a threshold, which is indicative of the likelihood of a thromboembolic event to determine if the patient whose blood has been exposed to the device is also likely to experience a thromboembolic event based upon said comparison.
Regarding claim 15, applicants argue that the references do not teach the surface area of the metal being greater than 1cm2/ml; however, Thor teaches a 25mm metal disc within 1.3 mL of blood; 25 mm equal 6.25 cm2 , thus the surface area of 6.25cm2/1.3mL is greater than 1cm2/ml.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TIFFANY MAUREEN GOUGH whose telephone number is (571)272-0697. The examiner can normally be reached M-Thu 8-5.
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/TIFFANY M GOUGH/Examiner, Art Unit 1651
/MELENIE L GORDON/Supervisory Patent Examiner, Art Unit 1651
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