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 .
Claim Objections
Claim 1 objected to because of the following informalities: Claim 1 recites steps (a), (b) and (d). Applicant may correct this by correcting (d) to be (c).
Appropriate correction is required.
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, 3-12 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without practical application and without significantly more. Claims 1 and 11 are directed to an abstract idea by determining the ratio of carnitine to ceramide and/or ceramide derivate (mental process/mathematical calculation), comparing the ratio to a reference value (mental process) determining the level of at least one metabolite in a sample (mental process). The instant claims encompass a naturally occurring correlation between carnitine, ceramide levels, and inflammation leading to diseases (“ inflammatory phenotype in chronic wounds”; instant specification; page 2, line 20)(Moretti, WO 97/05862) followed by an observation and evaluation through diagnosis and prognosis; however, after this step, there is no more action based on this known information. The rejected claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because they read on data gathering through the selection of carnitine, different kinds of ceramides, derivatives, and the associated levels based upon a reference value. These steps are an extension of mathematical relationships that exist naturally when a level of carnitine is administered since there is an inverse relationship between carnitine and ceramide as demonstrated below in Table 1 of Moretti (WO 97/05862; See attached foreign document). This relationship is solidified as Moretti states that “L-carnitine and isovaleryl L-carnitine are thus shown to inhibit the synthesis of ceramide in vitro” (page 5, last paragraph). A healthy patient demonstrates ceramide concentrations in the range of 5 to 50 picomoles/106 cells of ceramide whereas the increase in ceramide levels due to the administering of ceramide stimulant is outside of this range but is brought down to a level within this range with a carnitine treatment as shown in Table 1 of Moretti. Therefore, this data reveals that ceramide levels outside of this range indicate unhealthy patients that will receive a prognosis and diagnosis for inflammatory diseases and is a natural phenomenon (see rejection below).
In the instant case, based upon an analysis with respect to the claim as a whole, claims 1, 3-12 are determined to be directed to judicial exception without significantly more (See Mayo Collaborative Services v. Prometheus Laboratories, Inc., 566 U.S. _, 132 S. Ct. 1289, 101 USPQ2d 1961 (2012)). The rationale for this determination is explained below in view of 2019 Revised Patent Subject Matter Eligibility Guidance (84 FR 50) dated January 07, 2019.
The instant claims 1, 3-12 encompass a process. (Step 1: Yes).
Next, Step 2, is the two-part analysis from Alice Corp. (also called the Mayo test) to determine whether the claim is directed to laws of nature, natural phenomena, and abstract ideas (the judicially recognized exceptions). (In Alice Corp. v. CLS Bank Int’l, 134 S. Ct. 2347, 2354 (2014) the Supreme Court sets forth a two-step test for determining patent eligibility. First, determine if the claims encompass a judicial exception (a natural phenomenon/law of nature/abstract idea). If so, then ask whether the remaining elements/steps, either in isolation or combination with the other non-patent-ineligible elements, are sufficient to ‘“transform the nature of the claim’ into a patent-eligible application.” Id. At 2355 (quoting Mayo, 132 S. Ct. at 1297). Put another way, there must be a further “inventive concept” to take the claim into the realm of patent eligibility. Id. at 2355. In the recent Myriad v Ambry case, the CAFC found claims (drawn to methods comprising obtaining tissue samples, analyzing sequences of
cDNA and comparing germline sequences of a gene to wild-type sequences) to encompass the abstract mental processes of ‘comparing’ and ‘analyzing’. Recitation of specific techniques (in Myriad claims 7 and 8 further recited hybridization and PCR) were deemed not “enough” to make the claims patent eligible since the claims contained no otherwise new process. The elements/steps recited in addition to the judicial exception did nothing more than spell out what practitioners already knew). The instant claims encompass diagnosis or prognosis of a non-healing or chronic wound (mental process) and by determining the ratio of carnitine to ceramide and/or ceramide derivate in a sample from a mammalian, wherein said ratio is decreased when compared with a reference value (mathematical relationship), the process that is governed by a law of nature as well as observation and evaluation performed in the human mind, and thus is a judicial exception. The carnitine and ceramide levels are naturally occurring factors, which, as evidenced by the claims and the specification as filed, are present naturally within the samples obtained from patients. Thus, the relation between the presence of carnitine to ceramide in patients exists in principle and diagnosis and prognosis is a consequence of the ways these factors exist in the environment, entirely natural process, a natural phenomenon, and thus a judicial exception.
(Step 2A/1: Yes). Next, prong two of Step 2A requires identifying whether there are additional elements recited in the claim beyond the judicial exception(s) and evaluating those additional elements to determine whether they integrate the exception into a practical application of the exception. ‘“Integration in to a practical application” requires an additional element or combination of additional elements in the claim to apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception, such as the claim is more than a drafting effort designed to
monopolize the exception. In the instant case, the claims do not recite any additional elements to integrate the judicial exception into a practical application because all the steps of the claimed methods are limited to only those that measure naturally occurring factors during a naturally occurring biological compounds.
Regarding step (d) of claim 1 and step (b) of claim 11, no particular treatment is required, (i.e., administering of a specific drug, a physical treatment, a surgery, etc.). Additionally the instant specification is silent to any specific treatment. The background of the instant specification, (page 1, lines 29-31) at most states "So far, compression has been the mainstay of ulcer treatments, notably VLU, but it can be painful and time- consuming," as well as "this identification of biomarkers, as well as the method relied upon, is needed for disease prognostication and the development of novel therapy" (page 2, lines 29-31 ). However, a different treatment than the well-known treatment of compression is not mentioned nor is a novel therapy revealed in the application that takes into account the use of this ratio.
Although this limitation indicates that a treatment is to be administered, it does not provide any information as to how the patient is to be treated, or what the treatment is, but instead covers any possible treatment that a doctor decides to administer to the patient. Like the claims in Mayo Collaborative Servs. v. Prometheus Labs., Inc., 566 U.S. 66, 78 (2012), claim 1 here tells the relevant audience (doctors) about the mathematical concepts and at most adds a suggestion that the doctors take those laws into account when treating their patients. Limitations (d) of claim 1 and (b) of claim 11 thus fail to meaningfully limit the claim because it does not require any particular application of the recited calculation, and is at best the equivalent of merely adding the words “apply it” to the judicial exception. Accordingly, Limitations (d) of claim 1 and (b) of claim 11 do not integrate the recited judicial exception into a practical application and the claim is therefore directed to the judicial exception.
(Step 2A/2: No). The second step is determining if the claims recite or involve judicial exceptions, such as laws of nature, natural phenomena, or natural products. In this case, the claims involve a natural correlation: carnitine, ceramide levels, and inflammation leading to diseases. In the next step, it must be determined if the claim as a whole amounts to something significantly more than the judicial exception.
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception. Claims 1, 3-12 fail to include any limitations which would distinguish the method because they do not recite any elements, or combinations of elements to ensure that the claim as a whole amounts to significantly more than the judicial exception as there are no active steps included in the claims, only mathematical calculations of the ratio of carnitine to ceramide and comparing to a reference value. While this may be a form of mere data gathering for the ultimate abstract idea of diagnosis of prognosis, all steps are performed in the mind and thus relate to nothing significantly more. There is an inverse relationship between carnitine and ceramide as demonstrated below in Table 1 of Moretti (WO 97/05862; See attached foreign document). This relationship is solidified as Moretti states that “L-carnitine and isovaleryl L-carnitine are thus shown to inhibit the synthesis of ceramide in vitro” (page 5, last paragraph). A healthy patient demonstrates ceramide concentrations in the range of 5 to 50 picomoles/106 cells of ceramide whereas the increase in ceramide levels due to the administering of ceramide stimulant is outside of this range but is brought down to a level within this range with a carnitine treatment as shown in Table 1 of Moretti. Therefore, this data reveals that ceramide levels outside of this range indicate unhealthy patients that will receive a prognosis and diagnosis for inflammatory diseases and is a natural phenomenon (see rejection below) and hence the instant claims to not amount to significantly more.
As explained with respect to Step 2A Prong Two, the claim recites a single additional element in limitations (d) of claim 1 and (b) of claim 11, which do not require any particular application of the recited calculation and is at best the equivalent of merely adding the words “apply it” to the judicial exception. Mere instructions to apply an exception cannot provide an inventive concept
The instant claims only require the naturally occurring correlation to be observed by applying the known methods in the art. The instantly rejected claims do not recite any elements in addition to the natural correlation that impose meaningful limits on the claim scope and would substantially foreclose others from using this natural correlation of ceramide to carnitine levels for diagnosing and prognosing chronic wounds. The intended use of this method does not further limit or apply any significant action once the natural correlation has been observed using the claimed method. The natural correlation is found in nature whether it is observed or not and would be present and act quite independently of any effort of the patentee.
Note that recited specific methods of detection do nothing more to satisfy step 2B (Step 2B: No).
Thus, for reasons fully explained above, claims 1, 3-12 do not satisfy the requirement of 35 U.S.C.101 and are therefore rejected.
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 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.
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.
Claims 1,3-4, 6-11 are rejected under 35 U.S.C. 103 as being unpatentable over Scioli (Propionyl-L-Carnitine Enhances Wound Healing and Counteracts Microvascular Endothelial Cell Dysfunction; 2015) in view of Moretti (WO 97/05862; See attached foreign document).
Regarding claim 1, Scioli teaches a method of treating a non-healing or chronic wound (evaluation of granulation tissue of rat skin wounds; Fig 3; page 9, last paragraph lines 2-3) in a mammal (“Table 1. Plasma Propionyl-L-carnitine (nmol/mL) levels in vehicle and PLC-treated rats,” wherein vehicle is only water without PLC; page 5; page 3, last line)
(d) treating the wound (See wound decline upon treatment carnitine in Fig. 2).
Scioli fails to teach:
determining the ratio of carnitine to ceramide and/or ceramide
comparing the ratio to a reference value, wherein a favorable diagnosis or prognosis of healing is present when the ratio is higher than said reference value, or a poor diagnosis or prognosis of healing is present when the ratio is lower than said reference value,
treating the wound based on the diagnosis or prognosis of healing (emphasis added)
Moretti teaches:
(a) determining the ratio of carnitine to ceramide (In a first interpretation, the examiner interprets the ratio to be concentrations of L-carnitine compared to ceramide concentrations of Example 1,Table 1, wherein L-carnitine is a species of carnitine as discussed on page 4, lines 21-23 of the instant specification) (In a second interpretation, the examiner interprets the ratio to be concentrations of isovalery L-carnitine compared to ceramide concentrations of Example 1,Table 1, wherein isovalery L-carnitine is a species of carnitine as discussed on page 4, lines 21-23 of the instant specification)(In a third interpretation, the examiner interprets the ratio to be the carnitine dosage amount versus any measured ceramide levels pre-treatment, first post-treatment and indefinite post-treatments of Examples 2-5)
b) comparing the ratio to a reference value (In a first interpretation, the examiner understands Table 1 to depict the control as the reference value and the decrease of ceramide concentration with an increase of the carnitine concentrations; In a second interpretation, the examiner understands Table 1 to depict the control+ anti-Fas antibody as the reference value and the decrease of ceramide concentration with an increase of the carnitine concentrations. In a third interpretation the examiner understands the reference value to be any measured ceramide levels pre-treatment, first post-treatment and indefinite post-treatments of Examples 2-5)( Moretti states that “monitoring can begin any time following administration but suitably is commenced following 3 hours to ensure accurate results,” and that “monitoring can be continued indefinitely,” wherein the monitoring is the collection of ceramide levels (Page 4, paragraph 3, last 3 lines)(Therefore in example 2, each day for two months, ceramide levels can be obtained and this ratio of a 3g carnitine dosage and respective measured ceramide level serves as the new reference value).
(d) treating the wound based on the diagnosis or prognosis of healing (the carnitine dosages of Examples 2-5; pages 6-8. Moretti states that “Examples of illnesses or disorders characterized by elevated levels of ceramide include…damages by radiations and/or chemotherapy agents,” which are a kind of internal wound. Since this wound is characterized by high ceramide levels, then a prognosis (prediction of the likely course or outcome of the disease or condition) can be determined in that the illness with remain the same or possibly become even more detrimental (emphasis added).
Moretti is considered to be analogous to the claimed invention because it is in the same field of endeavor for the monitoring of an inflammatory disease using the relationship of carnitine levels. 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 have modified Scioli to incorporate the teachings of Moretti by exploring the ratio of carnitine to ceramide and/or ceramide derivate, as compared with a reference value while making a prognosis of chronic wound healing and further treating the wound based upon this. While Scioli teaches the use of carnitine to counteract cell dysfunction (Title), Moretti teaches “therapeutic treatment of cellular disorders accompanied by high levels of ceramide” (page 2, paragraph 3). Knowledge of the demonstration of a reverse relationship between carnitine and ceramide by Moretti in Table 1 would lead one of ordinary skill in the art to adopt the same analysis in treatment of a chronic wound. From the associated data, Moretti concludes that “L-carnitine and isovaleryl L-carnitine are thus shown to inhibit the synthesis of ceramide in vitro” (page 5, last paragraph) and would be an acceptable motivation to determine status of other cell dysfunctions.
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Moretti, Table 1
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Fig. 2, Scioli
Regarding claim 3, modified Scioli teaches the method of diagnosis or prognosis of a non-healing or chronic wound according to claim 1, wherein reference value is 40 (the reference value as shown in Table 1 can be between 20 or 81.6 picomoles/million cells that correspond to the control and the control+ anti-Fas antibody which is a range that includes the value of 40. This reference value is a result-effective variable that would vary depending upon routine optimization of the many different control groups and dosage amounts of anti-Fas antibody (MPEP 2144.05).
Regarding claim 4, modified Scioli teaches the method of diagnosis or prognosis of a non-healing or chronic wound according to claim 1, wherein reference value has been determined in people who healed (“Normal levels of ceramides in healthy patients depend on the age, size and weight of the individual, but are in general within the range of from 5 to 50 picomoles/106 cells,” wherein the control group of the first interpretation of Table 1 above (Moretti) shows a ceramide level of 20 picomoles/106 cells; page 4, paragraph 1).
Regarding Claim 6, modified Scioli teaches the method of diagnosis or prognosis of a non-healing or chronic wound according to claim 1, wherein the ceramide derivative is a ceramide-1-phosphate, or a sphingomyelin (Claim 1 recites ceramide and/OR ceramide derivate and therefore, a ceramide derivative that is a ceramide-1-phosphate, or a sphingomyelin is not required because claim 1 does not positively recite a ceramide derivate. Claim 6 is met by the teachings of Scioli in view of Moretti, which teaches ceramide).
Regarding Claim 7, modified Scioli teaches the method of diagnosis or prognosis of a non-healing or chronic wound according to claim 6, wherein the ceramide-1-phosphate is CerP d18:1/18:0 (Claim 1 recites ceramide and/OR ceramide derivate and therefore, ceramide derivate that is CerP d18:1/18:0 is not required because claim 1 does not positively recite a ceramide derivate. Therefore, claim 7 is met by the teachings of Scioli in view of Moretti, which teaches ceramide).
Regarding Claim 8, modified Scioli teaches the method of diagnosis or prognosis of a non-healing or chronic wound according to claim 6, wherein the sphingomyelin is SM d18:1/23:0 (Claim 1 recites ceramide and/OR ceramide derivate and therefore, sphingomyelin that is SM d18:1/23:0 is not required because claim 1 does not positively recite a ceramide derivate. Claim 8 is met by the teachings of Scioli in view of Moretti, which teaches ceramide).
Regarding Claim 9, modified Scioli teaches the method of diagnosis or prognosis of a non-healing or chronic wound according to claim 1, wherein the wound is an ulcer (delayed wound healing and chronic ulcers; Scioli; Abstract).
Regarding Claim 10, modified Scioli teaches the method of diagnosis or prognosis of a non-healing or chronic wound according to claim 1, wherein the sample is chosen among: blood (Blood samples were obtained; Scioli, Table 1), serum, urine and ulcer fluids
Regarding Claim 11, Scioli teaches a method of treating a non-healing or chronic wound in a mammal (evaluation of granulation tissue of rat skin wounds 7 days after wound are reported in Fig 3; page 9, last paragraph lines 2-3) comprising the steps of
(a) determining the level of at least one metabolite in a sample from a mammal (“Plasma PLC concentrations were determined,” wherein PLC is propionyl-L-carnitine; page 5, last paragraph, line 3), wherein:
- at least carnitine is lower than a reference value (Rat blood venous samples were collected before vehicle or PLC treatment; page 5, last paragraph)(Table 1 shows the basal level of PCL or propionyl-L-carnitine is lower than the basal level of the vehicle or only water where, therefore, the examiner considers the basal level of the vehicle to be the reference value; page 6), or
- at least one ceramide and/or one ceramide derivative is higher than a reference value, and/or
- at least one phosphatidylethanolamine is higher than a reference value.
(b) treating the wound based on the level of at least one metabolite (See wound decline upon treatment carnitine in Fig. 2).
Claims 5 and 12 is rejected under 35 U.S.C. 103 as being unpatentable over Scioli (Propionyl-L-Carnitine Enhances Wound Healing and Counteracts Microvascular Endothelial Cell Dysfunction; 2015) in view of Moretti (WO 97/05862; See attached foreign document) and in further view of Kamlage (EP 3 502 699 A1; See attached foreign document).
Regarding Claim 5, Scioli in view of Moretti teaches the method of diagnosis or prognosis of a non-healing or chronic wound according to claim 1.
Scioli in view of Moretti fails to teach the ceramide is Cer d18:1/24:0, Cer d18:1/24:1, Cer d18:1/23:0, Cer d18:2/23:0, Cer d18:1/22:0, and/or Cer d18:2/22:0.
Kamlage teaches - the ceramide is Cer d18:1/24:0 (Cer d18:1,C24:0; page 11; Table 1), Cer d18:1/24:1, Cer d18:1/23:0, Cer d18:2/23:0, Cer d18:1/22:0, and/or Cer d18:2/22:0
Kamlage is considered to be analogous to the claimed invention because it is in the same field of endeavor for the monitoring of a disease using ceramide levels. 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 have modified Scioli to incorporate the teachings of Kamlage by further specifying the ceramide to be Cer d18:1/24:0. Doing so would optimize the process of correlating carnitine levels to chronic wound prognosis because “each further biomarker determined decreases the false-positive rate and/or the false negative rate” ([0040]). Using this species of ceramide also “avoids determining biomarkers not contributing to improvement of diagnosis” and also envisaged that further biomarkers are determined which are diagnostic markers of other
diseases,” such as other non-healing or chronic wounds ([0040]). Scioli teaches “inflammation, causing delayed healing or chronic wounds” (page 2, lines 11-12) while Kamlage teaches “the association between chronic inflammation and the development of malignancies” leads to “precursor lesions” ([0004). Kamlage demonstrates using the combination of propionylcarnitine to Cer d18:1,C24:0 (page 11, Table 1, line 15) which is also the aim of Scioli in view of Moretti. Therefore, one of ordinary skill in the art would be motivated to combine the teaches of these two references to combat the inflammation source.
Regarding Claim 12, modified Scioli teaches the method of diagnosis or prognosis of a non-healing or chronic wound according to claim 11.
Scioli fails to teach wherein:
- the ceramide is Cer d18:1/24:0, Cer d18:1/24:1, Cer d18:1/23:0, Cer d18:2/23:0, Cer d18:1/22:0, and/or Cer d18:2/22:0, and/or
- the ceramide derivative is: * a ceramide-1-phosphate, preferably CerP d18:1/18:0, and/or * a sphingomyelin, preferably SM d18:1/23:0, and/or
- the phosphatidylethanolamine is PE 18:4/22:6.
Kamlage teaches - the ceramide is Cer d18:1/24:0 (Cer d18:1,C24:0; page 11; Table 1), Cer d18:1/24:1, Cer d18:1/23:0, Cer d18:2/23:0, Cer d18:1/22:0, and/or Cer d18:2/22:0
Kamlage is considered to be analogous to the claimed invention because it is in the same field of endeavor for the monitoring of a disease using ceramide levels. 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 have modified Scioli to incorporate the teachings of Kamlage by further specifying the ceramide to be Cer d18:1/24:0. Doing so would optimize the process of correlating carnitine levels to chronic wound prognosis because “each further biomarker determined decreases the false-positive rate and/or the false negative rate” (Kamlage, [0040]). Using this species of ceramide also “avoids determining biomarkers not contributing to improvement of diagnosis” and also “envisaged that further biomarkers are determined which are diagnostic markers of other diseases,” such as “other non-healing or chronic wounds” (Kamlage, [0040]). Scioli teaches “inflammation, causing delayed healing or chronic wounds” (page 2, lines 11-12) while Kamlage teaches “the association between chronic inflammation and the development of malignancies” leads to “precursor lesions” ([0004). Kamlage demonstrates using the combination of propionylcarnitine to Cer d18:1,C24:0 (page 11, Table 1, line 15) which is also the aim of Scioli in view of Moretti. Therefore, one of ordinary skill in the art would be motivated to combine the teaches of these two references to combat the inflammation source.
Response to Arguments
Applicant's arguments, see pages 4-7, filed 03/19/2025, with respect to the rejections of claims 1-2, under 35 U.S.C. 101 and 103 have been fully considered but they are not persuasive.
Applicant argues, “the pending claims are not directed to a judicial exception. The present claims all pertain to methods wherein the ratio of carnitine to ceramide and/or ceramide derivate is practically applied to the care of the wound. The claimed methods all include additional elements which are not mere mental steps or determination of a natural phenomenon, but rather active steps of obtaining samples and adapting the care of the wound when the ratio is lower than a reference value.
When these additional elements are viewed as a combination, they amount
to a claim as a whole that adds meaningful limits on the use of the correlation between said ratio and the diagnosis and prognosis of the wound. The totality of these claimed steps integrates the exception into the diagnosis and prognosis along with subsequent wound treatment, and amounts to more than a mental process based on a mathematical relationship.”
“The present claims can also be compared with claim 1 of Example 43 of the Office Subject Matter Eligibility Examples. In this Example, the method involves an initial step of diagnosing a patient having a non-responder phenotype and a final step of administering a treatment to said patient. Similarly, the present claims encompass the treatment of a wound which first involves an initial step of diagnosis/prognosis of a wound followed by subsequent treatment of the wound. For all these reasons, Applicant submits the rejection is moot. Withdrawal of the rejection is respectfully requested.
The examiner respectfully disagrees.
Even with the limitations of the amended claims 1, 3-12, the judicial exceptions of steps (a) and (b) of independent claim 1 and step (a) of independent claim 11 remain under Step 2A: Prong 1. These steps are still drawn to an abstract idea of mental processes (calculations performed in the mind), mathematical calculations (ratio of carnitine to ceramide and difference between carnitine to ceramide to a reference value) and are a result of natural correlation. Also, even with the addition of the treatment steps, they are still ineligible under Step 2A: Prong 2 of practical application and Step 2B of the claims as a whole amounting to significantly more (see 101 rejection above and explanation below).
Claim 1 of Example 43 of Appendix 1 to the October 2019 Update: Subject Matter Eligibility Life Sciences & Data Processing Examples was deemed ineligible because criteria Step 2A: Prong 1 by claiming the abstract idea of calculating a ratio of C11 to C13 levels measured in a blood sample from a patient diagnosed with Nephritic Autoimmune Syndrome Type 3 (NAS-3) to identify the patient as having a non-responder phenotype. The claim also does not integrate the abstract idea into a practical application of using specific treatments and the claim as a whole does not amount to significantly more than the recited exception.
Claims 1-12 of the instant application are also ineligible according to Steps 2A: prongs 1-2, and Step 2B. Regarding step (d), no particular treatment is required, (i.e., administering of a specific drug, a physical treatment, a surgery, etc.). Additionally the instant specification is silent to any specific treatment. The background of the instant specification, (page 1, lines 29-31) at most states "So far, compression has been the mainstay of ulcer treatments, notably VLU, but it can be painful and time- consuming," as well as "this identification of biomarkers, as well as the method relied upon, is needed for disease prognostication and the development of novel therapy" (page 2, lines 29-31 ). However, a different treatment than the well-known treatment of compression is not mentioned nor is a novel therapy revealed in the application that takes into account the use of this ratio.
Although this limitation indicates that a treatment is to be administered, it does not provide any information as to how the patient is to be treated, or what the treatment is, but instead covers any possible treatment that a doctor decides to administer to the patient. Like the claims in Mayo Collaborative Servs. v. Prometheus Labs., Inc., 566 U.S. 66, 78 (2012), claim 1 here tells the relevant audience (doctors) about the mathematical concepts and at most adds a suggestion that the doctors take those laws into account when treating their patients. Limitations (d) of claim 1 and (b) of claim 11 thus fail to meaningfully limit the claim because it does not require any particular application of the recited calculation, and is at best the equivalent of merely adding the words “apply it” to the judicial exception. Accordingly, Limitations (d) of claim 1 and (b) of claim 11 do not integrate the recited judicial exception into a practical application and the claim is therefore directed to the judicial exception (Step 2A: YES).
Step 2B: This part of the eligibility analysis evaluates whether the claim as a whole amounts to significantly more than the recited exception, i.e., whether any additional element, or combination of additional elements, adds an inventive concept to the claim. MPEP 2106.05. As explained with respect to Step 2A Prong Two, the claim recites a single additional element in limitations (c) of claim 1 and (b) of claim 11, which do not require any particular application of the recited calculation and is at best the equivalent of merely adding the words “apply it” to the judicial exception. Mere instructions to apply an exception cannot provide an inventive concept (Step 2B: NO). The claims are not eligible. Claims 3-12 are also ineligible based on the same criteria of these steps.
Therefore for these reasons, the amended claims fail to overcome the USC 101 rejection.
Applicant argues, “Moretti does not determine the ratio of carnitine to ceramide. Indeed, Table 1 of Moretti only illustrates that an anti-Fas antibody increases the production of ceramide, by comparison with a control, and that such increase is inhibited in presence of L-carnitine or isovaleryl L-carnitine. Therefore, Table 1 of Moretti cannot be considered as equivalent to the claimed feature of determination of the ratio of carnitine to ceramide, let alone for determining the outcome of wound healing.”
The examiner respectfully disagrees.
Anti-Fas antibody is included in each row of Table 1 (sans row 1) and is therefore held as a constant. Moretti states that “an anti-Fas antibody was employed to increase the production of ceramide from a basal value (20 picomoles per 106 cells) to 81.6 picomoles per 106 cells”. The addition of the anti-Fas antibody was only added so that a higher baseline was obtained for a more dramatic comparison of the relationship between carnitine and ceramide. Therefore, regardless of the addition of an anti-Fas antibody, the limitations of claim 1 are still met:
determining the ratio of carnitine to ceramide and/or ceramide derivate in a sample: the ratio of L-carnitine or isovaleryl L-carnitine to ceramide is still determined as shown in Table 1 of Moretti (100 mcg/ml/7.3 per 106 and 50 mcg/ml/8.6 per 106)
said ratio is decreased when compared with a reference value: (In a first interpretation, the examiner understands Table 1 to depict the control as the reference value and the decrease of ceramide concentration with an increase of the carnitine concentrations; In a second interpretation, the examiner understands Table 1 to depict the control+ anti-Fas antibody as the reference value and the decrease of ceramide concentration with an increase of the carnitine concentrations).
As a result, Moretti considers the ratios of Table 1 and concludes that “L-carnitine and isovaleryl L-carnitine are thus shown to inhibit the synthesis of ceramide in vitro” which satisfies the limitations of claim 1.
Applicant argues, “Other examples of Moretti disclose the ceramide levels of patients affected by several diseases (neuro-myopathy, hyperthyroidism, hepato-splenomegaly due to viral hepatitis of C type, protein catabolism and lipidic depletion as a consequence of tubercular infection); before and after the administration of ceramide. Moretti refers then to the treatment of cellular disorders accompanied by high level of ceramide, treated by carnitine; and as mentioned above, Scioli refers to the use of propionyl-L-carnitine to enhance wound healing. Consequently, both Moretti and Scioli relate to the therapeutic treatment of disorders by administering L-carnitine. L-carnitine is therefore herein considered as a "drug" and not a diagnostic biomarker. Indeed, in Moretti and Scioli the carnitine is considered in the treatment step, and not before in the diagnosis step, let alone in combination with ceramide level.
The examiner respectfully disagrees.
Examples 2 and 3 of Moretti teach that a known concentration of carnitine is administered and that a level of ceramide is obtained both pre-treatment and post-treatment. For example, in example 2, two patients were treated with 3 g per day of L-carnitine by oral route through two months. Moretti states that “monitoring can begin any time following administration but suitably is commenced following 3 hours to ensure accurate results,” and that “monitoring can be continued indefinitely,” wherein the monitoring is the collection of ceramide levels (Page 4, paragraph 3, last 3 lines). Therefore, each day for two months, ceramide levels can be obtained and this ratio of a 3g carnitine dosage and respective measured ceramide level serves as the biomarker to determine if more carnitine treatment is needed. Since a known amount of carnitine has been administered and a ceramide level has been measured, this ratio can be compared against the reference value of the measured ceramide level before treatment in the same way the ratio is shown in Example 1. The monitoring (ceramide measurements) can be continued indefinitely and the daily treatment will follow the previous day’s diagnostic biomarker of the ratio of 3g dose of l-carnitine and the measured ceramide. Therefore, Scioli in view of Moretti, teach carnitine as both the biomarker and the treatment.
Applicant argues, “ It should also be noted that Moretti discloses many diseases characterized by elevated levels of ceramide, but Moretti does not disclose that the level of ceramide is used to diagnose said diseases per se. Applicant therefore submits the following.
Moretti and Scioli do not teach or suggest that carnitine can be used for diagnosis nor prognosis, let alone of a non-healing or chronic wound;
(ii) Moretti and Scioli do not teach or suggest that ceramide can be used for diagnosis nor prognosis, let alone of a non-healing or chronic wound;
Moretti and Scioli do not teach or suggest that the ratio of carnitine to ceramide could be used to diagnose nor prognose a non-healing or chronic wound.”
The examiner respectfully disagrees.
Moretti states that “Examples of illnesses or disorders characterized by elevated levels of ceramide include…damages by radiations and/or chemotherapy agents,” which are a kind of internal wound. Since this wound is characterized by high ceramide levels, then a prognosis (prediction of the likely course or outcome of the disease or condition) can be determined in that the illness with remain the same or possibly become even more detrimental (emphasis added).
Conclusion
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/V.S./Examiner, Art Unit 1758
/SAMUEL P SIEFKE/Primary Examiner, Art Unit 1758