DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 8/11/2025 has been entered.
Claims 30, 33-35 are pending and have been considered on the merits herein.
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 30, 33-35 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) assaying a blood sample from a patient having AML to determine circulating levels of CD33 and correlating the levels and identifying a patient’s predicted survival or remission duration. The claimed invention is directed to a naturally occurring correlation between the levels of markers and predicted survival or remission, i.e., a law of nature or natural phenomenon with an abstract idea which are themselves the judicial exception. The steps of claim 30 set 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 bodily fluid 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 disease. Additionally, one uses the detection levels to determine the predicted survival or remission, which 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.
Applicant’s claim 30 includes a reference value, i.e., 2800U/µl, however the claims are still similar to the Prometheus case, i.e. correlating a known amount of the analyte in the sample with a purported purpose (emphasis added). The detected level does nothing more than inform the audience about the law of nature. Additionally, making a determination about survival or remission based upon detected levels 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."
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’s predicted survival or remission based upon the detected 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, in addition, to determining by immunoassay and applicants’ specification indicates as much (see applicants specification p. 14, (parag. 0053, 0054)- p. 17 (parag. 0060), as well as Albitar et al. (US20030068664, US2010022176, and US2011/0236994). As claimed, one merely determines whether a sample has above or below the cutoff value. Determining the level of circulating CD33 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 correlating the detected levels in a sample having a cut-off value and predicting 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 is integrated into a practical application.
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 assaying the level of circulating CD33 in a blood sample (step a) and detecting the level of CD33 in the blood sample by contacting the sample with an antibody specific for CD33 and detecting resultant levels of CD33 (steps (a). 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 CD33 is present in the blood sample merely instructs a scientist to use any detection technique with any generic CD33 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).
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) 30, 33-35 is/are determined to be directed to a judicial exception.
For these reasons the claims are rejected under section 101 as being directed tonon-statutory subject matter.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim 30, 33-35 is/are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over each of Albitar et al. (US20030068664 PGPUb of US7718387, IDS), (US2010022176 PGPub of US7943332, IDS), and (US2011/0236994, IDS).
Regarding claim 30, Albitar (‘664) teach a method of detecting or monitoring or staging hyperproliferative diseases including acute myelogenous leukemia (AML) (abstract, 0003, 0015, 0016, 0024, 0027, 0047, 0048, 0050, 0068, 0069, 0124, 0125) comprising assaying levels of soluble CD33 (0023, 0057, 0068, 0069, 0072, 0073, 0117) in a bodily fluid selected from blood, plasma and serum, synovial fluid, spinal fluid, urine and saliva (0069, 0073, 0119) comprising contacting the bodily fluid with an antibody specific for cCD33 (0070-0075 and an antibody overview teaching 0070-0114, 0117, 0118-0123) and comparing the levels to cut-off values to stage the disease as well as predict survival (0125, 0163-0166, for example). Albitar teach that any biological sample suspected of containing an antigen or antibody complex may be used for antigen, antibody, antibody: antigen complex detection including blood (0119).
Regarding claims 33 and 34, the antibody has a detectable label selected from a radioisotope, an enzyme, biotin, a luminescent or fluorescent substance and colored substances (0103, 0105-112, 0121, 0122).
Regarding claim 35, Albitar teach assay methods including ELISA, Western blot, and radioimmunoassay (0018-0020, 0117, 0118, 0120, 0126, for example).
The teachings of US’176, US‘994 are the same as US'664.
While Albitar does not specifically teach the claimed reference value of claim 30 in regards to AML patients, the reference teaches comparing the assayed levels in patients to predict survival (see example 7, 0169, for example), wherein the cut-off is not determined based upon comparison to a normal patient. While it is noted that Ex. 7 is drawn to sCD20, this is the preferred embodiment; however the reference teaches that the method can be applied to the soluble CD markers and their respective diseases, i.e. CD33 is present in AML patients. The reference also teaches that “Those of skill in the art are very familiar with differentiating between differences in types and/or amounts of biomarkers, which represent a positive identification, and/or low level and/or background changes of biomarkers. Indeed, background levels are often used to form a "cut-off" above which increased detection will be scored as significant and/or positive” (0125). Therefore, one of ordinary skill in the art would have a reasonable expectation of successfully predicting survival when assaying levels of cCD33 in AML patients, comparing said level to a reference value and using said assayed level for predicting survival duration when comparing assayed levels to cut-off/reference values. One of skill in the art, when practicing the method of Albitar, would be able to determine a cut-off or reference value with which the detected/assayed levels would be scored against to predict survival.
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 §§ 706.02(l)(1) - 706.02(l)(3) 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 30, 33-35 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5-13 of U.S. Patent No. 7943332. Although the claims at issue are not identical, they are not patentably distinct from each other because the claimed inventions are drawn to methods of monitoring, predicting and staging a disease in a patient with a hematopoietic proliferative disorder including AML comprising assaying levels of circulating cell-free CD33 with an antibody specific for CD33, correlating the measured levels with the disease, and using ELISA assay methods. The examined claims would be obvious over the reference claims as the reference claims generically claim correlating the levels to the disease and using the levels for staging the disease. One would have a reasonable expectation of predicting survival when using said levels to stage the disease.
Response to Arguments
Applicant's arguments filed 8/11/2025 have been fully considered but they are not persuasive.
Regarding the 101 rejection of record, applicant argues that because Albitar does not teach the claimed cut-off level, the claim cannot be considered routine or well-known in the art.
Applicant’s claim 30 includes a reference value, i.e., 2800U/µl, however the claims are still similar to the Prometheus case, i.e. correlating a known amount of the analyte in the sample with a purported purpose (emphasis added). The detected level does nothing more than inform the audience about the law of nature. Additionally, making a determination about survival or remission based upon detected levels 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."
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’s predicted survival or remission based upon the detected 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, in addition, to determining by immunoassay and applicants’ specification indicates as much (see applicants specification p. 14, (parag. 0053, 0054)- p. 17 (parag. 0060), as well as Albitar et al. (US20030068664, US2010022176, and US2011/0236994). As claimed, one merely determines whether a sample has above or below the cutoff value. Determining the level of circulating CD33 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 correlating the detected levels in a sample having a cut-off value and predicting 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 is integrated into a practical application.
Regarding the 103 rejection over Albitar, applicants argue that the reference does not teach the claimed reference level and thus there is no guidance in Albitar to suggest the claimed reference level could or should be used nor a reasonable expectation of arriving at the level when not comparing to a normal patient. Further applicants argue that Ex. 4 of the specficaiton makes no indication that a reference cut-off was achieved by comparing to normal patients but rather circulating cell-free CD33 was measure in AML patients and those with a level above the median had a longer survival.
Similar to Ex. 4 of the instant specification Albitar teaches at Ex. 7 detecting levels of sCD20 (this is the preferred embodiment) in CLL patients to predict survival based upon a cut-off level, wherein the cut-off is not compared to normal patients, but rather groups of CLL patients. The reference teaches that the method can be applied to the soluble CD markers and their respective diseases, i.e. CD33 is present in AML patients. The reference also teaches that “Those of skill in the art are very familiar with differentiating between differences in types and/or amounts of biomarkers, which represent a positive identification, and/or low level and/or background changes of biomarkers. Indeed, background levels are often used to form a "cut-off" above which increased detection will be scored as significant and/or positive” (0125). Therefore, one of ordinary skill in the art would have a reasonable expectation of successfully predicting survival when assaying levels of cCD33 in AML patients, comparing said level to a reference value and using said assayed level for predicting survival duration when comparing assayed levels to cut-off/reference values. One of skill in the art, when practicing the method of Albitar, would be able to determine a cut-off or reference value with which the detected/assayed levels would be scored against to predict survival.
Regarding the ODP rejection of record, applicants argue that because the reference patent does not recite any reference level or the claimed reference level, the Office has not shown that a person of ordinary skill in the art would have been motivated to alter the reference claims with any reasonable expectation of success.
The claimed inventions are drawn to methods of monitoring, predicting and staging a disease in a patient with a hematopoietic proliferative disorder including AML comprising assaying levels of circulating cell-free CD33 with an antibody specific for CD33, correlating the measured levels with the disease, and using ELISA assay methods. As stated in the rejection, the reference claims generically claim correlating the levels to the disease and using the levels for staging the disease and thus the examined claims would be obvious over the reference claims. One would have a reasonable expectation of predicting survival because the correlation of cCD33 levels are used to stage and monitor the disease. Thus, similarly with the 103 rejection, one of skill in the art, when practicing the method of Albitar, would be able to determine a cut-off or reference value with which the detected/assayed levels would be scored against to predict survival/staging.
Conclusion
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
/Adam Weidner/ SPE, Art Unit 1651