DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
2. Applicant’s election without traverse of the species of GATA6 in the reply filed on 07 July 2026 is acknowledged.
Claim Status
3. Claims 1-11, 27-32 and 34-36 are pending and have been examined herein. It is noted that claims 8 and 32 encompass non-elected subject matter of the KRT17, KRT5, S100A2, ECAD, CLDN18.2 and TTF1 genes and combinations of genes. Claims 8 and 32 have been examined herein only to the extent that they read on the elected species of GAT6 (in combination with HMGA2).
Claim Rejections - 35 USC § 101
4. 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 1-4, 7-9, 27, 29, 31-32 and 34 are rejected under 35 U.S.C. 101 because the claimed invention is directed to the judicial exception of a law of nature / natural phenomenon, and/or an abstract idea without significantly more. The judicial exception is not integrated into a practical application and the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons that follow.
Applicant' s attention is directed to MPEP 2106 “Patent Subject Matter Eligibility” which discusses the Alice/Mayo two-part test for evaluating subject matter eligibility.
Regarding Step 1 of the subject matter eligibility test set forth at MPEP 2106III, the claims are directed to the statutory category of a process.
Regarding Step 2A, prong one, the claims recite the judicial exception of a law of nature. The claims recite the correlation between the level of expression of the biomarker HMGA2 and the occurrence of PDA or a subtype of PDA gene expression of the biomarkers. For example, claims 1-11 recite “wherein a differential expression of the at least one biomarker in the biological sample of the subject relative to the expression of the biomarker in the reference/control sample identifies the subject as suffering from PDA.” Claims 27-32 and 34-36 recite “wherein a differential expression of the at least one biomarker in the biological sample of the subject relative to the expression of the biomarker in the reference/control sample identifies the subject as suffering from the subtype of PDA.” As in Mayo Collaborative Services v. Prometheus, the recited relationship is a natural phenomenon that exists apart from any human action. See also Cleveland Clinic Foundation v. True Health Diagnostic, LLC, 2018-1218 (Fed Cir. 2019) which states that “The re-phrasing of the claims does not make them less directed to a natural law.”
The claims also recite the judicial exception of an abstract idea and particularly mental processes.
MPEP 2106.04(a) states that the enumerated groupings of abstract ideas include:
“1) Mathematical concepts – mathematical relationships, mathematical formulas or equations, mathematical calculations (see MPEP § 2106.04(a)(2), subsection I);…
3) Mental processes – concepts performed in the human mind (including an observation, evaluation, judgment, opinion) (see MPEP § 2106.04(a)(2), subsection III).”
The claims require performing a step of "comparing" the expression levels in the sample to that of a reference, control sample. Neither the specification nor the claims set forth a limiting definition for "comparing" and the claims do not set forth how comparing is accomplished. The broadest reasonable interpretation of the “comparing” step is that this step may be accomplished by critical thinking processes. Such “comparing” thereby encompasses only an abstract idea / process.
Regarding Step 2A, prong two, having determined that the claims recite a judicial exception, it is then determined whether the claims recite additional elements that integrate the judicial exception into a practical application.
Herein, the claims do not recite additional steps or elements that integrate the recited judicial exceptions into a practical application of the exception(s). The additionally recited steps of obtaining a sample from a subject and determining, quantifying or measuring the level of a biomarker in the sample are part of the data gathering process necessary to observe the judicial exception. These steps do not practically apply the judicial exception. As set forth in MPEP 2106.05(g), steps of gathering data to be used in a claimed process are pre-solution activity and do not integrate a judicial exception into a practical application.
Claims 1-4,and 7-9 recite the additional step of “administering to the subject an effective amount of at least one therapeutic compound as a first-line treatment.” However, the claims do not define what constitutes the first-line treatment and the specification does not provide a limiting definition for what is encompassed by a first-line treatment per se. The claims do not particularly require that the treatment that is administered treats one or more symptoms of PDA.
Regarding specific treatments, see MPEP 2106.04(d)(2):
When determining whether a claim applies or uses a recited judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition, the following factors are relevant.
a. The Particularity Or Generality Of The Treatment Or Prophylaxis
The treatment or prophylaxis limitation must be "particular," i.e., specifically identified so that it does not encompass all applications of the judicial exception(s). For example, consider a claim that recites mentally analyzing information to identify if a patient has a genotype associated with poor metabolism of beta blocker medications. This falls within the mental process grouping of abstract ideas enumerated in MPEP § 2106.04(a). The claim also recites "administering a lower than normal dosage of a beta blocker medication to a patient identified as having the poor metabolizer genotype." This administration step is particular, and it integrates the mental analysis step into a practical application. Conversely, consider a claim that recites the same abstract idea and "administering a suitable medication to a patient." This administration step is not particular, and is instead merely instructions to "apply" the exception in a generic way. Thus, the administration step does not integrate the mental analysis step into a practical application….
b. Whether The Limitation(s) Have More Than A Nominal Or Insignificant Relationship To The Exception(s)
The treatment or prophylaxis limitation must have more than a nominal or insignificant relationship to the exception(s). For example, consider a claim that recites a natural correlation (law of nature) between blood glucose levels over 250 mg/dl and the risk of developing ketoacidosis (a life-threatening medical condition). The claim also recites "treating a patient having a blood glucose level over 250 mg/dl with insulin". Insulin acts to lower blood glucose levels, and administering insulin to a patient will reduce the patient’s blood glucose level, thereby lowering the risk that the patient will develop ketoacidosis. Thus, in the context of this claim, the administration step is significantly related to the recited correlation between high blood glucose levels and the risk of ketoacidosis. Because insulin is also a "particular" treatment, this administration step integrates the law of nature into a practical application. Alternatively, consider a claim that recites the same law of nature and also recites "treating a patient having a blood glucose level over 250 mg/dl with aspirin." Aspirin is not known in the art as a treatment for ketoacidosis or diabetes, although some patients with diabetes may be on aspirin therapy for other medical reasons (e.g., to control pain or inflammation, or to prevent blood clots). In the context of this claim and the recited correlation between high blood glucose levels and the risk of ketoacidosis, administration of aspirin has at best a nominal connection to the law of nature, because aspirin does not treat or prevent ketoacidosis. This step therefore does not apply or use the exception in any meaningful way. Thus, this step of administering aspirin does not integrate the law of nature into a practical application.
Claims 27,29, 31-32 and 34 recite a step of administering to the subject an effective amount of at least one PDA subtype specific therapeutic compound as a first-line treatment. However, neither the specification nor the claims define what is encompassed by a PDA subtype specific therapeutic compound. Because the recited treatment is generic, the administering step does not integrate the law of nature into a practical application.
Additionally, claims 1-4, 7-9, 27, 32, and 34 encompass methods wherein differential expression – i.e., either an increase or decrease in the expression level – of HMGA2 identifies the subject as having PDA or any subtype of PDA. Accordingly, administering the first line therapy or the PDA subtype specific therapy to subjects having either an increase or a decrease in the expression level of HMGA2 is not a practical application since essentially all subjects may be treated in the same manner.
Regarding Step 2B, the next question is whether the remaining elements/steps – i.e., the non-patent-ineligible elements/steps - either in isolation or combination, amount to significantly more than the judicial exception.
Herein, the claims as a whole are not considered to recite any additional steps or elements that amount to significantly more than routine and conventional activity and do not add something “significantly more” so as to render the claims patent-eligible. The additionally recited steps of obtaining a sample from a subject and determining the expression level of a biomarker in the sample are recited at a high degree of generality and were well-known, routine and conventional in the prior art. This finding is evidenced by the teachings in the specification. For instance, the specification (para [0046]) states “Overexpression can be detected using conventional techniques for detecting mRNA (i.e., RT-PCR, PCR, hybridization) or proteins (i.e., ELISA, immunohistochemical techniques, mass spectroscopy).” See also para [0047]).
Additionally, the teachings in the prior art establish that methods of obtaining a sample from a patient and determining gene expression levels in the sample and then administering a treatment, including a treatment for PDA to the patient, were well-known, routine and conventional in the prior art. For instance, Collisson et al (Nature Medicine. 2011. 17(4): 500-503) teaches methods of obtaining a sample from a patient, measuring mRNA expression levels, including GATA6 mRNA levels, in the sample, and then administering a personalized treatment for the patient based on a determined subtype of PDA detected in the patient (e.g., p. 1-2; p. 3 second para; and p. 4 final para). Rashid et al (Clinical Cancer Research. 2020. 26(1): 82-92) teaches methods comprising: obtaining a sample from a patient, assaying the sample for gene expression levels to determine a subtype of PDA, and treating the patient with a first-line therapy for PDA (e.g., abstract; p. 3-4 “Materials and Methods”; and p. 11-12).
See also MPEP 2106.05(d) II which states that:
The courts have recognized the following laboratory techniques as well-understood, routine, conventional activity in the life science arts when they are claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity.
i. Determining the level of a biomarker in blood by any means, Mayo, 566 U.S. at 79, 101 USPQ2d at 1968; Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1362, 123 USPQ2d 1081, 1088 (Fed. Cir. 2017);
ii. Using polymerase chain reaction to amplify and detect DNA, Genetic Techs. v. Merial LLC, 818 F.3d 1369, 1376, 118 USPQ2d 1541, 1546 (Fed. Cir. 2016); Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d 1371, 1377, 115 USPQ2d 1152, 1157 (Fed. Cir. 2015);
iii. Detecting DNA or enzymes in a sample, Sequenom, 788 F.3d at 1377-78, 115 USPQ2d at 1157); Cleveland Clinic Foundation 859 F.3d at 1362, 123 USPQ2d at 1088 (Fed. Cir. 2017); …
v. Analyzing DNA to provide sequence information or detect allelic variants, Genetic Techs., 818 F.3d at 1377; 118 USPQ2d at 1546;…
vii. Amplifying and sequencing nucleic acid sequences, University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 764, 113 USPQ2d 1241, 1247 (Fed. Cir. 2014); and
viii. Hybridizing a gene probe, Ambry Genetics, 774 F.3d at 764, 113 USPQ2d at 1247.
Note that while the claims recite detecting the expression of particular genes, the identity of the genes is part of the judicial exception and not something in addition to the recited judicial exceptions. The claims do not require using a particular non-conventional reagent, such as a particular, non-conventional probe or primer consisting of or comprising a specific nucleotide sequence so as to add something ‘significantly more’ to the recited judicial exceptions.
In Mayo v. Prometheus, the Supreme Court stated: "[t]o put the matter more succinctly, the claims inform a relevant audience about certain laws of nature; any additional steps consist of well understood, routine, conventional activity already engaged in by the scientific community; and those steps, when viewed as a whole, add nothing significant beyond the sum of their parts taken separately."
This is similar to the present situation wherein the additional steps and elements are recited at a high degree of generality and are all routine, well understood and conventional in the prior art. The recited steps and elements do not provide the inventive concept necessary to render the claims patent eligible. See also Genetic Technologies Ltd. v. Merial L.L.C. 818 F.3d at 1377, 1379 (Fed. Cir. 2016).
For the reasons set forth above, when the claims are considered as a whole, the claims are not considered to recite something significantly more than a judicial exception and thereby are not directed to patent eligible subject matter.
Claim Rejections - 35 USC § 112(b) - Indefiniteness
5. The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-11, 27-32 and 34-36 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 1-11, 27-32 and 34-36 are indefinite over the recitations of “determining/quantifying/measuring” (see claims 1, 7, 27 and 32) because it is not clear as to whether the claims are intended to require performing each of determining, quantifying and measuring or if the claims are considered to require performing determining, quantifying or measuring, or if determining, quantifying and measuring are considered to be the same and are intended to be synonyms for one another. Note that the specification does not provide a limiting definition for determining, quantifying and measuring which indicates that these processes are identical to one another.
Claims 1-11, 27-32 and 34-36 are indefinite over the recitations of “reference/control” (see claims 1, 5, 7, 7, 10, 11, 27, 28, 30, 32, 35 and 36) because it is not clear as to whether the claims intend to require both a reference and a control or either a reference or a control or if the reference and control are considered to be the same and are intended to be synonyms for one another. Note that the specification does not provide a limiting definition for reference and control which indicates that these two types of samples are identical to one another. Additionally, dependent claims 2 and 3 recite only a reference sample and it is unclear as to whether these claims intend to only define the reference sample but do not require that the comparison is made with a control sample and thereby include methods wherein the control sample is any control sample.
Claim 3 is indefinite over the recitation that the “biological sample corresponding to the biological sample obtained from the subject suffering from PDA” because in this context it is not clear as to what is meant by “corresponding.” There is no definition for this phrase in the specification and there is no art recognized definition for “corresponding” as it relates to two samples. It is unclear as to whether “corresponding” is intended to mean, for instance, the same sample from the subject but a different aliquot of the sample and/or the same sample type obtained from the subject at an earlier time, etc.
Claim 29 is indefinite over the recitation of “the subject is diagnosed with basal subtype PDA” and claim 31 is indefinite over the recitation of “the subject is diagnosed with classical subtype PDA.” It is not clear as to whether “is diagnosed” is intended to be an active process step of diagnosing, such that the method includes an additional step of diagnosing the subject for the basal or classical subtype of PDA and if so, if the diagnosing is considered to be distinct from the “identifying,” in which case it is unclear as to the criteria required to diagnose the subject as having basal or classical subtype PDA. Alternatively, it is unclear as to whether the method is one in which the subject has previously been diagnosed as having the basal (claim 29) or classical (claim 31) subtype of PDA.
Claim Rejections - 35 USC § 103
6. 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) 1-4, and 7 is/are rejected under 35 U.S.C. 103 as being unpatentable over Rosner et al (U.S. 20160078167) in view of Piscuoglio et al (Histopathology. 2012. 60: 397-404).
Rosner teaches a method for treating a subject identified as suffering from cancer comprising administering to the subject a therapeutically-effective amount of at a chemotherapeutic compound following identifying the subject as suffering from the cancer (e.g. para [0010]), wherein the subject is identified as suffering from cancer by a method comprising: (i) obtaining a biological sample from the subject; (ii) measuring the expression level of HMGA2 in the sample; and (iii) comparing the expression level of HMGA2 in the sample to that in a control sample, wherein an increase in the expression level of HMGA2 in the sample from the subject relative to that in the control sample identifies the subject as suffering from cancer (e.g., para [0009-0010] [0201] and [0203]; and claims 38 and 39).
Rosner (para [0201]) teaches:
“Additionally, it is believed that the high mobility group AT-hook 2 (HMGA2), a chromatin-remodeling factor, binds to AT-rich regions in DNA, altering chromatin architecture to either promote or inhibit the action of transcriptional enhancers. HMGA2 is highly expressed in ES cells but is generally low or lacking in normal somatic cells. Interestingly, HMGA2 is highly expressed in most malignant epithelial tumors, including, for example, breast, pancreas, oral squamous cell carcinoma, and non-small-cell lung cancer. HMGA2 overexpression in transgenic mice causes tumor formation, whereas Hmga2-knockout mice have a pygmy phenotype indicative of a growth defect.”
Rosner teaches that the cancer to be diagnosed therein includes pancreatic cancer (e.g., para [0201] and [0230]) but does not specifically teach that the cancer is pancreatic ductal adenocarcinoma (PDA/PDAC).
However, Piscuoglio teaches that increased expression of HMGA2 is diagnostic of a more aggressive phenotype of pancreatic ductal adenocarcinoma, including advanced tumor grade and lymph node metastasis (e.g., abstract and p. 403, col. 1, first para). Piscuoglio notes that a “previous study found increased HMGA2 expression by reverse transcription polymerase chain reaction in ductal pancreatic adenocarcinomas, and HMGA2 expression by immunohistochemistry” (p. 403, col. 2, first para).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have applied the method of Rosner specifically to pancreatic ductal adenocarcinoma. One would have been motivated to have done so because Rosner teaches that the method is applicable to pancreatic cancers in general and Piscuoglio teaches that the particular type of pancreatic cancer of pancreatic ductal carcinoma also expresses high levels of HMGA2 as diagnostic of the aggressiveness and advanced tumor stage and lymph node metastasis.
Regarding claim 2, Rosner teaches that the control sample can be from a normal non-disease state (i.e., healthy) subject (e.g., para [0211]).
Regarding claim 3, Rosner teaches that the comparison to a control “may be a level of expression that is determined from a previously evaluated sample or an average of levels of expression of previously evaluated sample(s)” (para [0064]). Rosner also teaches that the methods disclosed therein are “for monitoring the effectiveness of a course of treatment for a subject diagnosed cancer.” (para [0196]). Accordingly, the teachings of Rosner in combination with Piscuoglio suggest methods wherein the reference, control sample is a sample obtained at an earlier time point from the subject identified as having PDA– i.e., a “sample corresponding to the biological sample obtained from the subject.”
Regarding claim 4, Rosner teaches that the sample is a biopsy sample (e.g., para [0065-0066]).
Regarding claim 7, Rosner teaches that the method is one that measures the expression level of at least one additional biomarker (e.g., TET1, HOXA7 and/or HOXA9) and compares the expression level with that in a control sample (e.g., para [0009] and [0014]).
7. Claim(s) 1, 3-5, 7-10, 27-29, 32, 34 and 35 is/are rejected under 35 U.S.C. 103 as being unpatentable over Chan-Seng-Yue et al (Nature Genetics. 13 January 2020. 52: 231-240 and p. 1-8 of Supplemental Table 4, 40 pages total).
Chan-Seng-Yue teaches that an increase in expression of HMGA2 is part of the gene expression signature “Sig. 2” that is present in >75% of pancreatic ductal adenocarcinomas having a basal-like subtype (see caption / legend for “Extended Data Fig. 4”; Supplemental Table 4 at line 246; p. 5 of the attached 8 page printout that includes a portion of Supplemental Table 4, reproduced in part below):
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Chan-Seng-Yue teaches that gene expression levels were determined by obtaining surgical specimen samples from subjects having PDA; measuring gene expression levels in the samples by performing RNA sequencing; and comparing gene expression levels between different subtypes of PDA (e.g., “Methods” p. 1; Figure 1; and Extended Data Fig. 4).
Accordingly, Chan-Seng-Yue teaches a method for identifying a subject suffering from PDA, and particularly basal subtype PDA, comprising: (i) obtaining a biological sample from the subject; (ii) measuring the expression level of HMGA2 in the sample; and (iii) comparing the expression level of HMGA2 to that in a control sample, wherein an increase in the expression level of HMGA2 in the sample from the subject relative to that in the control sample identifies the subject as suffering from the basal subtype of PDA.
Regarding claims 1, 3-5 and 7-10, Chan-Seng-Yue does not teach administering a first-line cancer treatment to subjects diagnosed as having basal-type PDA, particularly the cancer treatment of a therapeutic compound comprising FOLFIRINOX..
However, Chan-Seng-Yue teaches that the majority of basal type PDA subjects treated with modified FOLIFIRNIOX showed a decrease in tumor size following treatment (e.g., Extended Data Fig. 3e and caption / legend).
Accordingly, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Chan-Seng-Yue so as to have included a step of treating subjects identified as having basal-type PDA based on the detection of a Sig. 2 expression profile (and thereby an overexpression of HMGA2) in a tumor tissue sample obtained from the subject by administering a modified FOLFIRINOX therapy to the subject. One would have been motivated to have done so since Chan-Seng-Yue teaches that detection of a Sig. 2 expression signature, including overexpression of HMGA2, in a tumor tissue sample from the subject, identifies the occurrence of a basal type of PDA and also teaches that administration of modified FOLFIRINOX reduced tumor size in the majority of patients having basal type PDA.
Regarding claim 3, Chan-Seng-Yue does not specifically disclose that “the reference sample is a biological sample corresponding to the biological sample obtained from the subject suffering from PDA.” However, this phrase is not clearly defined in the specification or the claims and a corresponding sample as broadly recited encompasses any PDA sample. Since Chan-Seng-Yue compared expression levels of the biomarkers between the different types of PDA, Chan-Seng-Yue is considered to teach comparing the expression level of HMGA2 in a sample from a subject to that in other (“corresponding”) PDA samples.
Regarding claim 4, Chan-Seng-Yue teaches that the sample is a resected PDA tumor tissue sample (e.g., see “Tumor samples” at col. 1 of “Methods”).
Regarding claims 7-10, Chan-Seng-Yue teaches that the method is one that further measures the expression level of GATA6 and compares the expression level to that in a control sample (e.g., Fig. 1a; and Extended Data Fig. 6d). Chan-Seng-Yue states “Lack of GATA6 expression confirms Basal-like phenotype” (Extended Data Fig. 10). Additionally, regarding claim 10, since Chan-Seng-Yue teaches that lack of expression of GATA6 is indicative of basal type PDA, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have administered FOLIFIRINOX to those patients having high expression of HMGA2 (i.e., subjects having the Sig. 2 expression profile) and having a lack of expression of GATA6 (which is encompassed by a low expression of GATA6). One would have been motivated to have done so because Chan-Seng-Yue teaches that these are the subjects having a basal type PDA and whose tumors are more likely to be reduced in size following treatment with FOLFIRINOX therapy.
Regarding claims 27-29, 32, 34 and 35, as discussed above, Chan-Seng-Yue teaches that overexpression of HMGA2 is part of the Sig. 2 expression profile that is diagnostic of basal type PDA and that lack of expression of GATA6 (which is encompassed by “lower expression of GATA6”) is indicative of basal type PDA. Chan-Seng-Yue also teaches that treatment with modified FOLFIRINOX leads to a decrease in tumor size in the majority of PDA patients having basal type PDA (e.g., Extended Data Fig. 3e).
Accordingly, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Chan-Seng-Yue so as to have included a step of administering a modified FOLFIRINOX therapy to those subjects identified as having a basal type PDA based on the detection of a Sig. 2 expression profile, and thereby a higher expression level of HMGA2 alone or in combination with a lack of expression / lower expression of GATA6, as compared to a control sample. One would have been motivated to have done so because Chan-Seng-Yue teaches that the majority of patients with basal type PDA had a reduction in tumor size following treatment with modified FOLFIRINOX therapy. Note that it is considered to be a property of modified FOLFIRINOX therapy that it is a “PDA subtype specific therapeutic compound.”8.. Claim( 2 is rejected under 35 U.S.C. 103 as being unpatentable over Chan-Seng-Yue et al (Nature Genetics. 13 January 2020. 52: 231-240 and p. 1-8 of Supplemental Table 4, 40 pages total), in view of Rosner et al (U.S. 20160078167).
The teachings of Chan-Seng-Yue are presented above.
Chan-Seng-Yue does not teach comparing the expression level of HMGA in the sample from the subject to that of a sample obtained from a healthy subject.
However, Chan-Seng-Yue does teach that “(m)arker genes from the single-cell transcriptome atlas of the normal human pancreas were used to discriminate normal from malignant epithelial cells (Extended Data Fig. 4d,e)” (see p. 232, col. 2).
Further, Rosner (e.g., para [0009-0010] [0201] and [0203]; and claims 38 and 39) teaches detecting the occurrence of cancer, including pancreatic cancer, by detecting an increase in expression of HMGA2 as compared to a normal control sample. Rossner (para [0201]) also teaches that HMGA2 expression is generally low or absent in normal cells, and specifically states:
“Additionally, it is believed that the high mobility group AT-hook 2 (HMGA2), a chromatin-remodeling factor, binds to AT-rich regions in DNA, altering chromatin architecture to either promote or inhibit the action of transcriptional enhancers. HMGA2 is highly expressed in ES cells but is generally low or lacking in normal somatic cells. Interestingly, HMGA2 is highly expressed in most malignant epithelial tumors, including, for example, breast, pancreas, oral squamous cell carcinoma, and non-small-cell lung cancer. HMGA2 overexpression in transgenic mice causes tumor formation, whereas Hmga2-knockout mice have a pygmy phenotype indicative of a growth defect.”
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Chan-Seng-Yue so as to have compared the expression level of HMGA2 in the sample of the subject to that in a sample from healthy subjects. One would have been motivated to have done so because Rosner teaches that HMGA2 expression is usually low or absent in normal cells. Accordingly, such a modification of the method of Chan-Seng-Yue would have provided an alternative means for identifying overexpression of HMGA2 as indicative of pancreatic ductal adenocarcinoma.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CARLA J MYERS whose telephone number is (571)272-0747. The examiner can normally be reached M-Th 6:30-5:00 EST.
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/CARLA J MYERS/Primary Examiner, Art Unit 1682
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