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 .
DETAILED ACTION
This Action is in response to the papers filed on January 13, 2025. Pursuant to the amendment filed on January 13, 2025, claims 1-12 are currently pending of which claims 1-11 have been amended and claim 12 newly filed. No claims have been cancelled. Therefore, claims 1-12 are currently under examination to which the following grounds of rejection are applicable.
Priority
The instant application claims foreign priority 35 U.S.C. 119(a)-(d) to European Patent Application No. EP 21383180.3 filed on December 21, 2021 and PCT Application No. PCT/EP2022/086485 filed on December 16, 2022. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Thus, the earliest possible priority for the instant application is December 21, 2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on October 18, 2024 was filed. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Specification
Cross-Reference to Related Applications
The disclosure filed on June 14, 2024 is objected to because the cross-reference to related applications on the first page of the specification is not provided. The cross-reference should contain the priority applications listed above in addition to the respective patent numbers. Correction is required.
Claim Objections
Claim 4 is objected to because the recited abbreviation, ‘LAMP2A,’ should be spelled out at the first encounter in the claims.
Claim 8 is objected to because the claim recites, “of the method of claim 7, wherein the cancer is glioblastoma.” when the appropriate correction is “The method according to claim 7, wherein the cancer is glioblastoma.”
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 11-12 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more.
Applicant is directed to the 2019 Revised Patent Subject Matter Eligibility Guidance published in the Federal Register (84 FR 50) on 1/07/2019, which is found at: https://www.govinfo.gov/content/pkg/FR-2019-01-07/pdf/2018-28282.pdf; and the October 2019 Update: Subject Matter Eligibility, which is found at https://www.uspto.gov/sites/default/files/documents/peg_oct_2019_update.pdf.
Briefly summarized here, the guidance cites a two part test: Is the claimed invention directed to a statutory class of invention (Step 1), if so, is the claimed invention as a whole directed to a law of nature, natural phenomena, or an abstract idea (i.e. set forth or described in the claim) (Step 2A, prong one), if so, does the claimed invention recite additional elements that integrate the judicial exception into a practical application (Step 2A, prong two), if not, then does the claim as a whole amount to significantly more than the judicial exception (Step 2B).
Step 1: Regarding step 1, the claims are directed to a method for the diagnosis and/or prognosis which falls under the statutory category of a process. Accordingly, the requirements of Step 1 are met.
Step 2A, Prong One: Claim 11 is directed to a method for the diagnosis and/or prognosis of glioblastoma in a subject which comprises assessing the level of at least a biomarker involving steps of identification of select biomarker levels, all of which is considered a mental process; and therefore is the judicial exception of an abstract idea.
Applicant is directed to MPEP 2106.04(a)(2) (III) which states that the courts consider a mental process (thinking) that "can be performed in the human mind, or by a human using a pen and paper" to be an abstract idea. CyberSource Corp. v. Retail Decisions, Inc., 654 F.3d 1366, 1372, 99 USPQ2d 1690, 1695 (Fed. Cir. 2011). As the Federal Circuit explained, "methods which can be performed mentally, or which are the equivalent of human mental work, are unpatentable abstract ideas the ‘basic tools of scientific and technological work’ that are open to all.’" 654 F.3d at 1371, 99 USPQ2d at 1694 (citing Gottschalk v. Benson, 409 U.S. 63, 175 USPQ 673 (1972)). See also Mayo Collaborative Servs. v. Prometheus Labs. Inc., 566 U.S. 66, 71, 101 USPQ2d 1961, 1965 (2012) ("‘[M]ental processes[] and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work’" (quoting Benson, 409 U.S. at 67, 175 USPQ at 675)); Parker v. Flook, 437 U.S. 584, 589, 198 USPQ 193, 197 (1978).
In the instant case, for claim 11, “A method for the diagnosis and/or prognosis of glioblastoma in a subject, which comprises assessing the level of at least a biomarker…” describes a correlation or relationship between the presence of a select marker in patient with a diagnosis/prognosis. This limitation sets forth a judicial exception, because this type of correlation is a consequence of natural processes, similar to the naturally occurring as this step could be performed by a human using mental steps or basic critical thinking, which are types of activities that represent abstract .
Step 2A Prong Two: The judicial exception is not integrated into a practical application despite reciting additional elements. Claim 11 recites the following additional elements, in step (a) the identification of a higher level of lumican and/or vitamin D as compared with a pre-established threshold level determined in healthy control subjects, and for step (b) the-the identification of a higher level of gelsolin, periostin and osteopontin as compared with a pre-established threshold level determined in healthy control subjects.
These steps of “identifying” do not integrate the mental process into a practical application because they are merely steps of identification by mental comparison. Further, the steps are recited at a high level of generality, and are considered routine, well-known steps in the field of diagnostics. The detection of select markers compared with pre-established threshold levels merely instructs a scientist to use any detection technique. When recited at this high level of generality, there is no meaningful limitation, such as a particular or unconventional machine or technique, in this step that distinguishes it from well understood, routine, and conventional diagnostics engaged by scientists prior to applicant’s invention, and at the time the application was filed. 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)).
Step 2B: The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception. 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. 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.
Judicial Exception – Conclusion
Therefore, the claims are directed to an abstract idea (mental process of screening the candidate drug on the basis of the neural cell) that is not integrated into a practical application, does not include elements that amount to significantly more than the abstract idea, and does not qualify as patent eligible subject matter under 35 U.S.C. § 101. The claims are not eligible.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-2, 5-7, and 9 are rejected under 35 U.S.C. 102(a)(1)(2) as being anticipated by Dominici et al. (US 9,572,838 B2).
Regarding claims 1-2 and 5, Dominici teaches an anti-tumour medicament, said medicament being characterized by comprising pericytes extracted from adipose tissue (AD-PC) transfected with a recombinant retroviral vector comprising a sequence encoding a secreted soluble TRAIL (sTRAIL) (claim 1 and 2, abstract). Given the broad scope of the medicament of claim 1, wherein the modified pericyte cell, or secretome derived thereof, has been pre-treated to impair chaperone-mediated autophagy (CMA) or to downregulate CMA levels to a value below a pre-established threshold level measured in untreated wildtype pericytes, Dominici anticipates this claim for the sole reason that modified pericyte inherently exhibits a down-regulated CMA level when compare to the upregulated CMA level of a peritumoral PC taken as the preestablished threshold. This is supported by the instant Specification stating such characteristic, wherein the glioblastoma adjacent pericytes would have up-regulated CMA expression:
“PC [pericytes] acquire an immunosuppressive function during the progression of GB that contributes to the establishment of immunotolerance and, therefore, to tumor growth. This immune function depends on the aberrant upregulation of GB-induced chaperone-mediated autophagy (CMA) through cell-cell interactions, that causes PC to present an anti-inflammatory phenotype and inactivate the T-cell responses for tumor removal.” (par 0003).
Therefore, the modified pericytes of Dominici are expected to have a lower CMA expression than glioblastoma adjacent pericytes, when used in treating cancers. Dominici does not teach PCs that have been pre-treated to impair chaperone-mediated autophagy (CMA) or to downregulate CMA levels, yet the modified PCs of Dominici are similar to that claimed when compared to cancer adjacent PCs, and secondly, this limitation is being considered a product-by-process limitation in reference to the claimed PCs. As such, the means by which the modified PCs are obtained hold no weight when the structure of the composition, e.g. modified PCs, is similar to the prior art.
Claims 6, 7, and 9 are anticipated by Dominici for the same reasons outlined above. In reference to the limitation of “substantially pure population of modified pericyte cells” of claim 9, Dominici teaches in Example 1 the process of obtaining such cells for modification from adipose tissue via liposuction, particularly the vascular stromal fraction, to obtain a population of PCs. Figure 4 shows testing of PC markers with immunophenotypic assessment by cytofluorimetric analysis (col 10). Moreover, in reference to the pharmaceutically acceptable carriers or excipients of claim 9, Dominici teaches the administering of the modified PCs with PBS in Example 3
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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 3, 4, 8 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Dominici et al. (US 9,572,838 B2) as applied to claims 1-2, 5-7, and 9 above, and further in view of Valdor et al. (Proc. Natl. Acad. Sci. U.S.A. 116 (41) 20655-20665; of record IDS).
The teachings of Dominici are discussed supra. Dominici does not teach treating cancer that is glioblastoma, and wherein the modified PCs have altered LAMP2A gene expression wherein LAMP2A is inhibited or deleted.
Valdor teaches how glioblastoma (GB) ablate anti-tumor immune functions of surrounding pericyte cells is what facilitates tumor progression. Pericyte cells (PCs) are perivascular stromal cells situated on the abluminal vessel wall of brain capillaries. Valdor describes murine primary PC with impaired CMA obtained by either isolation from brains of Lamp2a-/- mice, or transducing PC with lentivirus expressing Lamp2-specific shRNAs to silence Lamp2 expression (p.20664, "Cell culture" and p.2 of Supplemental ‘Supp.’). The culture media from WT and KO PC after 72 h of co-culture with GB cell lines, U373/U87, were collected for investigation (Legend on p. 10 of Supp. Fig.S3). GB interaction with co-cultured pericytes (PCs) upregulates CMA in PCs what leads to the acquisition of an immunosuppressive function in PCs (Figures 1-2). Co-culture of CMA-deficient PCs with GB cells results in the secretion of peptides/proteins that reduce tumor survival and prevent PC-GB interactions, since conditioned media treated with RNase but not with trypsin of these co-cultures could reproduce the results on GB cell death (Figures 3-5). Therefore, blockage of CMA in PC results in changes in the protein levels involved in cell-to-cell interaction and affects the pericyte secretory phenotype, resulting in defective GB adhesion and diminished tumor survival. These results highlight the possibility of targeting CMA in pericytes for the development of new therapies against GB.
Regarding claims 3, 4, and 8, it would have been prima facie obvious for one of ordinary skill in the art at the time of the effective filing date to have modified the PCs taught by Dominici et al. to downregulate LAMP2A expression as taught by Valdor et al. because it would have been obvious to combine prior art elements according to known methods to yield predictable results. Valdor teaches CMA inhibition in PC promotes GB cell death via downregulation of LAMP2A, and therefore it would obvious to modify the PCs of Dominici to effectively treat glioblastoma as has been shown by Valdor by administering these modified to a subject in need thereof.
Conclusion
Claims 1-12 are rejected. No claims are allowed.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maria G Leavitt can be reached at (571) 272-1085. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MICHAEL ANGELO RIGA/Examiner, Art Unit 1634
/TERESA E KNIGHT/Primary Examiner, Art Unit 1634
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