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
Preliminary amendment filed on 02/16/2023 is acknowledged. Claims 1 and 3-17 were amended and claims 17-20 are newly added. Claims 1-20 are pending in the instant application.
Priority
This application is a National Stage Application of PCT/EP2021/072963 filed 08/18/2021 which claims foreign priority to EPO 20305935.7 filed on 08/19/2020.
Information Disclosure Statement
The information disclosure statement (IDS) dated 02/16/2023 complies with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609. Accordingly, the IDS documents have been placed in the application file and the information therein has been considered as to the merits.
Election/Restrictions
Applicants’ election without traverse of the invention of Group I, claims 1-9 and 15-18, drawn to labeling or detecting of cells using a modified monosaccharide compound of the pentose phosphate pathway, excluding arabinose, and a compound with a first reactive group, in the reply filed on 03/25/2026 is acknowledged.
Claims 10-14 and 19-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group 1, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 03/25/2026.
Claims 1-9 and 15-18 are examined on the merits.
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 7 and 17 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more than the judicial exception.
The claim is evaluated below using the “Subject Matter Eligibility Test for Products and Processes” flow chart as shown in MPEP § 2106 III.
Step 1: Is the claim to a process, machine, manufacture or composition of matter?
Yes. The claims are drawn to a method (process) which is one of the four statutory categories.
Step 2A, Prong One: Does the claim recite an abstract idea, law of nature, or natural phenomenon?
Yes. The claims are directed towards a method of detecting the labeling and then identifying cancer cells based on the measuring of the label.
In the broadest reasonable interpretation of the claim, the step of determining whether the measuring of the label identifies cancer cells comprise mental steps, which are abstract ideas.
Step 2A, Prong Two: Does the claim recite additional elements that integrate the judicial exception into a practical application?
No. There are no additional steps recited in the claim that integrate the judicial exceptions into a practical application. The claimed method ends with identifying cancer cells based on the measuring of the label. The claim does not further limit the determination with additional steps beyond the mental step.
Step 2B: Does the claim recite additional elements that amount to significantly more than the judicial exception?
No. The judicial exception is recited without additional limitations amounting to significantly more than the judicial exception.
While the claims require detecting the labeling and identifying the cancer cells, which could require that tests be performed, these are considered to be insignificant extra-solution activity that do not amount to more than the recited judicial exceptions. See MPEP 2106.05(g).
As the active steps of the claim are considered to be well-understood, routine, and conventional in the field or significant extra-solution activity, these steps do not amount to significantly more than the recited judicial exceptions.
As the instant claims recite judicial exceptions that are not integrated into a practical application and recite no elements that amount to significantly more than the judicial exceptions, the claims were found to not be drawn to eligible subject matter under 35 USC 101.
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.
Claims 1-3 and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Hoogenboom et al. (BMC Plant Biology, published 10/10/2016, see IDS dated 02/16/2023).
Hoogenboom is directed to the direct imaging of glycans in Arabidopsis roots via click labeling of metabolically incorporated azido-monosaccharides (title). Hoogenboom exemplifies azido-containing analogs (Figure 1, page 2). Hoogenboom teaches that glycans, especially in plants, usually have highly complex and diverse structures containing monosaccharides such as glucose, N-acetylglucosamine, galactose, L-arabinose, xylose, L-fucose and 3-deoxy-D-manno-oct-2-ulosonic acid. The monosaccharides and their derivatives can also be recycled by plant cells (page 2). Through uptake of extracellular monosaccharides and by intracellular catabolism of complex plant glycans, these monosaccharides can be recycled through the glycan salvage pathways. Using this recycling pathway the monosaccharides again end up in plant cell-surface glycans and its glycoproteins. The metabolic incorporation of monosaccharide analogs with a latent imaging tag via these pathways would allow for the direct imaging of plant glycans (Fig. 1). These incorporated monosaccharide analogs can be visualized and studied through a tag that enables click chemistry, which allows for rapid, specific and versatile covalent labeling of plant glycans with a fluorescent reporter molecule. This technique is called Metabolic Oligosaccharide Engineering (MOE) and it has already been widely applied for studying glycobiology in various organisms (page 2). Hoogenboom exemplified the use of click-chemistry enabled L-arabinose for detecting Arabidopsis roots (Fig 1).
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Hoogenboom does not exemplify the use of ribose, D-ribose, L-ribose, ribose 5-P, D-ribose 5-P, D-ribose 1-P, D-ribose 1,5-P, ribulose, ribulose 5-P, L-ribulose, L-ribulose 5-P, D-ribulose, D-ribulose 5-P, arabinitol, L- arabinitol, xylulose, xylulose-5-P, D-xylulose, D-xylulose-5-P, L-xylulose, xylose, D-xylose, L- xylose, and xylitol for labeling or detecting a eukaryotic cell. Hoogenboom does not teach a kit.
It would have been prima facie obvious before the effective filing date of the claimed invention to select xylose rather than arabinose for detecting Arabidopsis roots as taught by Hoogenboom to arrive at the claimed invention. It would have been prima facie obvious for one of ordinary skill in the art to select xylose rather than arabinose because Hoogenboom teaches that glycans, especially in plants, usually have highly complex and diverse structures containing monosaccharides such as xylose and arabinose and that the plant uptakes the extracellular monosaccharides. One of ordinary skill in the art would have a reasonable expectation of success because Hoogenboom shows that arabinose can successfully be used to label Arabidopsis roots and Hoogenboom teaches that both arabinose and xylose are monosaccharides that the plant can uptake.
Regarding instant claim 9, although Hoogenboom is silent on a kit, it would have been further prima facie obvious to one of ordinary skill in the art to prepare a kit based on the combined prior art because the grouping together of various objects or compositions directed to a common purpose (i.e. forming a kit) when all the individual objects or compositions are prima facie obvious over the prior art does not make the kit patentable. The idea of preparing a kit based on a prima facie obvious composition flows logically from the perspective of providing organization, convenience and quality control.
Claims 1, 4-8 and 15-18 are rejected under 35 U.S.C. 103 as being unpatentable over Yamada et al. (US 2014/0154717 A1, published 06/05/2014, see PTO-892), Maksimovic et al. (JACS, published 05/10/2020, see PTO-892), Shanmugam et al. (Oncotarget, published 12/17/2017, see PTO-892), and Hoogenboom et al. (BMC Plant Biology, published 10/10/2016, see IDS dated 02/16/2023).
Yamada is drawn to the method for detecting cancer cells using fluorescently labeled L-glucose (title). Yamada teaches that cancer detection via labeled glucose visualizes a cancer by utilizing the nature of cancer cells to take up larger amounts of D-glucose into the cell than a normal cell (paragraph 0005). Yamada teaches a method of detecting cancer cells or suspected cells comprising binging a composition containing an L-glucose derivative with a fluorescent molecular group into contact with a target cell and detecting the presence of the L-glucose derivative in the target cell (claim 1). The target cells may be cells that are separated from a living body or cells in tissue, meeting the limitation of ex vivo and in vitro (paragraph 0032). The detection method is conducted by imaging the target cell (claim 5). Yamada teaches a method of diagnosing a subject comprising detection of cancer cells or suspected cancer cells are detected by labeling with the L-glucose derivative (claim 23).
Regarding instant claim 15, Yamada teaches that the kind of cancer cells which can be determined in the method is not particularly restricted, examples thereof include cancer cells in cancers in the ophthalmologic field such as of eyelid, lacrimal gland and the like, cancers of ear parts such as outer ear, middle ear and the like, cancers of nose parts such as nasal cavity, paranasal cavity and the like, lung cancer, digestive organ cancers such as oral cavity cancer, larynx cancer, pharynx cancer, esophageal cancer, stomach cancer, small intestinal cancer, large intestine cancer and the like, cancers in the gynecological field such as breast cancer, uterus cancer, ovary cancer, fallopian tube cancer and the like, cancers of genital organs, kidney cancer, urinary bladder cancer, prostate cancer, anus cancer, skin cancer, bone cancer, muscle cancer (sarcoma), blood cancers such as leukemia and the like, malignant lymphoma, cancers of peripheral and central nerves, glia cancer, and the like (paragraph 0077).
Regarding instant claim 16, Yamada teaches that the L-glucose derivative may be used for in vivo diagnosis as an imaging agent (paragraph 0091).
Regarding instant claim 17, Yamada teaches the detection of the L-glucose derivative present in a cancer cell by measuring the fluorescence of the target cell beforehand, then keeping the cell in contact with the target cell for a certain period of time before washing it away, measuring the fluorescence again, and then the evaluation is made according to an increase in the fluorescence intensity with respect to the fluorescence intensity of the target cell before contact (paragraph 0085).
Yamada does not teach labeling the cells by contacting the cells with a modified monosaccharide compound of the pentose phosphate pathway and then contacting the sample with a compound bearing a first reactive group.
The teachings of Maksimovic are discussed above.
Maksimovic further teaches that ribose glycation adducts accumulates on histones in cancer cells where ribose is required for rapid nucleic acid synthesis and is thus found at higher concentrations and in vitro histone glycation has been reported to be 20-30 times faster with ribose than other reducing sugars such as glucose (page 1000).
Shanmugam is drawn to the role of novel histone modifications in cancer (title). Shanmugam teaches that histones act like an endogenous signal when they locate at the extra-nuclear space. As a response to stress, immune cells, cerebellar neurons, Schwann cells, and microglia present histones on their cell surface or cytoplasm. The levels of circulating histones as well as nucleosomes are increased in cancer, inflammation and infection, which suggest that histones could be potentially useful as biomarkers and therapeutic targets for these diseases (page 11415).
The teachings of Hoogenboom are discussed above.
It would have been prima facie obvious to combine the teachings of Yamada, Maksimovic, Shanmugam, and Hoogenboom before the effective filing date of the claimed invention by modifying the in vitro or ex vivo method of identifying or diagnosing cancer cells in a subject taught by Yamada by substituting the L-glucose derivative with 5-AR with the DBCO-Cy5 fluorophore as taught by Maksimovic to arrive at the claimed invention. It would have been prima facie obvious for one of ordinary skill in the art to substitute the L-glucose derivate taught by Yamada with the 5-AR with the DBCO-Cy5 fluorophore as taught by Maksimovic because Maksimovic teaches that in cancer cells ribose is found in higher concentrations and that in vitro histone glycation has been reported to be 20-30 times faster with ribose than other reducing sugars such as glucose and Shanmugam teaches that histones are increased in cancer cells, present on the cell surface, and could be potentially useful as a biomarker. One of ordinary skill in the art would have a reasonable expectation of success because Yamada shows that labeled monosaccharide can be used to detect cancer cells, Hoogenboom exemplifies labeling of a eukaryotic cell with a monosaccharide from the pentose phosphate pathway and contacting the sample with a compound bearing a first reactive group, Maksimovic shows that 5-AR with the DBCO-Cy5 fluorophore can be used to label histones in a cell, and Shanmugam teaches that there is an increase of histones in cancer cells that are located on the surface of the cell.
Conclusion
No claims allowed.
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/SAMANTHA LYNN SCHACHERMEYER/Examiner, Art Unit 1693 /SCARLETT Y GOON/Supervisory Patent Examiner, Art Unit 1693
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