DETAILED ACTION
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 .
Status of the Claims
Claims 1-23 are pending (claim set as filed on 01/18/2024).
Priority
This application is a 371 of PCT/US2022/037874, which has provisional applications to: (a) PRO 63/317,642 filed on 03/08/2022; (b) PRO 63/240,669 filed on 09/03/2021; and (c) PRO 63/224,166 filed on 07/21/2021.
Information Disclosure Statement
The Information Disclosure Statements (IDS) submitted on 01/18/2024, 03/25/2025, 04/14/2025, 11/25/2025, and 01/22/2026 are acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the Examiner.
Drawings
The drawings filed on 01/18/2024 have been accepted.
Claim Objection
The claims recite the abbreviations of “CAML” and “CTCs” which are presumed to stand for cancer associated macrophage-like cells and circulating tumor cells, respectively. However, an abbreviation should be preceded in its first occurrence by the specific identity of the entity which said abbreviation is intended to represent. Thereafter, the use of the abbreviations in the claims will be understood.
Claim Rejections - 35 USC §101, Subject Matter Eligibility
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 1-23 are rejected under 35 U.S.C. 101 because they are drawn to ineligible subject matter (based on the 2019 Revised Patent Subject Matter Eligibility Guidance).
STEP 1: Is the claim directed to a process, machine, manufacture, or a composition of matter?
YES, the claims are directed to a process/method for predicting a treatment response in a subject having cancer.
STEP 2A: PRONG ONE: Does the claim recite an abstract idea, law of nature, or natural phenomenon?
YES, the claims recite at least one judicially recognized exception(s) of: a law of nature, natural phenomena, and/or an abstract idea.
(a) a law of nature/natural phenomena: the recitation of “wherein when at least one CAML in the post-treatment sample is greater in size than the largest CAML in the pre-treatment sample and wherein there are more CAMLs in the post-treatment sample than in the pre-treatment sample, the subject is predicted to not respond to treatment” describes a correlation or relationship between the CAML characteristics of pre- and post-treatment samples for a predictive treatment response. This limitation sets forth a judicial exception, because this type of correlation is a consequence of natural processes (law of nature). The MPEP 2106.04(b)(I) provides “the following concepts and products as examples of laws of nature or natural phenomena:
iv. a correlation that is the consequence of how a certain compound is metabolized by the body;
v. a correlation between the presence of myeloperoxidase in a bodily sample (such as blood or plasma) and cardiovascular disease risk; or
xi. the natural relationship between a patient’s CYP2D6 metabolizer genotype and the risk that the patient will suffer QTc prolongation after administration of a medication called iloperidone”.
(b) an abstract idea: the recitation of “predicting”, “determining”, and “comparing”, and “making a prediction” under the broadest reasonable interpretation describes an abstract idea that falls within the mental processes groupings of abstract ideas which are concepts performed in the human mind (including an observation, evaluation, judgment, or opinion) (MPEP 2106.04(a)).
PRONG TWO: Does the claim recite additional elements that integrate the judicial exception into a practical application?
NO, the exception is not integrated into a practical application of the exception. The additional elements or a combination of elements in the claims does not impose a meaningful limit on the judicial exception. For example, the claims stop after the judicial exception and thus, it does not apply or use the judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition (see Vanda Memo).
STEP 2B: Does the claim recite additional elements that amount to significantly more than the judicial exception?
NO, the claimed invention is directed to a law of nature and/or an abstract idea without significantly more. The claims recite “making a prediction” based upon comparative qualitative or quantitative characteristics of the pre- and post-CAML samples which denotes the judicial exception(s) because it describes a correlation or relationship and the recitation of “determining” or “predicting” if the subject will be treatment responsive. Moreover, it also describes an abstract idea that falls within the mental processes groupings of abstract ideas which are concepts performed in the human mind (including an observation, evaluation, judgment, or opinion). This judicial exception is not integrated into a practical application because the additional elements of obtaining a sample in order to perform tests are well-understood, routine, and conventional activity for those in the field of diagnostics. Further, the steps are recited at a high level of generality such that it amounts to insignificant pre-solution activity, e.g., a mere data gathering step necessary to use the correlation. Moreover, determining, evaluating, and comparative steps are considered various common practices that are routine and conventional activities performed by visual observation, abstract mental analysis, and pathological side by side comparison. Even when viewed as a combination, the additional elements fail to transform the exception into a patent-eligible application of that exception. The claim here does not invoke any of the considerations that courts have identified as providing significantly more than the exception.
Moreover, the dependent claims are not deemed to qualify as significantly more because they do not add a specific limitation other than what is well-understood, routine, and conventional in the field (in other words, these additional elements presented in the dependent claims are already known and established in the art as evidenced by the prior art of as identified below).
Therefore, the claims, as a whole, are considered as processes directed to judicially recognized exceptions without amounting to significantly more from what occurs in nature and thus, are not eligible subject matter under 35 U.S.C. §101.
Claim Rejections - 35 USC §102, Anticipation
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.
Claims 1-23 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Adams (US 2021/0041445 A1, which has a WO publication date of 09/19/2019 – cited by the ISA and in the IDS filed on 01/18/2024).
Adams’ general disclosure relates to methods of monitoring treatment response and disease progression in subjects having cancer, such as a solid tumor, using circulating cell biomarkers in the blood and other bodily fluids (see ¶ [0001], [0008]).
Adams teaches a “means for monitoring treatment response and disease progression in subjects are disclosed, where the predictions are based on the change of number and/or size of circulating cancer associated macrophage-like cells (CAMLs) found in a biological sample, such as blood, from the subject” (see abstract).
Adams teaches “In another aspect of the embodiment, the invention is directed to methods for predicting cancer progression in a subject having a cancer comprising determining the number of circulating cells, such as CAMLs, in a first and second biological sample, and optional additional biological samples, obtained from a subject having cancer, wherein the first sample is obtained from the subject prior to or during cancer treatment, wherein the second sample and optional additional samples are obtained from the subject after at least one cancer treatment, wherein when the number of circulating cells in the second and optional additional samples is decreased in comparison to the number of the circulating cells in the first sample, the cancer is predicted not to progress and the subject is optionally identified as responding to treatment, and wherein when the number of circulating cells in the second and optional additional samples is maintained or increased in comparison to the number of the circulating cells in the first sample, the cancer is predicted to progress and the subject is optionally identified as not responding to treatment” (see ¶ [0009]-[0034]).
Regarding the CTCs, Adams teaches “CAMLs may be used independently as a cancer marker, or in combination with other circulating cells, such as circulating tumor cells (CTCs), epithelial mesenchymal transition calls (EMTs), and circulating cancer associated vascular endothelial cells (CAVEs), as well as with cell-free DNA (cfDNA), circulating tumor DNA (ctDNA), methylated DNA, proteomic, metabolomic, lipidomic and other biomarkers to provide a more complete understanding of a patient’s disease” (see ¶ [0068]).
Regarding claims 9-10 pertaining to the CAML characteristics, Adams teaches “CAMLs are defined as having each of the following characteristics: (a) large atypical polyploid nucleus of about 14-64 μm in size, multiple individual nuclei and/or one or more fused nuclei having a size of about 14-64 μm; (b) cell size of about 20-300 μm in size; and (c) morphological shape selected from the group consisting of spindle, tadpole, round, oblong, two legs, more than two legs, thin legs, and amorphous. In certain aspects of the embodiments of the invention, the circulating cells can be further defined as having one or more of the following additional characteristics: (d) CD14 positive phenotype; (e) CD45 expression; (f) EpCAM expression; (g) vimentin expression; (h) PD-L1 expression; (i) CD11C marker expression; (j) CD146 marker expression; (k) CD202b marker expression; (I) CD31 marker expression; and (m) CK8, 18, 19 epithelial phenotype” (see ¶ [0045]-[0059]).
Regarding claims 11-13 pertaining to the sample, Adams teaches “the size of the biological sample is between 0.5 and 50 mL. The size of the biological sample may also be between 5 and 15 mL. In certain aspects of the invention, the size of the biological sample is about 7 .5 mL” and “the source of the biological sample is one or more of blood, lymph node, bone marrow, cerebral spinal fluid, tissue, urine, peripheral blood mononuclear cells (PBMCs),
and cryopreserved PBMCs. When the biological sample is blood, the blood may be peripheral blood, antecubital-vein blood, inferior-vena-cava blood, femoral vein blood, portal vein blood, or jugular-vein blood, for example” (see ¶ [0060]-[0061]).
Regarding claim 14 pertaining to the cancer, Adams teaches “the cancer is a solid tumor, Stage I cancer, Stage II cancer, Stage III cancer, Stage IV cancer, carcinoma, sarcoma, neuroblastoma, melanoma, epithelial cell cancer, breast cancer, prostate cancer, lung cancer, pancreatic cancer, colorectal cancer, liver cancer, head and neck cancer, kidney cancer, ovarian cancer, esophageal cancer or other solid tumor cancer” (see ¶ [0062]).
Regarding claims 15-21 pertaining to the isolation steps, Adams teaches “the circulating cells are isolated from the biological samples using one or more means selected from size exclusion methodology, immunocapture, dendrimer-mediated multivalent cell capture, affinity based surface capture, biomimetic surface coating capture, selectin coated surfaces capture, other functionalized surface captures, inertial focusing chips, red blood cell lysis, white blood cell depletion, FICOLL separation, electrophoresis, dielectrophoresis, flow cytometry, magnetic levitation, and various microfluidic chips, or a combination thereof” and “circulating cells are isolated from the biological samples using size exclusion methodology that comprises using a microfilter” (see ¶ [0063]-[0066]).
Regarding claims 22-23 pertaining to the cancer treatment, Adams teaches “the subject is undergoing treatment. The treatment may be one or more of chemotherapy, single drug, combination of drugs, immunotherapy, radiation therapy, chemoradiation, radiation combined with single or multiple drug, chemoradiation combined with single or multiple drugs, cancer vaccine, and cell therapy” (see ¶ [0067]).
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 claims at issue 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); and 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 a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form 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 http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-10 and 14-23 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over at least claims 1-3, 10-12, 15, 20, and 23-25 (claim set as filed on 03/31/2026) of co-pending Application no. 16/979,742. Although the claims at issue are not identical, they are not patentably distinct from each other because the claimed invention and co-pending ‘742 are directed to methods for predicting treatment decisions in a subject having cancer, the method comprising determining the size of CAMLs in a sample (see claims 1-3 of co-pending ‘742).
Regarding claims 9-10, co-pending ‘742 teaches the CAML having the additional characteristics as seen in claims 10-12.
Regarding claim 14, co-pending ‘742 teaches the cancer is a solid tumor, Stages I-IV as seen in claim 15.
Regarding claims 15-19, co-pending ‘742 teaches the microfilter has precision pore geometry and uniform pore distribution as seen in claim 20.
Regarding claims 22-23, co-pending ‘742 teaches treatment with cancer vaccine as seen in claims 23-25.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims were allowed.
Correspondence Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NGHI V NGUYEN whose telephone number is (571)270-3055. The examiner can normally be reached Mon-Fri: 9 - 3 pm (ET).
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/NGHI V NGUYEN/Primary Examiner, Art Unit 1653
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