Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Response to Amendments and Status of Claims
Applicant's amendments filed 10/21/2025 have been considered. Claims 1-2,4-26 remain pending, of which claims 1-2, 4-7 are being considered on their merits. Claims 8-26 remain withdrawn from consideration. References not included with this Office action can be found in a prior action. Any rejections of record not particularly addressed below are withdrawn in light of the claim amendments and applicant’s comments
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 1-2, 4-7 remain rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more. An analysis with respect to the claims as a whole reveals that the claims recite a natural phenomenon/correlation that do not include additional elements that are sufficient to amount to significantly more than the judicial exception. See MPEP §2106.
The existing two-step analysis of subject-matter eligibility under 35 U.S.C. § 101 includes: (Step 1) must be directed to one of the four statutory categories recited in §101; (Step 2A) whether the claim is directed to judicial exceptions (i.e., a law of nature, natural phenomenon, or natural product); and (Step 2B) whether the claim as a whole recites something that amounts to significantly more than the judicial exception. In this case, the claims are directed to a natural phenomenon/product. Therefore, they must each be considered to determine whether, given their broadest reasonable interpretation, they amount to significantly more than the judicial exception (natural phenomenon/product).
Regarding Step 1 (Yes), all of the claims are drawn to a process under 35 U.S.C. § 101.
Regarding Step 2A (Prong one, Yes), for independent claim 1, the judicial exception (JE) is a natural phenomenon/correlation. Claim 1 direct to a method of screening a subject for cancer comprising isolating and selecting cells with specified size and shape (detecting circulating cancer associated macrophage-like cells, CAMLs) and correlating the presence of the CAMLs with cancer. There is no indication in the specification that the claimed method has any characteristic that are different from nature correlation.
Does the claim recite additional elements that integrate the judicial exception into a practical application: (Prong two, No), because there is no difference in characteristics between the claimed method and natural phenomenon/ correlation. Regarding the limitation wherein “said method further comprises administering a cancer treatment to the subject”, this limitation is recited at a high level of generality and fails to meaningfully limit the claim (integrate the judicial exception). The limitation of administering a cancer treatment to the subject fails to meaningfully limit the claim because it is at best the equivalent of merely adding the word “apply it” to the judicial exception. Accordingly, this judicial exception is not integrated into a practical application as claims are directed to an exception recited at a high level of generality and fails to meaningfully limit the claim, and these limitations do not integrate the recited judicial exception into a practical application and the claim is therefore directed to the judicial exception (Step 2A: Yes).
Regarding Step 2B, the steps of isolating and selecting are done by routine and convention methods (such as flow cytometry, filtration, etc.) which do not add significantly more than the JE as set forth above. Therefore the isolating/selecting steps are recited broadly to include any routine/conventional method. There is nothing in the record to suggest that the isolating/selection steps are not done routinely together. Accordingly, the claims are directed to an exception with no additional elements (from both independent and dependent claims) amount to significantly more than the judicial exception, thus the claims are not eligible (Step 2B: NO).
Thus the claims amount to a correlation between the presence of CAMLs (with specified size and shape) and presence of cancer which are considered not significantly more than the law of nature/natural principle and therefore is not eligible under 101. Additional steps/limitations are needed to integrates the law of nature and transform the claims to a patent-eligible practical application.
Response to Arguments
Applicant's arguments filed 8/1/2024 have been fully considered but they are not persuasive.
Applicant argues that the amendment of administering a cancer treatment overcomes the 101 rejection. The argument is not found persuasive for the follow reasons. These judicial exceptions are not integrated into a practical application because there is no particular “cancer treatment”. The limitation of “administering a cancer treatment” is reciting at a high level of generality that is at best and the equivalent of merely adding the words “apply it” to the judicial exception when suitable. The administering step as claimed does not provide an information as to how the patient is to be treated, or what the treatment is, but instead covers all possible treatments that a practitioner decides to administer to the subject. Applicant has amended the claims to the wherein clause reciting the cancer is breast, prostate, lung, pancreatic or colorectal but this does not limit or correlate with the treatment step to integrate the judicial exception in a meaningful way. Therefore, the limitation of administering a cancer treatment to the subject fails to meaningfully limit the claim because it is at best the equivalent of merely adding the word “apply it” to the judicial exception.
Claim Rejections - 35 USC § 103
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 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.
Claims 1-2, 4-7 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Wang et al (U.S.PGPUB 2002/0098535; reference A) in view of Lin et al (U.S.PGPUB 2008/0206757; reference B).
Regarding claims 1, 4 and 7, Wang teaches a method of screening cancer in a subject, comprising detecting circulating cancer cells in peripheral blood of a subject, wherein said detecting comprises: (a) isolating intact cells of between 20 and 50 micron in size from a biological sample obtained from a subject using size exclusion methodology, immunocapture and magnetic levitation, and
(b) characterizing cells isolated in (a) having (i) multiple nuclei (for example, Wang’s “intermediate cells”), and (ii) a morphological shape that is round,
wherein when the after the cancer cells are detected in the biological sample, the subject having cancer, and said method further comprises administering a cancer treatment to the subject (see abstract, paragraphs 4-8, 14-35, 49, 51, 53-55, 61-62, 71-72, Examples 1-2, Figure 1C and Table 1).
Regarding claim 1, Wangs circulating cancer cells read on Cancer Associated Macrophage-Like cells (CAMLs) as described in the instant specification.
Regarding claims 1-2, Wang teaches the cells are carcinoma cells from breast or prostate cancer (see paragraphs 53, 55, 68 and 76).
Regarding claim 5, Wang teaches multiple density gradient separation (see paragraph 75 and 108-111); reads on using size exclusion methodology.
Wang does not exemplify selecting with cells based on nucleus characteristic of multiple nuclei and morphological shape, or that the exclusion methodology is use of a microfilter having pores ranging in size from 5 to 20 microns.
Regarding claim 1, Lin also teaches identification of circulating cancer cells from peripheral blood of a subject, and that said identification is often done by specific morphological criteria related to the characteristics of the nucleus and size & shape of the cell, and that said identifying may be used to determine the presence or status of cancer or a course of therapy (see abstract and paragraphs 22, 43, 117, 142 and 246). Regarding claims 1 and 5, Lin teaches that selecting can also be done using microfilter with pores about 1 to less than 10 microns, and that microfilter pores can be used to select cells based on both size and shape (see paragraphs 117, 142 and 182-185).
It would have been obvious to combine Wang and Lin to select Wang’s circulating cancer cells based on nucleus characteristic of multiple nuclei and morphological shape using a microfilter having pores ranging in size from 1 to 10 microns. A person of ordinary skill in the art would have had a reasonable expectation of success in selecting Wang’s circulating cancer cells based on nucleus characteristic of multiple nuclei and morphological shape using a microfilter having pores ranging in size from 1 to 10 microns because Wang teaches the circulating cancer cells have multiple nuclei and a round shape and Lin establishes that circulating cancer cells can be selected based on these morphological criteria, and can be done using microfilter having pores ranging in size from 1 to 10 microns. The skilled artisan would have been motivated to select Wang’s circulating cancer cells based on nucleus characteristic of multiple nuclei and morphological shape using a microfilter having pores ranging in size from 1 to 10 microns because Wang teaches the circulating cancer cells have multiple nuclei and a round shape and Lin establishes that circulating cancer cells can be selected based on these morphological criteria, and can be done using microfilter having pores ranging in size from 1 to 10 microns.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill at the time the invention was made.
Response to Arguments
Applicant's arguments filed 10/212025 have been fully but they are not persuasive.
Wang teaches on [0018] The invention further relates to a method of determining the presence or absence of metastatic cancer cells, comprising:
[0019] (a) isolating circulating cancer cells in a body fluid sample of a patient with cancer or a patient suspected of having cancer;
[0020] (b) characterizing said isolated cells using cytological and morphological analyses by fluorescence microscopy to distinguish cancer cell classes;
[0021] (c) determining the classification of the cancer cells isolated, wherein the cancer cell classification comprises terminal cells, proliferative cells, and/or intermediate cells; and
[0022] (d) assessing whether metastatic cancer is present or absent based on the classification determined in (c).
[0035] The medical procedure is selected from the group consisting of surgery, radiation, hormone therapy, gene therapy, and therapeutic agent(s) administration, and a combination thereof.
Applicant argues that Wang teaches cancer cells and the instant invention is directed to CAML cells. Applicant argues Wang does not teach CAML cells.
Paragraph [0084] of the instant specification is noted in which the characteristics of CAML cells are given and the specification state “CAMLs have one or more of the following features.”
Applicant’s attention is directed to paragraph [0053]: Molecular, cytological, and morphological analyses comprise a collection of factors to distinguish cancer cell classes and subclasses, which includes, but is not limited to, evaluating the shape of the cell and measuring its diameter, recording the gradient cell density at which the cells were isolated, determining the presence or absence of a nucleus, the shape of the nucleus, the dividing or resting state of the cell, whether there is a cluster of 3 or more cells, and the cell type. Cell type may be identified using cell-specific markers for the identification of epithelial cells, for example, or tissue or organ-specific markers that identify prostate, breast, pancreas, ovarian, bladder, liver, ovary, rectum, kidney, colon, gastric, lung, and the like. Specific molecular or biochemical markers including apoptotic, enzymatic such as thymidylate synthetase, and/or oncogenic such as p53, chromosome number, and any other state-of-the art protein, DNA, and RNA markers that are clinically relevant.
Wang further described the different cancer cell types and characteristics to indicate different type including polyploid [0090] [0055]; markers from tumor origin including the claimed prostrate, breast cancer [0053]; diameter of about 20-30 microns [0062]; irregular shape (round or elliptical) [0062]
Thus, Wang does teach CAMLs as characterized by the instant specification. The fact that applicant calls the cells CAMLs and Wang classifies these cells as subclass of cancer cells and intermediate cells, does not mean they are different cells. The critical aspect Wang teaches is identifying the morphological changes and isolating said cells based on the characteristics. Wang further teaches isolating said cell via several methods including magnetic cell sorting, double density gradient centrifugation; and immunoassays. Thus, Wang teaches isolating CAMLs cells as defined by the instant specification. Lin is merely relied upon for the specifics of isolation by size exclusion methodology. However, it should be noted that Lin also teaches detecting cancer cells or cancerous cells: [0171]. Lin teaches positively identifying as cells labeled by binding members recognizing one, or two, or three or more of the markers listed below, and specific morphological criteria related to the diameter of its nucleus, shape of the nucleus, diameter of the whole cell, or the ratio of the cytoplasmic portion of the cells to its nucleus [0043].
Regarding applicant’s argument that the rejection does not address b(i), it is pointed out that the recitation is about 14-64microns or multiple nuclei. Wang teaches in paragraph [0008]: Such criteria for classifying a cell as malignant included the following morphological examination: abnormal cell size and shape, a large nucleus with an abnormal chromatin network, prominent (often multiple) nucleoli, scanty cytoplasm, and cytoplasmic vacuolation. Lin teaches the morphological criteria used to further identify the cancer cells include the following: a) cell nucleus having a diameter larger than a statistically pre-determined value, b) cytoplasm diameter to nucleus diameter ratio between 1.01 and 20, c) overall cell diameter between 3 and 50 uM. see [0246].
Thus, applicant’s arguments are not persuasive.
Conclusion
No claims are free of the art. No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653
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