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 .
Application Status – Continued Examination Under 37 CFR 1.114
Claims 1-5 were previously pending.
An advisory action was mailed 11 June 2026.
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 30 June 2026 has been entered.
In their request for continued examination, Applicant has amended claims 1 and 4, and did not cancel or add claims.
Therefore, claims 1-5 remain pending and are under examination.
Priority
Examiner acknowledges Applicant’s claim to the following priority:
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Withdrawn Claim Rejections
I. The previous rejection of claim 1-5 under 35 USC 112(b) is hereby withdrawn.
Maintained Claim Rejections
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 1-3 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon judicial exception without significantly more. The claims are drawn to a human T-lymphoblastic leukemia/lymphoma cell strain ZYXY-T1. This judicial exception is not integrated into a practical application because the claims read on natural phenomena. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception.
According to the 2019 Revised Patent Subject Matter Eligibility Guidelines (2019PEG), a claim is first analyzed to determine if it is directed to one of the acceptable statutory categories on invention (i.e., process, machine, manufacture, or composition of matter).
Claims 1-3 are directed to a human T-lymphoblastic leukemia/lymphoma primary cell strain (Spec., [0026]) or a progeny cell thereof. Since a cell strain is a product, claims 1-3 are drawn to a composition of matter and meet the requirements for step 1 of the analysis.
Second, the claim is assessed to determine if it is directed to a judicial exception under step 2A. Under 2019PEG, “directed to” is determined via a two-prong inquiry: (1) Does the claim recite a law of nature, a product of nature, a natural phenomenon, or an abstract idea; and (2) Does the claim recite additional element(s) that integrate the judicial exception into a practical application. The phrase, “integration of a practical application,” requires the presence of an additional claim element(s) or a combination thereof to apply, rely on or use the judicial exception in a manner that imposes a meaningful limitation on the judicial exception, such that the claim does not monopolize the judicial exception. (See MPEP § 2106.05 for examples of integration of practical application).
Regarding the first prong (1), claims 1-3 are directed to a cell strain ZYXY-T1 and its progeny. The specification teaches the cell is obtained via a 6 mL blood sample from a male patient with ETP-ALL diagnosed by First Affiliated Hospital of Medical College of Zhejiang University (Spec., [0026]). As such, the cell strain was found within a human ETP-ALL patient in nature. Thus, the claimed cell strain is a product of nature which makes the claimed cell strain a judicial exception. The first prong (1) inquiry demonstrates that claims 1-3 recite a judicial exception.
Regarding the second prong (2), claims 1-3, by amendment, recite the additional element of a process by which the cell strain is made:
Isolating the leukemia mononuclear cells from the blood sample (Spec., [0026]);
Culturing the cells [0026] for 2 months (Spec., [0027]); and
Allowing the cells for proliferate, grow in suspension, and become an immortalized cell strain (Spec., [0027]).
If a judicial exception is present in the claim, it is further assessed to determine if the claim recites any additional elements or steps that are sufficient to ensure that the claim as a whole amounts to significantly more than the judicial exception. The cell strain did not undergo any modifications (e.g., genetic engineering) prior to its entry into the CCTCC depository under preservation number CCTCC No.: C202143. The claims encompass naturally occurring phenomena and nothing more because cell strain ZYXY-T1 is derived from a human patient’s blood without further substantial intervention to produce the cell culture claimed. Therefore, the claimed invention is not markedly different from naturally occurring products. Because there is no difference in the characteristics (structural, functional, or otherwise) between the claimed and naturally occurring proteins, the claimed invention does not have markedly different characteristics from what exists in nature. See, e.g., MPEP 2106, Ass’n for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. 576, 591-94, 106 USPQ2d 1972, 1979-81 (2013); Roche Molecular System, Inc. v. CEPHEID, 905 F.3d 1363, 1371, 128 USPQ2d 1221, 1227 (Fed. Cir. 2018).
Under the holding of Myriad, an isolated but otherwise unchanged nucleic acid was not patent eligible subject matter because it was not different enough from what exists in nature to avoid improperly tying up the future use and study of naturally occurring nucleic acid. The isolated cell strain of claim 1 is analogous to the isolated nucleic acid in Myriad. The claimed cell strain can be interpreted as being an isolated cell that is otherwise an unchanged. Thus, similar to the isolated nucleic acid, the isolated cell is not patent eligible subject matter because it is not different enough from cell that exists in nature to avoid improperly tying up the future use and study of the naturally occurring cell. As such, while being an isolated cell strain is structurally different from its natural counterpart because in nature the human T-lymphoblastic leukemia/lymphoma cell is found in a human subject, the isolated nature of the cell strain outside of the human body would not be considered a marked distinction from that natural counterpart, as the guidelines require. The claimed cell strain was derived directly from blood via primary cell culture and therefore maintains many of the original characteristics as the cells found within the body. In contrast, established cell lines are adapted for long-term growth and acquire mutations or altered behaviors that diverge from the original tissue. Thus, the additional elements recited by the claim add the structural element of the claimed cell strain being a human T-lymphoblastic leukemia/lymphoma cell that has been isolated from a human and placed in culture, but is essentially unaltered other than being isolated from the human subject.
Regarding claim 2, this claim further specifies the morphology of the cell has the expression profile of CD34 but not CD1α, CD8, and CD5 and has the functional property of being capable of growth in suspension. A review of the working examples in the specification indicate that these are properties characteristic of /inherent to the primary cell strain and are not properties gained by some type of transformation or exogenous addition/subtraction/alteration of the cell strain. As such, these additional elements do not further impart any additional elements that would markedly distinguish the claimed cell strain from its natural counterpart present in the human subject of origin.
Regarding claim 3, this claim is drawn to a progeny cell of the cell strain in claim 1. These are cells produced via cell proliferation and encompass cells that are structurally and functionally identical to the parent cell of base claim 1. As such, claim 3 does not recite any additional elements that markedly distinguish the claimed progeny cell from its natural counterpart. The isolated nature of the claimed cell strain does not impart a significant distinction to the claimed cell strain to distinguish it from its natural counterpart present in the human subject from which it was isolated.
Accordingly, the claims are directed to a judicial exception. Because the claims do not include any additional features that could add significantly more to the exception, the claims do not qualify as eligible subject matter under 35 U.S.C §101.
Response to Arguments
Applicant’s 30 June 2026 arguments have been fully considered, but are not found to be persuasive.
First, Applicant argues the cell strain of claim 1 was obtained through long-term culture and screening, and “is not a mere duplication of the prior art” (Remarks, p. 4). Further, Applicant argues the cultivation of leukemia cell lines is extremely challenging and unpredictable (Remarks, p. 5). These remarks are not considered persuasive because neither prior art analysis nor the degree of difficulty is considered relevant to an analysis under 35 U.S.C §101 or patentability of the invention.
Second, Applicant argues the cell stain was established outside the body under tailored culture and selection conditions, which establish the cell strain “exhibits characteristics markedly different from those of naturally occurring objects” (Remarks, p. 5). Applicant further argues the ZYXY-T1 strain has a complex karyotype while the primary parent cell has a normal karyotype, indicating changes during continuous culture (Remarks, p. 5). This argument is not considered persuasive for the following reasons:
Under the markedly different characteristics analysis, the claimed nature-based product is compared with its naturally occurring counterpart in its natural state. A difference in genetic makeup or karyotype may constitute a markedly different characteristic where the difference was directly caused by the inventor’s intervention. However, a characteristic that was inherent, innate, or naturally flows from the naturally occurring counterpart does not establish a markedly different characteristic merely because the cell was subsequently isolated or cultured.
In the present case, the claimed ZYXY-T1 cell strain was obtained directly from the peripheral blood of a patient having T-lymphoblastic leukemia/lymphoma. Accordingly, the relevant naturally occurring counterpart is the naturally occurring leukemic/lymphomatous cell population from which ZYXY-T1 was derived, rather than a normal, nonmalignant lymphocyte, a primitive cell, or other normal cell from the patient.
The present record does not establish that the naturally occurring leukemic cell population from which ZYXY-T1 was derived possessed Applicant’s asserted karyotype, or that the complex karyotype of ZYXY-T1 directly resulted from Applicant’s continuous culture process rather than representing a characteristic already present in the naturally occurring malignant population. The Specification, as originally filed, provides no disclosure establishing that the naturally occurring leukemic cells from which ZYXY-T1 was derived possessed a normal karyotype (source cell comparison) or that any complex karyotype exhibited by ZYXY-T1 arose as a consequence of the recited continuous culture process (direct causation). The record must provide a basis for concluding that the asserted difference resulted directly from Applicant’s efforts or influences.
Accordingly, Applicant has not established the claimed ZYXY-T1 cell strain possesses a markedly different characteristic relative to its proper naturally occurring counterpart that resulted directly from Applicant’s efforts or influences. The rejection under 35 USC 101 is therefore maintained.
New Claim Rejections
Claim Rejections - 35 USC § 112(b)
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 4 and 5 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.
Claim 4 is rejected under 35 USC 112(b) as being indefinite for the following reasons:
Claim 4 recites, in relevant part, “preparing progeny cells established from the cell strain or established by transfection specific genes into the cell strain, or introducing the progeny cells into an animal…” The phrase “transfection specific genes into the cell strain” renders the scope of the claim unclear. It is unclear whether the claim requires: transfecting the cell strain with one or more specific genes; transfecting genes that are themselves characterized as “transfection specific genes”; transfecting the parent ZYXY-T1 cells and thereafter producing progeny cells; or transfecting progeny cells after they have already been established from the parent cell strain. The grammatical relationship among the terms permits more than one reasonable interpretation.
Further, to the extent the intended meaning is “transfection of specific genes into the cell strain,” the claim provides no criterion for determining what constitutes a “specific gene.” The claim does not identify the gene, a class of genes, a function performed by the gene, or another objective boundary by which a person of ordinary skill could determine which genes satisfy this limitation.
Further, the claim recites “introducing the progeny cells into an animal.” There is insufficient antecedent basis for this limitation. Claim 4 is directed to a method of using the human T-lymphoblastic leukemia/lymphoma cell strain of claim 1, wherein the method steps comprise: 1) preparing progeny cells established from the cell strain; 2) established by transfecting specific genes into the cell strain; or 3) introducing the progeny cells into an animal. Claim 1, from which claim 4 depends, does not recite progeny cells. If the term ‘progeny cells’ is referencing the progeny cells established from the cell strain, it is unclear how method step 3) is an alternative method step if it also requires method step 1) of preparing progeny cells.
Further, claim 4 recites a method for use of the cell strain “for any one or more purposes of the following…” This is followed by recited purposes (a) through (g) ranging from a research study to developing tumor drug targets to developing in vitro tumor detection. The claim then recites the operative method steps of 1) preparing progeny cells established from the cell strain; 2) established by transfecting specific genes into the cell strain; or 3) introducing the progeny cells into an animal. It is unclear whether performance of any one of the later recited method steps constitutes the claimed method regardless of whether one of purposes (a) through (g) is actually achieved, or whether the claim affirmatively requires conducting the method for one or more of the listed purposes. The claim does not clearly establish whether purposes (a) through (g) are affirmative method limitations, intended use statements that do not require performance of an additional step, or alternative objectives, one of which must be affirmatively carried out. Because the claim recites “for any one or more purposes” but does not clearly connect each alternative purpose to corresponding affirmative method steps, the metes and bounds of the claimed method are uncertain. This uncertainty is particularly significant because the listed purposes are materially different from one another. For example, preparing an animal model involves a different set of acts compared with developing a diagnostic product or conducting an in vitro drug screen. The operative language proceeding the recited purposes does not clearly specify what conduct is necessary to satisfy each recited alternative. Thus, a person of ordinary skill could not be reasonably apprised whether merely preparing progeny cells established from the cell strain infringes on the claim, whether one of purposes (a) through (g) must also actually be performed, or whether the cells need only be suitable for or capable of one of those purposes.
Claim 5 is rejected under 35 USC 112(b) as being indefinite for the following reasons:
Claim 5 recites, in relevant part, “wherein an animal for preparing a tumor animal model in b is an immunodeficient mouse.” First, the recitation of ‘b’ lacks a clear formal referent and should be amended to identify the referenced limitation expressly. Second, the tumor animal model in claim 4 does not, as recited, require an animal. Animal models do not inherently require an organism as advanced laboratory methods allow for testing on animal cells without necessitating the entire animal.
Conclusion
Claims 1-5 are rejected. No claim is allowed.
Communication
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Julia A. Rossi whose telephone number is (571)272-0138. The examiner can normally be reached M-Th 7:30-5:30 (MST).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert A. Wax can be reached at (571)272-0623. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JULIA A. ROSSI/Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615
