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 .
Election/Restrictions
The amendments, dated 2/14/2026, change claims 5-6 from use claims to methods claims. As such, the amendment claims are analogous to newly submitted claims. Newly submitted claims 5-6 are directed to an invention that is independent or distinct from the invention originally claimed for the following reasons: The claims previously considered where product claims. Claims 5-6 were interpreted as product claims and therefore considered with the other claims. However, now claims 5-6 are expressly drawn to method claims, which is a distinctly different invention from the claimed product because the cells of claims 1-4 can be used in materially different methods than the ones of amended claims 5-6. The cells of claims 1-4 can be used in a cryopreservation method. Similarly, all of the use methods recited can be done with any myelofibrosis cell. As such, claims 5-6, by amendment, are now directed to a distinctly different invention from the originally considered claims in the office action 11/28/2025.
Since applicant has received an action on the merits for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits. Accordingly, claims 4-5 are withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
To preserve a right to petition, the reply to this action must distinctly and specifically point out supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, applicant must indicate which of the subsequently added claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
Withdrawn Rejections/Objections
The objection to claim 1 is with drawn because the amendments to the claim correct the misspelling.
The objection to claims 4 and 5 correct the grammar and thus are withdrawn.
The rejection of claims 4-6, 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, is withdrawn. The amendments clarify the issues of indefiniteness.
The rejection of claims 5-6, under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter, is withdrawn. The amendments to the claims recite a category of invention that is patent eligible subject matter.
The rejection of claim(s) 1-6, under 35 U.S.C. 102(a)(1) as being anticipated by Zhou et al (Blood, (NOV 23 2021) Vol. 138, No. Suppl. 1, pp. 4594.), is withdrawn. Applicant provided a certified translation of the foreign priority document. As such, Zhou et al no longer serves as prior art.
The following objections and rejections of record have been modified to take into consideration the amendments to the claims:
Drawings
The drawings dated 2/14/2026, are still objected to under 37 CFR 1.83(a) because they fail to show a Circos diagram that comprises information about genomic variation that cannot be discern as described in the specification. Any structural detail that is essential for a proper understanding of the disclosed invention should be shown in the drawing. MPEP § 608.02(d). Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Response to Arguments
Applicant's arguments filed 2/14/2026 have been fully considered but they are not persuasive. Applicant submits by way of amendments, figure 4 of the Drawings has been replaced with a new image that further shows mutation. In response, this amendment does not overcome the objection because the Circos diagram still cannot be discerned.
Claim Rejections - 35 USC § 112-Biological Deposit
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-4, and amended or originally presented, are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Independent claim 1, thus its dependent claims 2-6, recites “A human primary myelofibrosis cell strain, wherein the cell stain is named as human myelofibrosis cell ZYXY-M2, which is deposited in China Center for Type Culture Collection on January 20th, 2021, with a preservation number of CCTCC NO:C202145.”
As such, the invention of claims 1-6 employs specific biological matter. Since the cell strain is essential to the claimed invention, they must be obtained by a repeatable method set forth in the specification or otherwise readily available to the public. If the cell strain is not so obtainable or available, the requirements of 35 U.S.C.§ 112 may be satisfied by a deposit of the cell strain. The specification does not disclose a repeatable process to obtain the cell strain, and it is not apparent if the cell strain is readily available to the public. It is noted that Applicant has deposited the cell strain as recited in claim 1 but there is no indication in the specification of public availability. If the deposit is made under the Budapest Treaty, then an affidavit or declaration by Applicant, or a statement by an attorney of record over their signature and registration number, stating that the specific cell strain has been deposited under the Budapest Treaty and that the hybridoma will be irrevocably and without restriction or condition released to the public upon the issuance of a patent, would satisfy the deposit requirement made herein. If the deposit has not been made under the Budapest Treaty, then in order to certify that the deposit meets the criteria set forth in 37 C.F.R §§ 1.801-1.809, Applicant may provide assurance of compliance by an affidavit or declaration, or by a statement by an attorney of record over her or her signature and registration number, showing that:
(a) during the pendency of this application, access to the invention will be afforded to the Commissioner upon request;
(b) all restrictions upon availability to the public will be irrevocably removed upon granting of the patent;
(c) the deposit will be maintained in a public depository for a period of 30 years or 5 years after the last request or the effective life of the patent, whichever is longer;
(d) a test of the viability of the biological material at the time of deposit will be made (see 37 C.F.R.§ 1.807); and
(e) the deposit will be replaced if it should ever become inviable.
Applicant’s attention is directed to M.P.E.P §2411.05, as well as to 37 C.F.R.§ 1.809(d), wherein it is set forth that “the specification shall contain the accession number for the deposit, the date of the deposit, the name and address of the depository, and a description of the deposited material sufficient to specifically identify it and to permit examination.” The specification should be amended to include this information; however, Applicant is cautioned to avoid the entry of new matter into the specification by adding any other information. Finally, Applicant is advised that the address for the ATCC has been changed, and that the new address should appear in the specification. The new address is:
American Type Culture Collection
10801 University Boulevard
Manassas, VA 20110-2209
Applicant is cautioned the deposit requirement remains even if the deposit number in the claims is changed to match that disclosed. The reasoning is the same. Claims 1-6 require a specific cell strain, which can only be obtained from applicant.
Response to Arguments
Applicant's arguments filed 2/14/2026 have been fully considered but they are not persuasive.
Applicant submits that the CCTCC is an international depositary Authority designated under the Budapest Treaty. Applicant also declares that the cell strain will be irrevocably and without restriction or condition released to the public upon the issuance of a patent. Further, the deposit certificate records that the deposit will be maintained in a public depository for a period of 30 years after the date of deposit or 5 years after the last request for the cell strain.
In response, while some of the biological deposit requirements have been met, others still remain. See the reiterated rejection above for more details.
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 therefore, subject to the conditions and requirements of this title.
Claims 1-4, as amended or originally presented, are rejected under 35 U.S.C. 101 because the claimed invention is directed to product of nature without significantly more.
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 of invention (i.e. process, machine, manufacture, or composition of matter).
Claim 1-4 recite, “human primary myelofibrosis cell strain”. A cell strain is a product and thus claims 1-4 are drawn to a composition of matter comprising a cell strain. Thus claims 1-4 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 1-4 are directed to a cell strain, named ZYXY-M2, and its progeny. The specification teaches that the cell is obtained from a fresh white blood cell specimen isolated from a human male with primary myelofibrosis (see p. 6, [0029]). As such, the cell strain was found within a human PMF patient in nature. Thus, the claimed cell strain is a product of nature which makes the claimed cell strain a judicial exception. As such, the first prong of the inquiry demonstrates that claims 1-4 do recite a judicial exception.
Regarding the second prong (2), claims 1-4, by amendment, recite the additional element of a process by which the cell strain is made. The process by which it is made does not amount to integration into a practical application. Since the additional element solely provide structural/functional limitations and a process of making the cell strain, the claims do not recite any additional elements or a combination thereof that integrates the judicial exception identify in prong 1 as being integrated into a practical application. Further since the claims are not meaningfully limited to any particular practical application, the generic nature of the claim appears to monopolize the claimed cell population. Thus, claims 1-4 meet the requirement of step 2A as being directed to a judicial exception.
Third, 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.
Regarding claim 1, the additional elements recited describe the cell strain as “a human primary myelofibrosis cell”. “Human” indicates that species origin of the cell. “Primary” indicates that the cell is a primary cell. Fiveable (printout from https://fiveable.me/key-terms/cell-biology/primary-cell-culture printed 11/14/2025, pages 1/3-3/3) provides a definition for a primary cell stating, “ Primary cell cultures are derived directly from tissues and maintain many original characteristics of those tissues, providing a more accurate representation of physiological conditions. In contrast, established cell lines are adapted for long-term growth and may acquire mutations or altered behaviors that diverge from the original tissue. This distinction is important when selecting which type of culture to use for specific experiments, particularly those investigating drug responses or cellular behavior.” See pages 1/3-2/3. As such, primary indicates that the human myelofibrosis cell is one that is taken directly from tissue of a human and is isolated but unaltered. “Strain” as recited indicates that the cells are particular to one specific human from which the cell was isolated. The remainder of the recited limitations are descriptive of the name of the cell designated by Applicant and the deposit information for the cell and do not further structurally or functionally limit the claimed cell strain. Thus, the additional elements recited by the claim add the structural element of the claimed cell strain being a human myelofibrosis cell that has been isolated from a human and placed in culture and is essentially unaltered other than being isolated from the human subject.
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 the claim 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 myelofibrosis cell is found in a human subject, the isolated nature of the cell strain would not be considered a marked distinction from that natural counterpart, as the guidelines require. As such, claim 1 does not meet the requirements of step 2B of the 2019PEG because 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.
The amendments to claim 1 expressly disclose a method of isolating the claimed cells strain. Isolation does not amount to a marked enough distinction from the natural counterpart for reasons discussed above.
Regarding claim 2, this claim further specifies the morphology of the cell is one of a primitive red blood cell, has expression profiles of CD34-, CD11b-, and CD71+, and has the functional properties of being capable of growth in suspension or weak wall adherence. 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 element 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. As such, claim 2 does not meet the requirements of step 2B of the 2019PEG because 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.
Regarding claim 3, this claim further specifies genomic SNPs and InDel mutations closely associate with hematopoietic malignancies. The specification teaches that these SNP and Indel are present in endogenously in the cell strain and thus are not introduced by exogenous cell modification (see examples and Table 1). As such, these are markers inherent to the cell found in nature in the humans subject as well. Therefore, the limitations of claim 3 do not recite any additional elements that distinguish the claimed cell from its natural counterpart present in the human subject. As such, claim 3 does not meet the requirements of step 2B of the 2019PEG because 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.
Regarding claim 4, this claim specifies progeny cells. These are cell produced via cell proliferation and encompasses cells that are structurally and functionally identical to the parent cell of base claim 1. As such, claim 4 does not recite any additional elements that markedly distinguish the claimed progeny cell from its natural counterpart. As such, claim 4 does not meet the requirements of step 2B of the 2019PEG because 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.
In conclusion, claim 1-4, as amended, do not meet all the requirements of the 2019PEG and therefore are deemed patent ineligible.
Response to Arguments
Applicant's arguments filed 2/14/2026 have been fully considered but they are not persuasive.
Applicant submits that the claims have been amended to also recite the construction method of the claimed cell strain. Applicant submits that although the cells were isolated from a fresh white blood cell suspension from a human patient with primary myelofibrosis, they were further cultured by the specific construction method to obtained the specific claimed strain, which can be passaged indefinitely, and the cell shape in vitro is stable and accords with the biological characteristics of clinical tumors. The primary myelofibrosis cell strain originated from PMF patients, with JAK2 mutation negative, CALR mutation negative, MPL mutation negative, ASCL1 mutation positive, TP53 mutation positive, FLT3 mutation positive, and IKZF1 mutation positive. The cell strain can be used to study the mechanism of the occurrence and development of PMF. The cells can also be used to analyze the curative effects of new drugs and combination scheme, to screen and evaluate drugs, and to guide clinical medication. It is of great significance to reveal PMF, an MPL with poor prognosis.
In response, while the cell strain appears to be a valuable asset for drug discover, this is not the standard for determining patent eligible subject matter. Applicant’s remarks suggest that the cell is representative of tumor cells in PMF patients and acknowledges that the cell is a cell isolate from a specific patient. As previous stated isolated by unchanged cells are not considered a markedly different cells from its natural counterpart found in the body. Its ability to be passaged and its stability also does not provide any particular distinction to the cell from that of its natural counterpart because it is still indistinguishable from the cell when it is present in the patient’s body. As such, rejection of record is maintained because the cell strain made by the claimed method still is indistinguishable from its natural counterpart, albeit isolated.
The following new objections/rejections are necessitated by the amendments to the claims and drawings:
Specification/Drawings
The amendment filed 2/14/2026 is objected to under 35 U.S.C. 132(a) because it introduces new matter into the disclosure. 35 U.S.C. 132(a) states that no amendment shall introduce new matter into the disclosure of the invention. The added material which is not supported by the original disclosure is as follows: The additional drawings to show mutations in figure 4 have not been previously part of the original disclosure. Applicant submits in the remarks that [0040] provides support for this addition to figure 4. Paragraph [0040] recites a title of a section. No such support was found in this title or the paragraphs found under this section.
Applicant is required to cancel the new matter in the reply to this Office Action.
Claim Rejections - 35 USC § 112
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 1-6 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 1 recites, by amendment, “obtaining fresh peripheral blood of a patient with primary myelofibrosis (PMF) diagnosed at the first time”. This recitation is indefinite because it is not apparent what diagnosed at the first time is referring to. “At the first time” of what? The intended meaning of this recitation is not apparent.
Claim 1 contains the trademark/trade name “IMEM complete medium”. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe a specific medium and, accordingly, the identification/description is indefinite.
Claim 1 also recites, “IMDM complete medium (IMDM 90% + fetal bovine serum 10%)”. This recitation is indefinite because for two reasons: 1) it is not apparent if the limitations found in parentheses are intended to be requisite limitations of the claim or exemplary and 2) it recites a broad limitations and a narrow limitation, thus it is not apparent if the claim intended to broadly claim IMEM complete medium or the narrower embodiments in the parentheses.
Further, the newly recited claim introduces a scope uncertain scope of the claim as a whole. The method is a more generic method to isolating a human primary myelofibrosis that not generically obtains a myelofibrosis cells from a human patient with PMF. However, the present of a specific named cell and accession number means that the product is one exact cell isolated from one specific individual. While the method added by amendment was most likely applied peripheral blood from the one individual that resulted in the cell of accession number, the method does not require the used of the specific individual. As such, it is not apparent if the claimed cell strain is limited only to the cell strain of the accession number or a more generic myelofibrosis cell that could be result from the more generic method claim.
For purposes of interpretation, Examiner will continue to interpret the claim as being structurally limited to the cell strain of the recited accession number. However, the claim is indefinite because the scope of the resultant end-product of the newly recited process is broader than the recited product of the claim.
Claims 2-4 depend upon claim 1 and thus also has the above issues of indefiniteness.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARCIA STEPHENS NOBLE whose telephone number is (571)272-5545. The examiner can normally be reached M-F 9-5:30.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Peter Paras can be reached at 571-272-4517. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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MARCIA S. NOBLE
Primary Examiner
Art Unit 1632
/MARCIA S NOBLE/Primary Examiner, Art Unit 1632
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