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 .
Claim Status
Claims 1-18 and 21-22 are currently pending in this application.
Election/Restrictions
Applicant’s election without traverse of Group IV, claims 17-22, in the reply filed 8/8/25 is acknowledged. Claims 1-16 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected subject matter, there being no allowable generic or linking claim. Claims 17-18 and 21-22 have been considered on the merits, and all arguments have been fully considered.
Previous Rejections
Status of the rejections: the previous claim rejections under 35 USC 112(b) are withdrawn in view of the claim amendments.
Claim Interpretation
Claim 17 is interpreted as being implicitly limited to autologous adoptive cellular therapies as indicated by the current claim language: “from a human subject” and “to treat the cancer in the human subject.” Under a broadest reasonable interpretation, the term “medium” in claim 17 is interpreted as being limited to an aqueous composition compatible with immune cell culture (e.g., comprising a buffer and inorganic salts), such as an aqueous solution or hydrogel (see e.g., instant [0062]; [0037]). Under a broadest reasonable interpretation, the term “polyvinyl alcohol” (or PVA) is interpreted as encompassing any polymer of vinyl alcohol, e.g., [CH2CH(OH)]n wherein n is any positive integer, including crosslinked PVA, as this term is commonly used in the art.
Claim Rejections - 35 USC § 112(a) - Written Description (modified)
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 17-18 and 21-22 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 written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claimed invention as a whole is not adequately described if the claims require essential or critical elements that are not adequately described in the specification and that is not conventional in the art as of applicant’s effective filing date. Possession may be shown by actual reduction to practice, clear depiction of the invention in a detailed drawing, or by describing the invention with sufficient relevant identifying characteristics such that a person skilled in the art would recognize that the inventor had possession of the claimed invention. Pfaff v. Wells Electronics, Inc., 48 USPQ2d 1641,1646 (1998).
In making a determination of whether the application complies with the written description requirement under 35 U.S.C. 112(a) or 35 U.S.C. 112, first paragraph, it is necessary to understand what Applicant is claiming and what Applicant has possession of.
The claims are directed to methods comprising administering in vitro expanded T cells to subject for an autologous adoptive cellular therapy wherein the T cells were expanded in a serum albumin-free cell culture medium comprising polyvinyl alcohol.
The claims are broad in that the “expanded T cells” are only limited by the knowledge of the skilled artisan in view of the prior art. Furthermore, the claims are broad in that the method may be used to treat any cancer in any human subject in need thereof.
In analyzing whether the written description requirement is met for genus claims, it is first determined whether a representative number of species have been described. In the instant case, the specification fails to provide a single working example, and thus no exemplary species of cancer, subject, or human T cell is disclosed. Instead the specification describes prophetic methods with representative species at a high level of generality based on mouse or human T cells expanded in medium comprising polyvinyl alcohol (e.g., transformed leukemic cells or engineered CAR-T cells) (Example 1; FIG. 1-2). The instant application is silent as to any effective amount of expanded isolated human T cell to treat cancer to administer to a subject.
The genus of cancer or subject encompasses any cancer or any subject in need of treatment for any cancer. The genus of expanded T cells encompasses any type of human T cell, including unmodified T cells and subtypes thereof; however, the only type of T cells used in the working examples are T lymphocytes engineered to express a CAR transgene to produce a cell surface CAR that binds a cancer-associated epitope (CD19) (Example 1).
While the prior art teaches various adoptive cell therapies for human cancer subjects using various types of T cells (e.g., CD-19-CAR-T cells for hematological cancers or tumor-infiltrating lymphocytes (TILs) for melanoma) (see e.g., Wagner et al., Mol Ther 28: 2320-39 (2020) at abstract; Nguyen et al., Cancer Immunol Immunother 68: 773-85 (2019) at abstract, pg. 774), the prior art does not teach the full scope for any unmodified T cell or for treating any solid cancer with even modified T cells at least expressing a chimeric antigen receptor (CAR). Thus, the written description lacks a representative number of species for the scope of any cancer and scope of any T cells. The dependent claims are included in the basis of the rejection because they do not correct the primary deficiencies of the independent claim for all parameters.
The skilled artisan could not rely upon the disclosure in the specification such that the specification would sufficiently describe that Applicant was in possession of the breadth of subjects (e.g., having any cancer), breadth of cancer (unlimited), and breadth of T cells (e.g., unmodified or modified to express CAR that does not specifically bind a cancer epitope) as encompassed by the claims to effectuate a treatment for cancer as required by the claim limitations at the earliest effective filing date. Instead, a small set of representative species are described along with an invitation to the skilled artisan to adapt these to the broad scopes of each genus term without a clear nexus between the disclosed species and the full claim scope.
35 USC § 112(a), Scope of Enablement (modified)
Claims 17-18 and 21-22 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification does not enable any person, skilled in the art to which it pertains or with which it is most nearly connected to, to provide an adoptive cellular therapy with an effective amount of expanded immune cells over the full scope of the claims. The application is enabled wherein the cancer is hematological and the T cells are genetically modified prior to administering to produce a CAR that binds an already validated cancer epitope of a hematological cancer as of the earliest effective filing date (as partial described in dependent claims 21 and 22).
Enablement is considered in view of the Wands factors (MPEP 2164.01 (a)). The court in Wands states that "Enablement is not precluded by the necessity for some experimentation such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is 'undue.' Not 'experimentation;" (Wands, 8 USPQ2d 104). Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. "Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighting many factual considerations." (Wands, 8 USPQ2d 1404).
The factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation required is “undue” include, but are not limited to:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Furthermore, the USPTO does not have laboratory facilities to test if an invention will function as claimed when working examples are not disclosed in the specification. Therefore, enablement issues are raised and discussed based on the state of knowledge pertinent to an art at the time of the invention. And thus, skepticism raised in the enablement rejections are those raised in the art by artisans of expertise.
All of the Wands factors have been considered with regard to the instant claims, with the most relevant factors discussed below.
As noted in the written description rejection, the claims are broad in that genus terms “subject”, “cancer”, and “expanded T cells” are only limited by the knowledge of the skilled artisan in view of the prior art. As noted in the previous section, the prior art does not teach the full scope of adoptive cellular therapies encompassed by the claims regardless of the polyvinyl alcohol expansion step performed on isolated human T cells. Thus, these aspects of scope must be shown to a reasonable extent so that one of the ordinary skills in the art would be able to practice the invention without any undue or unreasonable burden being on such artisan.
The amount of direction and guidance as well as any working examples provided:
The instant specification provides no working example of administering any T cell to a subject or efficacious treatment of any cancer. Rather, the only example is a method of in vitro expanding T cells to prepare them for such uses, without guidance as to any details or how to adapt the methods for different types of cancers or T cell subtypes.
Thus, there is no evidence in the instant application or the prior art that the scope of subjects, cancers, and T cells (e.g., unmodified) encompassed by the claims could predictably result in adoptive cellular therapy for cancer across the entire scope of the claims. Undue experimentation would be required to fill these gaps and unpredictability. Undue experimentation is required to fill these gaps in the prior art with the breadth of the claims. Given the extreme breath of the claims, lack of any working example, the limited guidance provided in the specification, the lack of guidance in the prior art for such broad scope; undue and/or unreasonable experimentation would have been required for one skilled in the art to produce the recited product over the full scope of the methods of any of claims 17-18 and 21-22.
Response to Arguments
Applicant's remarks filed 6/15/26 regarding the previous 112(a) rejections (pg. 5-6) have been fully considered and found persuasive except regarding the breadth of the amended claims as set forth fully above. Moreover, applicant’s claim amendments resulted in new grounds of rejection laid out above regarding the scope of T cells.
Claim Rejections - 35 USC § 103 (modified)
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 17-18 and 21-22 are rejected under 35 U.S.C. 103 as being unpatentable over Westoby (US20210163893A1) in view of Abbot (US20160137980A1).
Regarding claim 17, Westoby teaches methods of adoptive cellular therapy comprising administering therapeutically effective amounts of engineered autologous T cells to a human subject to treat cancer, e.g., via intravenous injection and formulated for such ([0107]; [0184]; [0568]; [0932]; [0988]; [0197]; claim 1).). Westoby teaches wherein the T cells are isolated from a biological sample obtained from a human subject in need of adoptive cell therapy ([0197]; [0067]) and that such T cells can be isolated and expanded in vitro prior to administering for treating such subjects, such as via engineering ([0197], [0003]; Table E1; Example 1; FIG. 2-3). Westoby teaches using serum-free media in any step ([0675]; [0077]).
Westoby does not teach wherein the T cells are expanded in a serum albumin-free cell culture medium comprising polyvinyl alcohol.
However Abbot teaches methods of expanding in vitro T cells in a serum-free medium culture comprising polyvinyl alcohol (PVA-microsphere having an immobilized T-cell stimulatory ligand, such as anti-CD3) ([0004]; [0018]; [0038]-[0040]; [0057]). Abbot teaches T cells can be cultured under conditions appropriate for T cell culture, e.g., including appropriate media which may contain factors necessary for proliferation and viability, including serum-free medium ([0040], [0057]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective time of filing to perform an autologous adoptive cell therapy method of Westoby using T cells to treat a cancer/tumor wherein the T cells are expanding in vitro in a serum-free medium comprising polyvinyl alcohol as taught by Abbot. One of ordinary skill in the art would be motivated by Abbot teaching including the ligand-PVA microspheres both induces expansion and T cell activation ([0056]).
Regarding claim 18, Westoby teaches obtaining immune cell populations comprising T cells from a blood sample ([0067]; [0198]; [0203]).
Regarding claims 21-22, Westoby teaches wherein the T cells are genetically engineered to express a CAR that binds a cancer epitope for use in adoptive cell cancer therapies ([0170], [0184]; [0075]-[0076]).
Therefore the claimed invention as a whole is prima facie obvious before the effective filing date in the absence of evidence to the contrary.
Response to Arguments
Applicant's remarks filed 6/15/26 regarding the previous 103 rejections (pg. 6-8) have been fully considered but not found persuasive regarding the combination of Westoby and Abbot for the reasons set forth above. Applicant argues the prior art lacks a motivation to use PVA as an “active component” to expand T cells and instead relies on an anti-CD3 antibody. Regardless, as in claim 17, Abbot teaches PVA is present in the medium used to expand T cells and applicant admits the anti-CD3 antibody provides for expanding activity, supporting the reasonable expectation of success of obtaining expanded isolated human T cells by methods in the prior art.
The above rejection does not rely on any knowledge of the PVA being “active” and altering T cell expansion. Instead, the motivation found is to combine the methods of Westoby and Abbot to arrive at a method encompassed by claim 17 in order add the PVA microspheres to improve expansion and T cell activation in in vitro culture before administering to the cancer patient. Thus, there is sufficient motivation to perform all the active method steps in the prior art in combination regardless of whether any specific advantageous characteristics regarding PVA were appreciated or expected prior to the instant filing date. In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., “active” component) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Perhaps the claims can be amended to exclude PVA in the form of a microsphere in order to distinguish over the prior art of record.
Conclusion
No claim is 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 ERIC J ROGERS whose telephone number is (571)272-8338. The examiner can normally be reached Monday - Friday 9:00-6:00.
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, Tracy Vivlemore, can be reached on 571-272-2914. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ERIC J ROGERS/Examiner, Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638
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