DETAILED ACTION
Status of Application, Amendments and/or Claims
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1-20 are pending.
Election/Restrictions
Applicants' election without traverse of Invention I, claims 1-17, in the reply filed on 6/26/26 is acknowledged. Claims 18-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
The elections of (1) anti-CD3 antibody as the species of TCR-binding moiety, and (2) cancer as the species of disease, in the reply is also acknowledged. The elected species read on each claim of the elected invention.
Claims 1-17 are under consideration.
Specification
The disclosure is objected to because of the following informalities:
---The title of the invention, “T-Cell Activation” is not descriptive because it is directed general to any means of T-cell activation, whereas the claimed invention is limited to activation of T-cells with magnetic nanoparticles (MNPs) functionalized with T-cell receptor binding moiety. A new title is required that is clearly indicative of the invention to which the claims are directed. The following title is suggested: “T-Cell Activation with Magnetic Nanoparticles Functionalized with T-Cell Receptor Binding Moiety”.
Appropriate correction is required.
Claim Objections
Claims 3 and 5 are objected to because of the following informalities:
In claim 3, lines 1-2, “exposed to the magnetic field to at least 1 hour” should be “exposed to the magnetic field for at least 1 hour”.
In claim 5, the acronym “MHC” should be accompanied by the full terminology the first time it appears in a series of claims; e.g., “major histocompatibility complex (MHC)”. See the specification at ¶ 108 (published application
Appropriate correction is required.
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.
Claim 7 is 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 pre-AIA the applicant regards as the invention.
Claim 7 limits the method of claim 1 to one wherein “each [magnetic nanoparticle] has a surface load of the TCR binding moiety of from 0.5 µg to 20 µg”. At face, this limits each individual nanoparticle to having 0.5 µg to 20 µg of moiety on its surface. However, in the working examples, 1 µg of moiety (anti-CD3 antibody) is functionalized onto 1 mg particles (¶ 110, published application), which indicates significantly less moiety per individual particle. Furthermore, Applicants’ post-filing date publication of Clarke et al (2025. European Journal of Immunology. 55:e51716) includes a table, Table 2, that calculates the “[a]ntibodies per surface area unit” for two different sizes of nanoparticles and finds 81.9 antibodies per particle for 250 nM particles, and 2230 antibodies per particle for 1µm particles. This suggests that claim 7 is actually intended to be the total amount of antibody used rather than the amount per particle. Thus, claim 7 is indefinite because it is unclear if the amount of antibody is per particle or per total amount of particles.
Claim Rejections - 35 USC § 112(a), written description
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 1-17 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Per MPEP 2163, 35 U.S.C. 112(a) requires, “separate and distinct from the enablement requirement”, that the “specification shall contain a written description of the invention…” (Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1355 (Fed. Cir. 2010)). In making a determination of whether the application complies with the written description requirement of 35 U.S.C. 112(a), it is necessary to understand what Applicants are claiming and what Applicants have possession of.
Independent claim 1 is directed to a method that is intended to be used for activation of T cells, which is to be achieved via two method steps, including (1) contacting the T cells with a plurality of magnetic nanoparticles (MNPs),w herein each MNP is functionalized with a T cell receptor (TCR) binding moiety, and (2) exposing the T cells to a magnetic field. Independent claim 16 is directed to a similar method but intended for treatment, and where the first step is directed to administering the functionalized MNPs to a subject. Dependent claim 5 limits the TCR binding moiety of claim 1 to an antibody or MHC-peptide complex. The elected species of TCR binding moiety under consideration is an anti-CD3 antibody. The claims are directed to a method of use of a product rather than a product per se, but practicing said method of use requires a written description of the product to be used in the method; i.e., e.g., the requisite TCR binding moiety.
The specification does not provide a definition of the term “T-cell receptor (TCR) binding moiety”, only providing examples of structures that can have such activity, including “an antibody” in general (dependent claim 5; ¶ 105 of the published application); or more specifically “an anti-CD3 or anti-CD28 antibody” (¶ 107) or a MHC-peptide complex (claim 5; ¶ 41). Furthermore, the term “TCR” is well-known in the prior art as referring to a specific protein complex that does not include the CD28 molecule. Acuto et al (2003) teaches, “The TCR and CD28 are independent signalling units” (Acuto et al, 2003. Nature Reviews Immunology. 3:939). See also Figure 2 of Acuto. Thus, while the specification posits an anti-CD28 as an antibody of the invention, an anti-CD28 antibody does not qualify as moiety that binds to the T cell receptor (TCR).
In the independent claims, the moiety is only limited by functionality (i.e., binding to TCR) and is not limited structurally, encompassing any possible structure, including proteins, antibodies, nucleic acids, small organic molecules, lipids, carbohydrates, inorganic molecules and more. Each of these is a distinct subgenus that encompasses a group of species, each having the required functionality.
Thus, the claims are genus claims because they encompass use of a genus of structures having the required functionality, i.e., binding to the TCR. However, a product defined by function is not in and of itself sufficient to describe the product because it is only an indication of what the product does, rather than what it is; i.e., the specific structure of the product. It is only a definition of a useful result rather than a definition of what achieves that result. Per MPEP 2124, "describing a composition by its function alone typically will not suffice to sufficiently describe the composition". Furthermore, in the instant case the specification does not establish a correlation between structure and function; i.e., the structure of one TCR binding moiety, for example an anti-CD3 antibody, does not provide predictability regarding other structures having the same functionality.
Written description for a genus may also be satisfied through sufficient description of a relevant number of species. This is dependent on whether one of skill in the art would recognize necessary common attributes or features possessed by the members of the genus. Generally, in an unpredictable art, adequate description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. Also, “[w]hen a patent claims a genus using functional language to define a desired result, the specification must demonstrate that the applicant has made a generic invention that achieves the claimed result and do so by showing that the applicant has invented species sufficient to support a claim to the functionally-defined genus" (Capon v. Eshhar, 418 F.3d 1349 (Fed. Cir. 2005)). “[A] sufficient description of a genus … requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can 'visualize or recognize' the members of the genus” (AbbVie, 759 F.3d at 1297, reiterating Eli Lilly, 119 F.3d at 1568-69).
In support of the genus of TCR binding moieties, the specification only provides two examples that meet the definition, which are described above, an anti-CD3 antibody and an MHC-peptide complex. These two examples are not representative of a genus of compounds having different structures. Per MPEP 2163, "A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that "only describe[d] one type of structurally similar antibodies" that "are not representative of the full variety or scope of the genus.")
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111 (Fed. Cir. 1991), clearly states “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed” (pg 1117). The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed” (pg 1116).
Therefore, only a method of claim 1 or claim 16, wherein the T cell receptor (TCR) moiety is an anti-CD3 antibody or a major histocompatibility complex (MHC)-peptide complex, but not the full breadth of the claim meets the written description provision of 35 U.S.C. §112(a). Applicants are reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (pg 1115).
Note on Prior Art Rejection(s)
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 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.
Claim Rejections - 35 USC § 102
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-6 and 8-17 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Berenson et al, 2003/0124122, published 7/3/03 and filed 4/26/02. The earliest date to which the instant application claims priority is 11/23/22.
Claim 1 encompasses a method of activating T cells comprising contacting the T cells with a plurality of magnetic nanoparticles (MNPs) that are functionalized with a TCR-binding moiety and exposing the T cells to a magnetic field.
Berenson teaches, “In other aspects methods of inducing T-cell activation in vivo are provided, comprising providing paramagnetic particles to an animal, said particles having attached thereto, ligands specific for a T-cell surface moiety that induces T-cell activation; applying a magnetic field to a discrete region of the animal; and thereby inducing localization and activation of T-cells bound to said particles at said discrete region” (¶ 21). Berenson further teaches that the particle can be a nanoparticle (e.g., ¶ 13). As such, the teachings of Berenson anticipate claim 1.
Claim 2 encompasses a method of claim 1 wherein the magnetic field is an oscillating magnetic field. The instant specification defines an oscillating magnetic field as one that encompasses a field that is “turned on and off” (¶ 63, published application). Berenson further teaches that the magnetic field of the invention can be “turned off and on” (¶ 66), thereby meeting the definition of the term “oscillating” as used in the instant application. As such, the teachings of Berenson also anticipate claim 2.
Claim 3 encompasses a method of claim 1 wherein the T cells are exposed to the magnetic field for at least 1 hour. Berenson further teaches that the agent-coated surface, which includes the particles, may be drawn to the target cells using the force, which includes a magnetic field for time periods including “2 hours” or “4 hours” (¶ 127). As such, the teachings of Berenson also anticipate claim 3.
Claim 4 encompasses a method of claim 1 wherein the field is pulsed. Berenson further teaches that the magnetic field of the invention can be “pulsed (¶ 66). As such, the teachings of Berenson also anticipate claim 4.
Claim 5 encompasses a method of claim 1 wherein the TCR binding moiety comprises an antibody. Berenson further teaches that the ligands specific for a T-cell surface moiety include an antibody that binds to CD3 (e.g., at ¶ 128). As such, the teachings of Berenson also anticipate claim 5.
Claim 6 encompasses a method of claim 1 wherein the MNPs have a mean particle diameter of from 100 nm to 3 µm. The teachings of Berenson include use of paramagnetic beads that are 2.8 µm in diameter (¶ 141). As such, the teachings of Berenson also anticipate claim 6.
Claim 8 encompasses a method of claim 1 wherein the method is carried out in vivo. The teachings of Berenson set forth above for claim 1 are directed to an in vivo method. As such, the teachings of Berenson also anticipate claim 8.
Claim 9 encompasses a method of claim 1 wherein the method comprises exposing a magnetic field to a subject that has been administered the MNPs. The teachings of Berenson set forth above for claim 1 also meet these limitations. As such, the teachings of Berenson also anticipate claim 9.
Claim 10 encompasses a method of claim 9 that is for treating cancer. Berenson teaches that the T-cells of the invention are for use in treatment of cancer (e.g., Abstract, ¶ 8). As such, the teachings of Berenson also anticipate claim 10.
Claim 11 encompasses a method of claim 10 further comprising a step of administering to the subject the plurality of MNPs. The teachings of Berenson set forth above include a step of “providing paramagnetic particles to an animal”, which meets the further administration step of claim 11. As such, the teachings of Berenson also anticipate claim 11.
Claim 12 encompasses a method of claim 11 wherein the MNPs are not bound to the T cells prior to administration to the subject. In the teachings of Berenson set forth above, the MNPs are provided to the animal but are not taught to include T-cells. As such, the teachings of Berenson also anticipate claim 12.
Claim 13 encompasses a method of claim 11 wherein the MNPs are administered by injection. Berenson further teaches that the composition of the invention can be administered by intravenous administration (¶ 187), which is a form of injection. As such, the teachings of Berenson also anticipate claim 13.
Claim 14 encompasses a method of claim 9 wherein the method comprises administering a further therapeutic agent. Berenson further teaches that the treatments of the invention may be administered in combination with other therapies, teaching that “[v]irtually any therapy that would benefit by a more robust T-cell population is within the context of the methods of use” and providing examples including “one or more therapeutic antibodies (¶ 185). As such, the teachings of Berenson also anticipate claim 14.
Claim 15 encompasses a method of claim 1 wherein the method further comprises functionalizing MNPs with the TCR binding moiety. Berenson further teaches that that agents can be “cross-linked to the surface” (¶ 111). As such, the teachings of Berenson also anticipate claim 15.
Claim 16 is an independent claim that encompasses a method of treating cancer comprising administering to the subject a plurality of MNPs, wherein each MNP is functionalized with a TCR binding moiety and exposing the subject to the magnetic field. This method combines the limitations of claims 1, 9 and 10. As such, the teachings of Berenson that anticipate claims 1, 9 and 10 also anticipate claim 16.
Claim 17 encompasses a method of claim 16 wherein the magnetic field is an oscillating magnetic field. This is the same further limitation as claim 2 and is met by the teachings of Berenson for the same reasons as set forth above. As such, the teachings of Berenson also anticipate claim 17.
Conclusion
No claims are allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ZACHARY C HOWARD whose telephone number is (571)272-2877. The examiner can normally be reached on Monday to Friday from 9 AM to 5 PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Vanessa Ford, can be reached at telephone number (571) 272-0857. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ZACHARY C HOWARD/Primary Examiner, Art Unit 1674
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