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 .
DETAILED ACTION
Continued Examination Under 37 CFR 1.114
1. 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 6/9/2026 has been entered.
Status of the Claims
2. Claims 1-206 are the original claims filed 2/17/2023. In the Response to Pre-exam Formalities, claims 1-206 are canceled and new claims 207-226 are added. In the Response of 1/19/2026, claims 207, 210-212, 217, 221-222, 224 and 226 are amended, claim 223 is canceled, and new claim 227 is added. In the RCE, Claims 207-209, 221-222, 224, and 227 are amended.
Claims 207-222 and 224-227 are all the claims.
The Office Action contains new grounds for objection and rejection.
Priority
3. USAN 18/042,144, filed 02/17/2023, and having 1 RCE-type filing therein, is a National Stage entry of PCT/US2021/ 046674, International Filing Date: 08/19/2021, PCT/US2021/046674 is a Continuation of 16/997,570, filed 08/19/2020, now U.S. Patent # 11124568.
Information Disclosure Statement
4. As of 6/16/2026, a total of four (4) IDS are filed: 2/17/2023; 5/16/2023; 10/30/2024; and 9/24/2025. The corresponding initialed and dated 1449 form is considered and of record.
Withdrawal of Objections
Claim Objections
5. The objection to claims 209-214 and 227 because of informalities is withdrawn.
a) Claim 209 (and dependent claims 210-214) are amended replace “capable of binding” with “binds.”
b) Claim 227 is amended to replace “fc-null mutation” with “Fc-null mutation.”
Withdrawal of Rejections
Claim Rejections - 35 USC § 112(b)
6. The rejection of Claims 207-222 and 224-227 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is withdrawn.
a) Claims 207-222 and 224-227 are amended to replace “configured to bind” with “that binds”.
b) Claim 221 is amended to recite "antibody
c) Claim 221 is amended to recite "antibody
Claim Rejections - 35 USC § 112(a)
Written Description
7. The rejection of Claims 222 and 224-226 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 is withdrawn for the pending claims. Claim 22 is amended to delete prevention as an effect on the patient administered the antibody and to depend from Claim 209 for a bispecific antibody.
Claim Rejections - 35 USC § 103
8. The rejection of Claim(s) 207-211, 215, 217-222, and 224-226 under 35 U.S.C. 103 as being unpatentable over Liu et al (US 20220402998; 17/772,539; filed 2019/10/30) is withdrawn.
AS regards claims 210-214, Liu does not teach or suggest the anti-CD3 antibody, OKT-3 or muromab.
AS regards claims 207-208, Liu does not teach or suggest the instant claimed anti-CD25 species 7G7 or VP101 or VP100.
New Grounds for Objection
Claim Objections
9. Claims 207-222 and 224-227 are objected to because of the following informalities:
a) Amend claim 207 to recite “sequences of SEQ ID NO: 125, ATS and
b) Amend claim 209 to replace “being a” with “comprising.”
c) Claims 211, 214 and 216 are inconsistent for reciting “selected from SEQ ID NO: 6-10” and “selected from SEQ ID NO: 1-5 (Claim 211), “selected from SEQ ID NO: 11 through SEQ ID NO: 28” (Claim 214), and “selected from SEQ ID NO: 51 through SEQ ID NO: 69” (claim 216). Amend the claims to refer to the range of sequences using “-“ or “through” but not both.
d) Amend claim 210 to recite “sequences of SEQ ID NO: 73, DTS and
e) Amend claim 216 to recite “The antibody or fragment thereof according to claim 215.”
f) Amend claims 219-220 to replace “of claim _” with “according to claim _” in order to comport with the claim set.
g) Amend claim 221 to replace “having” with “comprising.”
h) Amend claims 224-226 to replace “of claim 222” with “[[of]] according to claim 222” in order to comport with the claim set.
Appropriate correction is required.
New Grounds for Rejection
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.
10. Claims 210-214 and 218-220 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.
a) Claims 210-214 are each indefinite for the phrase “wherein said antibody or fragment thereof” because in depending from claim 209, no clear relation is made between an antibody or fragment thereof corresponding to a multispecific or bispecific antibody that bind CD3 and that depends from claim 207. Generic claim 207 sets forth the antibody of fragment thereof against a CD25 antigen.
b) Claims 218-220 recite the limitation "antibody agent" in claim 218. There is insufficient antecedent basis for this limitation in the claim. Claim 207 from which the claims depend is not drawn to an antibody agent.
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.
Scope of Enablement
11. Claims 222 and 224-226 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating depression associated with autoimmune encephalomyelitis using the bispecific anti-CD3 x anti-CD25 antibody clone, VP021, does not reasonably provide enablement for any humanized CD25 VH/VL in a bispecific format with just any CD3 VH/VL in treating any neuro-immune disorder. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
Factors to be considered in determining whether undue experimentation is required, are summarized in In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988). They include the nature of the invention, the state of the prior art, the relative skill of those in the art, the amount of direction or guidance disclosed in the specification, the presence or absence of working examples, the predictability of the art, the breadth of the claims, the quantity of experimentation which would be required in order to practice the invention as claimed.
Claim interpretation
The method of treatment/alleviation for any inflammatory disease, any psycho-immune disorder, any auto-immune disease and any mood disorder in any patient using a therapeutically effective amount of the generic bispecific antibody of claim 209 is examined for enablement based on the specification and record evidence art.
Disclosure in the Specification
The specification depicts the hypothetic example 16 describing the administration of bispecific antibodies based on the Figure 12 plan that is not substantiated by data as filed.
PNG
media_image1.png
604
968
media_image1.png
Greyscale
Limited working examples using the bispecific antibody clone, VP021, the effect on Treg cells, in vitro,
[0362] FIG. 5 shows CD8+ T cells proliferation without the addition of Tregs and in the cocultures with Tregs in response to treatment with different compounds. VP008-PUR and VP021-2 treatment led to a decrease in CD8+T cell proliferation in the presence of Tregs in a dose-dependent manner. VP022 also showed some modest decrease in CD8+ T cell proliferation in the presence of Tregs. The same trends were not observed when the test articles were added to CD8+ T cell in the absence of Treg cells.
[0424] FIGS. 9a, 9b and 9c show the % Treg cells (defined as CD25+ FOXP3+) that expressed the 3 key activation markers at 24 hours of treatment: neuropilin (an induced Treg marker), IL-10, and LAP (precursor for TGFbeta). At both 1 μg/mL and 10 μg/mL, VP021 and VP008 had substantial increases in neuropilin compared to Teplizumab and media only control (FIG. 9a). At 10 μg/mL, VP021 and VP008 had increases in IL-10 compared to Teplizumab and media only control (FIG. 9b). At 10 μg/mL, VP021 and VP008 had small increases in LAP compared to Teplizumab and media only control (FIG. 9c).
[0425] FIGS. 10a, 10b and 10c show the % Treg cells (defined as CD25+ FOXP3+) that expressed the 3 key activation markers (neuropilin, IL-10 and LAP) at 72 hours of treatment. At both 1 μg/mL and 10 μg/mL, VP021 and VP008 had substantial increases in neuropilin compared to Teplizumab and media only control (FIG. 10a). At 1 μg/mL, VP021 and VP008 had increases in IL-10 compared to Teplizumab and media only control (FIG. 10b). At 1 and 10 μg/mL, VP021 and VP008 had increases in LAP compared to Teplizumab and media only control (FIG. 10c).
The scope of the claims must bear a reasonable correlation with the scope of enablement. See In re Fisher, 166 USPQ 19, 24 (CCPA 1970). "[T]o be enabling, the specification of a patent must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation.'" Genentech, Inc. v. Novo Nordisk, A/S, 108 F.3d 1361, 1365 (Fed. Cir. 1997) (quoting In re Wright, 999 F.2d 1557, 1561 (Fed. Cir. 1993)).
The Patent Act requires that patent applicant describes the invention in explicit terms to enable any person skilled in the art to make and use the invention. 35 U.S.C. 112. Applicants seek incalculable anti-CD3 x anti-CD25 antibodies that are not defined for the anti-CD3 binding aspect of the molecule. Humanized forms of the VH/VL CDR1-3 from the 7G7 clone in claim 207 are the only structural features defined for the bispecific antibody of the claimed method invention. Notably, the breadth and scope of the binding aspect of the bispecific antibody of claim 209 for CD3 is infinite. Most notably, the specification teaches the OKT3 antibody as an option (and claims 210-221 recite the VH/VL CDRs for the OKT3 antibody):
[0381] The sequence of anti-CD3 murine mAb muromomab (OKT3) is shown below, antigen contact residues are shown in bold and IMGT CDR sequences are underlined.
Applicant’s specification teaches the OKT3 antibody being exemplar as an anti-CD3 binding region in the construct as do Applicants endorse the use of the OKT3 antibody in the Response. The inherent toxicity of the OKT3 antibody used in the claimed invention is art-recognized at least by Weißmüller et al (PLoS One. 2016; 11(3): e0149093 (Published online 2016 Mar 9)) stating in part “Upon TGN1412 or OKT3 injection, humanized mice showed severe signs of illness such as limited mobility and ruffled fur (data not shown) and a massive drop of body temperature 2–6 hours after injection (Fig 5A). Finally, mice succumbed to TGN1412 and OKT3 application 2–6 hours after injection or had to be sacrificed, respectively (Fig 5B).”
The use of at least one antibody endorsed by the specification is suspect for its use within the field of art well prior to the filing date for this application.
The enablement requirement is a crucial aspect of the patent “bargain”: an inventor is granted limited protection from competition in exchange for publicly disclosing their new technology. See the decision in Morse, Incandescent Lamp, and Holland Furniture, establishing the requirement that if a patent claims an entire class or genus of processes, machines, or compositions of matter, the specification must enable a person skilled in the field to make and use the entire class. If a patent claims an entire class of processes, machines, manufactures, or compositions of matter, the patent’s specification must enable a person skilled in the art to make and use the entire class. In other words, the specification must enable the full scope of the invention as defined by its claims. The more one claims, the more one must enable. See §112(a); see also Continental Paper Bag Co. v. Eastern Paper Bag Co., 210 U. S. 405 (1908) (“[T]he claims measure the invention.”)
Claim Rejections - 35 USC § 102
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 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)(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.
12. Claim(s) 207, 209, 217-221 is/are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipate by Goubier et al (US 11879014, issued 2024-01-23, priority 2018-03-03).
AS regards claim 207, Goubier teaches an anti-CD25 antibody designated 7G7B6 having VHCDR1-3 and VLCDR1-3 with 100% identity to the instant claimed CDRs of claim 207:
VLCDR1-3
PNG
media_image2.png
478
520
media_image2.png
Greyscale
VHCDR1-3
PNG
media_image3.png
462
512
media_image3.png
Greyscale
Goubier teaches a humanized anti-CD25 antibody at (026) and claims at claim 11.
AS regards claim 209, Goubier teaches a bispecific antibody that binds CD3 in the form of a BITE® at (33).
AS regards claim 217, Goubier teaches the anti-CD25 antibody as a pharmaceutical composition at (30) with an excipient at (124).
AS regards claims 218-220, Goubier teaches the anti-CD25 antibody encoded by nucleic acids, vectors, and host cells at (98)-(99).
AS regards claim 221, Goubier teaches methods for expressing the anti-CD25 antibody at (98, 103).
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 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.
13. Claim(s) 207, 209, 222 and 224-226 is/are rejected under 35 U.S.C. 103 as being unpatentable over Goubier et al (US 11879014, issued 2024-01-23, priority 2018-03-03) in view of Li et al (WO 2020102591, priority 11/14/2019).
The claims are prima facie obvious over Goubier in view of Li.
AS regards claim 207, Goubier teaches an anti-CD25 antibody designated 7G7B6 having VHCDR1-3 and VLCDR1-3 with 100% identity to the instant claimed CDRs of claim 207:
VLCDR1-3
PNG
media_image2.png
478
520
media_image2.png
Greyscale
VHCDR1-3
PNG
media_image3.png
462
512
media_image3.png
Greyscale
Goubier teaches a humanized anti-CD25 antibody at (026) and claims at claim 11.
AS regards claim 209, Goubier teaches a bispecific antibody that binds CD3 in the form of a BITE® at (33).
AS regards claim 222, Goubier teaches methods of treating a disease using a bispecific at (97) such as cancer.
Li teaches the anti-CD25 antibody designated 7G7B6 used to treat cancer or an autoimmune disease (Abstract) and [0110].
AS regards claim 226, LI teaches the oral or nasal administration of the antibody at [0138].
Goubier and Li teach and appreciate that in a normal state, regulatory T cells constitutively express CD25 and act to suppress the expansion of effector cells. Regulatory T cells maintain the healthy state and inhibit effector T cells from reacting against self-antigens or over-reacting to foreign antigens. In a normal, protective immune response, effector T cells multiply after contact with foreign antigen and overcome inhibition by regulatory T cells. In case of proliferative diseases, however cancer cells disable the healthy immune response by increasing the amount of regulatory T cells and thereby limiting the generation of effector T cells against them. Additional molecular tools to alter the proliferation of CD25-expressing regulatory T cells are needed, for example to dampen the immune system for use in cancer therapies or to upregulate the immune system for use in autoimmune diseases; provided herein are such tools. Accordingly, the motivation and assurance of reasonable success in producing the instant claimed invention for an anti-CC25 antibody based on the 7G7B6 CDR domains, a bispecific further comprising an anti-CD3 binding domain and the treatment of an autoimmune disorder is facilitated by the combined disclosure of the references and the availability of art-known and commercially available antibody, 7G7B6.
Conclusion
14. No claims are allowed.
15. The sequence of SEQ ID NO: 120 and 121 is free from the art.
16. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LYNN A. BRISTOL whose telephone number is (571)272-6883. The examiner can normally be reached Mon-Fri 9 AM-5 PM.
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, Wu Julie can be reached at 571-272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
LYNN ANNE BRISTOL
Primary Examiner
Art Unit 1643
/LYNN A BRISTOL/Primary Examiner, Art Unit 1643
Prosecution Insights