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
Status of the Claims
1. 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.
Claims 207-222 and 224-227 are all the claims.
The amendment of the claims raises new grounds for objection and rejection. The Office Action is final.
Priority
2. USAN 18/042,144, filed 02/17/2023, 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
3. As of 3/11/2026, 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
Specification
4. The objection to the disclosure because of informalities is withdrawn.
a) The specification is amended to rectify the improper use an embedded hyperlink and/or other form of browser-executable code.
b) The specification is amended to rectify the improper use of the term, BiaCore, MabSelect, nanobody, nanobodies, which is a trade name or a mark used in commerce.
c) The specification is amended to rectify the improper citation of peptides > 4 amino acids by insertion of a corresponding sequence identifier.
Claim Objections
5. The objection to Claims 207-226 because of informalities is withdrawn
a) Claims 207-226 are amended to replace the phrase “capable of binding” with “configured to bind” in claims 207 and 222.
b) Claim 207 is amended to recite:
An antibody or fragment thereof configured to bind to CD25, wherein said antibody or fragment thereof is humanized and comprises either:
variable light chain (VL) CDR sequences of SEQ ID NO: 125, ATS and SEQ ID NO: 127 and variable heavy chain (VH) CDR sequences of SEQ ID NO: 128, 129 and 130, or
VL CDR sequences of SEQ ID NO: 79, DTS and SEQ ID NO: 81 and VH CDR sequences of SEQ ID NO: 82, 83 and 84.
c) Claims 207 and 210 are amended to replace SEQ ID NO: 126 with “ATS” and SEQ ID NO: 80 with “DTS”, and to replace SEQ ID NO: 74 with “DTS”, respectively.
d) Claim 221 is amended to reference a single claim directed to a single product invention, namely, claim 207.
Withdrawal of Rejections
Claim Rejections - 35 USC § 112(b)
6. The rejection of Claims 212, 217 and 224 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is withdrawn.
a) Claim 212 is amended to replace the trademark/trade name “nanobody” with “a single domain alpaca antibody.”
b) Claim 217 is amended to delete the entire phrase comprising "such as".
c) Claim 224 is amended to recite ”depression, major depressive disorder, autism (ASD) and attention deficit/hyperactivity disorder (ADHD), bipolar disorder, seasonal affective disorder (SAD), cyclothymic disorder, premenstrual dysphoric disorder, persistent depressive disorder, disruptive mood dysregulation disorder, depression related to medical illness, depression induced by substance use or medication, Alzheimer's disease, Parkinson's disease and Multiple sclerosis”, which is the narrower statement of the range/limitation.
Rejections Maintained
Claim Rejections - 35 USC § 112(a)
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.
Written Description
7. The rejection of Claims
Applicants allege amending generic method claim 222 to depend from the antibody of claim 207 overcomes the rejection.
Response to Arguments
Applicants have not addressed the original grounds for rejection, namely, that the application as filed does not provide support for methods of prevention using a monospecific anti-hCD25 antibody of claim 207. The response is incomplete.
Claim interpretation
Method claim 222 is drawn to using a monospecific, humanized antibody or fragment thereof that binds CD25 and either one of two paired VL/VH domains comprising the corresponding CDR1-3 of claim 207. The method claim is drawn to preventing, treating and alleviating the generic diseases with the antibody of claim 207 in a therapeutic amount. There is no explicit or implied proviso that the antibody of claim 207 is bispecific.
“therapeutic”: the specification does not define per se the meaning of the term. Accordingly, the term is construed as encompassing prevention given the absence of any reason to exclude prevention from the meaning.
Summary of species disclosed in the specification
Applicants specification DOES NOT support the prevention of any disease using a monospecific anti-CD25 antibody of Claim 207 for use in the prevention of the method claimed diseases. Applicants have not identified original description support by way of example in the specification.
MPEP 2163 (II)(3)(a)(ii)
Satisfactory disclosure of a “representative number” depends on whether one of skill in the art would recognize that the inventor was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are “representative of the full variety or scope of the genus,” or by the establishment of “a reasonable structure-function correlation.”
It is asserted that the POSA could reasonably conclude that the specification as filed is insufficient in its disclosure for the use of the antibody of claim 207 in the prevention of the diseases/disorders of method claim 222. Applicants have not addressed the original grounds for rejection.
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.
8. The rejection of Claim(s) 207-211, 215, 217-222, and 224-226 is/are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al (US 20220402998; 17/772,539; filed 2019/10/30) is moot for canceled claim 223 and maintained for the pending claims.
a) Applicants allege Lui is directed to a chimeric antigen receptor (CAR), a T cell comprising said CAR and methods of making and using said CAR and said T-cell for the treatment of a cancer and/or an immune disease.
Particularly, Lui combines an antigen binding domain with an anti-CD3 domain to kill the cell bearing the antigen. To do this, Liu uses CAR constructs, which are not the constructs used in the present application. Liu mentions a long list of antibodies known to bind cancer antigens, but the only cell killing effect appears to be demonstrated for CD19 and CD22 binding CARs. Not only is binding to CD25 (pending claim 207) and optionally to CD3 (pending claim 209) not disclosed, the underlying desire of Liu is cell killing.
Conversely, the present application is directed to the claimed constructs, which provide enhanced Treg suppressor activity and enhanced secretion of IL-10 while binding to CD25 and optionally to CD3 (claim 209), leading to the disclosed beneficial effects, none of which is contemplated by Liu.
Response to Arguments
i) No where in the Response do Applicants dispute the truth of the matter asserted, namely, that Liu teaches identical sequences for the claimed CD25 and CD3 binding elements. Applicants have not responded to the outstanding grounds for rejection:
“AS regards Claims 207-208, Lui teaches VH (SEQ ID NO:77) and VL (SEQ ID NO: 78) domains having 100% identity to the respective SEQ ID NOS: 32 and 29 of the instant claims that are identified as anti-CD25 antibody fragments. The VH/VL: CDR1-3 of claim 207 comprise the VH/VL domains of claim 208:
Ref SEQ ID NO: 78 (VL) vs SEQ ID NO: 32 (VL):
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388
954
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Ref SEQ ID NO: 77 (VH) vs SEQ ID NO: 29 (VH):
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384
958
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Lui teaches the VH/VL sequences correspond to Basiliximab in Table 2 of the reference.
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222
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ii) No where in the instant claims are the constructs required to possess a function but for binding to CD25 (207-208, 215, 217-222 and 224-226) and CD3 (claims 209-211). AS for method claims 222 and 224-226, the claims do not define how the pathway/mechanism by which prevention, treatment or alleviation is achieved: whether by cell killing (Liu); or enhanced Treg suppressor activity (instant specification). Notably, the method claims do not even require a bispecific anti-CD25 x anti-CD3 construct to achieve the purpose of prevention, treatment or alleviation. Amended claim 222 now depends on a monospecific antibody of claim 207.
iii) Liu specifically teaches bispecific antibodies irrespective of whether they are comprised within a CAR by broadest reasonably interpretation (MPEP 2111):
[0101] In some embodiments, a heavy and/or light chain domain of one variable domain of one antibody and a heavy and/or light chain of a second variable domain of a second antibody or of a second variable domain of a bi-specific or multi-specific antibody can be used to generate a CAR of the invention. In further embodiments, more than one heavy chain domain and more than one light chain domain can be combined by linkers to generate multi-specific CARs of the invention. The more than one heavy chain and more than one light chain domain can be from single variable domains of different antibodies or from different variable domains of bi- or multi-specific antibodies.
b) Applicants allege Liu does not teach or suggest an Fc-null mutation.
Response to Arguments
The truth of the matter is not disputed. Claim 227 does not fall within the outstanding grounds for rejection.
The motivation to combine separate antigen binding cites that include a CD25 binding aspect and a CD3 binding aspect is well known insofar as linking cell types such as a CD3-expressing T cell with another target antigen expressed on a different cell in order to effectuate enhance proliferation of the CD3 expressing cell and binding to the other target to mediate a treatment therapeutic effect. Accordingly, the predictable and reasonably assurance of success of combining CD25 and CD3 antibodies that fall within the VH/VL domains of the instant claims and identified in the Liu reference renders the invention obvious.
The rejection is maintained.
New Grounds for Objection
Claim Objections
9. Claims 209-214 and 227 are objected to because of the following informalities:
a) Claim 209 (and dependent claims 210-214) recite “capable of binding.” The phrase implies that some undefined structure or condition is what predicates whether binding does or does not occur. Capacity or capability suggest that the binding may or may not occur, and what determines the degree or amount of binding is not definite.
b) Amend clam 227 to replace “fc-null mutation” with “Fc-null mutation.” See [0303, 0317].
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 207-222 and 224-227 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 207-222 and 224-227 are indefinite for the phrase “configured to bind” in generic claim 207. The specification does mention the term “configure” much less variants thereof, e.g., configured, configuration. The specification is silent for the term much less any structure that is encompassed by or that can be imputed so that binding to CD25 is influenced by any such configurement.
b) Claim 221 recites the limitation "antibody agent or fragment thereof according to claim 207". There is insufficient antecedent basis for this limitation in the claim. Claim 207 does not mention or infer an antibody agent or fragment thereof.
c) Claim 221 is indefinite for reciting both "antibody agent or fragment thereof according to claim 207" and “the antibody or fragment thereof.” The breadth and scope are inconsistent within the claim itself.
Conclusion
11. No claims are allowed.
12. 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.
13. 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.
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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.
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LYNN ANNE BRISTOL
Primary Examiner
Art Unit 1643
/LYNN A BRISTOL/Primary Examiner, Art Unit 1643