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 .
Claims 2-9, 15, and 21-24 have been cancelled.
Election/Restrictions
Applicant's election with traverse of Group I in the reply filed on 10/24/2026 is acknowledged. The traversal is on the ground(s) that the claims as amended on 10/24/2025 have unity of invention. This is not found persuasive because the claims as originally presented lacked unity of invention for the reasons set forth in the requirement for restriction mailed 8/27/2025. In addition, as art can be applied to the claims even as amended, the claims still lack a special technical feature and still do not have unity of invention.
The requirement is still deemed proper and is therefore made FINAL.
Applicant elected the single domain antibody species comprising CDR1, CDR2, and CDR3 of SEQ ID NO: 3, 4, and 5, respectively, on 1/9/2026. Upon further consideration, the species election is withdrawn.
Claims 19-20 and 25-28 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 10/24/2025.
Claims 1, 10-14, 16-18, and 29 are under consideration.
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.
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 1, 16-18, and 29 are rejected under 35 U.S.C. 103 as being unpatentable over Garcia et al. (U.S. Patent Application Publication 2021/0206848) in view of Cooke et al. (WO 2020/146432, of record)
Garcia et al. describes a multivalent polypeptide (a "RIPR" molecule) which comprises: (i) a first amino acid sequence including a first polypeptide module capable of binding to one or more receptor protein-tyrosine phosphatases (RPTPs), and (ii) a second amino acid sequence including a second polypeptide module capable of binding to one or more cell surface receptors that signal through a phosphorylation mechanism, wherein the first polypeptide module is operably linked to the second polypeptide module. Garcia, et al. teach that such multivalent RIPR molecules are capable of bringing the ECD of the RPTP (e.g. a CD45 isoform) into proximity of the ECD of cell surface receptor that signals through a phosphorylation mechanism into proximity such that the intracellular domains of the two receptors are sufficiently close to enable the intracellular phosphorylase domain of the RPTP to dephosphorylate the intracellular domain of the cell surface receptor that signals through a phosphorylation mechanism to modulate (e.g. downregulate) the intracellular signaling of the cell surface receptor. Figures 12-13 disclose a CD45 (VHH)-PD1F2 bispecific binding module. Figure 14 discloses a CD45 (VHH)-CTLA4 bispecific binding module. Figure 15 discloses a CD45 (VHH)-CD28 bispecific binding module. See at least claims; paragraphs [0010, 0014, 0040, 0071, 0122, 0264]; Figures 12-15; Table 1; and Examples 12-16. Garcia et al. does not specifically state where within the CD45 extracellular domain the anti-CD45 VHH binds.
Cooke et al. teaches a CD45 binding molecule that selectively binds to the D4 extracellular domains of hCD45. The CD45 binding molecule can be a nanobody or a domain antibody such as a dAb consisting of a VH or a VL domain (i.e. an sdAb). The antibody can be humanized. See at least abstract; page 12, lines 22-33; and page 52, lines 15-23. SEQ ID NO: 27 of Cooke et al. corresponds to amino acids 511-527 of instant SEQ ID NO: 1 in the D4 extracellular domain.
It would have been obvious to use an anti-CD45 VHH (as taught by Garcia et al.) that selectively binds to the D4 extracellular domain of CD45 (as suggested by Cooke et al.) in the constructs of Garcia et al. One would have been motivated to do so in order to provide additional therapeutic constructs that bind the extracellular domain of CD45. The combination of Garcia et al. and Cooke et al. would have suggested the anti-CD45 VHH binding molecule of claims 1, 18, and 29 as well as the multispecific constructs of claims 16-17.
Claim Rejections - 35 USC § 112
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, 10-14, 16-18, and 29 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 genus of antibodies in claim 1 and particular antibodies in claims 10-14 are not adequately described with respect those antibodies having the binding properties of claim 1.
Paragraph [0011] of the specification discloses VHH antibodies as the HCab variable domain from camelids and cartilaginous fish.
Table 3 discloses the binding domains of CD45 bound by clones 1G1, 1E4, 2F8, 1G4, 2H5, 1A10, 1D6, 2G4, 2C5, and 2H7.
Table 7 discloses particular clonotypes and the CD45 domains they bind. SEQ ID NOS: 114 (1D1), 138 (1A7), 150 (2G4), 50 (1E4), 6 (2H8), 94 (1G4), 98 (2H5), 134 (2F4), 143 (2C5), 2 (2D6), 146 (1G1), 54 (2F8), 154 (2H7), 118 (1D2), 110 (1A10), and 122 (1D6) are disclosed.
None of the VHH antibodies disclosed bind to all four of D1, D2, D3, and D4 or combinations such as D1D4 or D2D3. (See claim 1.)
Many of the VHH antibodies in Tables 4 and 5 do not have the clonotypes or sequences in Tables 3 and 7. It is unknown which, if any, of the D1, D2, D3, and/or D4 extracellular domains are bound. See for example, the VHH of SEQ ID NO: 14 having clonotype 1E5 and the CDRs of SEQ ID NOS: 15, 16, and 17. See for example, the VHH of SEQ ID NO: 34 having clonotype 2C7 and the CDRs of SEQ ID NOS: 35, 36, and 37. See for example, the VHH of SEQ ID NO: 46 having clonotype 2E5 and the CDRs of SEQ ID NOS: 47, 58, and 59. See for example, the VHH of SEQ ID NO: 374 having clonotype 1H8 and the CDRs of SEQ ID NOS: 375, 376, and 377. See for example, the VHH of SEQ ID NO: 378 having clonotype 2A4 and the CDRs of SEQ ID NOS: 379, 380, and 381. See for example, the VHH of SEQ ID NO: 454 having clonotype 2E7 and the CDRs of SEQ ID NOS: 455, 456, and 457. (See instant claims 1 and 10-14.)
Ikeuchi et al. (2021) is cited to illustrate that those of ordinary skill in the art would have known that mutations to VHH antibodies are unpredictable with respect to the resulting characteristics and properties (i.e. antigen binding, thermostability, etc.) of the mutated VHH. Mutations in the CDRs and the framework regions can alter their properties. See at least abstract, discussion at pages 5-6, and Figure 5. This supports the position that VHH with structural variability cannot be predicted to have similar binding characteristics.
Edwards et al. (2003) is cited to illustrate over 1,000 antibodies to a single protein can be generated, all with different sequences and with extensive structural diversity. See at least abstract. This supports the position that claim 1 encompasses many structurally diverse antibodies that are not adequately described.
In the instant application, the specification and claims draw a fence around a perceivedgenus but the genus is not adequately described. The specification exemplifies some anti-CD45 VHH having the properties recited in the claims but the structural variability of the claimed antibodies is large. No reasonable structure-function correlation has been established that is commensurate in scope with the claims. The specification does not describe representative examples to support the full scope of the claims.
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 10-14 and 17-18 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 14 is indefinite for depending upon itself.
Claim 17 is confusing in reciting “molecule of claim 16 the second domain.” It appears that the claim is missing a few words. Clarification is requested.
Claims 10-13 and 18 are confusing in referencing the sdAb of claim 1 when claim 1 indicates that the sdAb is a VHH. A VHH is a specific (narrower) embodiment of an sdAb. It is unclear if applicant is attempting to broaden the subject matter of claims 10-13 and 18. Clarification is requested.
Claim 12 is confusing in reciting SEQ ID NO: 106. Claim 12 depends upon claim 11. None of the triads of CDRs in claim 11 are present in SEQ ID NO: 106.
Claim 13 is confusing in reciting “SEQ ID NO:.204, SEQ ID NO: 208, SEQ ID NO: 212, SEQ ID NO: 216, SEQ ID NO: 220, SEQ ID NO: 224, SEQ ID NO:228, SEQ ID NO: 232, SEQ ID NO: 236, SEQ ID NO: 240, SEQ ID NO: 244, SEQ ID NO: 248, SEQ ID NO: 252, SEQ ID NO: 256, SEQ ID NO: 260, SEQ ID NO: 264, SEQ ID NO: 268, SEQ ID NO: 272, SEQ ID NO: 276, SEQ ID NO: 280, SEQ ID NO: 284, SEQ ID NO: 288, SEQ ID NO: 292, SEQ ID NO: 296, SEQ ID NO: 300, SEQ ID NO: 304, SEQ ID NO: 308, SEQ ID NO: 312, SEQ ID NO: 316, SEQ ID NO:320, SEQ ID NO: 324, SEQ ID NO: 328, SEQ ID NO: 332, SEQ ID NO: 336, SEQ ID NO: 340, SEQ ID NO: 344, SEQ ID NO: 348, SEQ ID NO: 352, SEQ ID NO: 356, SEQ ID NO: 360, SEQ ID NO: 364, SEQ ID NO: 368, SEQ ID NO: 372, SEQ ID NO: 376, SEQ ID NO: 380, SEQ ID NO: 384, SEQ ID NO: 388, SEQ ID NO: 392, SEQ ID NO: 396, SEQ ID NO: 400, SEQ ID NO: 404, SEQ ID NO: 408, SEQ ID NO: 412, SEQ ID NO: 416, SEQ ID NO: 420, SEQ ID NO: 424, SEQ ID NO: 428, SEQ ID NO: 432, SEQ ID NO: 436, SEQ ID NO: 440, SEQ ID NO: 444, SEQ ID NO: 448, SEQ ID NO: 452, SEQ ID NO: 456, SEQ ID NO: 460, SEQ ID NO: 464.” First of all, the recitation “SEQ ID NO:.204” places a period (“.”) in the middle of the claim. Secondly, these sequences correspond to Chothia CDR2 sequences (see at least Table 5) and not sequences for sdAb (containing CDR1, CDR2, and CDR3 as recited in claim 10).
In addition, claim 13 is confusing in reciting duplicate sequences. At least SEQ ID NO: 134 is the same as SEQ ID NO: 474; SEQ ID NO: 86 is the same as SEQ ID NO: 478; SEQ ID NO: 106 is the same as SEQ ID NO: 486; SEQ ID NO: 50 is the same as SEQ ID NO: 490; SEQ ID NO: 130 is the same as SEQ ID NO: 494; SEQ ID NO: 150 is the same as SEQ ID NO: 498; SEQ ID NO: 98 is the same as SEQ ID NO: 506; and SEQ ID NO: 154 is the same as SEQ ID NO: 514.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 29 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. The kit of claim 29 requires nothing more than the CD45 binding molecule of claim 1. Claim 29 does not further limit the subject matter of claim 1. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARIANNE P ALLEN whose telephone number is (571)272-0712. The examiner can normally be reached 7:00-3:30 EST Monday-Friday.
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, Joanne Hama can be reached at 571-272-2911. 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.
/Marianne P Allen/Primary Examiner, Art Unit 1647
mpa