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 .
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.
DETAILED ACTION
The amendments filed on 6/12/2026 which claims 3, 6, 12, 20, 35, 39-41, 45, 48, 51, and 58 were amended and claims 73-77 were newly added is acknowledged. Claims 5, 11, 21, and 27-28 were canceled.
Claims 3, 6, 12, 20, 35, 39-41, 45, 48, 50-53, 55, 58, 64, 69, and 73-77 are pending in the instant application.
Priority
This application is a 371 of PCT/US2020/039466, filed on 6/24/2020 which claims priority to the provisional applications 62951765 filed on 12/20/2019 and 62870633 filed on 7/3/2019.
Election/Restriction
Applicant’s election without traverse of Group I (claims 3, 5-6, 11-12, 20-21, 27-28, 35, 39, 41, 48, 40, 45, and 50-53) in the reply filed on 1/14/2026 remains in effect.
Claims 55, 58, 64, and 69 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected group, here being no allowable generic or linking claim. Election was made without traverse in the reply filed on 1/14/2026.
Claims 3, 6, 12, 20, 35, 39-41, 45, 48, 50-53, and 73-77
Claims 3, 6, 12, 20, 35, 39-41, 45, 48, 50-53, and 73-77 are examined herein.
Claim Interpretation
Applicant has redefined “Bph” to refer to β-(4-biphenylyl)-alanine, contrary to its art-accepted acronym. The art-accepted acronym for β-(4-biphenylyl)-alanine is “BipA” (structure shown below). See De Faveri (doi: 10.1021/acs.chemrev.4c00181) for a comprehensive list of non-canonical amino acid residues and their acronyms. In the art “Bph” refers to biphenyl.
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Withdrawn Rejections
The rejection of claim 39 under § 112(b) is withdrawn in light of the amendments; the claim no longer recites an unordered hierarchy.
The rejection of claim 40 under § 112(b) is withdrawn in light of the amendments; the claim no longer recites an unordered hierarchy.
The rejection of claims 3, 5-6, 11-12, 20-21, 27-28, and 35 under 112(a) has been withdrawn in part as applicant has defined the structure of ABT in base claim 3, however applicant has still neglected to define the structure of the TBT necessary to preserve the function.
Sequence Compliance
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Sequences after SEQ ID NO: 176 lack a definition in the supplementary sequence file defining their variables.
Objections to the Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code on 61, para 0118). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Correction is required. See MPEP § 608.01(b).
Objections to the Claims
Claim 40 refers to “or a salt form thereof” wherein it has already been established in the first line of the claim to be drawn to “or pharmaceutically acceptable salt thereof”. Please address this redundancy and amend the claim to refer to the salt form only once.
Claim 48 includes the limitation “or a pharmaceutically acceptable salt thereof” twice in the same claim. Please remove one of these superfluous phrases.
Claim 77 includes the limitation “or a pharmaceutically acceptable salt thereof” twice in the same claim. Please remove one of these superfluous phrases.
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.
Claims 3, 6, 12, 20, 35, 39-41, 45, 50-53, and 73-76 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.
All except 48 and 77
Claim 3 is drawn to a series of acronyms for unnatural amino acid residues that were not defined in the specification, nor were they able to be clearly identified in the prior art. As a result, one of skill in the art would not definitively know what the chemical structures of K(MePEG4c) and Ado were referring to. See De Faveri (doi: 10.1021/acs.chemrev.4c00181) for a comprehensive list of non-canonical amino acid residues and their acronyms. Dependent claims 3, 6, 12, 20, 35, 39-41, 45, 50-53, and 73-76 fail to cure these deficiencies, thus are also rendered indefinite.
Claim 6, 12, 20
Claims 6, 12, and 20 refers to a list of Xaa residues being a certain SEQ ID NO. Because a single residue cannot refer to a chain of amino acids within a SEQ ID NO, this renders these claims indefinite. It’s unclear if the cited residue satisfied the variables within the SEQ ID NOs supplied, or if they are specifying an alternative sequence. For example, one of skill in the art would not know how to interpret the line “(Xaa)a11 is Ahp (SEQ ID NO:179)”. Examiner recommends the language “The agent of claim __ or pharmaceutically acceptable salt thereof, wherein the TBT comprises SEQ ID NO: __.” Note that variable residues are defined in the sequence listing file, thus by simply supplying the SEQ ID NO, the entirety of the sequence is defined. However, applicant must correct the sequence listing so that the sequences after SEQ ID NO: 177 comprise these definitions.
Claim Rejections – 35 USC § 112(d)
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 73 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.
Claim 73
Claim 73 is drawn to ABT being SEQ ID NO: 151 ALHXVLPXVWVC or SEQ ID NO: 161 DCAWHLGELVWCT, when the parent claim has already defined ABT as being SEQ ID NO: 49 DCAWHLGELVWCT. A selection of instant SEQ ID NO: 151 expands the scope over the parent claim, as this claim does not recite “further comprising”. A selection of instant SEQ ID NO: 161 fails to narrow the scope over the parent claim, as the sequences are identical.
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.
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.
Claims 3, 6, 12, 20, 35, 39-41, 45, 50-53, and 73-76 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.
all except 39-40, 48, 77
Claim 3 is drawn to an agent comprising an antibody binding moiety (ABT) and a target binding moiety (TBT), wherein there is insufficient structure supplied for a person of skill in the art to envisage the members of these genera. Applicant can meet the written description requirement by either (i) describing the core structure responsible for preserving the function or (ii) by supplying a representative number of species. Applicant has supplied 3 exemplary TBT structures and 5 exemplary ABT structures, which are then paired and linked. Furthermore, the supplied TBT structures solely target CD38, as opposed to the claim breadth which encompasses targeting anything. Given this narrow list of species, one of skill in the art could not envisage the breadth of structurally unrelated compounds under these broad genera of TBT. Base claim 3 supplies only one defined amino acid residue within SEQ ID NO: 177 XXXXXXXXXXXXC. Dependent claim 6 supplies only three defined amino acid residues within SEQ ID NO: 178 XXXYXXXXLXXXC. Dependent claim 12 supplies only six defined amino acid residues within SEQ ID NO: 180 ARXXHDXVXXXDC. Dependent claim 6 supplies only eight defined amino acid residues within SEQ ID NO: 179 ARXYHDXVLXXDC. Because Applicant has failed to disclose a representative number of species commensurate in scope with the genera claimed that possess the purported function and has also failed to claim the core structure responsible for the TBT’s function, applicant has failed to meet the written description requirement of target binding moieties (TBT). Dependent claims 6, 12, 20, 35, 41, 45, 50-53, and 73-76 fail to cure these deficiencies, thus are also rendered indefinite.
All except 48 and 77
Claim 3 is drawn to “or an amino acid analog thereof” wherein applicant did not provide the core structure of the amino acid analogue must retain in order to be identified as an “amino acid analog” nor did applicant provide a representative number of species of amino acid analogs. For example, applicant did not provide a single exemplary proline amino analogue (claim 20) and failed to describe the structures of the non-canonical amino acids (e.g. Ahp; see 112(b) rejection above). Applicant also failed to provide a definition of “amino acid analog.” As a result, one of skill in the art would not be able to envisage the species of this genus. Dependent claims 6, 12, 20, 35, 39-41, 45, 50-53, 55, 58, 64, 69, and 73-76 fail to cure these deficiencies, thus also fail to meet the written description requirement. Examiner recommends having Xaa being selected from a Markush group of defined amino acid structures. It is not necessary to separate canonical and non-canonical amino acids (e.g. “wherein Xaa is selected from 2-aminoheptanoic acid (Ahp), Y, W, …”).
Claim Rejections – 35 USC § 102/103
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.
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.
All except 39-40, 48, 77
Claims 3, 6, 12, 20, 35, 41, 45, 50-53, and 73-76 are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Spiegel (WO2019023501).
Claim 3
Regarding claim 3, Spiegel teaches an antibody binding moiety (ABT) linked to a target binding moiety (TBT) via a bivalent linker (L), as shown below in Formula I (pg 8, para 0027).
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Spiegel teaches an optional plurality of ABTs and TBTs being linked together, wherein variables a and b are independently 1-200, as shown below in Formula I-a (pg 10, para 0030).
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Spiegel teaches each TBT is composed of an (Rc)t group that is linked to an (Xaa)z group, wherein (Rc)t is (La-R’)t, wherein t is an integer from 2-50 and (La) is a covalent bond, and R’ is independently -R, -C(O)R, -CO2R, or -SO2R; wherein R is independently -H, or an optionally substituted group selected from C6-30 aliphatic, C6-30 heteroaliphatic having 1-10 heteroatoms independently selected from oxygen,
nitrogen, sulfur, phosphorus and silicon, C6-30 aryl, C6-30 arylaliphatic, C6.30 arylheteroaliphatic
having 1-10 heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus and
silicon, 5-30 membered heteroaryl having 1-10 heteroatoms independently selected from oxygen,
nitrogen, sulfur, phosphorus and silicon, and 3-30 membered heterocyclyl having 1-10
heteroatoms independently selected from oxygen, nitrogen, sulfur, phosphorus and silicon, or
two R groups are optionally and independently taken together to form a covalent bond. While Spiegel does not call out variable LT, it is envisaged by (Xaa) being a covalent bond. In sum, Spiegel teaches all the limitations of the formula described by instant claim 3. Instant formula -XaaT1-XaaT2-(Xaa)y'-XaaT3-XaaT4-XaaT5-, requires only that XaaT1 and XaaT5 comprise a C1-C8 aliphatic residue, while y’ is an integer from 0-8. Spiegel teaches (Xaa)z is composed of -X3X4XSX6X7X8X9X10X11X12-, wherein each of X3, X4, X5, X6, X7, X8, X9, X10, X11, and X12 is independently an amino acid residue (pg 218, claim 21). More specifically, Spiegel teaches X7, X10, and X11 are hydrophobic residues (pg 218, claims 21-26). Spiegel teaches Valine is an exemplary hydrophobic residue (pg 42, para 00121). Using Spiegel’s residue of X7 as an exemplary XaaT1, Spiegel’s residue of X11 as exemplary T5, and selecting y’ to be 1, arrives at a peptide sequence that is identical to the one that is claimed. Spiegel teaches the sequence, SEQ ID NO: 14, GVVRRWSGDCAWHLGELVWCTRSSIAYGGG, which comprises instant SEQ ID NO: 49. Note instant SEQ ID NO: 49 and 57 comprise the same structure of DCAWHLGELVWCT.
instant_49 --------DCAWHLGELVWCT--------- 13
Spiegel_14 GVVRRWSGDCAWHLGELVWCTRSSIAYGGG 30
*************
Claim 6
Claim 6 is drawn to an indefinite formula as described in the 112(b) rejection of this claim above. Applicant declares that instant structure I-9 reads on this claim, which includes the cyclic peptide shown below of instant SEQ ID NO: 146, ARXYHDGVLXXDC. It’s unclear what part of this sequence lines up with the instantly claimed formula.
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Spiegel teaches the sequence, SEQ ID NO: 14, GVVRRWSGDCAWHLGELVWCTRSSIAYGGG, which may satisfy the limitation by including the subsequence of HLGEL, which roughly approximates instant subsequence of HDGVL.
instant_175 --------ARXYHDGVLXXDC--------- 13
Spiegel_14 GVVRRWSGDCAWHLGELVWCTRSSIAYGGG 30
:* * *
It is presumed this sequence of Spiegel satisfies the instant claim as it includes a Y, L, and C residue as required by instant SEQ ID NO: 178. Again, a meaningful interpretation could not reasonably be performed because Xaa has been assigned to single residues in addition to full amino acid sequences, themselves containing nested variable residues which have not been defined in the sequence listing file.
Claim 12
Claim 12 is drawn to an amino acid sequence containing 13 variable residues which applicant claims reads on the species I-9, which does include a 13-amino acid sequence of instant SEQ ID NO: 180, ARXXHDXVXXXDC. To simplify the analysis, the first residue of this sequence was assigned to the 1 position.
instant_180 --------ARXXHDXVXXXDC--------- 13
Spiegel_14 GVVRRWSGDCAWHLGELVW-CTRSSIAYGGG 30
* *
It is presumed this sequence of Spiegel satisfies the instant claim as it includes a A, R, H, D, G/Q/N, V, D, C residue as required by instant SEQ ID NO: 180. Again, a meaningful interpretation could not reasonably be performed because Xaa has been assigned to single residues in addition to full amino acid sequences, themselves containing nested variable residues which have not been defined in the sequence listing file.
Claim 20
Claim 20 is drawn to the formula -XaaT6-(Xaa)y' -XaaT7 -XaaT8-XaaT9-XaaT10-XaaT11- wherein y is an integer from 0-8. Spiegel teaches (Xaa)z is composed of -X3X4XSX6X7X8X9X10X11X12-, wherein each of X3, X4, X5, X6, X7, X8, X9, X10, X11, and X12 is independently an amino acid residue (pg 218, claim 21). More specifically, Spiegel teaches X7, X10, and X11 are hydrophobic residues (pg 218, claims 21-26). Spiegel teaches Valine is an exemplary hydrophobic residue (pg 42, para 00121). Using Spiegel’s residue of X7 as an exemplary XaaT6, and Spiegel’s X10 and X11 as exemplary XaaT9 and XaaT10, respectively, wherein y’ is 0, this satisfies the limitations of XaaT6, XaaT9, and XaaT10 as being aliphatic residues such as Valine which contains 3 carbons. This analogy continues for XaaT7 which matches Spiegel’s X8, which is optionally aliphatic, leaving Spiegel’s X9 to be proline or an analogue thereof to correspond with instant XaaT8 (pg 218, claims 21-26). Spiegel teaches the exemplary species I-13 with XaaT8 being proline, in a sequence of (cy-Pro)(EtPh)KP(cy-Pro)HVGE(Et), which exemplifies the species where XaaT6 is C3 aliphatic (cy-Pro); using y’ is 1, Xaa-Xaa corresponds to (EtPh); XaaT7 is a C3 substituted aliphatic (K); XaaT8 is Proline (P); XaaT9 is C3 aliphatic (cy-Pro); XaaT10 is aromatic; and XaaT11 is C3 aliphatic (pg 121, entry 1). Note: “cy-Pro” refers to a cyclopropane residue; “EtPh” refers to an ethyl phenylene residue; and “Et” refers to an ethyl residue. This may satisfy the limitations of instant SEQ ID NO: 179, ARXYHDXVLXXDC, via including the residues of A,R,Y,H, D, V,L, D,C as mentioned previously. However it is unclear how the sequence of residues Ahp, Y, L, Bph, Ahp are to be interpreted. Again, a meaningful interpretation could not reasonably be performed because Xaa has been assigned to single residues in addition to full amino acid sequences, themselves containing nested variable residues which have not been defined in the sequence listing file.
claim 35
Regarding claim 35, Spiegel teaches two Xaa are linked together such as in the formula -X3X4X5X6X7X8X9X10X11X12- (pg 218, claim 21). Alternatively, Spiegel teaches individual Xaa can be linked together to form a bridge as seen in compounds 1-10, 1-12, 1-14, 1-18, 1-
19, 1-22, 1-23, 1-25, etc (pg 11, para 0032). In another embodiment, Spiegel teaches the individual Xaa can form a cycle such as this lysine (K) to a 2-amino-4-phenylbutanoic acid (EtPh) residue, thus satisfying when two Xaa are linked together, shown below (pg 121, entry 1).
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Spiegel also teaches where the amino acids are linked through a CO-CH2 linkage, shown below (pg 130, entry1)
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Claim 45
Regarding claim 45, Spiegel teaches the linker comprises –(CH2CH2O)n-; wherein n is 8 (pg 121, entry 2) thus satisfying part (i).
Claim 41
Regarding claim 41, Spiegel teaches instant SEQ ID NO: 57, DCAWHLGELVWCT (Spiegel’s SEQ ID NO: 12), wherein “the two cysteines in the middle of the sequence, can each independently
form a disulfide bond as in natural proteins” (pg 39, para 00117). Thus satisfying the limitation of forming an -S-S- linkage.
Claim 50-51
Regarding claim 50-51, Spiegel teaches a composition where the therapeutic agent may be combined with neutrophil medicines and made into a mixture (pg 161, para 00440). Spiegel teaches the agent may be combined with tumor-specific T cells, such as tumor-infiltrating lymphocytes (TILs) (pg 162, para 00441) or NK cells (pg 163, para 0042).
Claim 52
Regarding claim 52, Spiegel teaches the composition can comprise the agent and a pharmaceutically acceptable carrier (pg 158, para 00433).
Claim 53
Regarding claim 53, Spiegel teaches the agent can be combined with a monoclonal antibody (pg 146, para 00401), wherein both components are mixed together in a single composition prior to administration (pg 146, para 00402).
Claim 73
Regarding claim 73, Spiegel teaches instant SEQ ID NO: 161, DCAWHLGELVWCT (Spiegel’s SEQ ID NO: 12) (pg 39, para 00117).
Claim 74-76
Regarding claim 73, Spiegel teaches the amino acids are linked through a C(O)-CH2 linkage (pg 130, entry1; pg 19, para 4). Spiegel teaches instant SEQ ID NO: 57, DCAWHLGELVWCT (Spiegel’s SEQ ID NO: 12), wherein “the two cysteines in the middle of the sequence, can each independently
form a disulfide bond as in natural proteins” (pg 39, para 00117). Thus satisfying the limitation of comprising an -S-S- linkage and a -C(O)-CH2- linkage.
Relevant Prior Art
The reference of Kadiyala (WO2018222987) teaches linking an ABT (“protein-binding moiety”) to a TBT (“targeting moiety”). Kadiyala teaches the targeting moiety targets proteins active in cancer cells, such as CTLA4, VEGF, VCAM-1 (pg 72, para 0285), alternatively Kadiyala teaches the targeting moiety can be an antibody component that recruits NK cells (pg 72, para 0291).
The reference of Qi (US20180346543) teaches a method of inducing cell death in a cancer cell via enhancing the cytotoxicity of a lymphocyte (claims 1-3) via contacting the lymphocyte with a chimeric transmembrane receptor that comprises an antigen-interacting domain that targets CD38 (para 0010) and/or an Fc-binding peptide of SEQ ID NO: 21, DCAWHLGELVWCT (para 0179).
Allowable Subject Matter
Claim 40 is objected to for being dependent on a rejected base claim and for containing typos, but would be rendered allowable if the typos were corrected and it was rewritten in independent form, including all of the limitations of the base claim and any intervening claims. Claims 48 and 77 are objected to, but upon correction of the typos, would be rendered allowable. The structures of the specific CD38-targeting TBT moieties linked to the specific ABT moieties were not found in the prior art. The closest prior art is that of Spiegel which was discussed in detail in the above 102/103 rejection.
Art could not be found for the definite sequences within Claim 39 (i.e. sequences wherein the variable residues were neither K(MePEG4c); e.g. SEQ ID NO: 1), thus the non-Ado, non- K(MePEG4c) containing sequences were rendered allowable over the prior art. See the corresponding 112(b) rejection of this claim for further details.
Response to Arguments
Applicant’s arguments filed on 6/12/2026 have been fully considered but they are not persuasive.
Objections to the Specification, pg 87, para 2
Applicant argues paragraph [0118] has been removed from the specification.
A replacement specification has not been received.
112(a) Written Description, pg 88, para 2
Applicant argues claim 3 has been amended to satisfy the structural requirements of both the ABT and the TBT.
The amendments to claim 3 provided the requisite structure to meet the written description requirement for the ABT, however, they still fail to meet the written description of the TBT. Thus, the written description rejection was removed in part.
102/103; pg 89, para 1
Applicant argues that Spiegel does not teach or suggest a CD38 binding moiety.
None of the instant claims require that the TBT binds CD38, as a result this specific teaching was not addressed in the 102(a)(1) rejection. Unfortunately, if this were an added limitation, Spiegel does teach targeting CD38 (pg 29, para 0073). Examiner recommends defining the TBT by the variable sequences described in claims 39-40.
Conclusion
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 LAURA ANN ESSEX whose telephone number is 571-272-1103. The examiner can normally be reached Mon - Fri 8:30-5:00.
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, Jeffrey Stucker can be reached on 571-272-0911. 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.
/L.A.E./
Examiner, Art Unit 1675
/JEFFREY STUCKER/
Supervisory Patent Examiner, Art Unit 1675
