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
The Amendments and Remarks filed 2/2/26 in response to the Office Action of 7/31/25 are acknowledged and have been entered.
Claims 18-29 are pending.
Claims 18, 23, and 24 have been amended by Applicant.
Claims 18-29 are currently under examination.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
The following Office Action contains NEW GROUNDS of rejections Necessitated by Amendments.
Rejections Withdrawn
The rejection of claims 18-29 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, due to insufficient antecedent basis for instances of “the same single chain fusion polypeptide” is withdrawn.
Rejections Maintained
Claim Rejections - 35 USC § 112
The rejections of claims 18-29 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, due to insufficient antecedent basis for instances of “the spacer domain”, “the first part binding domain”, and “the second part binding domain” are maintained. Claim 18 recites multiple spacer domains, multiple first part binding domains, and multiple second part binding domains (see claim 18 preamble; see description of the first fusion protein prior to “a second fusion polypeptide”; see first and second parts of a binding domain of a single chain fusion polypeptide…”; see “a second fusion polypeptide specifically binding to a target comprising a first part of a binding domain, a second part of a binding domain and a spacer domain”) followed by “…the spacer domain is…the first part of the binding domain is…of the spacer domain…the second part of the binding domain…of the spacer domain…the first part of the binding domain…the second part of the binding domain….” Also, see numerous additional instances of “the spacer domain”, “the first part binding domain”, and “the second part binding domain” throughout dependent claims.
Response to Arguments
In the Reply of 1/2/26, Applicant argues amendments render these rejections moot.
The amendments to the claims and the argument found in the Reply of 2/2/26 have been carefully considered, but are not deemed persuasive. In regards to the argument amendments render these rejections moot, the examiner disagrees. The rejections are maintained for the reasons stated above.
Claim Rejections - 35 USC § 112
Claim 23 remains rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, because unclear how, or if, text in parenthesis limits the claim. It is unclear whether the text in parenthesis is exemplary or if the recited fragments of claim 23 are required to be C-terminal and N-terminal fragments.
Response to Arguments
In the Reply of 1/2/26, Applicant argues amendments render these rejections moot.
The amendments to the claims and the argument found in the Reply of 2/2/26 have been carefully considered, but are not deemed persuasive. In regards to the argument amendments render these rejections moot, the examiner disagrees. It is acknowledged amendments removed parenthesis around “N-terminal”; however, the term “C-terminal” remains within parenthesis. The rejection is maintained for the reasons stated above.
Claim Rejections - 35 USC § 102
Claim(s) 18-29 remain rejected under 35 U.S.C. 102(a)(1) as being anticipated by Gao et al (2014/0155581 A1; 6/5/14).
[0006] of Gao et al teaches innovative multi-mers (“iMers) include innovative monoclonal antibodies (“iMABs”). Figure 8A of Gao et al teaches the following “iMab”:
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Figure 3 of Gao et al illustrates a linear drawing (Figure 3A) of a fusion polypeptide that generates a construct comprising “Hinge-CH2-CH3” domains that form the above dimeric iMab fusion polypeptide (see Figure 3B illustration below). As acknowledged by the instant specification, such “Hinge-CH2-CH3” domains are dimerization domains that dimerize via Fc-regions (first paragraph on page 40 of the instant specification, in particular). Therefore, iMab of Gao et al is a “dimeric fusion polypeptide”, as recited by the instant claims.
Figure 3 (iMab hinge domains pointed-out by arrows drawn by Examiner):
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As recited by the instant claims, the iMab (Figure 8A) of Gao et al comprises first and second fusion proteins fused together (via a second linker) wherein a first fusion protein comprises an anti-EGFR binding functional domain and a second fusion protein comprises an anti-IGF1R binding functional domain. For the purpose of this rejection, the VL1-CL1-linker(same as “spacer”)-VH1-CH1-CH2-CH3 of Figure 3 of Gao et al is considered the “first” fusion protein and the VL2-CL2-linker (same as “spacer”)-VH2-CH1-CH2-CH3 of Figure 3 of Gao et al is considered the “second” fusion protein. Gao et al refers to the VH and VL domains of the iMab as “functional domains” ([0016], [0060], and [0062], in particular). As defined by the instant specification (at second paragraph on page 3): “VH1-CH1” and “VH2-CH1” of the iMab of Gao et al are heavy chain Fab fragments; and “VL1-CL1” and “VL2-CL2” of the iMab of Gao et al are light chain Fab fragments.
Gao et al further provides the amino acid sequence of iMab (Figure 6) wherein each linker sequences comprises at least 25 amino acids. The first and third linkers of Figure 3A of Gao et al (each a peptide greater than 25 amino acids in length) along with adjacent sequences permitting disulfide bonds between VH and VL regions of the iMab of Gao et al are equivalent to “spacers” recited by the instant claims. As recited by the instant claims, such spacers are covalently conjugated via multiple disulfide bonds (see Figure 8, in particular).
Gao et al further teaches a nucleic acid encoding iMab (Figure 5), which is equivalent to a fused pair of isolated nucleic acids encoding the iMab. Gao et al further teaches vectors comprising the nucleic acid encoding iMab expressed in host cells and methods of producing the iMab by culturing the host cells and recovering the iMab from the host cells ([0193]-[0201], in particular). In particular regards to instant claim 21, Gao et al further teaches the iMab wherein the functional domains are not portions of an antibody molecule ([0133]-[0136], in particular). Gao et al further teaches the iMab conjugated to a cytotoxic drug ([0159], in particular). Gao et al further teaches a pharmaceutical formulation comprising iMab and a pharmaceutically acceptable carrier ([0213], in particular) and methods of treating a disease in an individual comprising administering to the individual an effective amount of said pharmaceutical formulation ([0220], in particular). Noting a “fragment” of a CH3 domain, a CH2 domain, and a hinge region can be as little as any imaginable one amino acid, the spacers of Gao et al comprise a “fragment” of a CH3 domain, a CH2 domain, and/or a hinge region.
Response to Arguments
In the Reply of 2/2/26, Applicant states the intent of the claimed invention is that “the binding domains of the fusion proteins assemble in a circular fashion, thus it is essential that both parts of the binding domains are fused to the two different termini of the spacer.” Applicant further indicates Gao does not teach a first fusion polypeptide with a first part of a binding domain fused either directly or via a first linker to the N-terminus of a spacer domain and the second part of the binding domain fused either directly or via a second linker to the C-terminus of the spacer domain.
The amendments to the claims and the arguments found in the Reply of 2/26/26 have been carefully considered, but are not deemed persuasive. In regards to the statement that the intent of the claimed invention is that “the binding domains of the fusion proteins assemble in a circular fashion, thus it is essential that both parts of the binding domains are fused to the two different termini of the spacer,” Applicant is arguing limitations not required by the claims. The claims do not require binding domains assembled in a “circular fashion.” Further, binding domains of Gao et al are fused N-terminal and C-terminal to the spacer (same as “linker” of Gao et al). See annotations on one recited “fusion polypeptide” of Figure 3A of Gao et al:
[AltContent: arrow][AltContent: arrow][AltContent: arrow]First Part BD Spacer Second Part Binding Domain (BD)
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In regards to the indication Gao does not teach a first fusion polypeptide with a first part of a binding domain fused either directly or via a first linker to the N-terminus of a spacer domain and the second part of the binding domain fused either directly or via a second linker to the C-terminus of the spacer domain, the examiner disagrees. See above annotations on one recited “fusion polypeptide” of Figure 3A of Gao et al. Figure 3A is, from left to right, N-terminal to C-terminal. The annotated first fusion polypeptide has a first part of a binding domain (the “VL1” domain) fused either directly or via a linker to the N-terminus of a spacer (the “Linker” annotated as “Spacer” and also annotated being flanked by protease cleavage sites) and the second part of the binding domain (the “VH1” domain) fused either directly or via a second linker to the C-terminus of the spacer domain. Also, see annotations on the other recited “fusion polypeptide” of Figure 3A of Gao et al:
[AltContent: arrow][AltContent: arrow][AltContent: arrow] First Part BD Spacer Second Part BD
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Double Patenting
Claims 18-20, 22-25, and 29 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 12,227,594 B2. Although the claims at issue are not identical, they are not patentably distinct from each other because claims of the patent are directed to species of the instant claims. While the patent claims do not specifically recite the “spacer” domain comprising a “hinge” of the patent claims as comprising “at least 25 amino acid residues”, the patent specification discloses hinges of spacers of claimed constructs include those that are 25 amino acids in length (see “The hinge region generally comprises about 25 amino acid residues….” at lines 55-58 of column 37, in particular). Therefore, obvious embodiments of the patent claims include constructs with spacers comprising a hinge that comprises at least 25 amino acids in length.
Request
In the Reply of 2/2/26, Applicant requests this rejection be held in abeyance.
The amendments to the claims and the request found in the Reply of 2/2/26 have been carefully considered. The request has been denied. The Office does not hold rejections in abeyance.
Double Patenting
Claims 18-20 and 22-29 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 12,227,594 B2, as applied to claims 18-20, 22-25, and 29, and in further view of Gao et al (2014/0155581 A1; 6/5/14). Claims of the patent do not specifically recite the bispecific constructs of the patent are generated by culturing host cells comprising nucleic acids encoding the bispecific constructs (or a “pair” of nucleic acids encoding the bispecific constructs). However, one of skill in the art would have been motivated to generate bispecific constructs of the patent by culturing host cells comprising nucleic acids encoding the bispecific constructs (or a “pair” of nucleic acids encoding the bispecific constructs) because Gao et al teaches recombinant antibody constructs are generated by culturing host cells comprising nucleic acids encoding the bispecific constructs (or a “pair” of nucleic acids encoding the bispecific constructs) (see ([0193]-[0201], in particular). It is further noted the patent specification discloses such recombinant antibody constructs are generated by culturing host cells comprising nucleic acids encoding the bispecific constructs (or a “pair” of nucleic acids encoding the bispecific constructs) (see columns 67-68, in particular).
Request
In the Reply of 2/2/26, Applicant requests this rejection be held in abeyance.
The amendments to the claims and the request found in the Reply of 2/2/26 have been carefully considered. The request has been denied. The Office does not hold rejections in abeyance.
New Rejections Necessitated by Amendments
Claim Rejections - 35 USC § 112
Claim 24 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 24 recites “…wherein the F comprises….” There is insufficient antecedent basis for “the F” in the claim.
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.
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/SEAN E AEDER/Primary Examiner, Art Unit 1642