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 12/9/25 in response to the Office Action of 9/11/15 are acknowledged and have been entered.
Claims 24-37 and 39-44 are pending.
Claims 24 and 43 have been amended by Applicant.
Claims 3 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.
Necessitated by amendments, the following species has been rejoined: a fusion polypeptide comprising an ISV that specifically binds EGFR and an ISV that binds CEA.
The following Office Action contains NEW GROUNDS of rejections Necessitated by Amendments.
Objections Withdrawn
All previous objections are withdrawn.
Rejections Withdrawn
All previous rejections are withdrawn.
New Rejections Necessitated by Amendments
Claim Rejections - 35 USC § 103
Claims 24-37 and 39-44 are rejected under 35 U.S.C. 103(a) as being unpatentable over Laeremans et al (US 20090252681 A1; 4/21/22 IDS) in view of Dorvillius et al (Tumor Biology, 2003, 23(6): 337-347).
Laeremans et al teaches bispecific polypeptide that comprise two binding moieties, wherein each binding moiety is specific for an antigen expressed on a tumor cell, are highly advantageous in tumor targeting and that such bispecific polypeptides are capable of simultaneously targeting two tumor associated antigens, resulting in enhanced tumor specificity as compared to mono-specific binding moieties ([0509], in particular). Laeremans et al further teaches such bispecific polypeptides that are specific to two markers on tumor cells are much more tumor specific and provide a better specific binding than monospecific binding moieties ([0509], in particular). Laeremans et al further teaches such bispecific polypeptides include those that target the tumor markers EGFR, IGF-IR, HER2, HER3, HER4, CEA, VEGF, CD28, and/or CD138 ([0518], in particular). Laeremans et al further teaches such bispecific polypeptides include those comprising a binding moiety directed against a first antigen and a binding moiety directed against a second antigen, wherein each binding moiety is a VHH or nanobody ([0505] and [0513], in particular). Laeremans et al further teaches VHH which bind EGFR and block ligand binding to EGFR, prevent heterodimerization and induce apoptosis ([0920], in particular). Laeremans et al further teaches that binding moieties of the bispecific polypeptides bind their targets with a KD value that are “preferably less than 200 nM, more preferably less than 10 nM, such as less than 500 pM” (paragraph [0156] in particular). Laeremans et al further teaches the bispecific polypeptide constructs wherein the binding domains are linked by a linker ([0117], in particular). Laeremans et al further teaches the bispecific polypeptide constructs linked to a toxin or toxic residue or moiety when used in treatment for cancer ([0480], in particular). Laeremans et al further teaches the bispecific polypeptide constructs linked to radiolabels for imaging when using the nanobody constructs to screen for cancer ([0780], in particular).
Laeremans et al does not specifically demonstrate generating a bispecific polypeptide construct wherein VHH domains bind EGFR and CEA (not a growth factor receptor) are described as having KD values encompassed by the claims, such as 1 nM. However, these deficiencies are made-up by Dorvillius et al.
Dorvillius et al teaches bispecific polypeptide constructs that bind EGFR and CEA therapeutically target breast cancer cells expressing EGFR and CEA (Abstract, in particular). Dorvillius et al further teaches targeting two distinct tumor-associated antigens, such as EGFR and CEA, on the same cell could improve tumor localization (Abstract, in particular).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to generate the bispecific polypeptide constructs (fusion protein constructs) of Laeremans et al for use in prevention, diagnosis, and/or treatment of diseases and disorders associated with EGFR and CEA comprising identifying just any VHH domains of Laeremans et al that bind EGFR (an induce apoptosis by blocking ligand binding and heterodimerization, as taught by Laeremans et al) and CEA with KD values in the range of Laermans et al and using such VHH domains in a method of generating the bispecific pelypeptide constructs of Laeremans et al wherein either VHH domain of Laeremans et al (anti-EGFR VHH; anti-CEA VHH) is N-terminal to the other and wherein both VHH domains of the constructs are identified as having a KD of 1 nM or wherein both VHH domains of the constructs are identified as having a KD of 10 nM because Laeremans et al teaches that the constructs bind their targets with a KD value that are “preferably less than 200 nM, more preferably less than 10 nM, such as less than 500 pM” (paragraph [0156] in particular) and Dorvillius et al teaches bispecific polypeptide constructs that bind EGFR and CEA therapeutically target breast cancer cells expressing EGFR and CEA. Further, such bispecific polypeptide constructs would predictably result in decreased toxicities to non-cancer cells (as compared to monospecific constructs comprising either VHH alone) because Laeremans et al teaches such bispecific polypeptides that are specific to two markers on tumor cells are much more tumor specific and provide a better specific binding than monospecific binding moieties ([0509], in particular).
KD ranges recited by the instant claims and KD ranges of Laeremans et al overlap. In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. See MPEP 2144.05.
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
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