DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
The Applicant’s amendment filed October 21, 2025 is acknowledged.
Claims 9-11 are canceled.
Claims 12-23 are new.
Claims 1 and 16 are independent.
Claims 1-8 and 12-23 are pending and currently under consideration.
In view of Applicant’s amendment filed on October 21, 2025, the objections and rejections under U.S.C. 112(a) enablement and U.S.C. 112(b) set forth in the Office Action mailed on July 25, 2025 are withdrawn and the following rejections are set forth.
Claim Rejections - 35 USC § 112
Indefinite Language
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.
This is a New Ground of Rejection necessitated by applicant's amendment. Claims 13 and 16-23 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 13 recites the limitation “wherein the bispecific antibody comprises: (a) a first antigen-binding domain that specifically binds a STAT protein selected from the group consisting of STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, and STAT6; and (b) a second antigen-binding domain that specifically binds a second target selected from the group consisting of KRAS, AKT, or ERK” in lines 1-5. Claim 13 is dependent on claim 1 which recites that the bispecific antibody comprises a sdAb comprising SEQ ID NO: 1.
Claim 16 recites ““A bispecific antibody comprising:(a) a first antigen-binding domain that specifically binds a STAT protein selected from STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, and STAT6; and(b) a second antigen-binding domain that specifically binds a second target selected from KRAS, AKT, or ERK; and wherein the bispecific antibody comprises the amino acid sequence of SEQ ID NO:1” in lines 166, respectively.
It is noted that SEQ ID NO: 1 is a bispecific sdAb that specifically binds STAT3 and KRAS (e.g. see [0097]).
Thus, it is unclear whether the first and second antigen binding domains recited in claims 13 and 16 are meant to comprise the sdAb of SEQ ID NO: 1 or if the first and second antigen binding domains recited in claims 13 and 16 are in addition to the sdAb of SEQ ID NO: 1. If the first and/or second antigen binding domains are meant to comprise the sdAb of SEQ ID NO: 1, which specifically binds STAT3 and KRAS, then there is insufficient antecedent basis for the domains binding STATs1, 2, 4, 5a, 5b, 6, AKT, and/or ERK
Written Description - New Matter
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.
This is a New Ground of Rejection necessitated by the Applicant’s amendment. Claims 12-23 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.
This is a Written Description, New Matter rejection.
Claims 13 and 16 recite “wherein the bispecific antibody comprises: (a) a first antigen-binding domain that specifically binds a STAT protein selected from the group consisting of STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, and STAT6; and (b) a second antigen-binding domain that specifically binds a second target selected from the group consisting of KRAS, AKT, or ERK” in lines 1-5 and “A bispecific antibody comprising:(a) a first antigen-binding domain that specifically binds a STAT protein selected from STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, and STAT6; and(b) a second antigen-binding domain that specifically binds a second target selected from KRAS, AKT, or ERK; and wherein the bispecific antibody comprises the amino acid sequence of SEQ ID NO:1” in lines 166, respectively.
These limitations are not supported by the original disclosure or claim as filed.
Applicant’s amendment, filed October 21, 2025, asserts that no new matter has been added by the amendments or new claims.
However, the specification as filed does not provide sufficient written description of the above-mentioned limitations. The specification does not provide sufficient support for a bispecific antibody that comprises a first and a second antigen-binding domain. The only bispecific antibody disclosed by the Applicant is SBT-100 (SEQ ID NO: 1) which is a single domain antibody (sdAb) that binds to STAT3 and KRAS (e.g. see [0079]). SBT-100 has only one antigen binding domain. However, the instant claims now recite that the bispecific antibody has two antigen binding domains (a first and a second), which is not clearly disclosed in the specification. Therefore, the claims represent a departure from the specification and claims originally filed. Applicant’s reliance on generic disclosure and possibly a single or limited species (SBT-100) do not provide sufficient direction and guidance to the features currently claimed (a bispecific antibody that comprises a first and second antigen binding domain).
Such limitations recited in the instant claims, which did not appear in the specification as filed, introduce new concepts and violate the description requirement of the first paragraph of 35 U.S.C. 112.
Applicant is required to cancel the new matter in the response to this Office Action.
Alternatively, applicant is invited to provide sufficient written support for the “limitations” indicated above. See MPEP 714.02, 2163.05-06 and 2173.05 (i).
Enablement
This is a New Ground of Rejection necessitated by the Applicant’s amendment. Claims 13 and 16-23 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a bispecific antibody that comprises SEQ ID NO: 1, does not reasonably provide enablement for any bispecific antibody that binds STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, or STAT6 with a first antigen-binding domain and KRAS, AKT, or ERK with second first antigen-binding domain. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
The factors considered in determining whether a disclosure would require undue experimentation include:
A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
In re Wands, 8 USPQ2d, 1400 (CAFC 1988) and MPEP 2164.01.
Nature of the invention/Breadth of the claims
Dependent claim 13 is drawn to a method of treating aberrant cell proliferation in a subject by administering a bispecific antibody that comprises a single-domain antibody (sdAb) directed against an intracellular component, wherein the sdAb comprises the amino acid sequence of SEQ ID NO:1, and wherein the bispecific antibody comprises: (a) a first antigen-binding domain that specifically binds a STAT protein selected from the group consisting of STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, and STAT6; and (b) a second antigen-binding domain that specifically binds a second target selected from the group consisting of KRAS, AKT, or ERK.
Independent claim 16 is drawn to a bispecific antibody comprising:(a) a first antigen-binding domain that specifically binds a STAT protein selected from STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, and STAT6; and(b) a second antigen-binding domain that specifically binds a second target selected from KRAS, AKT, or ERK; and wherein the bispecific antibody comprises the amino acid sequence of SEQ ID NO:1.
Dependent claims 18-23 use the bispecific antibody of claim 16 in a method of treating cancer in a subject.
State of the prior art/Predictability of the art
How to make an antibody that binds to an antigen is well known but antibody science is still considered unpredictable. See Amgen v. Sanofi, 598 U.S. 594 (2023). The Supreme Court, citing Briney, B. et al. 2019 (Nature; 566: 393-397, a reference of record), stated that the 26 anti-PCSK9 species that Amgen disclosed were not enough to represent the potential “quintillion” unique species claimed. The amino acid sequences of six CDRs (an antigen binding site) do not necessarily dictate binding and other desired function(s). For example, two anti-PCSK9 antibodies, one developed by Amgen and the other by Sanofi, have completely different CDR structures and yet their function is identical.
It is well established in the art that the formation of an intact antigen-binding site in an antibody usually requires the association of the complete heavy and light chain variable regions of a given antibody, each of which comprises three CDRs (or hypervariable regions), which provide the majority of the contact residues for the binding of the antibody to its target epitope. The amino acid sequences and conformations of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity, which is characteristic of the parent immunoglobulin. All of the CDRs of the heavy and light chain, in their proper order of CDR1, then 2, then 3, and in the context of framework sequences which maintain their required conformation are generally required to produce a protein having antigen-binding function. Proper association of heavy and light chain variable regions is required to form a functional antigen binding site (Almagro, J.C. & Fransson, J. Frontiers in Bioscience 2008; 13:1619-33, a reference of record).
In Amgen v. Sanofi, 598 U.S. 594 (2023), the Supreme Court held that Amgen was not enabled for “the entire genus” of antibodies that (1) “bind to specific amino acid residues on PCSK9,” and (2) “block PCSK9 from binding to [LDL receptors]” (872 F. 3d 1367, 1372) even though Amgen identified the amino acid sequences of 26 antibodies and disclosed two “trial and error” methods (“the roadmap” and “conservative substitution”) that Amgen insisted scientists could use to make other antibodies that perform these two functions. The case law applies to the instant claims which require a genus of bispecific antibodies that bind STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, or STAT6 with one arm and KRAS, AKT, or ERK with the other. Functionally drawn claims, such as instant claims 13 and 16 reciting “a bispecific antibody comprising:(a) a first antigen-binding domain that specifically binds a STAT protein selected from STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, and STAT6; and (b) a second antigen-binding domain that specifically binds a second target selected from KRAS, AKT, or ERK” do not predict the structure necessary to have said function.
Whether a genus comprising less than the six CDRs with its associated binding function meets the enablement requirement has not been reviewed by our agency’s appeal’s court. Nonetheless, examples of antigen binding domains comprising only a VH (or less commonly, a VL), meaning those with less than 6 CDRs, certainly do exist in the literature. However, antibodies generally comprise unique structures, such as the VHH domains of camelids, similar to the instantly claimed sdAb of SEQ ID NO: 1 (e.g. see claims 1 and 16).
As reviewed in De Genst et al. 2006 (Dev Comp Immunol; 30:187-98, a reference of record), the antigen binding domains found in camelids (VHH, sdAb, Heavy-chain only antibodies (HCAb), nanobodies, etc.) share some similarities to human heavy chain variable regions (VH) of the VHIII family, but there are notable differences in framework 2 and the CDRs. In particular, there are residues in the framework 2 that are important for avoiding pairing with VL (e.g. see page 188, paragraph spanning left and right columns). Additionally, CDRs 1 and 3 are generally extended in length and are frequently tethered by a disulfide bond (e.g. see page 188, right column, second paragraph). De Genst et al. suggest that the hypervariable loops of the VHH are critical for the antigen specificity and affinity (e.g. see page 188, right column, second paragraph). Thus, sdAb still require a complete and defined set of three CDRs in their proper order of CDR1, then 2, then 3, and in the context of framework sequences to maintain their required conformation and produce a protein having antigen-binding function.
In light of the art, it would be unpredictable to one of ordinary skill in the art to make the genus of bispecific antibodies encompassed by claims 13 and 16-23 and use them commensurate in scope with the breadth of claims 13 and 18-23.
The amount of direction provided by the inventor/The existence of working examples
The only bispecific antibody disclosed by the Applicant is SBT-100 (SEQ ID NO: 1) which is a sdAb with a single antigen-binding domain that is able to bind both STAT3 and KRAS (e.g. see [0114]). However, the Applicant has not disclosed any bispecific antibodies that comprise a first and a second antigen binding domain. The Applicant has also not disclosed any bispecific antibodies that bind to any antigens other than STAT3 and KRAS.
Working example 6 teaches that SBT-100 (SEQ ID NO: 1) inhibits the growth of human cancers with KRAS mutations and constitutive expression of pSTAT3 in vitro (e.g. see page 32, [00133] and [00134]). SBT-100 (SEQ ID NO: 1) impaired growth in eleven human cell lines derived from a variety of cancers, including pancreatic cancers (PANC-1 and BxPC3), TNBCs (MDA-MB- 231, MDA-MB-468, MDA-MB-453), ER+PR+ breast cancer (MCF-7), HER-2+amplified breast cancer (BT474), glioblastoma (U87), osteosarcoma (SJSA-1), fibrosarcoma (HT-1080), and metastatic, chemo-resistant prostate cancer (DU-145) (e.g. see Table 2). Based on these results, the Applicant concludes that SBT-100 (SEQ ID NO: 1) possesses a wide spectrum of anti-cancer activity.
Working example 8 demonstrates the SBT-100 (SEQ ID NO: 1)-dependent reduction in tumor volume in tumor bearing mice (e.g. see page 34, [00137]-[00141]). The treatment group demonstrated rapid and lasting suppression of tumor growth (e.g. see page 34, [00137]-[00141]).
The quantity of experimentation needed to make or use the invention based on the disclosure
Based on the content of the disclosure in view of the recent Supreme Court ruling regarding nature of an antibody invention and the prior art, a skilled artisan, through extensive trial-and-error experimentation, would have to make bispecific antibodies that bind STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, or STAT6 with a first antigen-binding domain and KRAS, AKT, or ERK with second first antigen-binding domain, and that comprise the sdAb of SEQ ID NO: 1, validate their function by demonstrating binding to STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, or STAT6 and KRAS, AKT, or ERK, and then use those in the methods claimed to treat aberrant cell proliferation or cancer in a subject with a reasonable expectation of success. This quantity of experimentation goes beyond what is considered “a reasonable degree of experimentation” and constitutes undue further experimentation in order to enable the genus of bispecific antibodies for the breadth of what is claimed.
For all of these reasons, the specification does not enable one of ordinary skill in the art to make and/or use what is claimed and therefore claims 13 and 16-23 are rejected under 35 U.S.C. 112(a).
Applicant's arguments filed October 21, 2025 have been fully considered but they are not persuasive.
The Applicant argues that the disclosure clearly demonstrates that a person of ordinary skill in the art (POSA) could make and use it without undue experimentation.
This is not found persuasive for the following reasons:
Contrary to the applicant’s argument that the disclosure clearly demonstrates that a person of ordinary skill in the art (POSA) could make and use it without undue experimentation; note that functionally drawn claims, such as instant claims 13 and 16 reciting “a bispecific antibody comprising:(a) a first antigen-binding domain that specifically binds a STAT protein selected from STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, and STAT6; and (b) a second antigen-binding domain that specifically binds a second target selected from KRAS, AKT, or ERK” do not predict the structure necessary to have said function. Moreover, it is well known in the art that in order to produce a protein having antigen-binding function, all of the CDRs of the heavy and light chain (or all of the CDRs of the VHH in the case of an sdAb), in their proper order of CDR1, then 2, then 3, are generally required. This was echoed in Amgen v. Sanofi, 598 U.S. 594 (2023), where the Supreme Court held that Amgen was not enabled for “the entire genus” of antibodies that (1) “bind to specific amino acid residues on PCSK9,” and (2) “block PCSK9 from binding to [LDL receptors]” (872 F. 3d 1367, 1372) despite Amgen identifying the amino acid sequences of 26 antibodies and disclosing two “trial and error” methods (“the roadmap” and “conservative substitution”) that Amgen insisted scientists could use to make other antibodies that perform these two functions.
Therefore, based on the limited species of bispecific antibodies disclosed by the Applicant (SBT-100) in view of the recent Supreme Court ruling regarding nature of an antibody invention and the prior art, a skilled artisan, through extensive trial-and-error experimentation, would have to make the claimed bispecific antibodies, validate their binding function, and use those in the methods claimed to treat aberrant cell proliferation or cancer in a subject with a reasonable expectation of success. This quantity of experimentation goes beyond what is considered “a reasonable degree of experimentation” and constitutes undue further experimentation in order to enable the genus of bispecific antibodies for the breadth of what is claimed.
As such, the applicant’s argument has not been found persuasive.
Claim Rejections - 35 USC § 102
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 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.
Claims 1-8 and 12-23 stand rejected under 35 U.S.C. 102(a)(1) as being anticipated by Singh 2019 (US20190177437A1, an IDS reference filed April 13, 2023).
Independent claim 1 is drawn to a method of treating aberrant cell proliferation in a subject, the method comprising administering to the subject a therapeutically effective amount of a bispecific antibody, wherein the bispecific antibody comprises a single-domain antibody (sdAb) directed against an intracellular component, wherein the intracellular component comprises a protein, wherein the sdAb comprises the amino acid sequence of SEQ ID NO:1, and wherein the bispecific antibody penetrates cells and inhibits aberrant cell proliferation.
Independent claim 16 is drawn to a bispecific antibody comprising:(a) a first antigen-binding domain that specifically binds a STAT protein selected from STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, and STAT6; and(b) a second antigen-binding domain that specifically binds a second target selected from KRAS, AKT, or ERK; and wherein the bispecific antibody comprises the amino acid sequence of SEQ ID NO:1.
Dependent claims 18-23 use the bispecific antibody of claim 16 in a method of treating cancer.
Singh teaches a method of preventing aberrant cell proliferation in a subject using a single-domain antibody (sdAb) directed against an intracellular component (e.g. see claim 1). The sdAb may comprise the anti-STAT3 VHH13 (SEQ ID NO:3) sdAb (e.g. see claim 10). Singh also teach that the sdAb of their invention may be multivalent, and/or multispecific, which encompasses a bispecific sdAb (e.g. see [0066]). Indeed, the VHH13 (SEQ ID NO:3) sdAb is bispecific in that it can bind both KRAS and STAT3 (e.g. see [0219]). Singh also teaches the administration of VHH13 (as a pharmaceutical composition) to nude BALB/C Mice for treating human breast cancer xenografts (e.g. see [0148] – [0152]).
It is noted that STAT3 and KRAS are intracellular proteins and that Singh’s SEQ ID NO: 3 is identical to instant SEQ ID NO: 1 (see alignment below).
Singh also teach that the aberrant cell proliferation is cancer (e.g. see claim 2), wherein the cancer is osteosarcoma, fibrosarcoma or glioblastoma (e.g. see claim 3). Singh also teach that their studies show support for anti-STAT3 VHH13 (SEQ ID NO:3) sdAb (SBT-100) as a chemotherapeutic agent (alone or in combination with established chemotherapeutic agents) against various types of cancers including: Pancreatic (PANC-1), Osteosarcoma (SJSA-1), fibrosarcoma (HT1080) (U87MG) Glioblastoma (U87MG) and breast cancer (MDA-MB-231) (e.g. see page 56, [0279]).
Singh also teach that the sdAb is synergistic with one or more chemotherapeutic drugs and improves therapeutic efficacy of the one or more chemotherapeutic drug against cancer (e.g. see claim 4), and wherein the one or more chemotherapeutic drugs comprises doxorubicin (e.g. see claim 5) or gemcitabine (e.g. see example 18, [0204] and [0205]). Singh further teaches that the sdAb decreases the toxicity of one or more chemotherapeutic drugs and improves survival in the treated subject (e.g. see claim 6) and that the sdAb is used in combination with one or more compounds (e.g. see claim 7). Singh also teach that VHH13 (SEQ ID NO:3) sdAb blocks the translocation of Stat3 to the nucleus ([0233]).
Regarding the claims that are drawn to an antibody that comprises two antigen binding domains, Singh teach that their sdAb can be multivalent, that is, the sdAb can have two or more proteins or polypeptides which are directed against two or more different epitopes of the target (e.g. see [0067]). The different epitopes may be located on the same target, or it could be on two or more different targets (e.g. see [0067]). Some examples of targets for the sdAb include ERK, STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, STAT6, and KRAS (e.g. see [0088]).
Singh also teach that VHH13 can cross the blood-brain barrier (e.g. see [0213]) and that it can reduce the expression of VEGF (e.g. see [0238]) and IL-6 (e.g. see [0231] – [0233]).
Regarding the limitations drawn to the properties of the claimed antibodies as recited in claims 1, 4-7, 12, 14, 15, and 21-23, such as “wherein the bispecific antibody penetrates cells and inhibits aberrant cell proliferation” in line 7 of claim 1; given that the bispecific antibody of Singh and the instant invention are identical they would inherently have the same properties. It is noted that a compound and all of its properties are inseparable; they are one and the same thing. Therefore, the bispecific antibody that comprises instant SEQ ID NO: 1 taught by Singh would have the claimed properties recited in claims 1, 4-7, 12, 14, 15, and 21-23, especially in the absence of evidence to the contrary.
RESULT 1
AASEQ2_07102025_071759
Query Match 100.0%; Score 683; DB 1; Length 127;
Best Local Similarity 100.0%;
Matches 127; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 HVQLVESGGGSVQAGGSLRLSCAASGANGGRSCMGWFRQVPGKEREGVSGISTGGLITYY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 HVQLVESGGGSVQAGGSLRLSCAASGANGGRSCMGWFRQVPGKEREGVSGISTGGLITYY 60
Qy 61 ADSVKGRFTISQDNTKNTLYLQMNSLKPEDTAMYYCATSRFDCYRGSWFNRYMYNSWGQG 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ADSVKGRFTISQDNTKNTLYLQMNSLKPEDTAMYYCATSRFDCYRGSWFNRYMYNSWGQG 120
Qy 121 TQVTVSS 127
|||||||
Db 121 TQVTVSS 127
Search completed: July 10, 2025, 07:18:02
Job time : 1 secs
Thus, the instant claims are anticipated by Singh.
Applicant’s arguments filed October 21, 2025 have been fully considered but have not been found persuasive.
The Applicant argues that the cited art fails to teach or suggest the claimed combination of structural and functional features recited in amended Claim 1. The Applicant asserts that the cited art does not disclose or suggest a bispecific antibody and fails to teach or suggest the claimed combination recited in amended Claim 1, and as such does not anticipate the claimed invention.
This is not found persuasive for the following reasons:
Contrary to the applicant’s argument that the does not disclose or suggest a bispecific antibody; note that Singh teaches that the sdAb of their invention may be multivalent, and/or multispecific, which encompasses a bispecific sdAb (e.g. see [0066]). Furthermore, Singh teach that the VHH13 (SEQ ID NO:3) sdAb, which is identical to the instant SBT-100 (SEQ ID NO: 1) sdAb, is bispecific in that it can bind both KRAS and STAT3 (e.g. see [0219]). It is noted that the Applicant describes SBT-100 (SEQ ID NO: 1) as a bispecific antibody by the fact that it can bind two different targets, STAT3 and KRAS, but does not disclose any other definition of an antibody, namely a bispecific antibody with more than one antigen binding domain. Thus, Singh anticipates the instant invention by describing that the sdAb of their invention are bispecific in that they can bind two targets and by suggesting they can comprise more than one antigen binding domain.
As such, the applicant’s argument has not been found persuasive.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP § 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-8, 12, 14, and 15 stand rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of copending Application No. 17/750,341 (the ‘341 Application) for the reasons of record.
Claims 1 and 8 stand rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. 11,370,847 (cites as claims 11-14 and 16 copending Application No. 16/195,542 (the ‘542 Application) in the office action mailed on 07/25/2025) for the reasons of record.
This is a New Ground of Rejection necessitated by the Applicant’s amendment. Claims 13 and 16-23 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of copending Application No. 17/750,341 (the ‘341 Application) in view of Singh 2019 (US20190177437A1, an IDS reference filed April 13, 2023).
Instant claim 13 is drawn to a method of treating aberrant cell proliferation in a subject by administering a bispecific antibody that comprises a single-domain antibody (sdAb) directed against an intracellular component, wherein the sdAb comprises the amino acid sequence of SEQ ID NO:1, and wherein the bispecific antibody comprises: (a) a first antigen-binding domain that specifically binds a STAT protein selected from the group consisting of STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, and STAT6; and (b) a second antigen-binding domain that specifically binds a second target selected from the group consisting of KRAS, AKT, or ERK.
Instant claim 16 is drawn to a bispecific antibody comprising:(a) a first antigen-binding domain that specifically binds a STAT protein selected from STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, and STAT6; and(b) a second antigen-binding domain that specifically binds a second target selected from KRAS, AKT, or ERK; and wherein the bispecific antibody comprises the amino acid sequence of SEQ ID NO:1.
Instant claims 18-23 use the bispecific antibody of claim 16 in a method of treating cancer in a subject.
The claims of the ‘341 Application are drawn to a method of preventing aberrant cell proliferation in a subject using a single-domain antibody (sdAb) directed against an intracellular component, wherein the sdAb comprises anti-STAT3 VHH13 (SEQ ID NO:3) sdAb.
It is noted that the SBT-100 (SEQ ID NO: 1) sdAb of the instant invention is identical to the anti-STAT3 VHH13 (SEQ ID NO:3) sdAb of the ‘341 Application. See alignment below.
The claims in the ‘341 Application differ from the instant invention by not teaching that the bispecific VHH13 (SEQ ID NO:3) sdAb comprises a first and a second antigen binding domain.
Singh teaches a method of preventing aberrant cell proliferation in a subject using a single-domain antibody (sdAb) directed against an intracellular component (e.g. see claim 1). The sdAb may comprise the anti-STAT3 VHH13 (SEQ ID NO:3) sdAb (e.g. see claim 10).
It is noted that STAT3 and KRAS are intracellular proteins and that Singh’s SEQ ID NO: 3 is identical to instant SEQ ID NO: 1 (see alignment below).
Singh teaches that the sdAb of their invention may be multivalent, and/or multispecific, which encompasses a bispecific sdAb that comprise two different antigen binding domains (e.g. see [0066]). Indeed, the VHH13 (SEQ ID NO:3) sdAb is bispecific in that it can bind both KRAS and STAT3 (e.g. see [0219]).
Query Match 100.0%; Score 683; DB 1; Length 127;
Best Local Similarity 100.0%;
Matches 127; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 HVQLVESGGGSVQAGGSLRLSCAASGANGGRSCMGWFRQVPGKEREGVSGISTGGLITYY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 HVQLVESGGGSVQAGGSLRLSCAASGANGGRSCMGWFRQVPGKEREGVSGISTGGLITYY 60
Qy 61 ADSVKGRFTISQDNTKNTLYLQMNSLKPEDTAMYYCATSRFDCYRGSWFNRYMYNSWGQG 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ADSVKGRFTISQDNTKNTLYLQMNSLKPEDTAMYYCATSRFDCYRGSWFNRYMYNSWGQG 120
Qy 121 TQVTVSS 127
|||||||
Db 121 TQVTVSS 127
It would be obvious to one of ordinary skill in the art to modify the claims of the ‘341 Application incorporate the teachings of Singh to include that the bispecific sdAb of the ‘341 Application comprises a first and a second antigen binding domain. Given that Singh teaches the same bispecific sdAb as the instant claims and the claims in the ‘341 Application, and that Singh teaches that that bispecific sdAb can be multivalent, and/or multispecific in that it comprises more than one antigen binding site; it would be obvious to a skilled artisan to modify the bispecific sdAb of the ‘341 Application to have a first and a second antigen binding domain with a reasonable expectation of success.
Therefore, the claims in the ‘341 Application would render the instant claim obvious.
This is a New Ground of Rejection necessitated by the Applicant’s amendment. Claims 13 and 16-23 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 11-5 of U.S. Patent No. 11,370,847 (the ‘847 Patent) in view of Singh 2019 (US20190177437A1, an IDS reference filed April 13, 2023).
Instant claim 13 is drawn to a method of treating aberrant cell proliferation in a subject by administering a bispecific antibody that comprises a single-domain antibody (sdAb) directed against an intracellular component, wherein the sdAb comprises the amino acid sequence of SEQ ID NO:1, and wherein the bispecific antibody comprises: (a) a first antigen-binding domain that specifically binds a STAT protein selected from the group consisting of STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, and STAT6; and (b) a second antigen-binding domain that specifically binds a second target selected from the group consisting of KRAS, AKT, or ERK.
Instant claim 16 is drawn to a bispecific antibody comprising:(a) a first antigen-binding domain that specifically binds a STAT protein selected from STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, and STAT6; and(b) a second antigen-binding domain that specifically binds a second target selected from KRAS, AKT, or ERK; and wherein the bispecific antibody comprises the amino acid sequence of SEQ ID NO:1.
Instant claims 18-23 use the bispecific antibody of claim 16 in a method of treating cancer in a subject.
The claims of the ‘847 Patent are drawn to a method of method of treating viral infections using a single-domain antibody (sdAb), wherein the sdAb comprises the amino acid sequence as set forth in SEQ ID NO:3.
It is noted that the SBT-100 (SEQ ID NO: 1) sdAb of the instant invention is identical to the anti-STAT3 VHH13 (SEQ ID NO:3) sdAb of the ‘847 Patent. See alignment below.
The claims in the ‘847 Patent differ from the instant invention by not teaching that the bispecific VHH13 (SEQ ID NO:3) sdAb comprises a first and a second antigen binding domain or a method of treating cancer.
Singh teaches a method of preventing aberrant cell proliferation in a subject using a single-domain antibody (sdAb) directed against an intracellular component (e.g. see claim 1). The sdAb may comprise the anti-STAT3 VHH13 (SEQ ID NO:3) sdAb (e.g. see claim 10). Singh also teach that the aberrant cell proliferation is cancer (e.g. see claim 2), wherein the cancer is osteosarcoma, fibrosarcoma or glioblastoma (e.g. see claim 3).
It is noted that STAT3 and KRAS are intracellular proteins and that Singh’s SEQ ID NO: 3 is identical to instant SEQ ID NO: 1 (see alignment below).
Singh teaches that the sdAb of their invention may be multivalent, and/or multispecific, which encompasses a bispecific sdAb that comprise two different antigen binding domains (e.g. see [0066]). Indeed, the VHH13 (SEQ ID NO:3) sdAb is bispecific in that it can bind both KRAS and STAT3 (e.g. see [0219]).
Query Match 100.0%; Score 683; DB 1; Length 127;
Best Local Similarity 100.0%;
Matches 127; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 HVQLVESGGGSVQAGGSLRLSCAASGANGGRSCMGWFRQVPGKEREGVSGISTGGLITYY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 HVQLVESGGGSVQAGGSLRLSCAASGANGGRSCMGWFRQVPGKEREGVSGISTGGLITYY 60
Qy 61 ADSVKGRFTISQDNTKNTLYLQMNSLKPEDTAMYYCATSRFDCYRGSWFNRYMYNSWGQG 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ADSVKGRFTISQDNTKNTLYLQMNSLKPEDTAMYYCATSRFDCYRGSWFNRYMYNSWGQG 120
Qy 121 TQVTVSS 127
|||||||
Db 121 TQVTVSS 127
It would be obvious to one of ordinary skill in the art to modify the claims of the ‘847 Patent to incorporate the teachings of Singh to include that the bispecific sdAb of the ‘847 Patent comprises a first and a second antigen binding domain and is used in a method of treating cancer. Given that Singh teaches the same bispecific sdAb as the instant claims and the claims in the ‘847 Patent, that bispecific sdAb can be multivalent, and/or multispecific in that it comprises more than one antigen binding site, and it has been used to treat cancer; it would be obvious to a skilled artisan to modify the bispecific sdAb of the ‘847 Patent to have a first and a second antigen binding domain and to use it in a method of treating cancer with a reasonable expectation of success with a reasonable expectation of success.
Therefore, the claims in the ‘847 Patent would render the instant claim obvious.
Conclusion
No claims are allowed.
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 Grace H. Lunde whose telephone number is (703)756-1851. The examiner can normally be reached Monday - Thursday 5:00 a.m. - 3:00 p.m. (EST).
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, Misook Yu can be reached at (571) 272-0839. 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.
/GRACE H LUNDE/Examiner, Art Unit 1641
/MISOOK YU/Supervisory Patent Examiner, Art Unit 1641