Check that sequences are allowable, check copending applications for double patenting
DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on October 14, 2025 has been entered.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on October 14, 2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDS is being considered by the examiner.
Claim Status
Claims 1, 3-4, 6-7, 9-10, 12, 14, 16, 20, 25, 28, 31, 33-37, 41, 46-47, and 50-53 are under consideration in this office action.
Withdrawn Objections/Rejections
The objection of claim 50 is withdrawn in view of applicant’s amendment.
The rejection of claims 6-7, 20, 33-37, 41, and 52-53 under 35 U.S.C. 112(b) for being indefinite is withdrawn in view of applicant’s amendment of claim 20 to include the limitation wherein CDR1 to CDR3 of the ISVD are determined according to Kabat definition or AbM definition.
Applicant’s arguments regarding the rejection of claim 3 under 35 U.S.C. 112(a) for not being fully enabled and for failing to meet the written description requirement are persuasive, and these rejections of claim 3 are withdrawn.
The rejections of claim 16 under 35 U.S.C. 112(a) for not being fully enabled and for failing to meet the written description requirement are withdrawn in view of applicant’s amendment to limit the amino acid substitutions of CDR2 to specific amino acids at specific positions.
Nucleotide and/or Amino Acid Sequence Disclosures
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:
Specific deficiency – This application fails to comply with the requirements of 37 CFR 1.831-1.834 because the “Sequence Listing XML,” as a separate part of the disclosure, is defective, damaged or unreadable. SEQ ID NOs: 16 and 99 are defective. These SEQ ID NOs are blank in the Sequence listing XML because they only consist of three amino acids. Three amino acids sequences must be represented in text form and cannot have a SEQ ID NO.
Required response – Applicant must provide:
A "Sequence Listing" part of the disclosure, as described above in item 1); as well as
An amendment specifically directing entry of the "Sequence Listing" part of the disclosure into the application in accordance with 1.825(b)(2);
A statement that the "Sequence Listing" includes no new matter in accordance with 1.825(b)(5); and
A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(b)(4).
If the "Sequence Listing" part of the disclosure is submitted according to item 1) a) or b) above, Applicant must also provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter;
If the "Sequence Listing" part of the disclosure is submitted according to item 1) b), c), or d) above, Applicant must also provide:
A replacement CRF in accordance with 1.825(b)(6); and
Statement according to item 2) a) or b) above.
Modified Rejections Necessitated by Amendment
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.
Written Description
Claims 1, 10, 14, and 46-47 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 claims contain 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.
“[T]he purpose of the written description requirement is to ‘ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent specification.’” Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353-54 (Fed. Cir. 2010) (en banc) (quoting Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920 (Fed. Cir. 2004)). To satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163.04.
The claims are directed to polypeptides comprising immunoglobulin single variable domains comprised of three specific CDR1 to 3 (SEQ ID NOs: 7, 11, 15; SEQ ID NOs: 8, 12, 16; SEQ ID NOs: 32,36,15; and SEQ ID NOs: 33, 37, 16, respectively) and methods of making and using the polypeptides. Claim 1 is further directed to three ISVDs of CDR1 to 3 comprised of sequences with 2 or 1 amino acid differences compared to the specific CDR1 to 3 set forth in claim 1. Claim 14 is directed to a polypeptide comprised of amino acid sequence that is more than 90% identical with the polypeptide of claim 1. By virtue of the amino acid substitutions in the CDRs and the percent identity language, these claims encompass variants that do not require all three CDRs from a particular parental ISVD. Claims 10, 14, and 46-47 depend from claim 1 but do not sufficiently further define the sequence of the polypeptide. As written, these claims are drawn to a polypeptide comprised of a broad genus of ISVD amino acid sequences.
As is well-known in the antibody art, the structure each antibody uses to bind its particular epitope on an antigen is structurally distinct and is formed by a recombination event that results in high variability at the amino acid sequence level even when the same antigen is bound (see Edwards et al, abstract, PTO-892 from 2/14/2025). It is also well established 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 that provide the majority of the contact residues for the binding of the antibody to its target epitope (see Almagro & Fransson, section 3 and figure 1, PTO-892 from 2/14/2025).
While most antibodies utilize a VH+VL pair to form their antigen-binding site, examples of antigen binding domains comprising only a VH that in turn comprise only three CDRs also exist, often derived from camelids (see Muylderman, figure 2 and “Structure of the VHH”, IDS from 6/28/24). But these single domain antibodies still utilize highly variable amino acid sequences to contact antigen, and their CDRs are likewise formed by the same type of genetic recombination event between V-D-J gene segments. Accordingly, the skilled artisan recognizes that it is also the case for ISVD that, for it to be reasonably predictable, a variant would bind the same antigen as the parental sequence and that the conserved structure provided by the combination of the three CDRs in the context of appropriate framework sequences is generally still essential. Given the unpredictable effect on functional activity when residues in the CDRs are changed or not conserved between a parent and variant sequence, the skilled artisan generally would not be able to visualize or otherwise predict, a priori, which ISVD variant sequences would retain antigen binding and other desired properties unless, at a minimum, they contained a set of three CDRs that had been experimentally demonstrated to confer antigen binding.
“[A] sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus.” Ariad, 598 F.3d at 1350 (quoting Eli Lilly, 119 F.3d at 1568-69). What constitutes a "representative number" is an inverse function of the skill and knowledge in the art. Satisfactory disclosure of a "representative number" depends on whether one of skill in the art would recognize that the applicant was in possession of the necessary common attributes or features of the elements possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus.
To provide adequate written description and evidence of possession of the claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof. In the instant case, the only factors present in the claims are a recitation of one generic, broad genus that encompassed a diverse and huge number of possible antibodies that bind the disclosed antigen. The specification does not provide a consistent structure for all of the possible ISVDs and fails to provide a representative number of species for the claimed genus. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus.
The “structural features common to the members of the genus” needed for one of skill in the art to ‘visualize or recognize’ the members of the genus takes into account the state of the art at the time of the invention. The state of the prior art is such that it is well established that the formation of an intact antigen-binding site of antibodies generally requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three CDRs of an antibody, which provide the majority of the contact residues for the binding of the antibody to the epitope. See for example Kussie (PTO-892 from 2/14/2025) who demonstrates that a single amino acid change in the heavy chain of an antibody which binds p-azophenylarsonate (Ars) completely abrogates the ability of the antibody to bind Ars but adds the functionality of binding the structurally related p-azophenylsulfonate (see abstract).
The art recognizes that the CDRs define the binding properties of an antibody and that even single amino acid changes to this region can completely abrogate the binding specificity of an antibody. As a further example, see Chen et al., 1995, PTO-892 from 2/14/2025), which demonstrates single amino acid changes in the VH CDR2 sequence can increase binding, decrease binding, destroy binding, or have no effect on binding when compared to the wild-type antibody (see abstract).
Making changes to the CDR sequence of an antibody/ISVD is a highly unpredictable process and the skilled artisan could not a priori make any predictions regarding such mutations with any reasonable expectation of success nor envisage the breadth of structurally unrelated CDR combinations that would still possess the required functions. Without this guidance or direction, the skilled artisan would not consider applicant to be in possession of the claimed genus of ISVDs because the skilled artisan recognizes that even seemingly minor changes made without guidance or direction as to the relationship between the particular amino acid sequence of the instantly claimed ISVD and its ability to bind antigen, can dramatically affect antigen binding.
The specification discloses at least 7 new ISVDs of specific CDR1-3. However, there is no way to determine if these ISVDs represent the full breadth of what is claimed. The disclosure of these specific ISVDs would not convey to the artisan that applicant was in possession of the full genus of all ISVDs that possess the required functions nor does it allow the skilled artisan to envisage the specific structure of such ISVDs.
See also Koenig 2017 (PTO-892 from 2/14/2025), which provides a large mutation analysis study where every amino acid in both variable regions are substituted with every other amino acid. Looking at figure 1 of Koenig, the bottom half of each section (labeled VEGF) relates to the ability of the mutant to bind the original target, with blue meaning a reduced affinity and black meaning a complete loss of binding ability. In VH-CDR2, for example, mutating any given residue to cysteine, which is encompassed by the instant claims, resulted in reduced binding at 12 residues and a complete loss of binding at 5 residues. That is, at 100% of the positions, mutation to cysteine reduced or ablated the antibody’s ability to bind the target. Looking at a specific position, in 100% of the mutations of residue 55, binding was reduced (15/19) or eliminated (4/19). While residues 56-65 appear more tolerant of change, residues 50-55 are generally intolerant of change (see abstract).
It is appreciated that Koenig is studying one specific antibody and there is no evidence that the instant ISVDs would react in the same way. However, this is part of the problem. It is entirely unclear from the specification which residues of applicant’s CDRs are tolerant or intolerant to change, and whether those tolerant positions are only tolerant to conservative mutations. The fact that some residues might tolerate mutation does not convey to the skilled artisan that applicant knew which of the claimed residues were tolerant of such, i.e. does not convey that applicant was in possession of those sequences which are mutated yet preserve the claimed function. In other words, the specification fails to convey possession of an invention commensurate in scope with what is now claimed and therefore fails to meet the written description requirement. Looking at Koenig figure 2A, ~200 mutations in the CDR region of the VH chain completely abrogates any binding. While 2B appears to indicate that the CDRs of VL are more tolerant of change than the heavy chain CDRs, still over half of the mutations reduce binding compared to the parent.
With the exception of specifically disclosed ISVDs with specific CDRs, the skilled artisan cannot envision the detailed chemical structure of all of the encompassed ISVDs, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The product itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
As noted above, the art generally accepted that the combination of the CDRs within an ISVD was the minimum structure essential for binding specificity. In this case, the claims as currently recited do not require the CDRs that are essential to maintain binding to the target. Therefore, the rejected claims do not require a structure that could be considered to reasonably confer the claimed function or to define an identifying characteristic shared among the members of the claimed genus.
One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. In Fiddes, claims directed to mammalian FGF's were found to be unpatentable due to lack of written description for that broad class. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115).
Therefore, claims 1, 10, 14, and 46-47 do not meet the written description requirement.
Scope of Enablement
Claims 1, 10, 14, 41, and 46-47 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 polypeptide comprising an ISVD comprised of CDR1-3 of SEQ ID NOs: 7, 11, and 15; SEQ ID NOs: 8, 12, and 16; SEQ ID NOs: 32, 36, and 15; and SEQ ID NOs: 33, 37, and 16 and a method of treating liver cancer and lung cancer, does not reasonably provide enablement for:
the polypeptide comprising 2 or 1 amino acid differences of each CDR or a polypeptide having at least 90% sequence identity, as broadly recited in the independent claims;
or
a method of treating all cancer with the polypeptide, as in claim 41
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.
Case law holds that applicant’s specification must be “commensurately enabling [regarding the scope of the claims].” See Ex Parte Kung, 17 USPQ2d 1545, 1547 (Bd. Pat. Appl. Inter. 1989). Otherwise undue experimentation would be involved in determining how to practice and use applicant’s invention. Factors to be considered in determining whether a disclosure meets the enablement requirement of 35 USC 112, first paragraph, have been described in In re Colianni, 195 USPQ 150 (CCPA 1977) and have been adopted by the Board of Patent Appeals and Interferences in Ex Parte Forman, 230 USPQ 546 (BPAI 1986). Among these factors are:
1. the nature of the invention,
2. the state of the prior art,
3. the predictability or lack thereof in the art,
4. the breath of the claims,
5. the amount of direction or guidance present, and
6. the presence or absence of working examples.
The following is an analysis of these factors in relationship to this application.
Nature of the invention/Breadth of claims
The nature of the invention is an engineered polypeptide comprising one ISVDs where the relative level of skill of those in the art is deemed to be high. With respect to claim breadth, the standard under 35 U.S.C. §112, first paragraph, entails the determination of what the claims recite and what the claims mean as a whole. The claims are directed to polypeptides comprised of ISVDs of CDR1-3 of SEQ ID NOs: 7, 11, and 15; SEQ ID NOs: 8, 12, and 16; SEQ ID NOs: 32, 36, and 15; or SEQ ID NOs: 33, 37, and 16 or with 1-2 amino acid differences within SEQ ID NO: 7, 12, 36, or 37. Claim 41 is directed to a method for the treatment of any cancer.
State of the Art/Predictability
The polypeptide
The invention is related to a polypeptide comprising an ISVD. Claim 1, as currently formulated, does not require the presence of the three required CDR sequences for each ISVD, and, therefore, the scope of the claims encompasses ISVDs having up to 2 differences in a given ISVD amino acid sequence as well as up to 10% different amino acid sequence of SEQ ID NO: 3. In the case of CDR3 of the polypeptide of claim 1, subpart b and d, the CDR3 of SEQ ID NO: 16 only consists of 3 amino acids, and thus CDR3 only need include only 1 amino acid of SEQ ID NO: 16. The activity of the ISVD as claimed is not predictable, as it is well established in the art that the formation of an intact antigen-binding site consists of three CDRs, which provide the majority of the contact residues for the binding of the ISVD to its target epitope. The amino acid sequences and conformations of each combination of CDRs are critical in maintaining the antigen binding specificity and affinity, which is characteristic of the ISVD. It is expected that all of the CDRs in their proper order and in the context of framework sequences, which maintain their required conformation, are required in order to produce a protein having antigen-binding function and that proper.
Even minor changes in the amino acid sequences of the heavy and light variable regions of antibodies, particularly in the CDRs, may dramatically affect antigen-binding function, and by extension ISVD-binding function, as evidenced by Rudikoff et al (“Rudikoff”, pg 1979, see abstract; PTO-892 from 2/14/2025) and Wu et al (“Wu”, pg 152, column 1; PTO-892 from 2/14/2025). Rudikoff teaches that the alteration of a single amino acid in the CDR of a phosphocholine-binding myeloma protein resulted in the loss of antigen-binding function. Indeed, Wu states that it is difficult to predict which framework residues serve a critical role in maintaining affinity and specificity due in part to the large conformational change in antibodies that accompany antigen binding; certain residues, though, have been identified as important for maintaining conformation. As these single domain antibodies still utilize highly variable amino acid sequences to contact antigen, and their CDRs are likewise formed by the same type of genetic recombination event between V-D-J gene segments, the skilled artisan recognizes that it is also the case for ISVDs. In order to be reasonably predictable, a variant would bind the same antigen as the parental sequence and the conserved structure provided by the combination of the three CDRs in the context of appropriate framework sequences is generally still essential.
Taken together, these references demonstrate that an ISVD must comprise all three CDRs in order to maintain the antigen binding specificity and affinity.
Method of treating cancer
Claim 41 is directed to a method of treating cancer. Yang et al (US 20240409663, PTO-892 from 2/14/2025) teaches that GPC3 is overexpressed in liver gastric, pancreatic, esophageal, ovarian, and lung tumors and that inhibition of GPC3 is useful for treating these types of tumors [0126].
Guidance/working examples
The polypeptide
Claims 1, 10, 14, and 46-47 recite ISVD amino acid sequences that comprise partially defined structures. By virtue of the 2 or 1 amino acid different and percent identity language, the claims encompasses variants that do not require all three CDRs from a particular parental ISVD. There is no direction provided for use of an ISVD with three CDRs with 2 or 1 amino acids different or up to 10% different from SEQ ID NO: 3. Therefore, the enabling disclosure does not extend to the antibodies of these claims and their dependent claims.
In view of the lack of the predictability of the art to which the invention pertains (as evidenced by Almagro, Rudikoff, and Wu), the lack of guidance and direction provided by applicant, and the absence of working examples, the Examiner concludes that further undue experimentation would be required to practice the invention as claimed and goes beyond what is considered ‘routine’ within the art; claims 1, 10, 14, 41, and 46-47 are rejected under 35 U.S.C. 112, first paragraph, for failing to meet the enablement requirement.
Method of treating cancer
Applicant’s disclosure demonstrates that the claimed peptide is effective in reducing tumor volume in mice injected with Huh-7 tumor cells, a human liver cancer cell line (see Figure 13).
The instant specification is not enabling for the method of claim 41 because one cannot follow the guidance presented therein, or within the art at the time of filing, and predictably practice the claimed method without engaging in extensive and undue experimentation. Given that the nature of the invention is treatment of any cancer, a person having ordinary skill in the art would have to perform multiple further in vivo experiments, in animals and/or human subjects, in order to demonstrate whether the invention could or could not be used. For example, there is not support in the specification or existing art that an GPC3 inhibitor would be effective in the treatment of hematological cancers, which is included in the scope of the claim. The amount of experimentation required for enabling guidance, commensurate in scope with what is claimed, goes beyond what is considered ‘routine’ within the art.
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, 3-4, 6-7, 9-10, 14, 20, 33-37, 41, 46-47, and 50-53 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-28 of U.S. Patent No. 11,932,702. Although the claims at issue are not identical, they are not patentably distinct from each other because they are directed to the polypeptides comprising the same ISVDs.
Patent ‘702 claims 1-19 teach a polypeptide comprising an immunoglobulin single variable domain (ISVD), wherein each ISVD comprises three complementarity determining regions (CDRs), CDR1 to CDR3, respectively, of SEQ ID NOs: 7, 11, and 15 and SEQ ID NOs: 8, 12, and 16, and, in some embodiments, comprise one or more other groups, residues, moieties, or binding units, which reads on the ISVDs of instant claims 1, 3-4, 6-7, 9-10, 14, 20, 33-37, 41, 46-47, and 50-53. Patent ‘702 claims 20-23 teach a nucleic acid, host cell, and method for producing the polypeptide, which reads on instant claims 33-35. Patent ‘702 claims 24-26 teach a composition comprising the polypeptide, which reads on instant claims 36-37. ‘702 claims 27-28 are directed to a method of treating liver cancer, which reads on instant claim 41.
The scope of ‘702 claims fully overlaps with the instant claims, and the sequences of the ISVDs and methods of making and using the ISVDs of patent ‘702 anticipate the polypeptides comprised of an ISVD and methods of the instant claims.
Response to Arguments
Applicant's arguments filed October 14, 2025 have been fully considered but they are not persuasive.
The rejections of claims 1, 10, 46, and 47 under 35 U.S.C. 112(a) for failing to meet the written description requirement and the enablement requirement are maintained. Although applicant has amended claim 1 to remove language limiting the polypeptide to an ISVD, the specification details the utility of these polypeptides as antigen-binding domains comprised of CDR1-3 (pg 7-10). The polypeptides have utility even if the function is not mentioned in the claim. If applicant continues to assert that the polypeptides are not claimed by their function, then a rejection under 35 U.S.C. 101 will be considered for lack of a specific or substantial utility.
Regarding the rejection of claim 41 under 35 U.S.C. 112(a) for not being fully enabled for a method of treating cancer, applicant has not addressed how the claimed invention can be applied for the genus cancer, including hematological cancer and all solid tumors. The rejection is maintained.
With regard to the nonstatutory double patenting rejection, applicant indicates that they will consider filing a terminal disclaimer once the other claims are in condition for allowance. The applicant is reminded that a complete response to a nonstatutory double patenting (NSDP) rejection is either a reply by applicant showing that the claims subject to the rejection are patentably distinct from the reference claims, or the filing of a terminal disclaimer. The rejection is maintained for the reasons of record.
Allowable Subject Matter
Claims 16, 25, 28, and 31 are allowed.
Conclusion
Claims 1, 3-4, 6-7, 9-10, 14, 20, 33-37, 41, 46-47, and 50-53 are not allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JENNIFER BENAVIDES whose telephone number is (571)272-0545. The examiner can normally be reached M-F 9AM-5PM (EST).
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Jennifer Benavides
Examiner
Art Unit 1675
/JENNIFER A BENAVIDES/Examiner, Art Unit 1675