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
Status of the Claims
1. Claims 1-43 are the original claims filed on 8/28/2023. In the Preliminary amendment of 8/28/2023, claims 1-43 are canceled and claims 44-61 are added.
Claims 44-61 are the claims under examination.
2. The preliminary amendments to the specification of 8/28/2023; 12/20/2023; and 1/22/2023 are considered and of record.
Priority
3. USAN 18/239,052, filed 08/28/2023 is a Continuation of 16/946,451, filed 06/22/2020, now abandoned, 16/946,451 is a Continuation of 16/079,949, filed 08/24/2018, now abandoned, 16/079,949 is a National Stage entry of PCT/AU2017/050168, International Filing Date: 02/27/2017, and which claims foreign priority to AU 2016900708, filed 02/26/2016, and claims foreign priority to AU 2016900709, filed 02/26/2016. The priority claim for a filing date of 02/26/2016 is granted.
Information Disclosure Statement
4. As of 3/15/2026, a total of one (1) IDS is filed: 8/12/2024.
The information disclosure statement filed 8/12/2024 fails to comply with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609 because it does not list the name of the patentee or applicant of the corresponding cited document under the foreign patent documents. Instead, it lists the name of the first cited inventor of the cited document. The IDS has been considered in part except when lined thru.
Objections
Specification
5. The disclosure is objected to because of the following informalities:
a) The specification contains amino acid sequence > 4 amino acids in length that are required to be identified by sequence identifier under 37 CFR 1.812-1.825. See, e.g., p. 12, line 27; p. 33, line 32; p. 53, lines 10-11 and lines 19-20, p. 68, line 10, p. 83, line 10 and 11, etc.
b) Figure 1(c) includes an amino acid sequence > 4 amino acids in length that is required to be identified by sequence identifier under 37 CFR 1.812-1.825. Applicants could amend the figure legend for Figure 1 in the specification to rectify the deficiency.
Applicants could consider re-labeling the panels designated “(A)”, “B” and “C” in the figure legend for Figure 1 to bring them into consistency.
c) The use of the term, i.e., Tris, Biacore, Sepharose, BLITz Biosensor, ATCC, Expi293, Opti-MEM, ExpiFectamine, HiSpeed, ElectroTen-Blue, Cellfectin, Lipofectamine, Dynabeads, nanobody, NCBI, Uniprot, forteBio, pellicon, cellfectin, affibody, DARPin, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Appropriate correction is required.
6. The abstract of the disclosure is objected to because it fails to mention the VLD scaffold relating to human CTLA-4 much less comprising an extracellular portion thereof. Correction is required. See MPEP § 608.01(b).
Appropriate correction is required.
Claim Objections
7. Claims 44-61 are objected to because of the following informalities:
a) Claim 44 in element (ii) recites “…or antigen-biding fragment thereof…”. Replace “biding” with “binding”. Applicants are requested to check the spelling in the entire claim set for obvious typographical errors.
b) Amend claims 44-61 for consistency to recite “antigen-binding fragment thereof.”
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
8. Claims 44-61 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.
a) Claims 44-61 are indefinite and confusing for the phrase “or is coupled to a C-terminus of a polypeptide chain of the non-antibody protein or peptide” as regards the at least one BDM in claim 44. Claim 44 (ii) is limited to “an active protein or peptide” whilst the final “wherein” clause identifies the broader recitation for a polypeptide chain “of the non-antibody protein or peptide.” Neither of the “active protein or peptide” in element (ii) are recited as being in the context of a polypeptide chain but are what comprise the active protein or peptide. The POSA cannot reasonably ascertain the metes and bounds for the subject matter of the invention.
b) Claims 44-61 are indefinite for the recitation “human CTLA-4 form.” The phrase is not defined in the specification. The POSA cannot reasonably ascertain the structure associated with the phrase in order to construe the subject matter as a whole for the claimed invention. It is suggested that Applicant amend the textual description of the at least one BDM to reference an actual structure such as SEQ ID NO: 5 or 6 to address the ambiguity.
c) Claim 47 recites the limitation "antibody chains". There is insufficient antecedent basis for this limitation in the claim. Claim 44 from which claim 47 depends does not reference "antibody chains".
d) Claim 48 recites the limitation "antigen-binding fragment chains". There is insufficient antecedent basis for this limitation in the claim. Claim 44 from which claim 48 depends does not reference " antigen-binding fragment chains ".
e) Claim 53 recites the limitation "polypeptide". There is insufficient antecedent basis for this limitation in the claim. Claim 44 (ii) from which claim 53 depends does not reference a “polypeptide" but does recite a “peptide.” Claim 44 in the final “wherein” clause references “a polypeptide chain.”
f) Claims 56 is indefinite for reciting the parenthetical text “(or BDM pair).” The POSA cannot ascertain whether the text is intended subject matter or exemplary. See MPEP 2173.05(d).
g) Claim 57 recites the limitation "polypeptide". There is insufficient antecedent basis for this limitation in the claim. Claim 44 (ii) from which claim 57 depends does not reference a “polypeptide" but does recite a “peptide.” Claim 44 in the final “wherein” clause references “a polypeptide chain.”
h) Claim 58 is indefinite for including a period within the claim and concluding with a period:
“KAMHVAQPAVVLASSRGIASFVCEYASPGKATEVRVTVLRQADSQVTEVCAATYMMG NELTFLDDSICTGTS SGNQVNLTIQGLRAMDTGLYICKVELMYPPPYYLGI GNGTQIYVI DPEPSPDSN. and wherein the amino acid residues at positions 26 to 33, and/or positions 55 to 59 and/or positions 98 to 105 of SEQ ID NO: 1 are modified or replaced with heterologous sequence.”
The POSA cannot reasonably ascertain the metes and bounds of the subject matter.
i) Claims 59-60 recite both open and closed language for the same recitation, i.e., “comprises or consists of” in claim 60. Mixing these terms causes legal ambiguity, as "comprising" allows for additional, unrecited elements, whereas "consisting of" limits the claim strictly to listed components. MPEP 2111.03.
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
9. Claims 44-61 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 pre-AIA the inventors, at the time the application was filed, had possession of the claimed invention. This is a written description rejection.
The claims are drawn to a genus of multi-specific molecules comprising at least one BDM comprising a VLD corresponding to a CTLA-4 extracellular domain with at least 1 of the 3 binding loops modified by replacement for binding to a heterologous target antigen coupled to a pharmacologically active protein that can be an antibody, and antigen-binding fragment of an antibody, a non-antibody protein, or a peptide that binds to a second antigen. The claims cover a multitude of modified BDMs for element (i) of Claim 44 being linked to a highly structurally diverse set of pharmacologically active proteins or peptides that bind to any target antigen known and yet to be discovered for element (ii) of Claim 44.
Claim 59 seemingly recites the frameworks for the BDM of SEQ ID NO:5 without a suggestion as to what sequences the actual binding regions (BL) designated 1, 2 and 3 should comprise. The claim recites any amino acid residue without reference to whether it’s a natural amino acid, non-natural amino acid, mimetic, synthetic, etc.
Independent claim 44 therefor recites a desired function (binds to two or more different antigens or epitopes) provided by a structure that is defined at only a high level of generality. Applicants’ most generic claims do not even provide a de minimis structure for the genus of BMDs much less the structure for the pharmacologically active protein or peptide and its corresponding target antigen.
The interpretation encompasses a genus of multi-specific molecule variants beyond those taught in the specification. Because applicant seeks patent protection for all such molcules, this genus must be adequately described. A description adequate to satisfy 35 U.S.C. § 112(a) must clearly allow persons of ordinary skill in the art to recognize that the inventor invented what is claimed (Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010) (en banc) (citation omitted, alteration in original). The 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’s specification” (In re Katz Interactive Call Processing Patent Litig. 639 F.3d 1303, 1319 (Fed. Cir 2011).
Disclosure in the Specification
The specification adequately describes species of at most four BDM within the scope of the claims: the anti-B7-1 BDM set forth in SEQ ID NO: 13, the anti-sclerostin BDM set forth in SEQ ID NO: 14, the anti-B7-2 BDM contained within the multispecific molecule set forth in SEQ ID NO: 26 and SEQ ID NO: 28 (where it is coupled to the pharmacologically active protein human serum albumin), and the anti-CD3 BDM set forth in SEQ ID NO: 29 (where it is also coupled to the pharmacologically active protein human serum albumin). Both the anti-B7-1 BDM set forth in SEQ ID NO: 13 and the anti-sclerostin BDM set forth in SEQ ID NO: 14 are linked to the light or the heavy chain of an anti-lysozyme antibody. The light chain-linked structures are set forth in SEQ ID NOS: 21 and 22 and the heavy chain-linked structures are set forth in SEQ ID NOS: 19 (B7-1 BDM), 23 (B7-1 BDM), and 25 (sclerostin BDM).
Based on the limited disclosure in the specification, the POSA could reasonably conclude the at least one BL that is replaced in the scaffold in Claim 44 does not correlate to the structure depicted in Claims 59-60, where 1, 2, 3 indicates BLs 1, 2 and 3, respectively. The amino acids in Xn1, Xn2 and Xn3 of Claims 59-60 are not identified as being conserved or changeable to the extent the modified BDM would meet the structure/function requirements of the claims.
“[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.
Does the specification support the genus of multi-specific molecules?
The examples of a genus of antibodies that would be pharmacologically active with respect to their specific and/or cross-reactive binding to any target antigen when coupled by the C-terminus of the H- and/or L-chains is not shown much less those corresponding to any one or more of the myriad BDMs. There is substantial variation within the genus of the instant claims that encompass any modified CTLA-4 BDM and any pharmacologically active protein or peptide that binds the recited targets.
Here, the specification describes at most four BDM comprising a CTLA4 scaffold in which amino acids in one ore more of the binding loops have been substituted and then selected for the particular binding activity. Nothing in the description indicates how these four examples are representative of the genus of the independent claim and none of the dependent claims that result in a subgenus for which the species that are adequately described could be considered representative.
Thus, for any target binding site encompassed by the instant claims that is described by only a single species in the specification, the description is insufficient and the claims fail the written description requirement for this reason. Neither is there a clear correlation between the structures that are recited with a high level of generality and the function of binding to two or more different target antigens or epitopes.
Applicant is reminded that even though it may be possible to screen for structures with the desired function, the written description requirement requires that the skilled artisan be able to visualize a prior, what structures would possess the function. Here neither the specification nor the art as of the effective filing date provide the structure: function correlation that would be needed to provide adequate written description for the instant generically claimed structures.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
10. Claims 44, 49-52, 57, 58-59 and 61 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Tomlinson et al. (WO2008/096158; IDS).
As regards claim 44, Tomlinson teaches dual specific ligands. E.g. Abstract, “Claims”. According to Tomlinson, any of a variety of variable domain scaffolds including can be combined with one another to provide dual specific ligand compositions that bind two different antigens. E.g. pages 11, 24, 259; Claims 15, 42, 60.
In Example 17 on pages 192-194, Tomlinson teaches using CDR domains of the domain antibody dAb7hl4 to construct a cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) non-immunoglobulin scaffold polypeptide that binds human serum albumin. To make the binding domain molecule the CDR1 (RASQWIGSQLS; SEQ ID NO.:__), CDR2 (WRSSLQS; SEQ ID NO.:_), and CDR3 (AQGAALPRT ; SEQ ID NO.:_) sequences of dAb7hl4 are grafted into a soluble truncated mutant of CTLA-4 comprising the CTLA-4 V-like domain in which A2 and A3 domains are deleted. While Tomlinson does not define the CTLA4 scaffold framework by residue numbers, it inherently consists of the framework sequences identified in instant claims 61, 62, and 64 because Tomlinson references human CTLA4 and teaches replacing its binding loops. In addition, the CTLA4 scaffold loops that Tomlinson teaches are replaced are the same as or overlap with one or more of the loops defined by the position numbers recited in claim 63 and by wildcards in claim 64. Methods of selecting CTLA4 scaffolds specific to an antigen of interest are taught in the Example. And on page 200, lines 15-18, Tomlinson notes that removal of Cys120 results in a CTLA4 scaffold that is monomeric.
As regards claims 49-52, 57, 58-59 and 61, In Example 18, pages 194-205, Tomlinson teaches that the CDR-grafted CTLA-4 scaffold can be combined with antibody VH or VL domains to form a multivalent, dual-specific ligand comprising the serum albumin-binding CTLA4 scaffold.
Tomlinson teaches connecting a ligand that binds serum albumin with another biologically active moiety on either the N- or C-terminus. E.g., page 135 and also page 142. Linking the domains by a Gly-Ser peptide linker is taught at least at pages 138-139. Including a component that binds human serum albumin is useful according to Tomlinson because then the half-life of the molecule is extended. E.g., page 82.
The ligands can be linked so that a monomer such as the CTLA4-based ligand can be joined to other ligand(s) that bind a different target, so that the dual-specific ligands are at least bispecific. E.g., page 92 in view of pages 106 or 121. In the dual-specific ligand, the other ligand binds its native target antigen.
Pharmaceutical compositions are taught at least at page 196 but also page 106.
Addition of tags and labels is taught at least at page 117.
Tomlinson’s teachings therefore anticipate independent claim 44 as well as dependent claims 51-54, 59, 61-64, 67-69, 72, and 73.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102 of this title, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
11. Claims 44-46, 49-52, 54-56, 57, 58-61 are rejected under 35 U.S.C. 103 as being unpatentable over Tomlinson et al. (WO2008/096158; IDS).
The interpretation of the claims is discussed above with the ambiguity and uncertainty of the claimed subject factored into the analysis.
As noted, the teachings of Tomlinson anticipate claims 44, 49-52, 57, 58-59 and 61. Those claims are also therefore necessarily obvious over the teachings of Tomlinson and so are included in the rejection. The teachings of Tomlinson discussed above are incorporated here in full.
Tomlinson does not expressly teach preparing a dual-specific ligand in which at least one BDM is coupled to a C-terminus as required by the various antibody and Fab options of claims 45-46.
Tomlinson also does not expressly teach incorporating pairs of the CTLA4-based BDMs or linking more than one BDM, as recited in claims 54-56.
Tomlinson also does not exemplify incorporating CDRs into the BDM that meet the size limits of claim 60.
But Tomlinson teaches that the ligands can be linked so that a monomer such as the CTLA4-based ligand can be joined to other ligand(s) that bind a different target, so that the dual-specific ligands are at least bispecific. E.g., page 92 in view of pages 106 or 121. And in one embodiment, Tomlinson teaches connecting a ligand that binds serum albumin with another biologically active moiety on either the N- and/or C-terminus. E.g., page 135 and also page 142. Amongst the various skeletons that Tomlinson teaches can be used in the invention, skeletons based on immunoglobulin molecules, both those comprising the Fab constant domains and a full length antibody with full Fc domains, are taught as options. E.g., pages 15-16 and 70. While these more traditional antibody options are not the focus of Tomlinson’s constructs, Tomlinson recognizes they are art-recognized alternative scaffolds that can be included in dual-specific ligands. Substituting either a full length antibody or an antibody Fab for the single variable domains of Tomlinson therefore would have been an obvious alternative arrangement that the ordinary artisan prior to the effective filing date would have predictably prepared by linking a CTLA4-based ligand to the antibody skeleton at one or more of the constant domains of the antibody or Fab. The ordinary artisan would have been motivated to prepare these alternative constructs both to take advantage of the wide range of specificities available for both full length antibodies and Fab forms, as well as to provide control constructs for comparison to the variable domains that are described in more detail in Tomlinson’s teachings. Substitution of the antibody or Fab skeleton into dual ligand constructs in which the variable domain was linked to the CTLA4-based BDM of Tomlinson would result in the constructs and ratios recited in claims 45-50.
Regarding claims 55-57, Tomlinson teaches that the structures can be used to create higher order multimers and more complex arrangements at, e.g., page 11, so that the ordinary artisan prior to the effective filing date would have also predictably incorporated more than one CTLA4-based ligand (BDM) into the constructs with the reasonable expectation of increasing either binding activity or reducing clearance by the kidney in view of the small size of constructs comprising only a variable domain and a CTLA4-based ligand binding domain (BDM).
And while Tomlinson exemplifies incorporation of CDRs from an anti-serum albumin binding domain antibody that are outside the size ranges recited in claims 65 and 66, Tomlinson provides all of the methodology needed to incorporate CDRs from other antibodies into the CTLA4 scaffold. Accordingly, BDMs with CDRs of the recited lengths would be predictably obtained and the ordinary artisan would have been motivated to prepare alternate constructs at least to be able to target one or more of the other half-life enhancing molecules that Tomlinson notes might be substituted for serum albumin, the exemplified specificity.
Given the extensive teachings of Tomlinson regarding the substitutability of various ligand binding domains for one another and teachings regarding options for varying the number and arrangement of the domains depending upon the desired outcome, the ordinary artisan prior to the effective filing date would have predictably prepared any of a wide variety of CTLA4-based ligand binding domains specific to an antigen/epitope of interest and combined one or more of such domains with any of a variety of other domains to provide a dual or multi-specific molecule depending upon the interest of the artisan such as treating a particular condition. For these reasons, the invention as a whole would have been prima facie obvious to one ordinary skill in the art before the effective filing date of the claimed invention.
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.
11. Claims 44-61 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of U.S. Patent No. 11345736 (IDS). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims are drawn to a multispecific molecule comprising a 1st binding domain comprising a VLD scaffold relating to an extracellular portion of human CTLA-4 and a 2nd binding domain comprising a pharmacologically active protein or peptide, where the structure is coupled from N-to C-terminal to an HC and/or LC of an antibody, or is coupled C-terminal to the non-antibody protein or peptide.
Ref 1. A multi-specific molecule which binds to two or more different target antigens or epitopes, the molecule comprising: (i) at least one binding domain molecule (BDM) which binds to a first target antigen or epitope, the BDM has first, second, and third binding loops and has the amino acid sequence set forth in SEQ ID NO:5; and (ii) a full length antibody or an antigen-binding fragment thereof which binds to a second target antigen or epitope; wherein the at least one BDM is coupled via its N-terminus to a C-terminus of a heavy and/or light chain of the antibody or antigen binding fragment thereof by a peptide linker as set forth in SEQ ID NO: 16 or SEQ ID NO: 17.
Ref 2. The molecule according to claim 1, wherein at least one BDM is coupled to a C-terminus of all antibody heavy and light chains.
Ref 3. The molecule according to claim 1, wherein the antibody is a full length antibody.
Ref 4. The molecule according to claim 3, wherein the ratio of antibody chains to BDMs is 4:(2.sup.n) where n is a number between 1 and 5.
Ref 5. The molecule according to claim 1, wherein the antigen-binding fragment is selected from the group consisting of a Fab, Fab′, F(ab′)2 and chemically linked F(ab′).sub.2.
Ref 6. The molecule according to claim 5, wherein the ratio of antigen-binding fragment chains to BDMs is 2:(2.sup.n) wherein n is a number between 0 and 5.
Ref 7. The molecule according to claim 1, wherein at least one BDM is coupled to a C-terminus of the CH1, CH2 or CH3 domain of the heavy chain.
Ref 8. The molecule according to claim 1, wherein the first target antigen and the second target antigen are different.
Ref 9. The molecule according to claim 1, wherein the first target epitope and the second target epitope are on different antigens.
Ref 10. The molecule according to claim 1, wherein the molecule is bi-specific or tri-specific.
Ref 11. The molecule according to claim 1, wherein the molecule comprises one, two, three, four, five or six BDMs.
Ref 12. The molecule according to claim 1, wherein the molecule comprises one pair or two pairs of BDMs wherein the BDMs in the pair are identical.
Ref 13. The molecule according to claim 1, wherein the at least one BDM is linked to one or more further BDMs.
Ref 14. The molecule according to claim 1, wherein the molecule comprises at least two BDMs, or at least one pair of BDMs, wherein each BDM or BDM pair binds to a different target antigen or epitope.
Ref 15. The molecule according to claim 1, wherein each BDM binds to a target antigen or epitope that is different from the target antigen epitope to which the antibody or antigen binding fragment thereof binds.
Ref 16. The molecule according to claim 1, wherein the first binding loop is between 5 and 8 amino acids, the second binding loop is between 5 and 8 amino acids, and the third binding loop is between 10 and 15 amino acids.
Ref 17. The molecule according to claim 16, wherein: (a) the first binding loop is 8 amino acids; (b) the second binding loop is 5 amino acids; and (c) the third binding loop is between 10 and 15 amino acids.
Ref 18. The molecule according to claim 1, wherein the at least one BDM is present as a monomer or a series of BDM monomers linked together.
Ref 19. The molecule according to claim 1 comprising the BDM of SEQ ID NO: 13 or SEQ ID NO:14.
Ref 20. The molecule according to claim 1, wherein the molecule is labelled with an agent to facilitate detection.
Ref 21. A pharmaceutical composition comprising the molecule according to claim 1, together with a pharmaceutically acceptable carrier and/or excipient.
Conclusion
12. No claims are allowed.
13. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LYNN A. BRISTOL whose telephone number is (571)272-6883. The examiner can normally be reached Mon-Fri 9 AM-5 PM.
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, Wu Julie can be reached at 571-272-5205. 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.
/LYNN A BRISTOL/Primary Examiner, Art Unit 1643