Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Status of Application, Amendments, and/or Claims
The Information Disclosure Statements (IDS) filed 7 February 2024 have been entered. Applicant’s submission of the replacement drawings filed 21 March 2024 is acknowledged. Applicant’s amendment of the specification filed 8 February 2024 has been entered. Applicant’s amendment of the claims filed 31 December 2025 has been entered.
Election/Restriction
In the response received on 31 December 2025, Applicant elected, with traverse, the invention of Group I, claims 1-19, and the species of: A) wherein the variant of a protein of the Sac7d family comprises the mutated amino acids corresponding to K7, Y8, K9, K21, K22, W24, V26, M29, S31, T33, T40, R42, A44, and S46 of the Sac7d protein set forth in SEQ ID NO: 1; B) wherein the polypeptide binds to the protein pair of TNFalpha/IL-17; and C-c) wherein the variant of a protein of the Sac7d family comprises the amino acid sequence of SEQ ID NO: 37.
The traversal is on the ground that the non-elected claims are directed to constructs, vectors, host cells, and methods limited to making and expressing the elected antibody-Sac7d fusion polypeptides of Group I, which do not require a materially different field of search or present distinct prior-art issues beyond those already implicated by the elected polypeptide claims, therefore, restriction does not meaningfully reduce the search or examination burden. Regarding the requirement for species election, Applicant argues that claim 1 defines a single genus/platform characterized by (i) the Sac7d structural scaffold, (ii) mutations confined to the known binding surface, and (iii) a defined number of mutated positions within that surface. Applicant argues that the alleged "species" are simply variations within a single claimed mutagenesis framework, and they are not shown to be independent and distinct and require different field of search.
Applicant’s arguments have been fully considered but have not been found to be persuasive.
Although the DNA molecule and protein are related since the DNA encodes the specifically claimed protein, they are physically and functionally distinct chemical entities. The inventions as claimed are either not capable of use together or have a materially different design, mode of operation, function, or effect. Further, the protein product can be made by another and materially different process, such as by chemical conjugation, and the DNA may be used for processes other than the production of the protein, such as in a nucleic acid hybridization assay. There would be a search and/or examination burden if restriction were not required because the inventions require a different field of search and are likely to raise different non-prior art issues.
Regarding the requirement for species election, claim 1 recites independent and distinct species, i.e., different Sac7d variants, which vary in the structure (amino acid sequence) and function (binding specificity). These species are not obvious variants of each other. There is a search and/or examination burden for the patentably distinct species due to the mutually exclusive characteristics of such species. Should Applicant traverse on the ground that the species, or groupings of patentably indistinct species from which election is required, are not patentably distinct, Applicant should submit evidence or identify such evidence now of record showing them to be obvious variants or clearly admit on the record that this is the case. In either instance, if the Examiner finds one of the species unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 of the other species.
The requirement is still deemed proper and is therefore made FINAL. Claim 2 is cancelled. Claims 1 and 3-24 are pending. Claims 20-24 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claims 1 and 3-19 are under examination to the extent they read on the elected species. Claims 1, 3-9, 11-12, 14-16 and 19 read on the elected species, and claims 10, 13 and 17-18 are withdrawn as being drawn to the nonelected species.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Specification
The disclosure is objected to because of the following informalities:
U.S. Patent Application No. 16/764,116 is now patented. Applicant’s amendment of the specification filed 8 February 2024 does not include updated status for the related application.
Appropriate correction is required.
Claim Objections
Claim 11 is objected to because of the following informalities:
In claims 11, “TNFa / IL17” should be “TNFalpha / IL17”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 19 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 19 recites “The polypeptide of claim 15, wherein the antibody binds to a protein selected from IL17, CD20, IL24, …”. The claim fails to further limit the subject matter of the claim upon which it depends.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 112
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.
Claims 1, 3-9, 11-12, 15-16 and 19 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 inventor(s), at the time the application was filed, had possession of the claimed invention.
Independent claim 1 recites “A polypeptide comprising a modified antibody wherein at least one variant of a protein of the Sac7d family is fused to at least one heavy or light chain of the antibody, wherein the variant comprises between 4 and 20 or between 5 and 20 mutated residues in the binding site of the protein of the Sac7d family, wherein the mutated amino acids correspond to amino acids selected from V2, K3, K5, K7, Y8, K9, G10, E11, K13, E14, T17, K21, K22, W24, V26,G27, K28, M29, S31, T33, Y34, D36, N37, G38, K39, T40, R42, A44, S46, E47,K48, D49, A50 and P51 of the Sac7d protein set forth in SEQ ID NO: 1.” Depending claims further limit wherein the polypeptide binds to IL17, TNFalpha, or the pair of targets, including EGFR/EGFRvIII, EGFR/Her2, VEGFR2/PD1, EGFR/PD1, VEGF/PD-L1, PD1/OX40, PD1/CTLA4, EGFR/CD3, TNFalpha/IL17, and IL13/IL4.
The claims are broad and encompass a genus of fusion polypeptides in which a variant of the Sac7d protein (SEQ ID NO: 1) is fused to an antibody molecule, wherein the antibody and the Sac7d variant scaffold each binds a target molecule, e.g., the target pair of EGFR/EGFRvIII or IL13/IL4, however, the specification fails to provide adequate written description and evidence of possession of these molecules. What Applicant has described in the specification are bispecific or multispecific molecules in which one or more variants of the Sac7d protein (SEQ ID NO: 1) are fused to the heavy chain(s) and/or light chain(s) of an antibody. The specification describes that the variant of the Sac7d protein (“OB-fold domain” or “OB-fold protein”) can bind to a target protein. The specification describes the variants of the Sac7d protein which bind to IL-17 and comprise the amino acid sequence set forth in SEQ ID NO: 35 or 36 (generic sequences), with two representative species set forth in SEQ ID NOs: 37 and 38. The specification also describes the variants of the Sac7d protein which bind to TNFalpha and comprise the amino acid sequence set forth in SEQ ID NO: 39 or 40 (generic sequences), with one representative species set forth in SEQ ID NO: 41. The specification, however, does not provide adequate written description for the genus of the variants of the Sac7d protein, nor provides sufficient teachings regarding the correlation of structure to function. While the claims list 34 amino acid positions out of 66 amino acids of SEQ ID NO: 1 that may be mutated, however, the specification does not teach how the mutations correlate with the binding specificity or function. For example, what mutation(s) would result in a variant Sac7d polypeptide that binds to IL13 or IL4? Behar et al. (Protein Engineering, Design and Selection, 2013, Vol. 26(4):267-275) teaches generation of a combinatorial library by random mutagenesis at positions 7, 8, 9, 21, 22, 24, 26, 29, 31, 33, 40, 42, 44, 46 in Sac7d protein, and the estimated numbers of independent variants are about 1012. The specification does not teach the structural characteristics or their correlation with the binding specificities or functions for these variants. One skilled in the art cannot envision the detailed structures of the variants that can be used for making the fusion polypeptides, and thus, the claims do not meet the written description requirement under 35 U.S.C. 112(a).
To provide adequate written description and evidence of possession of a 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 of the claimed product, or any combination thereof. In this case, there is no sufficient teachings regarding the structural characteristics of the genus, nor the correlation of structure to function. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states that “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116). As discussed above, the skilled artisan cannot envision the detailed structures of the encompassed genus of molecules, 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 is part of the invention and reference to a method of isolating it. The compound 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.
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. The specification provided only the bovine sequence.
Except for the polypeptides comprising a variant of the Sac7d protein that comprises an amino acid sequence selected from SEQ ID NOs: 35-41 and binds to IL17 or TNFalpha as set forth above, the disclosure does not adequately describe the full scope of the claimed polypeptides.
Claims 1, 3-9, 11-12, 15-16 and 19 are further 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 a modified antibody wherein at least one variant of a Sac7d protein is fused to at least one heavy chain or light chain of the antibody, wherein the variant of the Sac7d protein comprises an amino acid sequence selected from SEQ ID NOs: 35-41, and wherein the variant of the Sac7d protein binds to IL17 or TNFalpha, does not reasonably provide enablement for the broad genus of polypeptides as claimed. 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 use the invention commensurate in scope with these claims.
As discussed above, the claims encompass the use of a large genus of the Sac7d variants for making the polypeptides, the specification, however, fails to provide sufficient teachings regarding the correlation of structure to function for the variants of the Sac7d protein. For example, what is the binding specificity or function for a Sac7d variant with mutations at each of the positions K7, Y8, K9, K21, K22, W24, V26, M29, S31, T33, T40, R42, A44, and S46, and what amino acid substitution(s) in the Sac7d protein would result in the variant protein to bind a specific target, e.g., IL13 or IL4? Peters et al. (Biochemistry, 2005, Vol. 44, 4794-4904) teaches that mutations in a Sac7d protein (with single, double or triple amino acid substitutions) led to different effects on the binding affinity and thermal stability (p. 4796, col. 2). Without knowing the structures and functions, a skilled artisan would not know how to make and use the genus of the polypeptides. It would require a tremendous amount of experimentation to determine how to make and use the broad genus of polypeptides as claimed. The scope of patent protection sought by Applicant as defined by the claims fails to correlate reasonably with the scope of enabling disclosure set forth in the specification.
Clearly, the instant specification does not enable one of skill in the art to make and use the broad genus of the polypeptides. See In re Wands', 858 F.2d at 737, 8 USPQ2d at 1404. The test of enablement is not whether any experimentation is necessary, but whether, if experimentation is necessary, it is undue. The factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is "undue" include, but are not limited to: (1) the breadth of the claims; (2) the nature of the invention; (3) the state of the prior art; (4) the level of one of ordinary skill; (5) the level of predictability in the art; (6) the amount of direction provided by the inventor; (7) the existence of working examples; and (8) the quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Given the breadth of the claims, in light of the predictability of the art as determined by the number of working examples, the level of skill of the artisan, and the guidance provided in the instant specification and the prior art of record, it would require undue experimentation for one of ordinary skill in the art to make and use 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.
Claims 1, 3-9, 11-12, 14-16 and 19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 11,932,674.
Although the claims at issue are not identical, they are not patentably distinct from each other. The claims of the ‘674 patent recite a polypeptide comprising a variant OB-fold polypeptide having the amino acid sequence set forth in SEQ ID NO: 35, 36, 37 or 38, wherein the variant OB-fold polypeptide binds to IL17, wherein the variant OB-fold polypeptide is fused to the heavy chain(s) and/or light chain(s) of an antibody that binds to a protein selected from TNFalpha, IL23, IL12, IL4, IL13, IL31, the receptor of IL31, and a tumor specific antigen. The essential features of the instant claims are present in the claims of the ‘674 patent. Thus, the claims of the ‘674 patent anticipate the instant claims.
Conclusion
NO CLAIM IS ALLOWED.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Xiaozhen Xie, whose telephone number is 571-272-5569. The examiner can normally be reached on M-F, 8:30-5.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Vanessa L. Ford, can be reached on 571-272-0857. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free).
/XIAOZHEN XIE/Primary Examiner, Art Unit 1674
Prosecution Insights