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 .
Claim status
The restriction election filed 03/16/2026 in response to restriction requirement filed 01/14/2026 is entered. Applicant elected, without traverse, Group I, drawn to claims directed to a human CCR8 binder.
Claims 1-9, 11-16 are pending.
Claims 12-15 are withdrawn according to the restriction election.
Claims 1-9, 11, and 16 are under examination.
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55, filed on 06/23/2023.
The application is a 371 application, filed 06/23/2023, of PCT application PCT/EP2021/087506, filed 12/23/2021, which claims priority benefits from Foreign Application No. EP21167288.6, filed 04/07/2021 and Foreign Application No. EP20217315.9, filed 12/24/2020. The effective filing date of this application is 12/24/2020, the filing date of the EP20217315.9.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 06/23/2023 and 09/19/2023 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
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 - The Incorporation by Reference paragraph required by 37 CFR 1.821(c)(1) is missing or incomplete. See item 1) a) or 1) b) above.
Required response – Applicant must 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.
Claim Rejections - 35 USC § 112(d)
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 11 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 11 recites the binder of claim 1 comprised in a medicine, which does not further limit the single-domain antibody moiety itself. 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(b)
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.
Claim 3, 4, 9, and 11 is 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.
Regarding claim 9, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claims 3, 4, 11 recite the limitation "the single-domain antibody moiety". There is insufficient antecedent basis for this limitation in the claim and in its parent claim.
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.
Claims 1-9, 11, and 16 rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
There are two types of written description issues:
(A) Lack of written description for the genus of human CCR8 binders.
(B) Lack of written description for the combination of CDRs.
THE CLAIMED INVENTION
Independent claim 1 is drawn to a human CCR8 (hCCR8) binder that comprises of CDR1-3, in which only CDR3 is defined specifically from a list of SEQ ID NO’s, or having at least 80% amino acid identity to one of these sequences, or 1-3 amino acid differences to one of these sequences. As defined by the specification, a “binder” of a specific antigen denotes a molecule capable of specific binding to said antigen (p. 7, line 1-2). The broadest reasonable interpretation (BRI) of the claims is that the “binder” with the claimed CDR’s constitute a genus that encompasses full-length antibodies, as well as single-domain antibody moieties.
Claim 2 further recites CDR1, CDR2, and CDR3 are defined specifically from a list SEQ ID NO’s, or having at least 80% amino acid identity to one of these sequences, or 1-3 amino acid differences to one of these sequences. The broadest reasonable interpretation of the claims allows for any combination of each sequence, choosing one each from the list for CDR1, CDR2, and CDR3; and allows for the claimed mutations in each of the CDRs.
Claim 3 further recites the frame work region sequences are defined specifically from a list SEQ ID NO’s, or having at least 85% amino acid identity to one of these sequences.
Claim 4 recites the genus of binders, which encompasses single-domain antibody moiety, and specifically limits only the single-domain antibody moiety species to comprise of the amino acid sequences defined by SEQ ID NO 21-25, which provides the exact combination and sequences of CDR1-3. However, the claim does not specifically limit the other binders in the genus.
Claim 16 further recites SEQ ID NO: 21-25 and defines the CDR1-3 by Kabat, Chothia, AHo or IMGT information system CDR number system. Therefore, the sequence, combination, and order of CDR1-3 are defined.
Claims 5-9 and 11 do not further define the sequence of the hCCR8 binders.
WHAT THE SPECIFICATION TEACHES
The specification teaches in preferred embodiments of single-domain antibody moiety comprising of three CDRS having the sequences of
SEQ ID NO: 1, 6, and 10; or
SEQ ID NO: 2, 7, and 11; or
SEQ ID NO: 3, 8, and 12, or
SEQ ID NO: 4, 8, and 12; or
SEQ ID NO: 5, 9, and 13 (p. 24, lines 28-33);
wherein the sequences were previously defined as either a CDR1, CDR2, or CDR3 sequence. Therefore, the specification teaches fives species of single-domain antibody moieties by their exact combination of CDR1-3 sequence.
The specification further teaches that the hCCR8 binder can be antibody-based or non-antibody based (p. 7, line 32-33).
WHAT WRITTEN DESCRIPTION IS MET BY THE ELECTED INVENTION
Written description is met for the species of human CCR8 single-domain antibody moieties within the genus of human CCR8 binders, as defined by the five embodiments of single-domain antibody moieties defined by the exact CDR sequences and combination, as taught on p. 24, lines 28-33 of the specification, as defined by SEQ ID NO: 21-25, which encompasses the entire sequence of FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4.
WHY THE INVENTION LACKS WRITTEN DESCRIPTION
The specification, providing only the disclosed permutation of CDR sequences for specific single-domain antibody moiety provides insufficient written description to support the entire scope of the genus of binders claimed, encompassed by the claimed mutations and the BRI of binders to include full-length antibodies and single-domain antibody moiety. The specification further lacks written description for the combination of CDRs needed to define the binders, outside those distinctly taught in the specification.
Independent claim 1 lacks written description for the genus of human CCR8 binders and the combination of CDRs needed to define the binders, outside those five embodiments distinctly taught in the specification. Those five single-domain antibody moiety do not represent the entire genus of binders, as they do not represent the entire genus of single-domain antibody moieties claimed by the mutations. They further do not represent any full-length antibodies, as three CDRs is insufficient to define a full-length antibody. Specifically, the CDR3 alone is insufficient to define even one entire hCCR8 binder, and subsequently cannot define the entire genus of hCCR8 binders.
Claim 2, although provides the CDR1-3 sequences, still lacks written description for the exact combination of CDR1-3 required for a hCCR8 binder and for the mutations allowed on these CDRs. The specification is silent on whether all combinations of CDRs would yield a hCCR8 binder and is silent on what amino acids of the CDR sequences to avoid to retain the claimed binding function.
Claims 4 and 16, although defines the exact sequence, combination, and order of CDR1-3; still lacks written description for the entire genus of hCCR8 binders, which encompass full-length antibodies.
Claims 3, 5-9 and 11 inherit the written description problems of their parent claim, do not further define the CDR sequences or combinations, and therefore also lack written description.
THE STATE OF THE ART REGARDING THE ELECTED INVENTION
The state of the art teaches that even individual CDRs that are known to exist in antigen-binding polypeptides, produce a high degree of functional variation when combined together in combinations unknown in the art or nature (Soderlind et al, Recombining germline-derived CDR sequences for creating diverse single-framework antibody libraries, Nature Biotech, 18, 852-856 (2000), published 08/2000; section Main, paragraph 2). In other words, the exact combination of 3 variable heavy chain CDR and 3 variable light chain CDR sequences determine the binding function of an antibody, but deviating from the exact permutation of CDR sequences leads to high functional variability. Specifically regarding antibodies, the state of the art teaches that even a single amino acid alteration in the CDR can result in loss of antigen-binding function (Rudikoff, S., et al, Single amino acid substitution altering antigen-binding specificity, Proc.Natl. Acad. Sci., Vol 79, pp 1979-1983, published 03/1982). This unpredictability prevents prediction of the effects that a given number of mutations or CDR sequence changes will have on an antibody. Therefore, even given the full sequence of an antibody, without sufficient written description of its function, the state of the art teaches its function is unpredictable.
These references teach that knowing one CDR sequences does not allow one skilled in the art to predictably arrive at another CDR sequence, even by one point mutation. Further, knowing individual CDR sequences does not enable one skilled in the art to arrive at a working permutation of these CDR sequences, outside of those already known in the art. Further, even knowing the exact sequences of the CDRs or antibody sequences does not enable one skilled in the art to reasonably predict its function if the exact permutation of CDRs is new in the art. The same holds true for single-domain antibody moieties, the difference being single-domain antibody moieties require only one set of CDR1-3 to be fully defined, whereas a full-length antibody requires a set of variable light chain CDR1-3 and a set of variable heavy chain CDR1-3, arriving at 6 CDRs total.
Because the properties and function of an antibody are highly dependent upon the exact combination and amino acid sequences of the CDRs, wherein even one amino acid difference in a CDR region leads to different functional properties, different permutations of CDR sequences could result in peptides having different properties. Thus, in order to demonstrate possession of the genus of antibodies as claimed, one must describe a sufficient variety of species of antibody and single-domain antibody moieties.
A "representative number of species" means that the species which are adequately described are representative of the entire scope of the genus. Thus, when there is substantial variation within the genus, which is true for antibodies and single-domain antibody moieties, one must describe a sufficient variety of species to reflect the variation within the genus.
CONCLUSION
The specification, providing only the disclosed permutation of CDR sequences for specific single-domain antibody moiety provides insufficient written description to support the entire scope of the genus of binders claimed.
Specifically, the claimed genus of binders encompasses full-length antibodies as binders but provides insufficient CDRs to define a full-length antibody.
The claimed genus of binders further encompasses more permutations of CDR1-3 than disclosed in the specification and the state of the art teaches one skilled in the art cannot predictably use one functional permutation of CDR1-3 to arrive at another functional permutation and that these disclosed species of single-domain antibody moiety are insufficient to represent the entire genus of binders.
The claimed genus of binders encompasses binders with CDRs mutated from the sequences distinctly claimed but the specification lacks support for which mutations will retain the claimed function and the state of the art teaches the critical connection between CDR sequences and function so that one skilled in the art cannot reasonably predict which mutation can retain the claimed function. Even if only conservative mutations are made, the resultant binder would not be substantially different enough from the parent binder to help represent the larger genus of binders.
Closest prior art
Islam et al. Identification of human CCR8 as a CCL18 receptor, J Exp Med (2013) 210 (10): 1889–1898; published 09/02/2013.
Islam et al teaches the identification of the CCR8 receptor for ligand CCL18, which is one of the most highly expressed chemokines in human chronic inflammatory diseases (Abstract), including some cancers (p. 1889, col 2, para 1). Additionally, CCR8 is expressed on and polarizes Th2 cells, which have far-reaching immune regulatory roles (Abstract). This provides motivation for targeting CCR8 in overexpressed CCL18- or Th2-associated human diseases, as is relevant to claim 11, and leveraging antibody Fc-mediated cytotoxic functions, as is relevant to claim 6-9.
Islam et al further teaches mCCL18 as the rodent functional analogue to human CCLl8, which will enable the study of the CCR8 receptor–ligand system in murine disease models to better understand CCL18-mediated human disease pathology (p. 1895, col 1, para 3), providing motivation to find human CCR8 targeting agents that are cross-reactive with murine CCR8, as is relevant to claim 5.
However, Islam et al does not explicitly teach any actual human CCR8 binders and their sequences, as is relevant to the rest of the claims.
McGrath et al, US11692038B2, Antibodies that bind chemokine (C-C motif) receptor 8 (CCR8), effective filing date from provisional app no. 62976869: 02/14/2020).
McGrath et al teaches the examples of antibodies and their CDR sequences that bind human CCR8 (col 1, section: Summary and e.g. section II. Anti-CCR8 Antibodies) and that these polypeptides could be used in methods to treat, for example, cancer (Abstract; Figure 9A-B). Figure 9A-B, comparing Fc-competent (mIgG2) vs. Fc-incompetent (mIgG1) CCR8 binders, teaches the superior therapeutic potential of binders with Fc-mediated functions, as is relevant to claims 6-9.
However, McGrath et al does not teach the same CDR sequences as the instant application. The instant specification teaches that the instant CCR8 binders bind to the extracellular loops of CCR8, instead of targeting the N-terminal region, as is common amongst prior art CCR8 binders, allowing for cross-reactivity with non-human primate CCR8 (p. 3, para 1). McGrath et al does not explicitly teach where their antibodies bind on CCR8 and whether they are cross-reactive to non-human primate CCR8, but judging by the explicit use of anti-mouse CCR8 in in vivo experiments, the anti-human CCR8 antibodies were likely not cross-reactive.
Lan et al, Anti-CCR8- antibodies for treating cancer, WO2021194942A1, effective filing date from provisional app no. 62993570: 03/23/2020).
Lan et al teaches examples of anti-CCR8- antibodies for treating cancer, where the antibodies were developed by immunizing mice with CCR8 N-terminal peptide or constrained peptides mimicking the extracellular loop of CCR8 (para 475), providing the motivation to target the extracellular loop of CCR8. In some cases, alternating human CCR8 (hCCR8) and cynomolgus CCR8 (cCCR8) antigens were given during immunization (para 476), motivating the development of anti-CCR8 antibodies that are cross-reactive between humans and non-human primates to help facilitate in vivo testing of candidate antibodies.
However, Lan et al does not teach the same CDR sequences as the instant application.
Conclusion
No claims are allowed.
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BONIRATH CHHAY
Examiner
Art Unit 1645
April 15, 2026
/BAO-THUY L NGUYEN/Supervisory Patent Examiner, Art Unit 1677 April 15, 2026
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