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 .
Election/Restrictions
Applicant’s election of Group I and species of anti-CCR8 antibody of claim 15 in the reply filed on 12/22/2025, and species of chemotherapeutic agent which is a platinum complex in the telephone interview with Hye Hyun Ahn on 03/20/2026, is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 9, 12, 13, 16, 17, 21 and 22 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.
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:
A) Specific deficiency – Nucleotide and/or amino acid sequences appearing in the drawings, Figures 1-7, are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, 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.
B) Specific deficiency - This application contains sequence disclosures in accordance with the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 CFR 1.821 - 1.825.
The sequence disclosures are located in Figure 1.
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.
Information Disclosure Statement
The listing of references in the specification ([0008]-[0009]) 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.
It is noted that WO 2018/181424 A1 (IDS 1/6/23) is drawn to “Heat-shielding and heat-insulating substrate”, completely unrelated to the instant invention.
Claim Interpretation
Claim 1 is drawn to a pharmaceutical composition comprising an anti-CCR8 antibody. The portion of the claim reciting “which is used with a chemotherapeutic agent”, is an intended use and does not appear to materially affect the pharmaceutical composition. The chemotherapeutic agent is not part of the pharmaceutical composition. This is distinct from a “medicament obtained by combining an anti-CCR8 antibody and a chemotherapeutic agent” (see [0068]) or a ‘pharmaceutical composition containing an anti-CCR8 antibody and a chemotherapeutic agent.’ See also Groups I and III of restriction requirement mailed 10/20/2025. Further, claim 3 recites “for cancer treatment”, which is an intended use and does not result in a structural difference of the antibody. Therefore, it is not limiting.
Specification
The use of the term “Thermo Fisher Scientific”,“BioLegend”, “Clontech” (e.g., [0077]), 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.
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. See last paragraph of p. 44 ([0087]).
Claim Objections
Claim 24 is objected to because of the following informalities: Claim 24 recites the abbreviation “ADCC”, which should be accompanied by what it stands for at its first occurrence in the claims. Appropriate correction is required.
Improper Markush Grouping
Claim 7 is rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of chemotherapeutic agents is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: each of the listed chemotherapeutic agents or class of agents are structurally distinct and do not share a single structural similarity.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
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.
Claims 1, 4, 5 and dependent claims 3, 6-8, 10, 14, 15, 18-20 and 23-25 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 is indefinite because it is drawn to a pharmaceutical composition comprising an anti-CCR8 antibody. A composition must comprise more than one thing (see MPEP § 2106.03(I)). It is unclear what the pharmaceutical composition includes besides the antibody, and it is unclear if the antibody is an active ingredient or merely present in trace amounts. Knowing whether the antibody is critical to the pharmaceutical activity is necessary to understand the breadth of the claim. If the antibody is the active ingredient, this rejection could be obviated by adding to the end of the claim a phrase such as, "and an excipient" (see 0074]). If the pharmaceutical product is, for example, only a lyophilized form of the antibody so that the antibody is the only component, then the word “composition” should be removed and "comprising" should be replaced with "consisting of".
Claim 4 recites the limitation "the treatment with an anti-PD-1 antibody or an anti-PD-L1 antibody”. There is insufficient antecedent basis for this limitation in the claim. Claim 4 depends from claims 3 and 1, neither of which recite treatment with an anti-PD-1 or anti-PD-L1 antibody. This rejection could be obviated by using phrasing in claim 4 such as, ‘wherein an anti-PD-1 antibody or an anti-PD-L1 antibody is ineffective for the cancer treatment.’
Claim 5 recites the limitation "the cancer" in lines 1-2. There is insufficient antecedent basis for this limitation in the claim. It appears this claim may have been intended to depend from claim 3.
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 14 and dependent claims 15, 18, 19 and 20 are 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 14 is drawn to a pharmaceutical composition of claim 1 “wherein the anti-CCR8 antibody is a monoclonal antibody or an antibody fragment…” However, independent claim 1 is drawn to a “pharmaceutical composition comprising an anti-CCR8 antibody.” Because it appears the specification distinguishes an “antibody” from an “antibody fragment”, dependent claims that include an antigen fragment do not further limit claim 1. That is, claim 1 reciting an antibody does not include an antibody fragment thereof. The specification defines “Antibody-producing techniques”, which require the use of an antibody-producing hybridoma, i.e., a full-length antibody ([0018], p, 20). This technique does not produce antibody fragments. The specification distinguishes an antibody from antibody fragments ([0020] and [0022], with specific examples of an antibody fragment provided in [0023]). Claims 15, 18, 19 and 20 depend directly or indirectly from claim 14, all depending ultimately from claim 1 and reciting an antibody fragment, which cannot further limit the antibody of claim 1 because the fragment is distinct from the antibody. 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.
Claims 3-8, 10 and 11 are 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 1 is drawn to a pharmaceutical composition comprising, as written, only an anti-CCR8 antibody. The fact that it is used with a chemotherapeutic agent does not materially affect the antibody. Further, the anti-CCR8 antibody is the only component of the pharmaceutical composition listed (see rejection under 35 USC 112(b) above). As a result, neither the intended use of the pharmaceutical composition nor its use with a chemotherapeutic agent further limits the claimed product, i.e., the pharmaceutical composition comprising the anti-CCR8 antibody. Therefore, dependent claims 3-8, 10 and 11 do not further limit the pharmaceutical composition. 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(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 14, 15 and 18-20 and 23 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for an anti-CCR8 antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) comprising CDR-H1 of SEQ ID NO:5 or 8, CDR-H2 of SEQ ID NO:6 and CDR-H3 of SEQ ID NO:7, and a light chain variable region (VL) comprising CDR-L1, CDR-L2 and CDR-L3 of SEQ ID NO:2-4, respectively, including wherein SEQ ID NO:2 has a G11R substitution and SEQ ID NO:3 has a N4Q substitution (a.k.a. G29R, N53Q) and/or wherein the VH comprises SEQ ID NO:41 and VL comprises one of SEQ ID NO:59, i.e., antibody 10A1, as well as having the VH and VL CDR1-3 of antibody 27G11, 1H4, 8F7, 2C7 and 19D7 (Tables 3, 6, 7, 12, 13), does not reasonably provide enablement for wherein the anti-CCR8 antibody or antigen binding fragment thereof does not comprise these CDR-H1-3 and CDR-L1-3. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
The factors considered when determining if the disclosure satisfies the enablement requirement and whether any necessary experimentation is undue include, but are not limited to: 1) nature of the invention, 2) state of the prior art, 3) relative skill of those in the art, 4) level of predictability in the art, 5) existence of working examples, 6) breadth of claims, 7) amount of direction or guidance by the inventor, and 8) quantity of experimentation needed to make or use the invention. In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
As the claims are currently written the anti-CCR8 antibody comprises “an amino acid sequence” of one of the SEQ ID NOs listed in the claims. The modifier “an” before sequence means that as few as two consecutive amino acids of the listed sequence are sufficient to meet the claim limitation. For example, for dependent claim 20, which recites the elected anti-CCR8 antibody light chain variable region (VL) has an amino acid sequence of SEQ ID NO:59 and a variable heavy chain region (VH) has an amino acid sequence of SEQ ID NO:41, each of the VL and VH are required to comprises no more than two consecutive amino acids of the sequence of SEQ ID NO:59 and 41, respectively, in order to meet the structural limitations. The specification is not enabling for an anti-CCR8 antibody having such minimal structural requirements. Claim 23 depends from independent claim 1 and requires a CCR8 antibody to have neutralizing activity but there is no structural limitation.
For an antibody or antigen-binding fragment thereof, it is expected that all of the heavy and light chain CDRs in their proper order and in the context of framework (FR) sequences, which maintain required antigen binding conformation of the CDRs, are required in order to produce a protein having antigen binding function and that proper association of heavy and light chain variable regions is required in order to form functional antigen binding sites. Even minor changes in the amino acid sequences of the heavy and light variable regions, particularly in the CDRs, may dramatically affect antigen binding function as evidenced by Chen et al. (EMBO J. 14 (12): 2784-2794, 1995), which teaches that the substitution of a single amino acid in CDR-H2 (HCDR2) of an antibody can totally ablate antigen binding and that the same substitution in closely related antibodies can have opposite effects on binding (e.g., see entire document, including Figure 1). The authors compared the effects of identical substitutions in related anti-phosphocholine antibodies DI6 and TI5, and as shown in Figure 3 some substitutions increased antigen binding in one antibody while ablating it in the other. Lee et al. (Antiviral. Res. 192:105105, 9 pages, 2021) engineered antibodies that bound Zika Virus FLEP epitope. They identified paratopes from antibody templates.
The paratope engineering process involved assembly and modifications
of both FRs and CDRs to enable binding to the FLEP epitope on
ZIKV. The FRs are important for (1) the positioning of the antibody
against the target epitope and (2) configuring the CDRs to achieve
desired binding affinity to the FLEP epitope. Five designs that met the
criteria for paratope engineering (based on AIF scores and network
properties), were tested experimentally for expression, yield, binding
affinity, and neutralization (Supplementary Table 3). Two of the
designed constructs showed poor expression, while one of them showed
poor binding to ZIKV and DENV. For one of the constructs, the optimization
of the paratope resulted in a rare amino acid substitution that
negatively impacted developability. The only construct that cleared all
the key protein filters including expression, binding affinity, neutralization
potency and developability was subsequently referred to as
ZAb_FLEP. (p. 4, col. 1, second paragraph)
Like Chen et al. (supra), Lee et al. was found (p. 5, col. 2, middle) that, “[E]ven a conservative substitution in a CDR loop (VH-Ser52Thr) can lead to drastic changes in the interatomic interactions with the adjacent residues, with potential to impact epitope-paratope contacts (Fig. 4C).” Further, placing the same six CDRs into a different FR sequence can significantly decrease or remove antibody neutralizing activity (paragraph bridging pp. 4-5). They found that (p. 5, start of first full paragraph), “The structure-function relationships of the three test antibodies also emphasize the fact that amino acid substitutions in the framework or VH/VL interface or epitope paratope interface substantially impact the inter-residue interaction network (Fig. 4), and hence impact the functional attributes of the antibody…. The test antibodies clearly demonstrate the significance of the mutations introduced to optimize key network properties of the FR of the starting scaffold and CDRs.” While some amino acid changes in antibodies produce only small or insignificant changes in binding affinity, others are highly impactful and the complexity of antigen binding and affinity by antibodies is high. Even though there are some publications which acknowledge that CDR-H3 is important, the conformation of other CDRs as well as framework regions (FRs) influence binding. The specification shows that three antibodies,10A11, 27G1 and 1H4, bind CCR8 and are highly related in their CDR sequences (see Table 3), having only a single amino acid difference in CDR-H1. However, the claims are much broader and unpredictability due to additional or different changes much greater. Antibody-antigen binding is complex. For example, MacCallum et al. (J. Mol. Biol 262:732, 1996) analyzed a variety of antibodies for their interaction with their antigen and found that although CDR-H3 dominated the interaction, a number of residues outside the CDRs make antigen contact and residues in the CDRs which do not contact antigen are important for backbone conformations (e.g., p. 733, section beginning at the end of col. 1, and p. 735, paragraph bridging cols. 1-2). The CDR-H3 of instant SEQ ID NO:7 is 14 amino acids. If 2 specific amino acids are changed in the CDR-H3 (with 20 possible natural amino acids), that makes ~400 possible CDR-H3 sequences. If any 2 amino acids can be changed anywhere in CDR-H3 that is over 5,000 possible sequences. The number of possible VH and VL CDRs if only 2 consecutive amino acids are required to be maintained is enormous. There is no reasonable expectation that an antibody comprising a substituted CDR-H3 or with significantly changed other CDR(s) would bind CCR8 or bind with sufficient affinity to be used, nor does the specification provide guidance or direction about which substitutions, additions or deletions throughout the CDRs could be made with a reasonable expectation of successfully maintaining the necessary antibody specificity and function to be used with very few exceptions disclosed. This is even more so for an antibody that has neutralizing activity. Note that claims 14, 15 and 23, in particular, ignore framework (FR) region sequences, which make up about 72% of the VL and 70% of the VH of the elected antibody.
The importance of the unpredictability and complexity of changing amino acid is also illustrated in the instant specification in the humanization for antibodies 10A11 (Example 7 and Table 6), with only a limited number of active constructs identified. Further analysis of humanized 10A11 showed that several positions in the VL and more in the VH reduced CCR8- neutralizing activity by at least 10-fold, but only 3/21 VL and 2/36 VH amino acid substitutions did not have lower neutralizing activity than the wildtype sequence (Example 8 Tables 8 and 9). It was found that activity could be enhanced with particular substitutions in the VL at three particular amino acids, N53, N28 and G29, and one in the V, T94R (Example 9 and Table 12). These findings do not support enablement of full breadth of the claims. Consistent with the prior art, while changing some of the amino acids did not negatively affect binding, most did. The complex association of CDRs with FRs and their effect on antigen binding sites in the context of VH and VL is discussed by Herold et al. (Nature Scientific Reports, 7:12276, DOI:10.1038/s41598-017-12519-9, Sept. 2017). When CDR regions were switched between variable domains, it was found that for the VH binding to antigen, not only the CDRs but framework regions were also a determining factor (p 9, 6th paragraph). The interaction between the VH and VL was found to be important as shown by when the VL was absent, the antigen binding loop VH:93-107 showed large fluctuations. “Hence, complex formation of the VL and VH domains appears to lock some of the antigen binding loops into distinct conformations.” (p. 11, first paragraph) It was discussed that (p. 11, start of 3rd paragraph), “The relationship between structure, stability and binding affinity of VH and VL is still unclear. This is an important aspect for understanding antibody architecture both as the basis of our immune system and also in the context of the engineering of antibodies for therapeutic purposes. In this context, it was found that in mutants an increase in affinity is often accompanied by a decrease in stability and vice versa - and these consequences are difficult to predict33–39.” Further (p. 13, start of last paragraph), “It seems that during antibody biogenesis the effect of CDRs on the stability of VH domains is a decisive, so far underappreciated factor…. The grafting constructs revealed that CDRs, in addition to antigen binding, affect variable domain structure strongly.” It is reported previous studies using CDR grafting for antibody humanization showed the importance of framework residues in the context of antigen binding and stability (p. 14, 1st paragraph). The reference concludes (p. 14, end of 2nd paragraph and 3rd paragraph), “[B]inding to the antigen is affected by each CDR loop differently and changes in loop mobility can in principle affect antigen binding affinity in an unpredictable way. (¶) Taken together our data indicate that multiple determinants regulate the VH/VL association and the affinity for the antigen. The interplay between interface interactions and CDRs turned out to be complex with mutual influences on VH/VL association and antigen binding.”
Therefore, for the reasons discussed above, including the breadth of the claims as they relate to amino acid substitutions, deletions or additions which may be in the CDR(s), the support by the prior art of the complexity and unpredictability of antigen binding as it relates to the CDR and FR regions, the paucity of working examples of modified CDRs, VH and/or VL that can function together within the context of the claimed antibodies to bind CCR8, and the lack of guidance for or direction about which modifications and/or substitutions would reasonably be expected to produce a functional antibody, including one with neutralizing activity, it would require undue experimentation to make and use the invention commensurate in scope with the claims.
Claims 14, 15, 18-20 and 23 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims are drawn to an antibody that binds CCR8 and comprises an amino acid sequence of particular VH and VL CDR1-3 or of the VH and VL themselves. Use of the word “an” before amino acid sequence means that the CDR or variable chain region may have as few as 2 consecutive amino acids of the recited sequence and still fulfil the structural requirements of the claim. Nevertheless, the specification discloses only a limited number of species of antibodies that meet the requirements of the claims. There is not support for the broad genus of CCR8-binding antibodies encompassed by the claims, nor could the skilled artisan readily envisage which of the enormous number of encompassed CDR and VH or VL sequences are part of an anti-CCR8 antibody, including for claim 23 that has neutralizing activity.
The specification discloses anti-human CCR8 antibodies 10A11, 27G11, 1H4, 8F7, 2C7, 19D7 (Table 3) and anti-mouse CCR8 antibody 2-7B (Table4) and VH and VL and CDR1-3 sequences thereof. As shown in Table 5, these antibodies had some level of neutralizing activity. Humanized versions of 10A11 and 19D7 were analyzed and shown to have certain amino acids that were important for activity (Examples 8 and 9 and Tables 8-11). Further optimized version of these antibodies are shown in Tables 12-13, with 10A11 having 3 amino acid substitutions in the VL and 1 in the VH, and with 19D7 having a small number of mutations in the VH and VL CDRs and one in the VH framework region (FR). These antibodies particularly defined by CDR-L1-3 and CDR-H1-3 and/or VL and VH sequences meet the written description provision of 35 USC 112(a). However, the claims are directed to or encompass sequences comprising less than the disclosed six full CDR sequences, e.g., comprising as few as 2 consecutive amino acids. None of these sequences meets the written description provision of 35 USC 112(a).
This is supported by the prior art showing that the effects of substitution in variable chain regions of an antibody on antigen binding cannot be readily envisaged. For example, Chen et al. (EMBO J. 14 (12): 2784-2794, 1995), which teaches that the substitution of a single amino acid in CDR-H2 (HCDR2) of an antibody can totally ablate antigen binding and that the same substitution in closely related antibodies can have opposite effects on binding (e.g., see entire document, including Figure 1). The authors compared the effects of identical substitutions in related anti-phosphocholine antibodies DI6 and TI5, and as shown in Figure 3 some substitutions increased antigen binding in one antibody while ablating it in the other. Lee et al. (Antiviral. Res. 192:105105, 9 pages, 2021) engineered antibodies that bound Zika Virus FLEP epitope. They identified paratopes from antibody templates.
The paratope engineering process involved assembly and modifications
of both FRs and CDRs to enable binding to the FLEP epitope on
ZIKV. The FRs are important for (1) the positioning of the antibody
against the target epitope and (2) configuring the CDRs to achieve
desired binding affinity to the FLEP epitope. Five designs that met the
criteria for paratope engineering (based on AIF scores and network
properties), were tested experimentally for expression, yield, binding
affinity, and neutralization (Supplementary Table 3). Two of the
designed constructs showed poor expression, while one of them showed
poor binding to ZIKV and DENV. For one of the constructs, the optimization
of the paratope resulted in a rare amino acid substitution that
negatively impacted developability. The only construct that cleared all
the key protein filters including expression, binding affinity, neutralization
potency and developability was subsequently referred to as
ZAb_FLEP. (p. 4, col. 1, second paragraph)
Like Chen et al. (supra), Lee et al. found (p. 5, col. 2, middle) that, “[E]ven a conservative substitution in a CDR loop (VH-Ser52Thr) can lead to drastic changes in the interatomic interactions with the adjacent residues, with potential to impact epitope-paratope contacts (Fig. 4C).” Further, placing the same six CDRs into a different FR sequence can significantly decrease or remove antibody neutralizing activity (paragraph bridging pp. 4-5). They found that (p. 5, start of first full paragraph), “The structure-function relationships of the three test antibodies also emphasize the fact that amino acid substitutions in the framework or VH/VL interface or epitope paratope interface substantially impact the inter-residue interaction network (Fig. 4), and hence impact the functional attributes of the antibody…. The test antibodies clearly demonstrate the significance of the mutations introduced to optimize key network properties of the FR of the starting scaffold and CDRs.”
It is stated in AbbVie Deustschland GmbH v. Janssen Biotechnology, Ltd., 111 USPQ 1780, 1789 (759 F.3d 1285, 1298), (Fed. Cir. 2014) discussing Capon v. Eshhar, 418 F.3d 1349 (Fed. Cir. 2005) that “When a patent claims a genus using functional language to define a desired result, the specification must demonstrate that the applicant has made a generic invention that achieves the claimed results and do so by showing that the applicant has invented species sufficient to support a claim to the functionally-defined genus." Again in AbbVie at 1788, reiterating Enzo Biochem., Inc., 323 F.3d at 964, “It is true that functionally defined claims can meet the written description requirement if a reasonable structure-function correlation is established, whether by the inventor as described in the specification or known in the art at the time of the filing date…” In the instant situation, the application discloses a limited number of anti-CCR8 antibody species, including a subspecies of which have neutralizing activity. However, the genus of anti-CCR8 antibodies encompassed is far larger than that which is supported by the specification or prior art and there is no structure-function relationship disclosed to support the broadly claimed genus.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111 (Fed. Cir. 1991), 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).
With the exception of the sequences referred to above, the skilled artisan cannot envision the detailed chemical structure of the encompassed polynucleotides, 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. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016 (Fed. Cir. 1991).
Therefore, only an antibody comprising CDR-H1 of SEQ ID NO:5 or 8, CDR-H2 of SEQ ID NO:6 and CDR-H3 of SEQ ID NO:7, and a light chain variable region (VL) comprising CDR-L1, CDR-L2 and CDR-L3 of SEQ ID NO:2-4, respectively, including wherein SEQ ID NO:2 has a G11R substitution and SEQ ID NO:3 has a N4Q substitution (a.k.a. G29R, N53Q) and/or wherein the VH comprises SEQ ID NO:41 and VL comprises one of SEQ ID NO:59, i.e., antibody 10A11, as well as having the VH and VL CDR1-3 of antibody 27G11, 1H4, 8F7, 2C7 and 19D7 (Tables 3, 6, 7, 12, 13) that bind CCR8, and for claim 23 requiring neutralizing activity only the original antibodies (Table 5) and antibody 10A11 comprising VL CDR mutation L54I or L92I and VH T94R as in (Table 8) or antibody 19D7 comprising the VH CDR mutation D65E or D61E (Table 9), but not the full breadth of the claim meets the written description provision of 35 U.S.C. § 112(a). 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).
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, 3-8, 10, 11, 14, 15, 18-20 and 23-25 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 119, 121- 134, 136, 157, 159, 160 and 165-168 of copending Application No. 17/418,417 (‘417, reference application).
The instant claims are drawn to a pharmaceutical composition comprising an anti-CCR8 antibody (claim 1), wherein the antibody comprises the CDRs of or the VL and VH themselves of SEQ ID NO:59 and 41 (claims 14, 15 and 19, 20). Dependent claims 3, 5 and 6 specify the composition is for cancer treatment, including claim 4 specifying treatment with an anti-PD-1 or anti-PD-L1 antibody is ineffective. Claims 7-13 are drawn to chemotherapeutic agents which may be used with the pharmaceutical composition. Claim 18 depends from claim 14 and limits the antibody to a humanized monoclonal antibody or antibody fragment (see rejection under 35 USC 112(d) above). Claim 23 recites that the antibody of claim 1 is neutralizing, claim 24 that it has ADCC activity and claim 25 that it is an IgG antibody. Note that the instant claims as written only require a product which is an anti-CCR8 antibody.
These instant claims correspond to the claims of ‘417 drawn to an anti-CCR8 antibody or fragment thereof comprising a VL of SEQ ID NO:59 and VH of SEQ ID NO:41 (claims 119 and 157), which is comprised by a pharmaceutical composition (claims 121, 129 and 167). The antibody may be neutralizing or be an IgG antibody or have ADCC activity (claims 160, 168, 122, 130, and 124-126, 133, 134, and 123, 133, respectively).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 3-8, 10, 11, 14, 15 and 18-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 7-9, 32 and 39-42 of copending Application No. 18/285,304 (‘304).
The instant claims are drawn to a pharmaceutical composition comprising an anti-CCR8 antibody (claim 1), wherein the antibody comprises the CDRs of or the VL and VH themselves of SEQ ID NO:59 and 41 (claims 14, 15 and 19, 20). Dependent claim 3 specifies the composition is for cancer treatment. Claim 18 depends from claim 14 and limits the antibody to a humanized monoclonal antibody or antibody fragment (see rejection under 35 USC 112(d) above). Note that the instant claims as written only require a product which is an anti-CCR8 antibody.
‘304 claims a chimeric antigen receptor (CAR) binding CCR8 and having the scFv antigen-binding region comprising a VH and VL of SEQ ID NO:13 and 12 (identical to instant SEQ ID NO:59 and 41), respectively, and CDRs thereof (claims 1-5 and 7-9). These claims represent an anti-CCR8 antibody fragment. Also claimed is a cell expressing the CAR (claim 32) and pharmaceutical composition comprising the cell for treating cancer (claims 39-42). These claims represent a pharmaceutical composition comprising an anti-CCR8 antibody for treatment of cancer.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 3-8, 10, 11, 14, 15, 18-20 and 24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 13, 20, 22, 23 and 35 of copending Application No. 19/154,354 (‘354, reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because the method of treating cancer with an anti-CCR8 antibody of ‘354 makes obvious the pharmaceutical comprising an anti-CCR8 antibody for treatment cancer.
The instant claims are drawn to a pharmaceutical composition comprising an anti-CCR8 antibody (claim 1), wherein the antibody comprises the CDRs of or the VL and VH themselves of SEQ ID NO:59 and 41 (claims 14, 15 and 19, 20). Dependent claims 3, 5 and 6 specify the composition is for cancer treatment, including for breast or lung cancer. Claim 24 recites that the antibody has ADCC activity. Note that the instant claims as written only require a product which is an anti-CCR8 antibody.
Claim 1 of ‘354 is drawn to a method of treating cancer comprising administering an anti-CCR8 antibody having ADCC activity. Dependent claims 22 and 23, section bb, are drawn to a CCR8 antibody comprising a variable heavy chain region (VH) of SEQ ID NO:271 and variable light chain region (VL) of SEQ ID NO:275, or CDRs thereof, which VH and VL are identical to instant SEQ ID NO:41 and 59, respectively. Claim 13 specifies the antibody binds human CCR8. Claim 35 lists treatable cancers, including lung cancer and breast cancer. Even though the method of ‘354 also includes administration of a DGK inhibitor, it still renders obvious the administration of an anti-CCR8 antibody for treatment of cancer.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 3-8, 10, 11 and 23-25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5, 6, 17, 18, 20, 22 and 23 of US Patent No. 10,550,191 B2 (‘191).
Although the claims at issue are not identical, they are not patentably distinct from each other because the method of treating cancer with an anti-CCR8 antibody of ‘191 makes obvious the pharmaceutical comprising an anti-CCR8 antibody for treatment cancer. The instant claims are drawn to a pharmaceutical composition comprising an anti-CCR8 antibody (claim 1), wherein the antibody comprises the CDRs of or the VL and VH themselves of SEQ ID NO:59 and 41 (claims 14, 15 and 19, 20). Dependent claims 3, 5 and 6 specify the composition is for cancer treatment, including for breast or lung cancer. Claim 24 recites that the antibody has ADCC activity. Note that the instant claims as written only require a product which is an anti-CCR8 antibody.
US 10,550,191 claims a method of treating cancer comprising administering a therapeutic amount of an anti-CCR8 antibody having ADCC activity, including where the cancer is breast cancer, sarcoma or kidney cancer (claims 1, 3, 5, 6). Claim 2 specifies the antibody is a neutralizing antibody. Claims 17 and 18 is a similar method of treating cancer with a therapeutically effective amount of an IgG antibody against CCR8 that has ADCC activity, including wherein the cancer is breast cancer, sarcoma or kidney (also claims 20, 22, 23).
Priority
Applicant cannot rely upon the certified copy of the foreign priority application to overcome this rejection because a translation of said application has not been made of record in accordance with 37 CFR 1.55. When an English language translation of a non-English language foreign application is required, the translation must be that of the certified copy (of the foreign application as filed) submitted together with a statement that the translation of the certified copy is accurate. See MPEP §§ 215 and 216.
Note if translations are provided, the rejection as anticipated by CA2134332 A1 or US Patent No. 10,550,191 B2 will convert to a rejection under 102(a)(2), assuming the prior documents describe the necessary subject matter.
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.
Claim Rejections - 35 USC § 102
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.
OR
(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.
Claim(s) 1, 3-8, 10, 11, 14, 15, 18-20 and 23-25 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by CA3124332 A1 (2020/07/02).
CA3124332 teaches a pharmaceutical composition comprising a humanized anti-CCR8 antibody, wherein the antibody comprises the CDRs set forth in instant claim 15 and variable heavy chain region (VH) and variable light chain region (VL) of SEQ ID NO:41 and 59, respectively, which are identical to instant SEQ ID NO:41 and 59, respectively (p. 12, section (22) and p. 14, section (28)). VH and VL CDRs thereof are also taught (p. 6, section (8), through p. 7, section C), and p. 9, section (12)). The antibody may be a neutralizing and/or antibody fragment (p. 14, sections (28)-(29)) and may be a monoclonal antibody (p. 15, section (51)). The antibody may have ADCC activity and be an IgG antibody (p. 14, sections (32)-(33)). The pharmaceutical composition may be used for the treatment of cancer, including ovary, lung and breast cancer (section (34) bridging pp. 14-15, and p. 35, fourth paragraph).
Claim(s) 1, 3-8, 10, 11 and 23-25 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by US 11,427,649 B1.
An anti-CCR8 antibody inducing ADCC for use in treatment of a tumor is taught (col. 403, lines 6-11). The tumor may be ovarian, breast, lung or kidney cancer or a sarcoma (col. 401, lines 38-55). A pharmaceutical composition comprising the antibody is taught, optionally with a chemotherapeutic agent such as cisplatin, carboplatin or oxaliplatin (col. 400, lines 36-41 and 53-59, see also col. 157, line 5, through col. 158, line 11). The antibody may be a blocking/neutralizing antibody (e.g., col. 116, lines 14-15 and col. 117, lines 33-26) and/or an IgG antibody or antibody fragment (e.g., col. 144, lines 42-47).
Claim(s) 1, 3-8, 10, 11, 14, 15, 18-20 and 23-25 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by US 2022/0064312 A1 (cited in the IDS filed 1/6/2023).
US 2022/0064312 teaches a pharmaceutical composition comprising an anti-CCR8 antibody or fragment thereof comprising a VL of SEQ ID NO:59 and VH of SEQ ID NO:41 ([0180], claims 121, 129 and 167). The CDRs thereof are taught in claim 9. A pharmaceutical composition comprising the antibody, which may be neutralizing or be an IgG antibody or have ADCC activity is taught (e.g., p. 7(29) and (32)-(34)).
Claim(s) 1, 3-8, 10, 11 and 23-25 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by US Patent 10,550,191 B2 (cited in the IDS filed 1/6/2023).
US 10,550,191 teaches a method of treating cancer comprising administering a therapeutic amount of an anti-CCR8 antibody having ADCC activity, including where the cancer is breast cancer, sarcoma or kidney cancer (claims 1, 3, 5, 6). It teaches a pharmaceutical composition comprising the antibody useful for treatment of cancer (col. 3, lines 60-62). Claim 2 specifies the antibody is a neutralizing antibody. Claims 17 and 18 is a similar method of treating cancer with a therapeutically effective amount of an IgG antibody against CCR8 that has ADCC activity, including wherein the cancer is breast cancer, sarcoma or kidney (also claims 20, 22, 23).
Claim(s) 1, 3-8, 10, 11 and 23-25 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by CA 3057274 A1 (cited in the IDS filed 1/6/2023).
CA 3057274 teaches a pharmaceutical composition for cancer treatment comprising an antibody that binds CCR8 and has ADCC and CCR8-neutralizing activity ([0010], bottom of p. 4). The antibody may be a monoclonal or antibody fragment ([0015]). The antibody may be an IgG molecule ([0030]).
Claim(s) 1, 3-8, 10, 11, 23 and 24 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Dépis et al. (Canc. Res. 80:(16_Supplement): Abst. 4532, 15 Aug. 2020, cite in the IDS filed 1/6/2023)
Dépis et al. teaches an anti-CCR8 antibody with enhanced ADCC activity that depletes tumor-infiltrating regulator T cells (Title). The antibody has neutralizing activity in that it blocked CCR8 signaling induced by its ligand (Methods and Results). It was shown that a mouse-specific anti-CCR8 antibody having an Fc region led to tumor growth inhibition across several murine tumor models, including models in which anti-PD-1 antibody was ineffective. However, the combination of anti-CCR8 antibody and anti-PD-1 antibody resulted in 50% complete tumor regression in PD-1 resistant models. (Methods and Results).
Prior Art
The prior art made of record and not relied upon is considered pertinent to Applicant's disclosure.
US Patent No. 10,640,565 B2 is drawn to an anti-human CCR7 antibody useful for treatment of cancer (e.g., col. 1, lines 48-66). An anti-CCR7 antibody may be administered with cisplatin (e.g., col. 27, lines 5-7 and 48-49). The cancer to be treated may be a lung or breast cancer (col. 3, lines 52, through col. 4, line 4). This reference is cited to show that anti-CCR antibodies were taught as used to treat cancer with a chemotherapeutic agent, including cisplatin.
Marcuzzi et al. (Int. J. Mol. Sci. 20:96, 27 pages, 2019) teaches involvement of CCRs in tumor metastasization, including CCR7 involved in breast and lung cancers and CCR8 involved in breast cancer (Table 1). Further, it is stated (p. 7, second to last paragraph), “CCR8 also supports cancer dissemination, as its ligand CCL1, produced by lymphatic endothelial cells in the subcapsular sinus, can attract CCR8+ tumor cells to the lymph nodes to promote metastasis [90].” This reference teaches the state of the art as it relates to CCR8 involvement in cancer.
WO 2019/157098 A1 (cited in the IDS filed 1/6/2023) teaches a pharmaceutical composition comprising a neutralizing anti-CCR8 antibody and its administration for cancer treatment, e.g., kidney, bladder, sarcoma, with a chemotherapeutic agent such as a platinum complex, e.g., cisplatin ([0196], [0204]-[0205], and [0015], [0017],[0064]-[0065]). This reference is cumulative with those applied above under 35 USC 102(a)(1).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Claire Kaufman, whose telephone number is (571) 272-0873. Examiner Kaufman can generally be reached Monday through Friday 7am-3:30pm, Eastern Time.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Vanessa Ford, can be reached at (571) 272-0857.
Any inquiry of a general nature or relating to the status of this application should be directed to the Group receptionist whose telephone number is (571) 272-1600.
Official papers filed by fax should be directed to (571) 273-8300. NOTE: If applicant does submit a paper by fax, the original signed copy should be retained by the applicant or applicant's representative. NO DUPLICATE COPIES SHOULD BE SUBMITTED so as to avoid the processing of duplicate papers in the Office.
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 .
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.
Claire Kaufman
/Claire Kaufman/
Primary Examiner, Art Unit 1674
March 20, 2026
Prosecution Insights