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
Applicant’s amendments and remarks, filed 11/04/2025, are acknowledged.
Claims 3, 6-8, 11, and 14 are canceled.
Claims 1-2, 4-5, 9-10, 12-13, and 15-31 are pending.
DETAILED ACTION
Election/Restrictions
Applicant’s election without traverse of Group I, drawn to a polypeptide which comprises a variant Fc region composed of two polypeptide chains, represented by claims 1-2, 4-5, 9-10, 12-13, 15-17, and 22-27 in the reply filed on 11/04/2025 is acknowledged.
Claims 18-21 and 28-31 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 11/04/2025.
As such, claims 1-2, 4-5, 9-10, 12-13, 15-17, and 22-27 are pending examination and currently under consideration for patentability under 37 CFR 1.104.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 02/24/2023, 09/08/2023, and 11/04/2025 are acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
The references lined through were not considered because a copy of the references was not provided (see 37 CFR 1.98(a)).
Notably, the disclosure statement filed lists a Search Report. The listing of the references cited in a Search Report itself is not considered to be an information disclosure statement (IDS) complying with 37 CFR 1.98. 37 CFR 1.98(a)(2) requires a legible copy of: (1) each foreign patent; (2) each publication or that portion which caused it to be listed; (3) for each cited pending U.S. application, the application specification including claims, and any drawing of the application, or that portion of the application which caused it to be listed including any claims directed to that portion, unless the cited pending U.S. application is stored in the Image File Wrapper (IFW) system; and (4) all other information, or that portion which caused it to be listed. In addition, each IDS must include a list of all patents, publications, applications, or other information submitted for consideration by the Office (see 37 CFR 1.98(a)(1) and (b)), and MPEP § 609.04(a), subsection I. states, "the list ... must be submitted on a separate paper." Therefore, the references cited in the Search Report have not been considered. Applicant is advised that the date of submission of any item of information or any missing element(s) will be the date of submission for purposes of determining compliance with the requirements based on the time of filing the IDS, including all "statement" requirements of 37 CFR 1.97(e). See MPEP § 609.05(a).
Note: If copies of the individual references cited on the Search Report are also cited separately on the IDS (and these references have not been lined-through) they have been considered.
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:
Para. [0154]: “Thermo fisher” should read “Thermo Fisher”.
Appropriate correction is required.
The use of the term ALIGN, Megalign, DNASTAR, Invitrogen, Expi293, Sepharose™, Biacore, GE Healthcare, Thermo Fisher Scientific, CaptureSelect, Promega, Bio-Glo, SIGMA, WAKO, CORNING, Thermo Fisher, ATCC, and Calbiochem, 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.
Claim Objections
Claims 2 and 5 are objected to because of the following informalities:
Claims 2 and 5 comprise alphabetical subparts (i.e., (a) and (b)), whereas the base claim comprises Roman numeral subparts. For the purpose of maintaining consistency, Examiner suggests amending the alphabetical subparts to Roman number subparts.
Claim 2 is missing a colon (:) after the term “comprises”.
Claim 5: “comprises;” should read “comprises:”.
Appropriate correction is required.
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.
Claims 12 and 23 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. Part (i) of claims 12 and 23 recite “Val at position 250”, “Pro at position 307”, “Asp at position 326”, “Met at position 330”, and “Glu at position 332”; and, part (ii) of claims 12 and 23 recite “Ala at position 236”, “Val at position 250”, “Pro at position 307”, “Met or Lys at position 330”, “Asp or Glu at position 332”. These positions were not previously recited in the claims from which claims 12 and 23 depend from (i.e., claims 1 and 9, respectively); as such, claims 12 and 23 broaden the scope of the claims.
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.
Claims 1-2, 4-5, 9-10, 12-13, 15-17, and 22-27 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.
Claims 1-2, 4-5, 9-10, 12, and 22-23 disclose of amino acid positions without actually setting forth the sequences of the two polypeptide chains. Thus, one of skill in the art would not be apprised to which amino acid residues are altered as there is no sequence to compare or reference. As such, claims 1-2, 4-5, 9-10, 12, 22-23, and their dependent claims are rejected.
Claims 1-2, 4-5, 9-10, 12, and 22-23 recite the limitations "the first polypeptide chain” and “the second polypeptide chain". There is insufficient antecedent basis for this limitation in the claim.
The terms “enhanced” and “improved” in claims 13 and 24 are relative terms which renders the claim indefinite. The terms “enhanced” and “improved” are not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. While the claims recite “wherein binding activity to at least one Fcy receptor selected from the group consisting of FcyRIa, FcyRIIa, FcyRIIb, and FcyRIIIa is enhanced in the variant Fc region as compared to an Fc region that does not contain the amino acid alterations or wherein selectivity between an activating Fcy receptor and an inhibitory Fcy receptor is improved in the variant Fc region as compared to an Fc region that does not contain the amino acid alterations”, the claims do not disclose the binding activity of the non-modified Fc region. Therefore, one of skill in the art would not be apprised as to what is considered an enhancement or improvement to binding activity or selectivity, respectively. As such, claims 13 and 24 are rejected.
Claim Rejections - 35 USC § 112(a) Written Description
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 1-2, 4-5, 9-10, 12-13, 15-17, and 22-27 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 MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed. The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include “level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention.”
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, disclosure of drawings, or by disclosure of relevant identifying characteristics, for example, structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the Applicants were in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
Claim 1 is drawn to a polypeptide which comprises a variant Fc region composed of two polypeptide chains, and wherein the variant Fc region comprises amino acid alterations at the following positions: (i) positions 234, 235, 236, 239, 268, 270, and 298 according to EU numbering in the first polypeptide chain; and (ii) positions 270, 298, 326, and 334 according to EU numbering in the second polypeptide chain.
Claim 2 is drawn to the polypeptide of claim 1, wherein the variant Fc region further comprises (a) an amino acid alteration at position 326 according to EU numbering in the first polypeptide chain; or (b) an amino acid alteration at position 236 according to EU numbering in the second polypeptide chain.
Claim 4 is drawn to the polypeptide of claim 1, wherein the variant Fc region comprises amino acid alterations at the following positions: (i) positions 234, 235, 236, 239, 268, 270, 298, and 326 according to EU numbering in the first polypeptide chain; and (ii) positions 236, 270, 298, 326, and 334 according to EU numbering in the second polypeptide chain.
Claim 5 is drawn to the polypeptide of claim 1, wherein the variant Fc region further comprises; (a) an amino acid alteration at position 332 according to EU numbering in the first polypeptide chain; (b) an amino acid alteration at position 330 according to EU numbering in the first polypeptide chain;(c) an amino acid alteration at position 332 according to EU numbering in the second polypeptide chain; or (d) an amino acid alteration at position 330 according to EU numbering in the second polypeptide chain.
Claim 9 is drawn to a polypeptide which comprises a variant Fc region composed of two polypeptide chains, and wherein the variant Fc region comprises amino acid alterations at the following positions: (i) positions 234, 235, 236, 239, 268, 270, 298, 330, and 332 according to EU numbering in the first polypeptide chain; and (ii) positions 236, 270, 298, 326, 330, 332, and 334 according to EU numbering in the second polypeptide chain.
Claim 10 is drawn to the polypeptide of claim 1, wherein the variant Fc region further comprises amino acid alterations at positions 250 and 307 according to EU numbering in the first polypeptide chain or the second polypeptide chain.
Claim 12 is drawn to the polypeptide of claim 1, which comprises at least one amino acid alteration selected from the following amino acid alterations: (i) Tyr or Phe at position 234, Gln or Tyr at position 235, Trp at position 236, Met at position 239, Val at position 250, Asp at position 268, Glu at position 270, Ala at position 298, Pro at position 307, Asp at position 326, Met at position 330, and Glu at position 332 according to EU numbering in the first polypeptide chain; and (ii) Ala at position 236, Val at position 250, Glu at position 270, Ala at position 298, Pro at position 307, Asp at position 326, Met or Lys at position 330, Asp or Glu at position 332, and Glu at position 334 according to EU numbering in the second polypeptide chain.
Claim 13 is drawn to the polypeptide of claim 1, wherein binding activity to at least one Fcy receptor selected from the group consisting of FcyRIa, FcyRIIa, FcyRIIb, and FcyRIIIa is enhanced in the variant Fc region as compared to an Fc region that does not contain the amino acid alterations or wherein selectivity between an activating Fcy receptor and an inhibitory Fcy receptor is improved in the variant Fc region as compared to an Fc region that does not contain the amino acid alterations.
Claim 15 is drawn to the polypeptide of claim 1, wherein the polypeptide comprising the variant Fc region is an antibody.
Claim 16 is drawn to the polypeptide of claim 15, wherein the antibody binds to an antigen present on the cell surface of a target cell.
Claim 17 is drawn to the polypeptide of claim 16, wherein the target cell is a tumor cell.
Claim 22 is drawn to the polypeptide of claim 9, wherein the variant Fc region further comprises amino acid alterations at positions 250 and 307 according to EU numbering in the first polypeptide chain or the second polypeptide chain.
Claim 23 is drawn to the polypeptide of claim 9, which comprises at least one amino acid alteration selected from the following amino acid alterations: (i) Tyr or Phe at position 234, Gln or Tyr at position 235, Trp at position 236, Met at position 239, Val at position 250, Asp at position 268, Glu at position 270, Ala at position 298, Pro at position 307, Asp at position 326, Met at position 330, and Glu at position 332 according to EU numbering in the first polypeptide chain; and (ii) Ala at position 236, Val at position 250, Glu at position 270, Ala at position 298, Pro at position 307, Asp at position 326, Met or Lys at position 330, Asp or Glu at position 332, and Glu at position 334 according to EU numbering in the second polypeptide chain.
Claim 24 is drawn to the polypeptide of claim 9, wherein binding activity to at least one Fcy receptor selected from the group consisting of FcyRIa, FcyRIIa, FcyRIIb, and FcyRIIIa is enhanced in the variant Fc region as compared to an Fc region that does not contain the amino acid alterations or wherein selectivity between an activating Fcy receptor and an inhibitory Fcy receptor is improved in the variant Fc region as compared to an Fc region that does not contain the amino acid alterations.
Claim 25 is drawn to the polypeptide of claim 9, wherein the polypeptide comprising the variant Fc region is an antibody.
Claim 26 is drawn to the polypeptide of claim 25, wherein the antibody binds to an antigen present on the cell surface of a target cell.
Claim 27 is drawn to the polypeptide of claim 26, wherein the target cell is a tumor cell.
The specification discloses the production of Fc region variants with enhanced FcγR-binding activity (see Example 1). The specification discloses that variants with symmetrically engineered CH2 domains and low-fucose antibodies made by sugar chain modifications all still had room for further enhancement of FcγR binding (see [0125]). In addition, although the variants with asymmetrically engineered CH2 domains described in prior art had greatly enhanced FcγR-binding ability compared to symmetrically-engineered Fc region variants, they had room for further improvement (see [0125]). Existing Fc region variants to be used as references for comparison were prepared as follows: First, antibody heavy chain gene H240-G1d (SEQ ID NO: 1) was produced (see [0126]). G1d is a sequence obtained by deleting C-terminal Lys and Gly from the heavy chain constant region sequence of native human IgG1 (see [0126]). Knobs-into-holes modifications were introduced into the CH3 domain of H240-G1d, and modifications for enhancing FcγR-binding were asymmetrically introduced into the CH2 domain, to produce Fc region variants to be used as references for comparison, ART1 and ART2 (see [0126]). ART1 was produced as follows: modifications for enhancing FcγR-binding, L234Y/L235Q/G236W/S239M/H268D/D270E/S298A, were introduced into the CH2 domain of H240-G1d, and Y349C/T366W were introduced into the CH3 domain, to produce H240-Kn125 (SEQ ID NO: 2) (see [0126]). In addition, D270E/K326D/A330M/K334E were introduced into the CH2 domain of H240-G1d, and D356C/T366S/L368A/Y407V were introduced into the CH3 domain, to produce H240-H1076 (SEQ ID NO: 3) (see [0126]). Similarly, an Fc region variant with enhanced binding to both FcγRIIa and FcγRIIIa, EGL-ART2, was produced (see [0127]). Further, different combinations of FcγR binding-enhancing modifications, G236A, S239D, A330L, and I332E, were symmetrically introduced into the CH2 domain to produce known FcγR binding-enhanced antibodies, EGL-SDALIE, EGL-GASDIE, and EGL-GASDALIE (see [0127]). The specification also discloses of Fc region variants that are superior to these existing variants, wherein all of these variants had L234F, L235Q, G236W, S239M, H268D, D270E, and S298A introduced into one of the heavy chains and D270E, S298A, K326D, and 334E introduced into the other heavy chain (see Table 1; [0128]).
Example 2 discloses the evaluation of FcγR-binding of Fc region variants. ART3, ART4, ART5, ART6, ART8, ART10, ART11, and ART12 were all enhanced as compared to G1d for FcγRIIIaF and FcγRIIIaV (see [0133]). These variants were also more enhanced than the existing symmetrically-modified FcγR-enhanced antibodies GASDALIE, SDALIE, GASDIE, and Afucosyl antibody for both FcγRIIIaF and FcγRIIIaV (see [0133]).
Example 3 discloses the evaluation of antibodies having modified Fc regions by ADCC reporter bioassay. Specifically, Table 3 discloses the EC50 value of each modified Fc-containing antibody induction activity to hFcγRIIIaV-mediated reporter gene. The results showed that the antibodies with modified Fc produced a stronger reporter gene activity against Hepa1-6/hEREG cells than the wildtype human IgG1 constant region, and that all these variants exhibited the activity at lower concentrations than variants with symmetrically engineered CH2 domains and low-fucose antibodies produced by sugar chain modification (see [0140]).
Example 4 discloses the evaluation of antibodies having modified Fc regions by ADCP reporter bioassay. Specifically, Table 4 discloses the EC50 value of each modified Fc-containing antibody induction activity to hFcγRIIaH-mediated reporter gene. The results showed that the antibodies with modified Fc produced a stronger reporter gene induction activity against Hepa1-6/hEREG cells than the wildtype human IgG1 constant region, and exhibited the activity at lower concentrations than variants with symmetrically engineered CH2 domains and low-fucose antibodies produced by sugar chain modifications (see [0143]). Among the variants, ART2, ART3, ART5, ART6, and ART8 were shown to have the activity at lower concentration than ART1 (see [0143]). In particular, ART3, ART6, and ART8 exhibited the activity at lower concentrations even when compared to ART2, which has more enhanced hFcγRIIaH binding (see [0143]).
Example 5 discloses the evaluation of the antitumor effect of antibodies having modified Fc regions in a syngeneic tumor cell transplant model using human FcγR transgenic mice. The specification discloses both FcγR binding-enhanced antibodies EGL-afucosyl and EGL-ART6, administered at 10 mg/kg, showed an efficacy of TGI=80 or higher on day 19 after administration; on the other hand, the control antibody EGL-G1d showed TGI=31 (see Fig. 3; [0150]). This confirmed that the in vivo antitumor effect of EGL-ART6 is also enhanced as compared to EGL-afucosyl (see [0150]).
Lastly, Example 6 discloses the evaluation of C1q-binding activity of antibodies having modified Fc regions. As shown in Fig. 4 and Fig. 5, among the variants evaluated, ART3, ART5, and ART11 had an enhanced C1q binding ability as compared to G1d (see [0155]). In addition, the C1q binding of ART1, ART2, ART4, ART6, ART10, ART12, GASDALIE, SDALIE, and GASDIE was reduced as compared to that of G1d (see [0155]). The common amino acid modifications shared by these variants with greatly reduced C1q binding include a modification at Ala330 or a modification at Ile332; these regions, in particular Ala330, are very important regions for interaction with C1q (see [0155]). On the other hand, ART3, ART5, and ART11, which had enhanced C1q binding as compared to G1d, did not have a modification introduced at position 330 or position 332, suggesting that the enhanced binding was due to the effect of the S298A modification or a modification at position 326, which is believed to improve the binding to C1q (see [0155]).
However, the specification fails to disclose that Applicant was in possession of the large genus of polypeptides comprising a variant Fc region composed of two polypeptide chains as claimed. Specifically, the specification fails to disclose that Applicant was in possession of the large genus of polypeptides comprising a variant Fc region wherein positions 234, 235, 236, 239, 268, 270, 298, 330, and 332 according to EU numbering in the first polypeptide chain; and (ii) positions 236, 270, 298, 326, 330, 332, and 334 according to EU numbering in the second polypeptide chain, and further position 250 and 307 in the first or second polypeptide chains, are altered by any means (e.g., substitution, addition, or deletion). Additionally, the specification fails to disclose the structure of the claimed polypeptide comprising a variant Fc region nor a non-modified Fc region, thus it cannot be determined how the variant Fc region enhanced FcγR binding activity or improved selectivity. Lastly, the specification fails to disclose that Applicant was in possession of the large genus of antibodies that bind to a large genus of antigens on the cell surface of a large genus of target cells, specifically tumor cells.
Although the specification discloses of different species of Fc region variants (see Table 1), the claims are not limited to these variants, and are inclusive of any polypeptide which comprises a variant Fc region composed of two polypeptide chains, and wherein the variant Fc region comprises amino acid alterations at the following positions: (i) positions 234, 235, 236, 239, 268, 270, and 298 according to EU numbering in the first polypeptide chain; and (ii) positions 270, 298, 326, and 334 according to EU numbering in the second polypeptide chain. This indicates that there are hundreds, if not thousands, of possible polypeptides comprising a variant Fc region encompassed by the claims. Thus, the claims encompass a vast genus of polypeptides that have the claimed functions. However, the specification provides limited guidance on the structure required for maintaining the claimed function(s). Therefore, the specification does not provide adequate written description to identify the broad and variable genus of polypeptides because, inter alia, the specification does not disclose a correlation between the necessary structure of the polypeptide and the function(s) recited in the claims; and thus, the specification does not distinguish the claimed genus from others, except by function. Although the term antibody does impart some structure, the structure that is common to antibodies is generally unrelated to its specific binding function; therefore, correlation is less likely for antibodies than for other molecules. Accordingly, the specification does not define any structural features commonly possessed by the members of the genus, because while the description of an ability of the claimed substance may generically describe the molecule’s function, it does not describe the substance itself. A definition by function does not suffice to define the genus because it is only an indication of what the substance does, rather than what it is; therefore, it is only a definition of a useful result rather than a definition of what achieves the result. In addition, because the genus of substances is highly variable (i.e. each substance would necessarily have a unique structure, See MPEP 2434), the generic description of the substance is insufficient to describe the genus. Further, given the highly diverse nature of antibodies, particularly in CDRs, even one of skill in the art cannot envision the structure of an antibody by only knowing its binding characteristics. Thus, the specification does not provide substantive evidence for possession of this large and variable genus, encompassing a potentially massive number of antibodies/polypeptides and variants thereof claimed only be a functional characteristic(s) and/or partial structure.
A biomolecule sequence described only by a functional characteristic, without any known or disclosed correlation between that function and the structure of the sequence, normally is not sufficient identifying characteristics for written description purposes, even when accompanied by a method of obtaining the agent. The specification does not adequately describe the correlation between the chemical structure and function of the genus, such as structural domains or motifs that are essential and distinguish members of the genus from those excluded. Thus, the genus of antibodies has no correlation between their structure and function.
MPEP § 2163.03(V) states:
While there is a presumption that an adequate written description of the claimed invention is present in the specification as filed, In re Wertheim, 541 F.2d 257, 262, 191 USPQ 90, 96 (CCPA 1976), a question as to whether a specification provides an adequate written description may arise in the context of an original claim. An original claim may lack written description support when (1) the claim defines the invention in functional language specifying a desired result but the disclosure fails to sufficiently identify how the function is performed or the result is achieved or (2) a broad genus claim is presented but the disclosure only describes a narrow species with no evidence that the genus is contemplated. See Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1349-50 (Fed. Cir. 2010) (en banc). The written description requirement is not necessarily met when the claim language appears in ipsis verbis in the specification. "Even if a claim is supported by the specification, the language of the specification, to the extent possible, must describe the claimed invention so that one skilled in the art can recognize what is claimed. The appearance of mere indistinct words in a specification or a claim, even an original claim, does not necessarily satisfy that requirement. “Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 968, 63 USPQ2d 1609, 1616 (Fed. Cir. 2002).
Applicant has not shown possession of a representative number of species of polypeptides comprising a variant Fc region composed of two polypeptide chains. The disclosure of only one or two species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure "indicates that the patentee has invented species sufficient to constitute the gen[us]." See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004) ("[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated.") (MPEP 2163).
The instant claims do not fully describe the structure of the polypeptide to achieve the required function. Accordingly, the specification also does not provide adequate written description to identify the broad genus of polypeptides/antibodies, claimed only by a function characteristic(s) and not structures per se, because inter alia, it does not describe a sufficient number and/or a sufficient variety of representative species to reflect the breadth and variation within the claimed genus. Consequently, based on the lack of information within the specification, there is evidence that a representative number and a representative variety of the numerous polypeptides/antibodies had not yet been identified and thus, the specification represents little more than a wish for possession. Therefore, one of skill in the art would not conclude that Applicant was in possession of the broad and highly variable genus of polypeptides/antibodies claimed only by a partial structure and functional characteristic(s). Thus the polypeptides/antibodies described by the instant claims encompasses an overly broad genus, the structure of variant Fc region, and the functional outcome.
In Amgen Inc. v. Sanofi, 124 USPQ2d 1354 (Fed. Cir. 2017), relying upon Ariad Pharms., Inc. v. Eli Lily & Co., 94 USPQ2d 1161 (Fed Cir. 2010), it is noted that to show invention, a patentee must convey in its disclosure that is “had possession of the claimed subject matter as of the filing date. Demonstrating possession “requires a precise definition” of the invention. To provide this precise definition” for a claim to a genus, a patentee must disclose “a representative number of species within the scope of the genus of structural features common to the members of the genus so that one of skill in the art can visualize or recognize the member of the genus” (see Amgen at page 1358). Also, it is not enough for the specification to show how to make and use the invention, i.e., to enable it (see Amgen at page 1361). An adequate written description must contain enough information about the actual makeup of the claimed products — “a precise definition, such as structure, formula, chemic name, physical properties of other properties, of species falling with the genus sufficient to distinguish the gene from other materials”, which may be present in “functional terminology when the art has established a correlation between structure and function” (Amgen page 1361). Most significant to the present case, the Court held that "knowledge of the chemical structure of an antigen [does not give] the required kind of structure-identifying information about the corresponding antibodies" (Amgen at 1361). The idea that written description of an antibody can be satisfied by the disclosure of a newly-characterized antigen “flouts basic legal principles of the written description requirement” as it “allows patentees to claim antibodies by describing something that is not the invention, i.e., the antigen... And Congress has not created a special written description requirement for antibodies” (Amgen at page 1362).
Abbvie v. Centocor (Fed. Cir. 2014) is also relevant to the instant claims. In Abbvie, the Court held that a disclosure of many different antibodies was not enough to support the genus of all neutralizing antibodies because the disclosed antibodies were very closely related to each other in structure and were not representative of the full diversity of the genus. The Court further noted that functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description support especially in technology fields that are highly unpredictable where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus.
The instant case has many similarities to AbbVie above. First, the claims clearly attempt to define the genus of polypeptides by the functions of enhancing binding activity of at least one Fcγ receptor or improving the selectivity between an activating Fcγ receptor and an inhibitory Fcγ receptor. Additionally, the claims attempt to define the genus of variant Fc regions by the vast substitutions recited in claims 12 and 23. As noted by AbbVie above, functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description. Second, there is no information in the specification based upon which one of skill in the art would conclude that the disclosed species for which applicant has identified as having the recited functions would be representative of the entire genus. The specification discloses no structure to correlate with the function. Therefore, the specification provides insufficient written description to support the genus encompassed by the claim.
Furthermore, regardless whether a compound is claimed per se or a method is claimed that entails the use of the compound, the inventor cannot lay claim to that subject matter unless he can provide a description of the compound sufficient to distinguish infringing compounds from non-infringing compounds, or infringing methods from non-infringing methods. Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920-23, 69 USPQ2d 1886, 1890-93 (Fed. Cir. 2004).
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear 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.)
Further, the skilled artisan cannot envision the detailed chemical structure of the encompassed polypeptides/antibodies, 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 for isolating it. The nucleic acid and/or protein itself is required. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. In Fiddes v. Baird, 30 USPQ2d 1481, 1483, claims directed to mammalian FGF's were found unpatentable due to lack of written description for the broad class. The specification provided only the bovine sequence.
Finally, University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1404. 1405 held that: ... To fulfill the written description requirement, a patent specification must describe an invention and does so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (1997); In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (" [T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using “such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d 1966.
Regarding the encompassed polypeptides that are antibodies, the functional characteristics of antibodies (including binding specificity and affinity are dictated on their structure. Amino acid sequence and conformation of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity which is characteristic of the parent immunoglobulin. For example, Vajdos et al. (J Mol Biol. 2002 Jul 5;320(2):415-28 at 416) teaches that, “ … Even within the Fv, antigen binding is primarily mediated by the complementarity determining regions (CDRs), six hypervariable loops (three each in the heavy and light chains) which together present a large contiguous surface for potential antigen binding. Aside from the CDRs, the Fv also contains more highly conserved framework segments which connect the CDRs and are mainly involved in supporting the CDR loop conformations, although in some cases, framework residues also contact antigen. As an important step to understanding how a particular antibody functions, it would be very useful to assess the contributions of each CDR side-chain to antigen binding, and in so doing, to produce a functional map of the antigen-binding site." The art shows an unpredictable effect when making single versus multiple changes to any given CDR. For example, Brown et al. (J Immunol. 1996 May;156(9):3285-91 at 3290 and Tables 1 and 2), describes how the VH CDR2 of a particular antibody was generally tolerant of single amino acid changes, however the antibody lost binding upon introduction of two amino changes in the same region.
The claims encompass an extremely large number of possible antibodies and polypeptides that have specific required functions. In the instant application, neither the art nor the specification provide a sufficient representative number of antibodies/polypeptides or a sufficient structure-function correlation to meet the written description requirements.
Regarding the encompassed polypeptides, protein chemistry is one of the most unpredictable areas of biotechnology. This unpredictability prevents prediction of the effects that a given number or location of mutation will have on a protein (such as TNF or a cytokine) as taught by Skolnick et al. (Trends Biotechnol. 2000 Jan;18(1):34-9), sequence-based methods for predicting protein function are inadequate because of the multifunctional nature of proteins (see e.g. abstract). Further, just knowing the structure of the protein is also insufficient for prediction of functional sites (see e.g. abstract). Sequence to function methods cannot specifically identify complexities for proteins, such as gain and loss of function during evolution, or multiple functions possible within a cell (see e.g. page 34, right column). Skolnick advocates determining the structure of the protein, then identifying the functionally important residues since using the chemical structure to identify functional sites is more in line with how a protein actually works (see e.g. page 34, right column).
The sensitivity of proteins to alterations of even a single amino acid in a sequence are exemplified by Burgess et al. (J. Cell Biol. 111:2129-2138, 1990) who teach that replacement of a single lysine residue at position 118 of acidic fibroblast growth factor by glutamic acid led to the substantial loss of heparin binding, receptor binding and biological activity of the protein and by Lazar et al. (Mol. Cell. Biol., 8:1247-1252, 1988) who teach that in transforming growth factor alpha, replacement of aspartic acid at position 47 with alanine or asparagine did not affect biological activity while replacement with serine or glutamic acid sharply reduced the biological activity of the mitogen. These references demonstrate that even a single amino acid substitution will often dramatically affect the biological activity and characteristics of a protein.
Further, Miosge (Proc Natl Acad Sci U S A. 2015 Sep 15;112(37):E5189-98) teach that Short of mutational studies of all possible amino acid substitutions for a protein, coupled with comprehensive
functional assays, the sheer number and diversity of missense mutations that are possible for proteins means that their functional importance must presently be addressed primarily by computational inference (see e.g. page E5189, left column). However, in a study examining some of these methods, Miosge shows that there is potential for incorrect calling of mutations (see e.g. page E5196, left column, top paragraph). The authors conclude that the discordance between predicted and actual effect of missense mutations creates the potential for many false conclusions in clinical settings where sequencing is performed to detect disease-causing mutations (see e.g. page E5195, right column, last paragraph). The findings in their study show underscore the importance of interpreting variation by direct experimental measurement of the consequences of a candidate mutation, using as sensitive and specific an assay as possible (see e.g. page E5197, left column, top paragraph). Additionally, Bork (Genome Research, 2000,10:398-400) clearly teaches the pitfalls associated with comparative sequence analysis for predicting protein function because of the known error margins for high-throughput computational methods. Bork specifically teaches that computational sequence analysis is far from perfect, despite the fact that sequencing itself is highly automated and accurate (p. 398, column 1). One of the reasons for the inaccuracy is that the quality of data in public sequence databases is still insufficient. This is particularly true for data on protein function. Protein function is context dependent, and both molecular and cellular aspects have to be considered (p. 398, column 2). Conclusions from the comparison analysis are often stretched with regard to protein products (p. 398, column 3). Further, although gene annotation via sequence database searches is already a routine job, even here the error rate is considerable (p. 399, column 2). Most features predicted with an accuracy of greater than 70% are of structural nature and, at best, only indirectly imply a certain functionality (see legend for table 1, page 399). As more sequences are added and as errors accumulate and propagate it becomes more difficult to infer correct function from the many possibilities revealed by database search (p. 399, paragraph bridging columns 2 and 3). The reference finally cautions that although the current methods seem to capture important features and explain general trends, 30% of those features are missing or predicted wrongly. This has to be kept in mind when processing the results further (p. 400, paragraph bridging cols 1 and 2).
One key issue is the prediction of protein function based on sequence similarity, which could be one way to identify the functional proteins that are useful in the instant claims. Kulmanov et al (Bioinformatics, 34(4), 2018, 660–668), teach that there are key challenges for protein function prediction methods (see e.g. page 661, left column). These challenges arise from the difficulty identifying and accounting for the complex relationship between protein sequence structure and function (see e.g. page 661, left column). Despite significant progress in the past years in protein structure prediction, it still requires large efforts to predict protein structure with sufficient quality to be useful in function prediction (see e.g. page 661, left column). Another challenge is that proteins do not function in isolation. In particular higher level physiological functions that go beyond simple molecular interactions will require other proteins and cannot usually be predicted by considering a single protein in isolation (see e.g. page 661, left column). Due to these challenges it is not obvious what kinds of features should be used to predict the functions of a protein and whether they can be generated efficiently for a large number of proteins, such as the vast genus of proteins and peptides that may be encompassed by the instant claims (see e.g. page 661, left column).
The state of the art regarding the structure-function correlation cannot be relied upon because functional characteristics of any peptide/protein are determined by its structure as evidenced by Greenspan et al. 1999 (Defining epitopes: It's not as easy as it seems; Nature Biotechnology, 17:936-937). Greenspan et al. teach that as little as one substitution of an amino acid (e.g. alanine) in a sequence results in unpredictable changes in the 3-dimenstional structure of the new peptide sequence which, in turn, results in changes in the functional activity such as binding affinity of the peptide sequence (page 936, 1st column). Greenspan et al. teach that contribution of each residue (i.e. each amino acid) cannot be estimated with any confidence if the replacement affects the properties of the free form of the molecule (page 936, 3rd column).
Given not only the teachings of Skolnick et al., Lazar et al., Burgess et al., and Greenspan et al., but also the limitations and pitfalls of using computational sequence analysis and the unknown effects of alternative splicing, post translational modification and cellular context on protein function as taught by Bork, the claimed polypeptides could not be predicted based on sequence identity. Clearly, it could not be predicted that a polypeptide or a variant that shares only partial homology with a disclosed protein or that is a fragment of a given SEQ ID NO. will function in a given manner.
The claimed invention as a whole may not be adequately described where an invention is described solely in terms of a method of its making coupled with its function and there is no described or art-recognized correlation or relationship between the structure of the invention and its function (see MPEP 2163). A patent specification must set forth enough detail to allow a person of ordinary skill in the art to understand what is claimed and to recognize that the inventor invented what is claimed. In the case of proteins, an adequate written description requires a precise definition, such as by structure, formula, chemical name, or physical properties, not a mere wish or plan for obtaining the claimed chemical invention (see Lilly, 119 F.3d at 1566 (quoting Fiers, 984 F.2d 15 1171 ). Because the specification does not describe the amino acid sequences nor any core structures for potentially numerous different antibody amino acid sequences which would have the recited dissociation constant, one of skill in the art would reasonably conclude that applicant was not in possession of the claimed genus of all polypeptides.
A key role played by the written description requirement is to prevent “attempt[s] to preempt the future before it has arrived.” Ariad at 1353, (quoting Fiers v. Revel, 984 F.2d at 1171). Upholding a patent drawn to a genus of antibodies that includes members not previously characterized or described could negatively impact the future development of species within the claimed genus of antibodies.
While "examples explicitly covering the full scope of the claim language" typically will not be required, a sufficient number of representative species must be included to "demonstrate that the patentee possessed the full scope of the [claimed] invention." Lizard tech v. Earth Resource Mapping, Inc., 424 F.3d 1336, 1345, 76 USPQ2d 1724,1732 (Fed. Cir. 2005).
In the absence of sufficient recitation of distinguishing characteristics, the specification does not provide adequate written description of the claimed genus. One of skill in the art would not recognize from the disclosure that the applicant was in possession of the claimed polypeptides/antibodies. Possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features (see, Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916,927, 69 USPQ2d 1886, 1895 (Fed. Cir. 2004); accord Ex Parte Kubin, 2007-0819, BPAI 31 May 2007, opinion at p. 16, paragraph 1). 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).
Without an adequate structural description of the claimed components and descriptive support on how to put them together, one of ordinary skill in the art would not be reasonably apprised that Applicant was in possession of the genus of polypeptides/antibodies as claimed. 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).
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Mimoto et al
Claims 1-2, 4-5, 9-10, 12-13, 15-17, and 22-27 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Mimoto et al (US 2014/0199294 A1, publication date: 07/17/2014).
The applied reference has a common inventor and assignee with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement.
With respect to instant claims 1-2, 4-5, 9-10, and 22, Mimoto et al disclose of a heterodimerized polypeptide having an Fc region formed from two polypeptides with different amino acid sequences (a first polypeptide and a second polypeptide), and succeeded in producing a heterodimerized polypeptide containing an Fc region with improved Fc region function compared to that of a homodimer (see Abstract and claims). Particularly, Mimoto et al disclose that the Fc region comprises one or more mutations consisting of: Ala at position 231; Pro at position 232; Glu at position 233; Leu at position 234; Leu at position 235; Gly at position 236; Gly at position 237; Pro at position 238; Ser at position 239; Val at position 240; Asp at position 265; Val at position 266; Ser at position 267; His at position 268; Glu at position 269; Asp at position 270; Pro at position 271; Gln at position 295; Tyr at position 296; Ser at position 298; Tyr at position 300; Ser at position 324; Asn at position 325; Lys at position 326; Ala at position 327; Leu at position 328; Pro at position 329; Ala at position 330; Pro at position 331; Ile at position 332; Glu at position 333; Lys at position 334; Thr at position 335; Ile at position 336; and Ser at position 337, wherein all positions are by EU numbering (see claim 80).
Additionally, Mimoto et al disclose that the site to be altered is not particularly limited as long as it is in an Fc region, and it can be appropriately set within a range that can achieve the objectives of the present invention and examples include the hinge region, CH2 region, and CH3 region; wherein the CH2 domain refers to positions 231 to 340 (EU numbering) and the CH3 domain refers to positions 341 to 447 (EU7 numbering) (see [0154]-[0157]). Thus, positions 250 and 307 are encompassed within the invention.
With respect to instant claims 12 and 23, Mimoto et al disclose that at least one of the first and second polypeptides of the heterodimerized polypeptide comprises an IgG1 CH2 domain comprising one or more of the following amino acid substitutions: substitution of L at position 234 with Y (i.e., Tyr); substitution of L at position 235 with Y (i.e., Tyr) or Q (i.e., Gln); substitution of G at position 236 with W (i.e., Trp); substitution of S at position 239 with M (i.e., Met); substitution of H at position 268 with D (i.e., Asp); substitution of D at position 270 with E (i.e., Glu); substitution of S at position 298 with A (i.e., Ala); substitution of K at position 326 with D (i.e., Asp); substitution of A at position 327 with D (i.e., Asp); substitution of L at position 328 with W (i.e., Trp); substitution of A at position 330 with M (i.e., Met) or K (i.e., Lys); and substitution of K at position 334 with E (i.e., Glu) or L (i.e., Leu) (see claims 124 and 128).
With respect to instant claims 13 and 24, Mimoto et al disclose that the polypeptide comprising the heterodimeric Fc region increases the function of (i) binding affinity for an Fc receptor, or (ii) selectivity of binding to one type of Fc receptor over another type of Fc receptor (see claims 79, 97-99, 108, 111-112, 115, 118, 121, 129, 132, 134, 136, 138, and 140).
Lastly, with respect to instant claims 15-17 and 25-27, Mimoto et al disclose that the polypeptide can be an antibody (see claims 145 and 146; [0080]), wherein the antibody targets the surface antigens of a cell, including tumor cells (see [0312]-[0313]).
As such, Mimoto et al anticipates the present invention.
Igawa et al
Claims 1-2, 4-5, 9-10, 12-13, 15-17, and 22-27 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Igawa et al (US 2015/0344570 A1, publication date: 12/03/2015).
The applied reference has a common inventor and assignee with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement.
With respect to instant claims 1-2, 4-5, 9-10, 12, and 22-23, Igawa et al disclose of a heterodimerized polypeptide having an Fc region formed from two polypeptides with different amino acid sequences (a first polypeptide and a second polypeptide), and succeeded in producing a heterodimerized polypeptide containing an Fc region with improved Fc region function compared to that of a homodimer (see Abstract and claims). Particularly, Igawa et al disclose that the heterodimerized polypeptide comprising a first polypeptide and a second polypeptide, wherein either one of the first polypeptide and the second polypeptide comprises an Fc region introduced with the mutations of (i) or (ii), which is a polypeptide whose function of the Fc region is altered compared to a polypeptide comprising an Fc region mutations: (i) according to EU numbering, the amino acid at position 234 is L, S, F, E, V, D, Q, I, M, T, A, G, or H; the amino acid at position 235 is Y or Q; the amino acid at position 236 is W; the amino acid at position 239 is M or I; the amino acid at position 268 is D; and the amino acid at position 298 is A; (ii) according to EU numbering, the amino acid at position 270 is E; the amino acid at position 326 is D; the amino acid at position 330 is A, K, M, F, I, Y, or H; and the
amino acid at position 334 is E (see claims 1-7).
Additionally, Igawa et al disclose that the site to be altered is not particularly limited as long as it is in an Fc region, and it can be appropriately set within a range that can achieve the objectives of the present invention and examples include the hinge region, CH2 region, and CH3 region; wherein the CH2 domain refers to positions 231 to 340 (EU numbering) and the CH3 domain refers to positions 341 to 447 (EU7 numbering) (see [0109]-[0112]). Thus, positions 250 and 307 are encompassed within the invention.
With respect to instant claims 13 and 24, Igawa et al disclose that the polypeptide comprising the heterodimeric Fc region enhances the binding activity or improves the selectivity of binding to an Fcγ receptor (see claims 8-11 and 13).
Lastly, with respect to instant claims 15-17 and 25-27, Igawa et al disclose that the polypeptide can be an antibody (see claims 18; [0038]), wherein the antibody targets the surface antigens of a cell, including tumor cells (see [0283]-[0285]).
As such, Igawa et al anticipates the present invention.
Statutory Double Patenting
A rejection based on double patenting of the “same invention” type finds its support in the language of 35 U.S.C. 101 which states that “whoever invents or discovers any new and useful process... may obtain a patent therefor...” (Emphasis added). Thus, the term “same invention,” in this context, means an invention drawn to identical subject matter. See Miller v. Eagle Mfg. Co., 151 U.S. 186 (1894); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Ockert, 245 F.2d 467, 114 USPQ 330 (CCPA 1957).
A statutory type (35 U.S.C. 101) double patenting rejection can be overcome by canceling or amending the claims that are directed to the same invention so they are no longer coextensive in scope. The filing of a terminal disclaimer cannot overcome a double patenting rejection based upon 35 U.S.C. 101.
Claims 1-2, 4, 9-10, 12-13, 15, and 22-25 are provisionally rejected under 35 U.S.C. 101 as claiming the same invention as that of claims 1-3, 5-6, 10-13, 15-18, and 20 of copending Application No. 18/022,342 (reference application).
The ‘342 application is drawn to a heterodimeric polypeptide which comprises a variant Fc region comprising amino acid alterations as compared to a parent Fc region, wherein the parent Fc region is composed of a first polypeptide and a second polypeptide, and wherein the variant Fc region comprises amino acid alterations at the following positions as compared to the parent Fc region: (A) (i) positions 234, 235, 236, 239, 268, 270, and 298 according to EU numbering in the first polypeptide of the parent Fc regions and (ii) positions 270, 298, 326, and 334 according to EU numbering in the second polypeptide of the parent Fc region; (B) (i) positions 234, 235, 236, 239, 268, 270, 298, and 326 according to EU numbering in the first polypeptide of the parent Fc region, and (ii) positions 236, 270, 298, 326, and 334 according to EU numbering in the second polypeptide of the parent Fc region; or (C) (i) positions 234, 235, 236, 239, 268, 270, 298, 330, and 332 according to EU numbering in the first polypeptide of the parent Fc region, and (ii) positions 236, 270, 298, 326, 330, 332, and 334 according to EU numbering in the second polypeptide of the parent Fc region (see claim 1).
The ‘342 application is drawn to the heterodimeric polypeptide of claim 1, which comprises at least one amino acid alteration as compared to the parent Fc region selected from the following amino acid alterations: (i) Tyr or Phe at position 234, Gln or Tyr at position 235, Trp at position 236, Met at position 239, Val at position 250, Asp at position 268, Glu at position 270, Ala at position 298, Pro at position 307, Asp at position 326, Met at position 330, and Glu at position 332 according to EU numbering in the first polypeptide of the parent Fc region; and (ii) Ala at position 236, Val at position 250, Glu at position 270, Ala at position 298, Pro at position 307, Asp at position 326, Met or Lys at position 330, Asp or Glu at position 332, and Glu at position 334 according to EU numbering in the second polypeptide of the parent Fc region (see claim 12).
The ‘342 application is drawn to the heterodimeric polypeptide of claim 1, wherein: (a) binding activity to at least one Fcy receptor selected from the group consisting of FcyRIa, FcyRIIa, FcyRIIb, and FcyRIIIa is enhanced in the variant Fc region as compared to the parent Fc region; or (b) selectivity between an activating Fcy receptor and an inhibitory Fcy receptor is improved in the variant Fc region as compared to the parent Fc region (see claim 13). The ‘342 application is drawn to the heterodimeric polypeptide of claim 1, which further comprises an antigen binding domain (see claim 15). Specifically, the ’342 application is drawn to heterodimeric polypeptide of claim 15 which is an antibody (see claim 20).
This is a provisional statutory double patenting rejection since the claims directed to the same invention have not in fact been patented.
Non-Statutory 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.
12,371,511 B2
Claims 1-2, 4-5, 9, 12, 15-17, 23, and 25-27 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 and 7-29 of U.S. Patent No. 12,371,511 B2 (patent date: 07/29/2025. Although the claims at issue are not identical, they are not patentably distinct from each other because:
The ‘511 patent is drawn to a molecule comprising a heterodimeric Fc region that is a heterodimer of a first Fc polypeptide and a second Fc polypeptide that differs in amino acid sequence from the first Fc polypeptide, wherein the first Fc polypeptide comprises a hinge region or a part thereof, a first human IgGI CH2 domain and a CH3 domain, wherein the first human IgGI CH2 domain comprises a set of substitutions selected from sets (i) to (vi), and wherein all positions are by EU numbering: (i) substitution of Leu at position 234 with Tyr, Ala, Glu, Gly, His, or Ser, substitution of Leu at position 235 with Tyr, Ala, Glu, Phe, Ile, Leu, Met, Asn, Pro, Gln, Thr, Val, or Trp, substitution of Gly at position 236 with Trp or Tyr, substitution of His at position 268 with Asp, Glu, or Ala, and substitution of Ser at position 298 with Ala; (ii) substitution of Leu at position 234 with Tyr, Ala, Glu, Gly, His, or Ser, substitution of Leu at position 235 with Tyr, Ala, Glu, Phe, Ile, Leu, Met, Asn, Pro, Gln, Thr, Val, or Trp, substitution of Gly at position 236 with Trp or Tyr, substitution of His at position 268 with Asp, Glu, or Ala, substitution of Asp at position 270 with Glu, and substitution of Ser at position 298 with Ala; (iii) substitution of Leu at position 234 with Tyr, Ala, Glu, Gly, His, or Ser, substitution of Leu at position 235 with Tyr, Ala, Glu, Phe, Ile, Leu, Met, Asn, Pro, Gln, Thr, Val, or Trp, substitution of Gly at position 236 with Trp or Tyr, substitution of Ser at position 239 with Met, substitution of His at position 268 with Asp, Glu, or Ala, substitution of Asp at position 270 with Glu, and substitution of Ser at position 298 with Ala; (iv) substitution of Leu at position 234 with Tyr, Ala, Glu, Gly, His, or Ser, substitution of Leu at position 235 with Tyr, Ala, Glu, Phe, Ile, Leu, Met, Asn, Pro, Gln, Thr, Val, or Trp, substitution of Gly at position 236 with Trp or Tyr, substitution of His at position 268 with Asp, Glu, or Ala, substitution of Ser at position 298 with Ala, and substitution of Ala at position 327 with Asp; (v) substitution of Leu at position 234 with Tyr, Ala, Glu, Gly, His, or Ser, substitution of Leu at position 235 with Tyr, Ala, Glu, Phe, Ile, Leu, Met, Asn, Pro, Gln, Thr, Val, or Trp, substitution of Gly at position 236 with Trp or Tyr, substitution of Ser at position 239 with Met, substitution of His at position 268 with Asp, Glu, or Ala, substitution of Ser at position 298 with Ala, and substitution of Ala at position 327 with Asp; (vi) substitution of Leu at position 234 with Tyr, Ala, Glu, Gly, His, or Ser, substitution of Leu at position 235 with Tyr, Ala, Glu, Phe, Ile, Leu, Met, Asn, Pro, Gln, Thr, Val, or Trp, substitution of Gly at position 236 with Trp or Tyr, substitution of Ser at position 239 with Met, substitution of His at position 268 with Asp, Glu, or Ala, substitution of Ser at position 298 with Ala, substitution of Ala at position 327 with Asp, substitution of Leu at position 328 with Trp, and substitution of Lys at position 334 with Ile, Glu, or Asp; and wherein the second Fc polypeptide comprises a hinge region or a part thereof, a second human IgG1 CH2 domain and a CH3 domain, wherein the second human IgG1 CH2 domain comprises a set of substitutions selected from sets (vii) and (viii), and wherein all positions are by EU numbering:(vii) substitution of Lys at position 326 with Thr, Asp, or Ile, substitution of Ala at position 330 with Lys, Pro, Met, or Phe, and substitution of Lys at position 334 with Ile, Glu, or Asp; (viii) substitution of Asp at position 270 with Glu, substitution of Lys at position 326 with Thr, Asp, or Ile, substitution of Ala at position 330 with Lys, Pro, Met, or Phe, and substitution of Lys at position 334 with Ile, Glu, or Asp (see claims 1 and 7-26).
The ’511 patent is drawn to the molecule of claim 1, wherein the molecule is an antibody (see claims 2 and 3).
While the ‘511 claims do not identify what residues are encompassed in the CH2 or CH3 domains, the specification of the ‘511 patent discloses that the CH2 domain refers to positions 231 to 340 (EU numbering) and CH3 domain refers to positions 341 to 447 (EU numbering) (see col. 25, lines 1-4).
As such, the ‘511 patent anticipates the present invention.
11,673,947
Claims 1-2, 4-5, 9-10, 12-13, 15-17, and 22-27 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-51 of U.S. Patent No. 11,673,947 B2 (patent date: 06/13/2023). Although the claims at issue are not identical, they are not patentably distinct from each other because:
The ‘947 patent is drawn to an antigen-binding molecule comprising an antigen-binding domain whose antigen-binding activity varies depending on the concentration of a compound that is present at a higher concentration in a target tissue than in a non-target tissue in a subject, wherein the compound is not the antigen or a fragment thereof and is selected from adenosine, inosine, adenosine monophosphate, cyclic adenosine monophosphate, adenosine diphosphate, and adenosine triphosphate, wherein the antigen-binding domain comprises an antibody heavy-chain variable region and an antibody light-chain variable region; wherein at least one of the following amino acid residues is in the antibody heavy-chain variable region and binds to the compound: Ser at position 52, Ser at position 52a, Arg at position 53, Gly at position 96, Leu at position 100a, and Trp at position 100c, with all positions by Kabat numbering; and wherein that binding to the compound increases the antigen-binding activity of the antigen-binding domain (see claim 1). The ‘947 patent is drawn to the antigen-binding molecule of claim 1, wherein the target tissue is a cancer tissue (see claim 2). The ‘947 patent is drawn to the antigen-binding molecule of claim 1, wherein the antigen-binding molecule comprises an Fc region (see claim 7).
Particularly, the ‘947 patent is drawn to the antigen-binding molecule of claim 7, wherein the Fc region is a modified Fc region whose binding affinity for an Fcγ receptor is increased compared to the binding affinity of a native human IgG Fc region for the Fcγ receptor, wherein the native human IgG Fc region is of the same IgG subclass as the modified Fc region (see claim 9). The ‘947 patent is drawn to the antigen binding molecule of claim 9, wherein the modified Fc region differs from the native human IgG Fc region at one or more of the following EU numbering positions: 221, 222, 223, 224, 225, 227, 228, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 243, 244, 245, 246, 247, 249, 250, 251, 254, 255, 256, 258, 260, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 278, 279, 280, 281, 282, 283, 284, 285, 286, 288, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 311, 313, 315, 317, 318, 320, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 339, 376, 377, 378, 379, 380, 382, 385, 392, 396, 421, 427, 428, 429, 434, 436, 440 (see claims 10 and 13). Specifically, the ‘947 patent is drawn to the antigen-binding molecule of claim 10, wherein at least one of the following EU numbering positions in the modified Fc region is occupied by the indicated amino acid: either Lys or Tyr at position 221; any one of Phe, Trp, Glu, or Tyr at position 222; any one of Phe, Trp, Glu, or Lys at position 223; any one of Phe, Trp, Glu, or Tyr at position 224; any one of Glu, Lys, or Trp at position 225; any one of Glu, Gly, Lys, or Tyr at position 227; any one of Glu, Gly, Lys, or Tyr at position 228; any one of Ala, Glu, Gly, or Tyr at position 230; any one of Glu, Gly, Lys, Pro, or Tyr at position 231; any one of Glu, Gly, Lys, or Tyr at position 232; any one of Ala, Asp, Phe, Gly, His, Ile, Lys, Leu, Met, Asn, Gln, Arg, Ser, Thr, Val, Trp, or Tyr at position 233; any one of Ala, Asp, Glu, Phe, Gly, His, Ile, Lys, Met, Asn, Pro, Gln, Arg, Ser, Thr, Val, Trp, or Tyr at position 234; any one of Ala, Asp, Glu, Phe, Gly, His, Ile, Lys, Met, Asn, Pro, Gln, Arg, Ser, Thr, Val, Trp, or Tyr at position 235; any one of Ala, Asp, Glu, Phe, His, Ile, Lys, Leu, Met, Asn, Pro, Gln, Arg, Ser, Thr, Val, Trp, or Tyr at position 236; any one of Asp, Glu, Phe, His, Ile, Lys, Leu, Met, Asn, Pro, Gln, Arg, Ser, Thr, Val, Trp, or Tyr at position 237; any one of Asp, Glu, Phe, Gly, His, Ile, Lys, Leu, Met, Asn, Gln, Arg, Ser, Thr, Val, Trp, or Tyr at position 238; any one of Asp, Glu, Phe, Gly, His, Ile, Lys, Leu, Met, Asn, Pro, Gln, Arg, Thr, Val, Trp, or Tyr at position 239; any one of Ala, Ile, Met, or Thr at position 240; any one of Asp, Glu, Leu, Arg, Trp, or Tyr at position 241; any one of Leu, Glu, Leu, Gln, Arg, Trp, or Tyr at position 243; His at position 244; Ala at position 245; any one of Asp, Glu, His, or Tyr at position 246; any one of Ala, Phe, Gly, His, Ile, Leu, Met, Thr, Val, or Tyr at position 247; any one of Glu, His, Gln, or Tyr at position 249; either Glu or Gln at position 250; Phe at position 251; any one of Phe, Met, or Tyr at position 254; any one of Glu, Leu, or Tyr at position 255; any one of Ala, Met, or Pro at position 256; any one of Asp, Glu, His, Ser, or Tyr at position 258; any one of Asp, Glu, His, or Tyr at position 260; any one of Ala, Glu, Phe, Ile, or Thr at position 262; any one of Ala, Ile, Met, or Thr at position 263; any one of Asp, Glu, Phe, Gly, His, Ile, Lys, Leu, Met, Asn, Pro, Gln, Arg, Ser, Thr, Trp, or Tyr at position 264; any one of Ala, Leu, Phe, Gly, His, Ile, Lys, Leu, Met, Asn, Pro, Gln, Arg, Ser, Thr, Val, Trp, or Tyr at position 265; any one of Ala, Ile, Met, or Thr at position 266; any one of Asp, Glu, Phe, His, Ile, Lys, Leu, Met, Asn, Pro, Gln, Arg, Thr, Val, Trp, or Tyr at position 267; any one of Asp, Glu, Phe, Gly, Ile, Lys, Leu, Met, Pro, Gln, Arg, Thr, Val, or Trp at position 268; any one of Phe, Gly, His, Ile, Lys, Leu, Met, Asn, Pro, Arg, Ser, Thr, Val, Trp, or Tyr at position 269; any one of Glu, Phe, Gly, His, Ile, Leu, Met, Pro, Gln, Arg, Ser, Thr, Trp, or Tyr at position 270; any one of Ala, Asp, Glu, Phe, Gly, His, Ile, Lys, Leu, Met, Asn, Gln, Arg, Ser, Thr, Val, Trp, or Tyr at position 271; any one of Asp, Phe, Gly, His, Ile, Lys, Leu, Met, Pro, Arg, Ser, Thr, Val, Trp, or Tyr at position 272; either Phe or Ile at position 273; any one of Asp, Glu, Phe, Gly, His, Ile, Leu, Met, Asn, Pro, Arg, Ser, Thr, Val, Trp, or Tyr at position 274; either Leu or Trp at position 275; any one of Asp, Glu, Phe, Gly, His, Ile, Leu, Met, Pro, Arg, Ser, Thr, Val, Trp, or Tyr at position 276; any one of Asp, Glu, Gly, His, Ile, Lys, Leu, Met, Asn, Pro, Gln, Arg, Ser, Thr, Val, or Trp at position 278; Ala at position 279; any one of Ala, Gly, His, Lys, Leu, Pro, Gln, Trp, or Tyr at position 280; any one of Asp, Lys, Pro, or Tyr at position 281; any one of Glu, Gly, Lys, Pro, or Tyr at position 282; any one of Ala, Gly, His, Ile, Lys, Leu, Met, Pro, Arg, or Tyr at position 283; any one of Asp, Glu, Leu, Asn, Thr, or Tyr at position 284; any one of Asp, Glu, Lys, Gln, Trp, or Tyr at position 285; any one of Glu, Gly, Pro, or Tyr at position 286; any one of Asn, Asp, Glu, or Tyr at position 288; any one of Asp, Gly, His, Leu, Asn, Ser, Thr, Trp, or Tyr at position 290; any one of Asp, Glu, Gly, His, Ile, Gln, or Thr at position 291; any one of Ala, Asp, Glu, Pro, Thr, or Tyr at position 292; any one of Phe, Gly, His, Ile, Leu, Met, Asn, Pro, Arg, Ser, Thr, Val, Trp, or Tyr at position 293; any one of Phe, Gly, His, Ile, Lys, Leu, Met, Asn, Pro, Arg, Ser, Thr, Val, Trp, or Tyr at position 294; any one of Asp, Glu, Phe, Gly, His, Ile, Lys, Met, Asn, Pro, Arg, Ser, Thr, Val, Trp, or Tyr at position 295; any one of Ala, Asp, Glu, Gly, His, Ile, Lys, Leu, Met, Asn, Gln, Arg, Ser, Thr, or Val at position 296; any one of Asp, Glu, Phe, Gly, His, Ile, Lys, Leu, Met, Pro, Gln, Arg, Ser, Thr, Val, Trp, or Tyr at position 297; any one of Ala, Asp, Glu, Phe, His, Ile, Lys, Met, Asn, Gln, Arg, Thr, Val, Trp, or Tyr at position 298; any one of Ala, Asp, Glu, Phe, Gly, His, Ile, Lys, Leu, Met, Asn, Pro, Gln, Arg, Ser, Val, Trp, or Tyr at position 299; any one of Ala, Asp, Glu, Gly, His, Ile, Lys, Leu, Met, Asn, Pro, Gln, Arg, Ser, Thr, Val, or Trp at position 300; any one of Asp, Glu, His, or Tyr at position 301; Ile at position 302; any one of Asp, Gly, or Tyr at position 303; any one of Asp, His, Leu, Asn, or Thr at position 304; any one of Glu, Ile, Thr, or Tyr at position 305; any one of Ala, Asp, Asn, Thr, Val, or Tyr at position 311; Phe at position 313; Leu at position 315; either Glu or Gln at position 317; any one of His, Leu, Asn, Pro, Gln, Arg, Thr, Val, or Tyr at position 318; any one of Asp, Phe, Gly, His, Ile, Leu, Asn, Pro, Ser, Thr, Val, Trp, or Tyr at position 320; any one of Ala, Asp, Phe, Gly, His, Ile, Pro, Ser, Thr, Val, Trp, or Tyr at position 322; Ile at position 323; any one of Asp, Phe, Gly, His, Ile, Leu, Met, Pro, Arg, Thr, Val, Trp, or Tyr at position 324; any one of Ala, Asp, Glu, Phe, Gly, His, Ile, Lys, Leu, Met, Pro, Gln, Arg, Ser, Thr, Val, Trp, or Tyr at position 325; any one of Ala, Asp, Glu, Gly, Ile, Leu, Met, Asn, Pro, Gln, Ser, Thr, Val, Trp, or Tyr at position 326; any one of Ala, Asp, Glu, Phe, Gly, His, Ile, Lys, Leu, Met, Asn, Pro, Arg, Thr, Val, Trp, or Tyr at position 327; any one of Ala, Asp, Glu, Phe, Gly, His, Ile, Lys, Met, Asn, Pro, Gln, Arg, Ser, Thr, Val, Trp, or Tyr at position 328; any one of Asp, Glu, Phe, Gly, His, Ile, Lys, Leu, Met, Asn, Gln, Arg, Ser, Thr, Val, Trp, or Tyr at position 329; any one of Cys, Glu, Phe, Gly, His, Ile, Lys, Leu, Met, Asn, Pro, Arg, Ser, Thr, Val, Trp, or Tyr at position 330; any one of Asp, Phe, His, Ile, Leu, Met, Gln, Arg, Thr, Val, Trp, or Tyr at position 331; any one of Ala, Asp, Glu, Phe, Gly, His, Lys, Leu, Met, Asn, Pro, Gln, Arg, Ser, Thr, Val, Trp, or Tyr at position 332; any one of Ala, Asp, Glu, Phe, Gly, His, Ile, Leu, Met, Pro, Ser, Thr, Val, or Tyr at position 333; any one of Ala, Glu, Phe, Ile, Leu, Pro, or Thr at position 334; any one of Asp, Phe, Gly, His, Ile, Leu, Met, Asn, Pro, Arg, Ser, Val, Trp, or Tyr at position 335; any one of Glu, Lys, or Tyr at position 336; any one of Glu, His, or Asn at position 337; any one of Asp, Phe, Gly, Ile, Lys, Met, Asn, Gln, Arg, Ser, or Thr at position 339; either Ala or Val at position 376; either Gly or Lys at position 377; Asp at position 378; Asn at position 379; any one of Ala, Asn, or Ser at position 380; either Ala or Ile at position 382; Glu at position 385; Thr at position 392; Leu at position 396; Lys at position 421; Asn at position 427; either Phe or Leu at position 428; Met at position 429; Trp at position 434; Ile at position 436; any one of Gly, His, Ile, Leu, or Tyr at position 440 (see claims 11 and 14).
The ‘947 patent is drawn to the antigen-binding molecule of claim 1, wherein the antigen-binding molecule is an IgG antibody (see claims 21-22 and 44). The ‘947 patent is drawn to the antigen-binding molecule of claim 15, wherein at least one of the antigen binding domains binds to an antigen expressed on a cancer cell membrane (see claims 17 and 20).
As such, the ‘947 patent anticipates the present invention.
10766960 and Mimoto
Claims 1-2, 4-5, 9-10, 12-13, 15-17, and 22-27 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 10,766,960 in view of Mimoto et al (US 2014/0199294 A1, publication date: 07/17/2014).
The ‘960 patent is drawn to a heterodimer comprising a first polypeptide and a second polypeptide, wherein the first polypeptide comprises an IgG Fc region comprising a set of amino acids selected from the group consisting of sets (a) to (aj) below (all positions by EU numbering): (a) amino acid E at position 234; amino acid Y at position 235; amino acid W at position 236; amino acid M at position 239; amino acid D at position 268; amino acid A at position 298; amino acid D at position 327; (b) amino acid S at position 234; amino acid Y at position 235; amino acid W at position 236; amino acid M at position 239; amino acid D at position 268; amino acid A at position 298; and amino acid D at position 327; (c) amino acid L at position 234; amino acid Q at position 235; amino acid W at position 236; amino acid M at position 239; amino acid D at position 268; amino acid E at position 270; and amino acid A at position 298; (d) amino acid L at position 234; amino acid Y at position 235; amino acid W at position 236; amino acid M at position 239; amino acid D at position 268; amino acid A at position 298; and amino acid D at position 327; (e) amino acid S at position 234; amino acid Q at position 235; amino acid W at position 236; amino acid M at position 239; amino acid D at position 268; amino acid E at position 270; and amino acid A at position 298; (f) amino acid F at position 234; amino acid Q at position 235; amino acid W at position 236; amino acid M at position 239; amino acid D at position 268; amino acid E at position 270; and amino acid A at position 298; (g) amino acid E at position 234; amino acid Q at position 235; amino acid W at position 236; amino acid M at position 239; amino acid D at position 268; amino acid E at position 270; and amino acid A at position 298; (h) amino acid F at position 234; amino acid Y at position 235; amino acid W at position 236; amino acid M at position 239; amino acid D at position 268; amino acid A at position 298; and amino acid D at position 327; (i) amino acid V at position 234; amino acid Q at position 235; amino acid W at position 236; amino acid M at position 239; amino acid D at position 268; amino acid E at position 270; and amino acid A at position 298; (j) amino acid D at position 234; amino acid Q at position 235; amino acid W at position 236; amino acid M at position 239; amino acid D at position 268; amino acid E at position 270; and amino acid A at position 298; (k) amino acid Q at position 234; amino acid Q at position 235; amino acid W at position 236; amino acid M at position 239; amino acid D at position 268; amino acid E at position 270; and amino acid A at position 298;(1) amino acid I at position 234; amino acid Q at position 235; amino acid W at position 236; amino acid M at position 239; amino acid D at position 268; amino acid E at position 270; and amino acid A at position 298; (m) amino acid M at position 234; amino acid Q at position 235; amino acid W at position 236; amino acid M at position 239; amino acid D at position 268; amino acid E at position 270; and amino acid A at position 298; (n) amino acid T at position 234; amino acid Q at position 235; amino acid W at position 236; amino acid M at position 239; amino acid D at position 268; amino acid E at position 270; and amino acid A at position 298;(o) amino acid A at position 234; amino acid Q at position 235; amino acid W at position 236; amino acid M at position 239; amino acid D at position 268; amino acid E at position 270; and amino acid A at position 298; (p) amino acid G at position 234; amino acid Q at position 235; amino acid W at position 236; amino acid M at position 239; amino acid D at position 268; amino acid E at position 270; and amino acid A at position 298; (q) amino acid H at position 234; amino acid Q at position 235; amino acid W at position 236; amino acid M at position 239; amino acid D at position 268; amino acid E at position 270; and amino acid A at position 298; (r) amino acid V at position 234; amino acid Y at position 235; amino acid W at position 236; amino acid M at position 239; amino acid D at position 268; amino acid A at position 298; and amino acid D at position 327; (s) amino acid D at position 234; amino acid Y at position 235; amino acid W at position 236; amino acid M at position 239; amino acid D at position 268; amino acid A at position 298; and amino acid D at position 327; (t) amino acid Q at position 234; amino acid Y at position 235; amino acid W at position 236; amino acid M at position 239; amino acid D at position 268; amino acid A at position 298; and amino acid D at position 327; (u) amino acid I at position 234; amino acid Y at position 235; amino acid W at position 236; amino acid M at position 239; amino acid D at position 268; amino acid A at position 298; and amino acid D at position 327;(v) amino acid M at position 234; amino acid Y at position 235; amino acid W at position 236; amino acid M at position 239; amino acid D at position 268; amino acid A at position 298; and amino acid D at position 327; (w) amino acid T at position 234; amino acid Y at position 235; amino acid W at position 236; amino acid M at position 239; amino acid D at position 268; amino acid A at position 298; and amino acid D at position 327; (x) amino acid A at position 234; amino acid Y at position 235; amino acid W at position 236; amino acid M at position 239; amino acid D at position 268; amino acid A at position 298; and amino acid D at position 327; (y) amino acid G at position 234; amino acid Y at position 235; amino acid W at position 236; amino acid M at position 239; amino acid D at position 268; amino acid A at position 298; and amino acid D at position 327; (z) amino acid H at position 234; amino acid Y at position 235; amino acid W at position 236; amino acid M at position 239; amino acid D at position 268; amino acid A at position 298; and amino acid D at position 327; (aa) amino acid F at position 234; amino acid Q at position 235; amino acid W at position 236; amino acid I at position 239; amino acid D at position 268; amino acid E at position 270; and amino acid A at position 298; (ab) amino acid E at position 234; amino acid Q at position 235; amino acid W at position 236; amino acid I at position 239; amino acid D at position 268; amino acid E at position 270; and amino acid A at position 298; (ac) amino acid D at position 234; amino acid Q at position 235; amino acid W at position 236; amino acid I at position 239; amino acid D at position 268; amino acid E at position 270; and amino acid A at position 298; (ad) amino acid V at position 234; amino acid Y at position 235; amino acid W at position 236; amino acid I at position 239; amino acid D at position 268; amino acid A at position 298; and amino acid D at position 327; (ae) amino acid I at position 234; amino acid Y at position 235; amino acid W at position 236; amino acid I at position 239; amino acid D at position 268; amino acid A at position 298; and amino acid D at position 327; (af) amino acid L at position 234; amino acid Y at position 235; amino acid W at position 236; amino acid I at position 239; amino acid D at position 268; amino acid A at position 298; and amino acid D at position 327; (ag) amino acid E at position 234; amino acid Y at position 235; amino acid W at position 236; amino acid I at position 239; amino acid D at position 268; amino acid A at position 298; and amino acid D at position 327; (ah) amino acid D at position 234; amino acid Y at position 235; amino acid W at position 236; amino acid I at position 239; amino acid D at position 268; amino acid A at position 298; and amino acid D at position 327; (ai) amino acid F at position 234; amino acid Y at position 235; amino acid W at position 236; amino acid I at position 239; amino acid D at position 268; amino acid A at position 298; and amino acid D at position 327; and (aj) amino acid T at position 234; amino acid Y at position 235; amino acid W at position 236; amino acid I at position 239; amino acid D at position 268; amino acid A at position 298; and amino acid D at position 327; and the second polypeptide comprises an IgG Fe region that is different from the Fe region of the first polypeptide and comprises a set of amino acids selected from the group consisting of sets (ak) to (aq) (all positions by EU numbering): (ak) amino acid E at position 270; amino acid D at position 326; amino acid K at position 330; and amino acid E at position 334; (al) amino acid E at position 270; amino acid D at position 326; amino acid M at position 330; and amino acid E at position 334;(am) amino acid E at position 270; amino acid D at position 326; amino acid A at position 330; and amino acid E at position 334; (an) amino acid E at position 270; amino acid D at position 326; amino acid F at position 330; and amino acid E at position 334; (ao) amino acid E at position 270; amino acid D at position 326; amino acid I at position 330; and amino acid E at position 334; (ap) amino acid E at position 270; amino acid D at position 326; amino acid Y at position 330; and amino acid E at position 334; and (aq) amino acid E at position 270; amino acid D at position 326; amino acid H at position 330; and amino acid E at position 334 (see claim 1).
The ‘960 patent is drawn to the claimed heterodimer, wherein the heterodimer is an antibody (see claim 5). The ‘960 patent is drawn to the claimed heterodimer, wherein, when compared to a naturally occurring IgG Fc region, the IgG Fc regions of the first and second polypeptides together exhibit an alteration of function selected from the group consisting of enhanced binding to an Fcy receptor, or increased selectivity of binding to one Fcy receptor over another (see claims 12-16).
The ‘960 patent, however, fails to teach of the second polypeptide comprising alterations at position 236 and 298. Further, the ‘960 patent fails to teach of the variant second polypeptide comprising amino acid alterations at positions 250 and 307 in the first or second polypeptide chains. However, Mimoto et al disclose of a heterodimerized polypeptide having an Fc region formed from two polypeptides with different amino acid sequences (a first polypeptide and a second polypeptide), and succeeded in producing a heterodimerized polypeptide containing an Fc region with improved Fc region function compared to that of a homodimer (see Abstract and claims). Additionally, Mimoto et al disclose that the site to be altered is not particularly limited as long as it is in an Fc region, and it can be appropriately set within a range that can achieve the objectives of the present invention and examples include the hinge region, CH2 region, and CH3 region; wherein the CH2 domain refers to positions 231 to 340 (EU numbering) and the CH3 domain refers to positions 341 to 447 (EU7 numbering) (see [0154]-[0157]). Thus, positions 250 and 307 are encompassed within the invention.
As such, the teachings of the ‘960 patent and Mimoto et al make obvious the present invention. Applicant’s attention is drawn to MPEP 2144.05(II)(A), Routine Optimization - Optimization Within Prior Art Conditions or Through Routine Experimentation:
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree “will not sustain a patent”); In re Williams, 36 F.2d 436, 438 (CCPA 1929) (“It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.”). See also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007) (identifying “the need for caution in granting a patent based on the combination of elements found in the prior art.”).
Although this passage does not specifically point to, for example, amino acid alterations, this passage points to numerous variables that affect the function of inventions, such as concentration of reagents and temperature ranges. Furthermore this passage indicates that the optimization of such variables is often obvious activity for one of ordinary skill in the art. It is submitted that the claimed amino acid alterations are akin to the variables discussed in the cited MPEP passage, because said amino acid alterations are optimizable variables that would affect at least the toxicity and/or efficacy, i.e., function, of the claimed invention. Given the “normal desire of scientists or artisans to improve upon what is already generally known,” it would have been prima facie obvious to one of ordinary skill in the art to optimize the claimed amino acid alterations, because such optimization would produce a more effective invention.
Also as set forth in MPEP 2144.05(II)(B), There is a Motivation to Optimize Result-Effective Variables:
In In re Antonie, 559 F.2d 618, 195 USPQ 6 (CCPA 1977), the CCPA held that a particular parameter must first be recognized as a result-effective variable, i.e., a variable which achieves a recognized result, before the determination of the optimum or workable ranges of said variable might be characterized as routine experimentation, because “obvious to try” is not a valid rationale for an obviousness finding. In KSR International Co. v. Teleflex Inc., 550 U.S. 398 (2007), the Supreme Court held that “obvious to try” was a valid rationale for an obviousness finding, for example, when there is a “design need” or “market demand” and there are a “finite number” of solutions. 550 U.S. at 421 (“The same constricted analysis led the Court of Appeals to conclude, in error, that a patent claim cannot be proved obvious merely by showing that the combination of elements was ‘[o]bvious to try.’ ... When there is a design need or market pressure to solve a problem and there are a finite number of identified, predictable solutions, a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense. In that instance the fact that a combination was obvious to try might show that it was obvious under §103.”). Thus, after KSR, the presence of a known result-effective variable would be one, but not the only, motivation for a personal of ordinary skill in the art to experiment to reach another workable product or process.
In the instant case, the claims are drawn to amino acid alterations which achieves a recognized result, such as drug toxicity and/or therapeutic benefit. Accordingly the recited amino acid alterations are result-effective variables that achieve a recognized result, such as drug toxicity and/or therapeutic benefit for a patient with a tumor, and it is submitted that since one of ordinary skill in the art would have thus been motivated to determine the optimum or workable ranges of said variables, the amino acid alterations recited were prima facie obvious to one of ordinary skill in the art.
9890218 and Mimoto
Claims 1-2, 4-5, 9-10, 12-13, 15-17, and 22-27 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-39 of U.S. Patent No. 9,890,218 in view of Mimoto et al (US 2014/0199294 A1, publication date: 07/17/2014).
The ‘218 patent is drawn to a molecule comprising a heterodimeric Fc region that is a heterodimer of a first polypeptide comprising a first CH2 domain and a second polypeptide comprising a second CH2 domain that differs in amino acid sequence from the first CH2 domain, wherein the first CH2 domain is an IgGI CH2 domain comprising a set of amino acid mutations selected from sets (i)-(vi) (all positions by EU numbering): (i) substitution of L at position 234 with Y, substitution of L at position 235 with Y, substitution of G at position 236 with W, substitution of H at position 268 with D, and substitution of S at position 298 with A; (ii) substitution of L at position 234 with Y, substitution of L at position 235 with Y, substitution of G at position 236 with W, substitution of H at position 268 with D, substitution of D at position 270 with E, and substitution of S at position 298 with A; (iii) substitution of L at position 234 with Y, substitution of L at position 235 with Q, substitution of G at position 236 with W, substitution of S at position 239 with M, substitution of H at position 268 with D, substitution of D at position 270 with E, and substitution of S at position 298 with A; (iv) substitution of L at position 234 with Y, substitution of L at position 235 with Y, substitution of G at position 236 with W, substitution of H at position 268 with D, substitution of S at position 298 with A, and substitution of A at position 327 with D; (v) substitution of L at position 234 with Y, substitution of L at position 235 with Y, substitution of G at position 236 with W, substitution of S at position 239 with M, substitution of H at position 268 with D, substitution of S at position 298 with A, and substitution of A at position 327 with D; (vi) substitution of L at position 234 with Y, substitution of L at position 235 with Y, substitution of G at position 236 with W, substitution of S at position 239 with M, substitution of H at position 268 with D, substitution of S at position 298 with A, substitution of A at position 327 with D, substitution of L at position 328 with W, and substitution of K at position 334 with L; and the second CH2 domain is an IgGI CH2 domain comprising a set of amino acid mutations selected from sets (vii)-(ix) (all positions by EU numbering): (vii) substitution of K at position 326 with D, substitution of A at position 330 with M, and substitution of K at position 334 with E; (viii) substitution of D at position 270 with E, substitution of K at position 326 with D, substitution of A at position 330 with M, and substitution of K at position 334 with E; (ix) substitution of D at position 270 with E, substitution of K at position 326 with D, substitution of A at position 330 with K, and substitution of K at position 334 with E (see claim 1).
The ‘218 patent is drawn to the claimed heterodimer, wherein the heterodimer is an antibody (see claims 5 and 6). The ‘218 patent is drawn to the generated molecule has increased binding affinity for an Fc receptor or selectivity of binding to one type of Fc receptor over another type of Fc receptor (see claims 9-12).
The ‘218 patent, however, fails to teach of the second polypeptide comprising alterations at position 236 and 298. Further, the ‘218 patent fails to teach of the variant second polypeptide comprising amino acid alterations at positions 250 and 307 in the first or second polypeptide chains. However, Mimoto et al disclose of a heterodimerized polypeptide having an Fc region formed from two polypeptides with different amino acid sequences (a first polypeptide and a second polypeptide), and succeeded in producing a heterodimerized polypeptide containing an Fc region with improved Fc region function compared to that of a homodimer (see Abstract and claims). Additionally, Mimoto et al disclose that the site to be altered is not particularly limited as long as it is in an Fc region, and it can be appropriately set within a range that can achieve the objectives of the present invention and examples include the hinge region, CH2 region, and CH3 region; wherein the CH2 domain refers to positions 231 to 340 (EU numbering) and the CH3 domain refers to positions 341 to 447 (EU numbering) (see [0154]-[0157]). Thus, positions 250 and 307 are encompassed within the invention.
As such, the teachings of the ‘218 patent and Mimoto et al make obvious the present invention. Applicant’s attention is drawn to MPEP 2144.05(II)(A), Routine Optimization - Optimization Within Prior Art Conditions or Through Routine Experimentation:
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree “will not sustain a patent”); In re Williams, 36 F.2d 436, 438 (CCPA 1929) (“It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.”). See also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007) (identifying “the need for caution in granting a patent based on the combination of elements found in the prior art.”).
Although this passage does not specifically point to, for example, amino acid alterations, this passage points to numerous variables that affect the function of inventions, such as concentration of reagents and temperature ranges. Furthermore this passage indicates that the optimization of such variables is often obvious activity for one of ordinary skill in the art. It is submitted that the claimed amino acid alterations are akin to the variables discussed in the cited MPEP passage, because said amino acid alterations are optimizable variables that would affect at least the toxicity and/or efficacy, i.e., function, of the claimed invention. Given the “normal desire of scientists or artisans to improve upon what is already generally known,” it would have been prima facie obvious to one of ordinary skill in the art to optimize the claimed amino acid alterations, because such optimization would produce a more effective invention.
Also as set forth in MPEP 2144.05(II)(B), There is a Motivation to Optimize Result-Effective Variables:
In In re Antonie, 559 F.2d 618, 195 USPQ 6 (CCPA 1977), the CCPA held that a particular parameter must first be recognized as a result-effective variable, i.e., a variable which achieves a recognized result, before the determination of the optimum or workable ranges of said variable might be characterized as routine experimentation, because “obvious to try” is not a valid rationale for an obviousness finding. In KSR International Co. v. Teleflex Inc., 550 U.S. 398 (2007), the Supreme Court held that “obvious to try” was a valid rationale for an obviousness finding, for example, when there is a “design need” or “market demand” and there are a “finite number” of solutions. 550 U.S. at 421 (“The same constricted analysis led the Court of Appeals to conclude, in error, that a patent claim cannot be proved obvious merely by showing that the combination of elements was ‘[o]bvious to try.’ ... When there is a design need or market pressure to solve a problem and there are a finite number of identified, predictable solutions, a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense. In that instance the fact that a combination was obvious to try might show that it was obvious under §103.”). Thus, after KSR, the presence of a known result-effective variable would be one, but not the only, motivation for a personal of ordinary skill in the art to experiment to reach another workable product or process.
In the instant case, the claims are drawn to amino acid alterations which achieves a recognized result, such as drug toxicity and/or therapeutic benefit. Accordingly the recited amino acid alterations are result-effective variables that achieve a recognized result, such as drug toxicity and/or therapeutic benefit for a patient with a tumor, and it is submitted that since one of ordinary skill in the art would have thus been motivated to determine the optimum or workable ranges of said variables, the amino acid alterations recited were prima facie obvious to one of ordinary skill in the art.
18/022,342
Claims 5, 16-17, and 26-27 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5-6, 10-13, and 15-20 of copending Application No. 18/022,342 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because:
The ‘342 application is drawn to a heterodimeric polypeptide which comprises a variant Fc region comprising amino acid alterations as compared to a parent Fc region, wherein the parent Fc region is composed of a first polypeptide and a second polypeptide, and wherein the variant Fc region comprises amino acid alterations at the following positions as compared to the parent Fc region: (A) (i) positions 234, 235, 236, 239, 268, 270, and 298 according to EU numbering in the first polypeptide of the parent Fc regions and (ii) positions 270, 298, 326, and 334 according to EU numbering in the second polypeptide of the parent Fc region; (B) (i) positions 234, 235, 236, 239, 268, 270, 298, and 326 according to EU numbering in the first polypeptide of the parent Fc region, and (ii) positions 236, 270, 298, 326, and 334 according to EU numbering in the second polypeptide of the parent Fc region; or (C) (i) positions 234, 235, 236, 239, 268, 270, 298, 330, and 332 according to EU numbering in the first polypeptide of the parent Fc region, and (ii) positions 236, 270, 298, 326, 330, 332, and 334 according to EU numbering in the second polypeptide of the parent Fc region (see claim 1). The ‘342 application is drawn to the heterodimeric polypeptide of claim 1, which comprises at least one amino acid alteration as compared to the parent Fc region selected from the following amino acid alterations: (i) Tyr or Phe at position 234, Gln or Tyr at position 235, Trp at position 236, Met at position 239, Val at position 250, Asp at position 268, Glu at position 270, Ala at position 298, Pro at position 307, Asp at position 326, Met at position 330, and Glu at position 332 according to EU numbering in the first polypeptide of the parent Fc region; and (ii) Ala at position 236, Val at position 250, Glu at position 270, Ala at position 298, Pro at position 307, Asp at position 326, Met or Lys at position 330, Asp or Glu at position 332, and Glu at position 334 according to EU numbering in the second polypeptide of the parent Fc region (see claim 12).
The ‘342 application is drawn to the heterodimeric polypeptide of claim 1, wherein: (a) binding activity to at least one Fcy receptor selected from the group consisting of FcyRIa, FcyRIIa, FcyRIIb, and FcyRIIIa is enhanced in the variant Fc region as compared to the parent Fc region; or (b) selectivity between an activating Fcy receptor and an inhibitory Fcy receptor is improved in the variant Fc region as compared to the parent Fc region (see claim 13). The ‘342 application is drawn to the heterodimeric polypeptide of claim 1, which further comprises an antigen binding domain (see claim 15). Specifically, the ’342 application is drawn to heterodimeric polypeptide of claim 15 which is an antibody (see claim 20).
As such, the ‘342 application anticipates the present invention.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
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/DANAYA L MIDDLETON/Examiner, Art Unit 1674
/VANESSA L. FORD/Supervisory Patent Examiner, Art Unit 1674