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 .
Priority
This application is a U.S. national phase of International Application No. PCT/EP2020/077609, filed on 10/01/2024. This application claims priority to United Kingdom of Great Britain and Northern Ireland Application Nos. GB1914165.4, filed 10/01/2019; GB1917059.6, filed 11/22/2019; and GB2008248.3, filed 06/02/2020. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Claim Status
The amendment, filed on 09/30/2025, in which claims 31, 36, and 39-50 are amended; claims 1-30, 32-35, 37, and 38 are canceled; and claims 31-50 are new, is acknowledged. Claims 31, 36, and 39-52 are pending in the instant application and are examined on the merits herein.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 09/30/2025 has been considered by the examiner.
Withdrawn Objections and Rejections
In the office action dated 06/03/2025,
The drawings (Figures 2-3, 5-9, 12, 14, 16, 17 and 19) were objected to for non-compliance with 37 CFR 1.84 standards. Applicant’s submission of replacement drawing sheets in compliance with 37 CFR 1.121(d) have overcome the objections and the objections are withdrawn.
The specification was objected to for minor informalities in the text and for containing an embedded hyperlink. Applicant’s submission of an amended specification with appropriate corrections has overcome the objections and the objections are withdrawn.
The specification was further objected to for failing to provide proper antecedent basis for the claimed subject matter “immunologic binding agent”. Applicant’s amendment to remove this claimed subject matter has overcome the objection and the objection is withdrawn.
The claims were objected to for lack of singular of dependency between claims 37-39. Applicant’s cancelation of claims 37-38 has rendered the objection moot and the objection is withdrawn.
Claim 41 was rejected under 35 USC 112(b) for reciting “the mutation” with insufficient antecedent basis. Applicant’s amendment to the claim has overcome the rejection and the rejection is withdrawn.
Claims 32-35 and 37-38 were rejected under 35 USC 112(a) as failing to comply with the written description requirement. Applicant’s cancellation of the claims has rendered the rejections moot and the rejections are withdrawn.
Claims 43, 44, and 47-49 were rejected under 35 USC 112(a) as lacking enablement for the recited antibodies having variation in sequences containing critical binding epitopes. Applicant’s arguments, see Remarks filed 09/30/2025 (pg. 12-14), have been fully considered and are persuasive, therefore the 112(a) enablement rejections of claims 43, 44, and 47-49 are withdrawn.
Claims 31-34 and 50 were rejected under 35 USC 102(a)(1) as being anticipated by Sigal as evidenced by Booth. Applicants cancellation of claims 32-34 has rendered these rejections moot and the rejections are withdrawn. Applicant’s amendment to claim 31 to recite a “hybrid antibody comprising one or more variable domains” upon which claim 50 is dependent has overcome the rejection for claims 31 and 50 and the rejections are withdrawn. However, upon further consideration, new grounds of rejection are made in view of newly found prior art.
Claims 32-34 were provisionally rejected on the grounds of nonstatutory double patenting over copending Application No. 17/764,850. Applicant’s cancellation of the claims has rendered the rejections moot and the rejections are withdrawn.
The following grounds of objections and/or rejections are either maintained or necessitated by applicant’s amendment to the claims.
Specification
The use of the terms as noted office action dated 06/03/2025, which are trade name or marks used in commerce, has been noted in this application. While applicant has amended the specification for capitalization of terms, many do not 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.
Modified Claim Rejections - 35 USC § 112(a)
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 31, 36, 41, 43-49 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.
Regarding claim 31, the instant claim is drawn to a hybrid antibody that binds an Fc[Symbol font/0x65] receptor (Fc[Symbol font/0x65]R) and a neonatal Fc receptor (FcRn), comprising one or more variable domains; and a C[Symbol font/0x65]2 domain, a C[Symbol font/0x65]3 domain, and a C[Symbol font/0x65]4 domain wherein (a) the hybrid antibody comprises a binding site for FcRn derived from an IgG antibody; OR (b) FcRn binding is provided by one or more amino acid substitutions in at least one Fc domain of a tetrameric IgE, wherein the amino acid substitution in the IgG comprise non-native histidine residues present at a corresponding position in an IgG.
Regarding limitation (a), by broadest reasonable interpretation of the instant claim, a “hybrid antibody” that binds an Fc[Symbol font/0x65]R and a FcRn with a “binding site for FcRn derived from an IgG antibody” does not limit wherefrom the IgG molecule the residues are derived. While the specification discloses “the FcRn receptor binding site may be provided by way of one or more sequences derived from IgG found in one or more constant domains of IgG” (pg. 7, lines 3-4) limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Thus, as currently written, the claim includes embodiments drawn to hybrid antibody wherein the FcRn binding domain could be derived from variable domains an IgG with an FcRn specific antigen binding domain fused to IgE Fc domain (i.e. site of Fc[Symbol font/0x65]R binding), and therefore does not exclude a genus of antibodies defined by function instead of structure. MPEP 2173.05(g) teaches that “Unlimited functional claim limitations that extend to all means or methods of resolving a problem may not be adequately supported by the written description or may not be commensurate in scope with the enabling disclosure, both of which are required by 35 U.S.C. 112(a) and pre-AIA 35 U.S.C. 112, first paragraph. In re Hyatt, 708 F.2d 712, 714, 218 USPQ 195, 197 (Fed. Cir. 1983); Ariad, 598 F.3d at 1340, 94 USPQ2d at 1167. In this case, the antibodies claimed are based on the epitope to which they bind, not the structure of the antibody that would result in the claimed epitope binding. The instant disclosure does not demonstrate an adequate number of species of the claimed genus nor does it adequately describe the structure required to achieve the claimed function in such a way as to demonstrate to a skilled artisan that applicant was in possession of the genus as claimed at the time of filing.
Regarding limitation (b), the limitation is drawn to one or more amino non-native histidine substitutions in at least one Fc domain of a tetrameric IgE domain (corresponding to histidine positions in native IgG) that facilitates binding to FcRn. By broadest reasonable interpretation, the claim encompasses IgE histidine mutations that correspond to any IgG native histidine residues (i.e. species variants and isoforms).
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, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., 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 applicant was in possession of the claimed genus. However, the state of the art near the effective filing date of the claimed invention demonstrates that there is no sufficient correlation between the structure of the modification and required function.
The specification defines “hybrid antibody” as one whose structure is derived from more than one class of antibody and “is typically the Fc region that is a hybrid” (page 6, lines 3-4). Moreover, the specification discloses hybrid antibodies wherein the IgG and IgE derived species are restricted to the Fc domain (Example 1; page 32, line 22- page 33, line 9) though only a construct containing heavy chain with full IgE Fc plus IgG1 Hinge-CH2-CH3 (xiv) were confirmed to bind both FcRn and FcεR (Table 8, Table 9, Figure 14(b), Figure 16(b)). Furthermore, of non-native histidine mutations the specification only provides examples comprising one or more of T78H, S95H, and Q98H. Therefore, the aforementioned hybrid antibodies are not commensurate in scope with the claims as described above.
Wurzburg (previously cited) teaches IgG histidine domains that vary depending on isoform (i.e. IgG1 vs IgG4) and species (i.e. human vs mouse) (page 376; Figure 1B legend - annotated below with arrows indicating potential IgE non-native histidine residues that correspond to an IgG molecule; and black arrowheads indicating mutated residues from the instant disclosure). Notably, one of the human specific IgG histidine residues corresponds to the first FcεR binding loop (pink color bar - residue P365).
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Presta (Presta L, Shields R, O'Connell L, et al. The binding site on human immunoglobulin E for its high affinity receptor. J Biol Chem. 1994;269(42):26368-26373) teaches that IgE Fc point mutations with different amino acids can differentially affect IgE-FcεR binding affinity (Table 1). Furthermore, swapping full IgE loops for structural analogues in IgG can prevent or reduce FcεR binding (e.g. loop AB in Cε3 identical to instant SEQ ID NO: 4)).
Farrington (US 2007/0148164A1, pub. date: 6/28/2007) similarly discloses that IgG Fc point mutations at different positions with different amino acid modifications, even at same positions with different amino acid modifications (for example K288D, K288E and K288M) affect IgG-FcRn binding differently (Figure 7).
Booth (Booth BJ, Ramakrishnan B, Narayan K, et al. Extending human IgG half-life using structure-guided design. MAbs. 2018;10(7):1098-1110) teaches that while certain mutations may optimize affinity for FcRn binding, binding to other affinity receptors and downstream effector functions (i.e. antibody-dependent cell-mediated cytotoxicity) can be compromised as a result (page 1098, column 2, ¶ 2). Furthermore, while certain mutations can individually destabilize CH domains (T256D/H285D/Q311V), introduction of additional otherwise non-functional mutations (T307R) can compensate to provide thermal stability (page 1103, column 1, ¶ 1), demonstrating that the full mutational landscape (i.e. the effects of multiple mutations) can unpredictably affect FcRn binding .
The effects of individual mutations combine to impact the overall stability and function of a protein is unpredictable. Thus, the effects of any given non-native histidine mutation derived from any IgG or combination of said mutations can differ depending on the position(s) modified. Some mutations may have no discernible effect on the protein function, some may lead to varying degrees of instability or functional impairment, and some may actually improve protein activity or impart other desirable properties, such as improved stability. One skilled in art cannot predict the stability and function of the broadly claimed fragments, variants and derivatives, thus cannot visualize or recognize the members of the genus.
Examiner recommends amending the claim to recite “a hybrid Fc domain antibody”, explicitly restricting the variability to the Fc domain, and further reciting specific mutations that facilitate both FcεR and FcRn binding to overcome current issues with written description.
Regarding Claims 36, 41, 43, 44, and 47-49, instant claim 36 is drawn to the hybrid antibody of claim 31, comprising: (i) at least one amino acid substitution in C[Symbol font/0x65]3 of IgE;(ii) at least one amino acid substitution in C[Symbol font/0x65]4 of IgE; and/or (iii) one amino acid substitution in C[Symbol font/0x65]3 and two amino acid substitutions in C[Symbol font/0x65]4 of IgE; and instant claims 41, 43, 44, and 47-49 are drawn to derivatives of the hybrid antibody of claim 31 having 90%, 95%, or 99% identity to specific sequences.
As discussed above, the base claim 31 does not necessarily limit the mutations to non-native histidine residues present at a corresponding position in an IgG (“or” as recited between limitations (a) and (b)) and thus the instant claims by broadest reasonable interpretation does not exclude a genus of hybrid antibodies with various residue substitutions along the entirety of IgE C[Symbol font/0x65]3 and C[Symbol font/0x65]4 or those up to 90% identity to various sequences as recited in dependent claims. The specification does not adequately describe all the species encompassed by said genus that would predictably maintain dual Fc[Symbol font/0x65]R and FcRn binding nor with up to 90% identity to various sequences as recited in dependent claims.
The specification discloses various variant/hybrid species (Example 1; page 32, line 22- page 33, line 9), though only one species containing heavy chain with IgE plus IgG1 Hinge-CH2-CH3 (xiv) was confirmed to bind both FcRn and FcεR (Table 8, Table 9, Figure 14(b), Figure 16(b)).
Therefore, the aforementioned hybrids are not commensurate in scope with the claims which encompasses hybrid species comprising substitutions in C[Symbol font/0x65]3 domain and/or C[Symbol font/0x65]4 domains as recited in claim 36, or sequences with less than 100% identity to disclosed mutated sequences as recited in claims 41, 43, 44, and 47-49 that does not restrict the locations and/or residues of mutation to predictably maintain both FcRn and FcεR binding (i.e. issues presented under the base claim), these claims were found to not meet the written description requirement of 35 USC 112(a).
Response to Arguments - 35 USC § 112(a)
Applicant's arguments filed 09/30/2025 have been fully considered but they are not persuasive.
Applicant states:
“As described by the specification at page 6, lines 23-26, the "amino acid substitution may be
made in either or both of Ce3 and Ce4 of IgE. The substitution may be replacement of a
native residue in IgE with an amino acid found at a corresponding position in IgG, so that
the FcRn binding property of IgG may be imparted into IgE." This strategy "transfer[s] IgG
functionality onto an IgE background'' as described in the application at page 7, line 6” (Remarks, page 11, ¶ 2)
In response to applicant’s argument regarding amended claims, the claim amendments do not rectify written description issues as discussed above. Although the claims are interpreted in light of the specification, limitations from the specification (i.e. restricting substitutions to Fc domains or specific embodiments) are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Applicant states:
“The specification demonstrates a correlation between the structure of the Fc domain
of the hybrid antibodies and its function. Namely, the specification describes the IgG
regions and amino acids (i.e., structures) that confer FcRn binding (i.e., functions) to IgE.” (Remarks, page 12, ¶ 2)
As discussed above, the base claim recites the hybrid antibody binds FcRn in addition to FcεR, as discussed above mutating residues in the Fc domain can have unpredictable effects to Fc receptor binding. Therefore, while transplanting IgG residues into IgE may allow said IgE variants to bind to FcRn, these residue substitutions may negatively affect native FcεR binding. Therefore, without specific binding data to verify dual binding activity, a skilled artisan would not recognize that the instant inventors provide sufficient description for possession of the claimed genus.
Applicant states:
“Moreover, claim 36 further limits claim 31 by specifying the numbers and locations
of the substitutions recited by claim 31 (i.e., at least one amino acid substitution in Ce3 of
IgE; at least one amino acid substitution in Ce4 of IgE; and/or one amino acid substitution
in Ce3 and two amino acid substitutions in Ce4 of IgE) (Remarks, page 12, ¶ 3)
In response to applicant’s argument regarding claim 36, the base claim does not necessarily restrict mutations to non-native histidine residues as the limitation is included after an “or” statement. Therefore, the mutated residues encompass species under limitation (a) which could include any residue derived from an IgG involved in FcRn binding, which as discussed above does not meet written description requirements.
Applicant states:
“As amended, claims 41, 43, 44, and 47-49 do not recite a minimum 85% identity and instead
recite at least "90%, 95%, or 99% sequence identity'' Applicant requests the Office to
withdraw the rejection.” (Remarks, page 12, ¶ 4)
In response to applicant’s argument regarding claims 41, 43, 44, and 47-49, as discussed above, the base claim (31) does not necessarily restrict mutations to non-native histidine residues as the limitation is included after an “or” statement, which encompass species under limitation (a) which could include any residue derived from an IgG involved in FcRn binding, which as discussed above does not meet written description requirements. Therefore, sequences with less than 100% identity to the recited sequences encompasses species, which could include any residue derived from an IgG involved in FcRn binding, and therefore the instant claims do not meet written description requirements.
Modified Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 31, 36-43, 45, and 51-52 are rejected under 35 U.S.C. 103 as being unpatentable over WO 93/04173 (herein Jardieu), Booth (cited above), and Wurzburg (Wurzburg BA, Garman SC, Jardetzky TS. Structure of the human IgE-Fc C epsilon 3-C epsilon 4 reveals conformational flexibility in the antibody effector domains. Immunity. 2000;13(3):375-385).
Jardieu teaches variants of IgE Fc residues and mutational differences in FcεR binding. While substituting whole IgE loops for analogous IgG1 loops can reduce affinity for FcεRI binding, mutating individual residues maintained homologous receptor binding (page 56, lines 3-5; e.g. Table 6, mutant 4 identical to EF loop mutation in Table 11; page 74, line 5). Furthermore, Jardieu teaches some mutations facilitate differential binding affinity; T78H mutation in Cε3 improves affinity for FcεRI (Table 11; Loop EF – mutant 86 - identical to instant SEQ ID NO: 31). Jardieu also teaches that mutating Cε4 residues ASPSQT (SEQ ID NO: 61) with LHNHY (SEQ ID NO: 62; e.g. S95H and Q98H instant mutations) does not significantly change FcεR affinity.
While Jardieu teaches substitution of IgE Fc residues for those found in IgG1 can have varying effects on homologous FcεR binding, Jardieu does not discuss whether these mutations can also facilitate heterologous Fc Receptor binding (e.g. variant IgE that can bind FcRn – an IgG specific receptor).
Booth teaches that the relatively high IgG serum half-life is attributed to interaction with FcRn and this binding is enhanced at pH 6.0 in comparison to neutral pH (i.e. 7.4) (page 1098, ¶ 1-2). This interaction is driven by histidine residues at positions 310 and 435 (Kabat numbering), which undergo protonation at acidic pH to make critical contacts with the FcRn receptor (page 1099, column 1, ¶ 3). This interaction is also influenced by pH dependent lateral displacement of the 250-helix and helix resident residues M252, I253, and S254 (page 1101, column 2). However, Booth does not discuss IgG Fc homology with IgE Fc domains.
Wurzburg teaches that the Cε3 and Cε4 domains are respectively homologous to Cγ2 and Cγ3 domains based on quaternary structure, despite only 32% sequence identity (page 375, column 2, ¶ 3; Figure 1B - shown above and annotated with residues corresponding to instant mutations indicated with black triangles; structural differences are highlighted in the sequence). This structure based alignment reveals IgG FcRn residues H310 and H435 analogous to IgE T407 and Q535 (residues T78 and Q98 from instant application), respectively, but IgG1 residue I253 is structurally distinct from IgE as it is accommodated as a bulge after the AB helix (page 376; Figure 1B legend). Wurzburg teaches that the conserved IgG isoleucine and adjacent residues form a shallow pocket that interacts with similarly conserved histidine on the EF helix (page 380, column 2, ¶ 4; Figure 4D). In contrast, IgE AB helix residues interact primarily with Cε4 domain and contacts with the EF helix are limited (page 381, ¶ 3).
One of ordinary skill would recognize that IgE mutations taught by Jardieu, which structurally fall within species of hybrid antibodies as recited in the instant claims, correspond to IgG1 residues H310 and H435 responsible for FcRn binding as taught by Booth based on structure based alignment taught by Wurzburg. Furthermore, while IgG1 interactions with FcRn are also dependent on I253 because of IgG1 of nacent AB and EF helix interactions, one of ordinary skill would recognize these interactions are not important in IgE where the AB isoleucine bulge is absent as taught by Wurzburg. Therefore, it would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention that histidine mutations in corresponding IgE Fc residues as claimed would facilitate binding of FcRn without negatively impacting FcεR binding, and a skilled artisan would be motivated to incorporate said mutations to increase the serum half-life of functional IgE antibodies as taught by Booth.
Claims 44, 46, and 47-50 are rejected under 35 U.S.C. 103 as being unpatentable over Jardieu, Booth, and Wurzburg as applied to claim 31 above, and further in view of US 9,783,613 B2 (herein Karagiannis).
The combined teachings of Jardieu, Booth and Wurzburg teach claim 31, an immunologic binding agent with variant IgE Fc capable of binding FcεR and FcRn, as discussed previously. However, Jardieu, Booth and Wurzburg do not construct mutants from antibodies that bind to cancer antigens (e.g. trastuzumab).
Karagiannis teaches an antibody or functional fragment thereof capable of binding HMW-MAA with an IgE isotype (Figure 1B). The antibodies disclosed have identity to sequences within the claimed identity range of at least 90%, 95%, or 99% (alignments below).
Karagiannis also teaches a pharmaceutical composition of the antibody with CDRs disclosed in SEQ ID NO:7 and SEQ ID NO:8 (alignments below) and a pharmaceutically acceptable carrier (claims 1, 10, and 11). This IgE isotype antibody improved melanoma tumor growth restriction and infiltration of immune effector cells in tumor lesions in antigen-specific manner in comparison with corresponding IgG1 isotype (column 31, ¶ 3; Figure 8).
Qy = Instant SEQ ID NO:186; Db = Karagiannis SEQ ID NO:7
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Qy = Instant SEQ ID NO:188; Db = Karagiannis SEQ ID NO:7
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Qy = Instant SEQ ID NO:187; Db = Karagiannis SEQ ID NO:8
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One of ordinary skill in the art would recognize that the HMW-MAA IgE isotype antibody as taught by Karagiannis can additionally be modified to further increase anti-tumor function by increasing serum half-life (i.e. via mutations to enable FcRn affinity). It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to combine the histidine mutations as taught by the combined teachings of Jardieu, Booth, and Wurzburg with the HMW-MAA IgE isotype antibody taught by Karagiannis to generate an improved anti-cancer therapeutic with comparable half-life to IgG1 counterparts.
Response to Arguments - 35 USC § 103
Applicant's arguments filed 09/30/2025 have been fully considered but they are not persuasive.
Applicant states:
“Applicant respectfully asserts that the Office combined Jardieu, Booth, and Wurzburg using hindsight reasoning. One of ordinary skill in the art would not have been motivated to combine these three unrelated documents prior to Applicant's filing.” (Remarks, page 16, ¶ 1)
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). In this instance Jardieu teaches chimeric IgE/IgG molecules that fall within the scope of the instant claims (e.g. instant SEQ ID NO:31 and mutations corresponding to S95H and Q98H instant mutations as discussed above), and with the combined teachings of Booth and Wurzberg a skilled artisan would recognize that these chimeric antibodies could possess dual receptor binding capabilities.
Applicant states:
“Applicant respectfully asserts that Wurzburg does not in any way suggest that specific residues in IgG are directly transferrable to an IgE.” (Remarks, page 16, ¶ 5)
“…Booth's discussion of FcRn binding is limited to FcRn binding in the context of IgG antibodies.” (Remarks, page 16, ¶ 6)
“Applicant asserts that the Office has focused on specific residues shown in Figure 1 of Wurzburg to conclude that it would have been obvious for one of ordinary skill in the art to transfer these specific residues from IgG to IgE to provide FcRn binding to IgE.” (Remarks, page 18, ¶ 2)
“…one of ordinary skill in the art would not have known from Wurzburg which specific residues in IgE should be mutated to confer FcRn binding, and one of ordinary skill in the art would not have had a reasonable expectation of success of transferring FcRn binding to an IgE because of the many and significant functional and structural differences between IgE and IgG as explained in detail by Wurzburg.” (Remarks, page 18, ¶ 2)
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In this instance the known hybrid antibodies as taught by Jardieu that retain FcεR, based on the additional teachings of Booth and Wurzburg, would suggest to someone of ordinary skill in the art that the recombinant antibody as taught by Jardieu, within scope of the genus of hybrid antibodies encompassed by instant claims, would also likely bind to FcRn.
Applicant states:
“…Karagiannis does not remedy the deficiencies of Jardieu, Booth, and Wurzburg with respect to the subject matter of claim 31 or claims depending therefrom..” (Remarks, page 18, last ¶)
In response to applicant's argument regarding deficiencies in the analysis of the base claim, these issues are addressed above, and therefore this argument, made on the basis that additional references do not cure the primary deficiency, is deemed unpersuasive.
Modified 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.
US 17/764,850
Claims 31, 44, 46, and 50 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 44, 56, 60 and 68 of copending Application No. 17/764,850 (herein US850). Although the claims at issue are not identical, they are not patentably distinct from each other. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding claims 31, claim 44 of US850 claims a fusion protein that binds to an FcεR and FcγR comprising (i) Cε2, Cε3, Cε4, Cγ2 and Cγ3 domains (ii) one or more variable domains and/or CDRs. This is within scope of the instant claim 31 as FcRn binding is mediated by residues derived from IgG Cγ2 and Cγ3 domains.
Regarding claim 44 (dependent on claim 31), claim 56 of US850 (dependent on US850 claim 44) claims an amino acid having at least 90% sequence identity to the instant SEQ ID NO:1 (Trastuzumab WT IgE_VH_CH1_CH2) (US850 SEQ ID NO: 25, 26, and 163-166 contain sequences with 100% identity).
Regarding claim 46 (dependent on claim 31), claim 60 of US850 (dependent on US850 claim 44) claims the fusion protein (which is within scope of the instant hybrid antibody as discussed above) binds specifically to a cancer antigen.
Regarding claim 50 (dependent on claim 31), claim 68 of US850 (dependent on US850 claim 44) claims a pharmaceutical composition of the fusion protein and pharmaceutically acceptable excipient, diluent, or carrier.
Response to Arguments - Double Patenting
Applicants are reminded 37 CFR 1.111 requires that replies by applicant or patent owner must reply to every ground of objection and rejection in the prior Office action. Only objections or requirements as to form not necessary to further consideration of the claims may be requested to be held in abeyance until allowable subject matter is indicated. Non-statutory double patenting rejections may not be held in abeyance. See MPEP 714.02. Applicants did not traverse the NSDP rejection. The rejection is maintained (or modified).
New Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(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.
Claims 31, 50, and 52 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Kimes (WO 2020/172473 A1; effectively filed 02/20/2019) as evidenced by Booth (cited above).
Regarding claim 31, Kimes teaches a chimeric binding agent comprising (ii) one or more of C[Symbol font/0x65]1, C[Symbol font/0x65]2, C[Symbol font/0x65]3, and/or C[Symbol font/0x65]4 domains, and (ii) one or more C[Symbol font/0x67]1, C[Symbol font/0x67]2, C[Symbol font/0x67]3 and/or a hinge region (¶ [0006]), wherein the chimeric binding agent is capable of binding to Fc[Symbol font/0x67]Rs and Fc[Symbol font/0x65]Rs, wherein Fc[Symbol font/0x67]Rs include Fc[Symbol font/0x67]RI, Fc[Symbol font/0x67]RIIA, Fc[Symbol font/0x67]RIIB, Fc[Symbol font/0x67]RIIIA and Fc[Symbol font/0x67]RIIIB, and Fc[Symbol font/0x65]Rs include Fc[Symbol font/0x65]RI and Fc[Symbol font/0x65]RII (¶ [0072]). Kimes teaches “Compound B” (SEQ ID NO:28) comprising human IgE-Fc fused to IgG-Fc, which inherently maintains FcRn binding domains as evidence by Booth (i.e. claim 31(a) - hybrid molecule with FcRn binding site derived from an IgG antibody). Kimes further teaches that the chimeric binding agent may further comprise a Fab (i.e. variable domains) (¶ [0067]) or may be fused to a molecule (e.g. a small molecule, a peptide, a polypeptide, or a protein) with targeting or homing function for a cell of interest or a target cell (i.e. antigen binding domain) (¶ [0090]).
Regarding claim 50, Kimes teaches a pharmaceutical composition comprising the chimeric binding agent, and carrier (¶ [0145]).
Regarding claim 52, Kimes teach that the fusion protein increases protein half-life (¶ [0115]).
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/HANNAH SUNSHINE/Examiner, Art Unit 1647 /JOANNE HAMA/Supervisory Patent Examiner, Art Unit 1647