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 .
Application Status
Claims 1, 3-11, and 15-37 are pending.
Claims 1, 3-11, and 15-37 are examined on the merits herein.
Grounds of Objection Withdrawn
Previous objection of the specification is withdrawn in view of amendment.
Previous rejection of claims 34 and 36 under U.S.C. 35 11(b) is withdrawn in view of claim amendment.
Claim Interpretation
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
The instant claims are single means claims. The claims are directed to an antigen-binding molecule comprising means for binding to HER2 with S310F mutation, which is a single function. Thus, the claims recite one - and only one - element, with that one element being expressed in “means-plus-function” format, is a “single means” claim.
If the claims were a proper means-plus-function claims, according to MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
In particular, claim 1 recites an antigen-binding molecule comprising a “means for specifically binding.” The claimed protein binder is modified by functional language (i.e., binding to HER2 with S310F mutation without binding to wild type human HER2). The term “means for specifically binding” is not modified by sufficient structure or materials for performing the claimed functions in claim 1, and is thus being interpreted under 35 U.S.C. § 112(f). Claims 3-10 and 15-27, which depend from or recite the protein binder of claim 1 and also do not disclose sufficient structure or materials for performing the claimed function, are similarly interpreted under 35 U.S.C. § 112(f).
With respect to the structure of the “means for specifically binding” that corresponds to the instantly claimed functional properties of the protein binder, the specification (pages 6-12) recites that the antigen-binding molecule comprises:
a1) an antibody variable region that comprises a HCDR1 comprising an amino acid sequence of SEQ ID NO: 29, a HCDR2 comprising an amino acid sequence of SEQ ID NO: 41, a HCDR3 comprising an amino acid sequence of SEQ ID NO: 53, a LCDR1 comprising an amino acid sequence of SEQ ID NO: 65, a LCDR2 comprising an amino acid sequence of SEQ ID NO: 77, and a LCDR3 comprising an amino acid sequence of SEQ ID NO: 89;
a2) an antibody variable region that comprises a HCDR1 comprising an amino acid sequence of SEQ ID NO: 30, a HCDR2 comprising an amino acid sequence of SEQ ID NO: 42, a HCDR3 comprising an amino acid sequence of SEQ ID NO: 54, a LCDR1 comprising an amino acid sequence of SEQ ID NO: 66, a LCDR2 comprising an amino acid sequence of SEQ ID NO: 78, and a LCDR3 comprising an amino acid sequence of SEQ ID NO: 90;
a3) an antibody variable region that comprises a HCDR1 comprising an amino acid sequence of SEQ ID NO: 31, a HCDR2 comprising an amino acid sequence of SEQ ID NO: 43, a HCDR3 comprising an amino acid sequence of SEQ ID NO: 55, a LCDR1 comprising an amino acid sequence of SEQ ID NO: 67, a LCDR2 comprising an amino acid sequence of SEQ ID NO: 79, and a LCDR3 comprising an amino acid sequence of SEQ ID NO: 91;
a4) an antibody variable region that comprises a HCDR1 comprising an amino acid sequence of SEQ ID NO: 32, a HCDR2 comprising an amino acid sequence of SEQ ID NO: 44, a HCDR3 comprising an amino acid sequence of SEQ ID NO: 56, a LCDR1 comprising an amino acid sequence of SEQ ID NO: 68, a LCDR2 comprising an amino acid sequence of SEQ ID NO: 80, and a LCDR3 comprising an amino acid sequence of SEQ ID NO: 92;
a5) an antibody variable region that comprises a HCDR1 comprising an amino acid sequence of SEQ ID NO: 33, a HCDR2 comprising an amino acid sequence of SEQ ID NO: 45, a HCDR3 comprising an amino acid sequence of SEQ ID NO: 57, a LCDR1 comprising an amino acid sequence of SEQ ID NO: 69, a LCDR2 comprising an amino acid sequence of SEQ ID NO: 81, and a LCDR3 comprising an amino acid sequence of SEQ ID NO: 93;
a6) an antibody variable region that comprises a HCDR1 comprising an amino acid sequence of SEQ ID NO: 34, a HCDR2 comprising an amino acid sequence of SEQ ID NO: 46, a HCDR3 comprising an amino acid sequence of SEQ ID NO: 58, a LCDR1 comprising an amino acid sequence of SEQ ID NO: 70, a LCDR2 comprising an amino acid sequence of SEQ ID NO: 82, and a LCDR3 comprising an amino acid sequence of SEQ ID NO: 94;
a7) an antibody variable region that comprises a HCDR1 comprising an amino acid sequence of SEQ ID NO: 35, a HCDR2 comprising an amino acid sequence of SEQ ID NO: 47, a HCDR3 comprising an amino acid sequence of SEQ ID NO: 59, a LCDR1 comprising an amino acid sequence of SEQ ID NO: 71, a LCDR2 comprising an amino acid sequence of SEQ ID NO: 83, and a LCDR3 comprising an amino acid sequence of SEQ ID NO: 95;
a8) an antibody variable region that comprises a HCDR1 comprising an amino acid sequence of SEQ ID NO: 36, a HCDR2 comprising an amino acid sequence of SEQ ID NO: 48, a HCDR3 comprising an amino acid sequence of SEQ ID NO: 60, a LCDR1 comprising an amino acid sequence of SEQ ID NO: 72, a LCDR2 comprising an amino acid sequence of SEQ ID NO: 84, and a LCDR3 comprising an amino acid sequence of SEQ ID NO: 96;
a9) an antibody variable region that comprises a HCDR1 comprising an amino acid sequence of SEQ ID NO: 37, a HCDR2 comprising an amino acid sequence of SEQ ID NO: 49, a HCDR3 comprising an amino acid sequence of SEQ ID NO: 61, a LCDR1 comprising an amino acid sequence of SEQ ID NO: 73, a LCDR2 comprising an amino acid sequence of SEQ ID NO: 85, and a LCDR3 comprising an amino acid sequence of SEQ ID NO: 97;
a10) an antibody variable region that comprises a HCDR1 comprising an amino acid sequence of SEQ ID NO: 38, a HCDR2 comprising an amino acid sequence of SEQ ID NO: 50, a HCDR3 comprising an amino acid sequence of SEQ ID NO: 62, a LCDR1 comprising an amino acid sequence of SEQ ID NO: 74, a LCDR2 comprising an amino acid sequence of SEQ ID NO: 86, and a LCDR3 comprising an amino acid sequence of SEQ ID NO: 98;
a11) an antibody variable region that comprises a HCDR1 comprising an amino acid sequence of SEQ ID NO: 39, a HCDR2 comprising an amino acid sequence of SEQ ID NO: 51, a HCDR3 comprising an amino acid sequence of SEQ ID NO: 63, a LCDR1 comprising an amino acid sequence of SEQ ID NO: 75, a LCDR2 comprising an amino acid sequence of SEQ ID NO: 87, and a LCDR3 comprising an amino acid sequence of SEQ ID NO: 99;
a12) an antibody variable region that comprises a HCDR1 comprising an amino acid sequence of SEQ ID NO: 40, a HCDR2 comprising an amino acid sequence of SEQ ID NO: 52, a HCDR3 comprising an amino acid sequence of SEQ ID NO: 64, a LCDR1 comprising an amino acid sequence of SEQ ID NO: 76, a LCDR2 comprising an amino acid sequence of SEQ ID NO: 88, and a LCDR3 comprising an amino acid sequence of SEQ ID NO: 100;
wherein the CDRs are embedded in a suitable protein framework so as to be capable of binding to HER2 S310F without binding wild type HER2. Because this claim limitation is being interpreted under 35 U.S.C. § 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, it is being interpreted to cover these corresponding structural elements described in the specification (pages 6-12) and equivalents thereof, which are understood to sufficiently modify the “means for binding” of the protein binder of the invention. Accordingly, claim 11 and dependent claims 28-37, which recite these structural elements, are not being interpreted under 35 U.S.C. § 112(f).
Because this claim limitation is being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, it is being interpreted to cover the corresponding structure described in the specification as performing the claimed function, and equivalents thereof.
If applicant does not intend to have this/these limitation(s) interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant may: (1) amend the claim limitation(s) to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph (e.g., by reciting sufficient structure to perform the claimed function); or (2) present a sufficient showing that the claim limitation(s) recite(s) sufficient structure to perform the claimed function so as to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph.
Claim Rejections - 35 USC § 112(a)
Rejection Maintained
Claims 1, 3-10, and 15-27 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.
This is a NEW MATTER rejection.
In the amendment filed April 10, 2025, Claim 1 has been amended to recite a limitation of “means for specifically binding” which does not appear to be supported in the instant disclosure. The specification has support for an antigen-binding molecule that specifically binds to HER2 S310F with the CDRs and VH/VL combinations recited on pages 6-12 as well as in claim 11, but does not include support for all the equivalents thereof which the “means for” interpretation includes. Lack of possession for the equivalents is detailed in the maintained 112a rejection below.
Claims 3-10 and 15-27 depend from claim 1, therefore these claims are included in this rejection.
Therefore, given the apparent difference in the breadth of the claims, and that of the pertinent disclosures, it is submitted that this clearly illustrates that such amendments have in fact introduced new concepts, thereby violating the written description requirement set forth under 35 U.S.C. §112, first paragraph. For these reasons, it is not apparent that Applicant had originally contemplated the subject matter encompassed by the claims at the time the application was filed.
Otherwise this issue might be resolved if Applicant were to point to other disclosures in the specification, including the claims, as originally filed, which are believed to provide the necessary written support for the language of the instant claims.
Claims 1, 3-10 and 15-27 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. This is a written description rejection.
“[T]he purpose of the written description requirement is to ‘ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent specification.’” Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353-54 (Fed. Cir. 2010) (en banc) (quoting Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920 (Fed. Cir. 2004)). To satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163.04.
For a claim to a genus, a generic statement that defines a genus of substances by only their functional activity does not provide an adequate written description of the genus. Reagents of the University of California v. Eli Lilly, 43 USPQ2d 1398 (CAFC 1997). “[A] sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus.” Ariad, 598 F.3d at 1350 (quoting Eli Lilly, 119 F.3d at 1568-69). A “representative number of species” means that those species that are adequately described are representative of the entire genus. AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number” of species. The “structural features common to the members of the genus” needed for one of skill in the art to ‘visualize or recognize’ the members of the genus takes into account the state of the art at the time of the invention. For example, the Federal Circuit has found that possession of a mouse antibody heavy and light chain variable regions provides a structural "stepping stone" to the corresponding chimeric antibody, but not to human antibodies. Centocor Ortho Biotech Inc. v. Abbott Labs., 97 USPQ2d 1870, 1875 (Fed. Cir. 2011).
Amgen Inc. v. Sanofi, Aventisub LLC, 872 F.3d 1367 (Fed. Cir. 2017)
supported previous decisions (Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341 (Fed. Cir. 2011); AbbVie Deutschland GmbH & Co. v. Janssen Biotech, Inc., 759 F.3d 1285 (Fed. Cir. 2014)) that defining an antibody solely by what it binds does not satisfy the written description requirement, stating that this would allow patentees to “claim antibodies by describing something that is not the invention, i.e., the antigen”. Thus, claiming an antibody by describing the invention by what it does (function) rather than what it is (structure) is invalid. This can be overcome if a relevant number of species with structure/function correlation is known to the art or present in the specification. As indicated below, there are not a representative number of species of known HER2 antibodies that bind an S310F mutation but not the wild type in the art or within the specification to define a structure/function relationship for HER2 S310F specific antibodies that indicate binding by only defining the epitope.
The teachings of the specification and the claimed invention:
Regarding claim 1: The nature and scope of the claimed invention at issue is a subgenus of antibodies that bind to HER2 S310F with CDRs defined as detailed above in the 112(f) claim interpretation that include a recitation of 95% sequence identity.
The nature and scope of the claimed invention at issue is a genus of antibodies that bind to HER2 with a S310F mutation but not wild type HER2, as equivalents of the structurally defined antibodies under the 112(f) claim interpretation detailed above.
Regarding claims 3-10 and 15-27: As the claims depend from claim 1 but do not resolve the issue with claim 1, they are included in this rejection.
The instant specification does not define the structural features of the paratope-epitope binding and the residues therein that facilitate binding within the CDRs other than to specify that it must bind the S310F mutant and not the wild type sequence.
There were 13 clones disclosed in the specification that demonstrated specific binding to HER2 S310F without binding the wild type HER2 but the corresponding epitope mapping was not done for any clones.
A genus of species is not present in the instant specification or prior art that would demonstrate a structure activity relationship would be known for antibody CDR residues for the recited function of binding HER2 with a S310F mutation. There is a lack of an appropriate number of species with identical or alternative amino acid residues within the CDR binding determinant region that indicate which amino acid residues: i) are essential for binding; ii) can be changed and still allow protein target binding; iii) disrupt protein target binding; or iv) alter antibody secretion. The alignment of the disclosed antibody species is included below to further illustrate the issue.
Additionally, 13 antibodies would not cover all possible CDRs for epitope binding. All of the antibodies disclosed in the instant specification bind the mutant HER2 as shown in Fig 1. It is unknown which amino acids are essential for binding. Further, the antibodies that show the highest signal in Fig 1 are 7, 9, 10, and 17, which are the most different from the genus of the antibodies tested.
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The disclosed HER2 S310F antibody clones are not representative of the other claimed antibodies. This is because when antibodies are raised to an antigen each monoclonal antibody raised comes from one unique cell with unique CDRs which are responsible for antibody binding, such that the structure of CDRs for one antibody cannot be considered representative of other antibodies with different CDRs that bind the same antigen or even substantially the same epitope. Notably, the epitope structure that one antibody binds on an antigen, do not inform the skilled artisan as to what other antibodies would bind the same or substantially the same structure.
In the absence of a representative number of species, the written description requirement for a claimed genus may be satisfied 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.
One of skill in the art would reasonably conclude that applicant was not in possession of the required genus of antibodies defined by epitope binding of claims 1, 3-10 and 15-25 of the antibody at the time of filing.
Claim analysis:
Regarding claim 1: As detailed below, absent empirical evidence one skilled in the art would be unable to envision the entire genus of antibodies that would bind to HER2 S310F but not wild type HER2.
Regarding claims 3-10 and 15-27: As the claims do not resolve the issue with claim 1, they are included in this rejection.
The state of the art as it applies to the claimed invention:
Regarding definition of an antibody by epitope:
Antibody binding to the same antigen, or even the same epitope on that antigen, can be accomplished with an impressively wide variety of antibody structures, even when the antibodies are limited to those from a particular source (Gershoni et al., Biodrugs (2007), 21 (3): 145-156; page 146, section 1.1). The skilled artisan therefore understood that antibodies from a variety of different sources may bind the same antigen and even mediate the same functional effects, but differ widely in the details of the structure of their antigen-binding sites, particularly in the amino acid sequence.
Tiller (Annu Rev Biomed Eng, 2015, 17:191-216) teaches that the holy grail of antibody design is to accurately and reliably predict the sequences of antibodies that will bind with high affinity and specificity based solely on the sequence or composition of the antigen (section 3.1) and a computational approach has been developed named OptCDR to design CDRs of antibodies to recognize specific epitopes on a target antigen. The predicted CDR sequences must then be grafted into antibody scaffolds for evaluation (section 3.1). Despite these advances de novo design continues to be challenging because of several factors, including the difficulty in accurately predicting the conformation of CDR loops as well as the structures of antibody-antigen complexes for which there are no initial crystal structures (section 9). Further, Tiller teaches that another critical problem in antibody design is the need to simultaneously optimize multiple attributes of antibodies wherein methods aimed at designing CDRs of antibodies to ensure high affinity need to identify sequences that also maximize folding stability and solubility (section 9). Tiller further teaches that the rational approach of antibody design has not eliminated the need for immunization or screening but instead have focused such efforts to make them more productive (section 10).
Jespersen (Frontiers in Immunology 10: 298, 2019) teaches detailed information on the molecular interactions between an antibody and its cognate antigen target is currently only available from protein 3D structures of antibodies co-crystallized with their target antigen, and currently the protein databank (PDB) only contains ~600 of such antibody-antigen (Ab-Ag) structures (Introduction). Jesperson further teaches that sequence-based and structure-based methods are available for predicting B-cell epitopes for an antibody but many benchmark studies have, as expected, demonstrated that structure-based methods display superior performance compared to sequence-based methods. However, even the best current structure-based methods for B-cell epitope prediction have limited predictive power (introduction).
Abbott (Immunology, 2014, 142: 526-535; cited in last office action) teaches that the most commonly used method to map the fine details of the interaction between an antigen and an antibody is X-ray crystallography but this technique requires a high level of sophistication and expense and cannot be used when the antigen cannot be crystallized Abbott further teaches that nuclear magnetic resonance spectroscopy offers a similar level of detail to crystallography but the technical hurdles are even higher such that it is rarely used in this context. Mutagenesis of either antigen or antibody offers the potential to give information at the amino acid level but suffers from the uncertainty of not knowing whether an effect is direct or indirect due to an effect on the folding of a protein. Other methods such as hydrogen deuterium exchange coupled to mass spectrometry and the use of short peptides coupled with ELISA-based approaches tend to give mapping information over a peptide region rather than at the level of individual amino acids (summary, pg 526). Abbott further teaches that even with X-ray crystallography further experimental approaches are needed to understand which residues inside or outside the structural epitope are contributing to binding affinity and therefore forming the functional epitope (summary, pg 534).
There are numerous antibodies to HER2 known in the art, but not antibodies specific to a HER2 S310F mutation. Karuvi (Cancer Discov, 2015, 5(8)): 832-841; IDS entered October 26, 2021) teaches that trastuzumab is a HER2 antibody and that colorectal cancer cells with the HER2 S310F mutation are still sensitive to treatment with trastuzumab (page 837, column 2, paragraph 2). Chumsri (J Natl Compr Canc Netw, 2015, 13: 1066-1070; cited in last office action) teaches that the S310F mutation promotes noncovalent dimerization and downstream activation and that this is not the site where trastuzumab binds which is why cancers harboring this mutation are still sensitive to trastuzumab and small molecule inhibitors (page 1069, column 2, paragraph 1). Chumsri further teaches that pertuzumab is a HER2 antibody that involves the amino acid 310 as part of the binding epitope but does not teach whether this antibody binds the mutated S310F HER2 (page 1070, column 1, paragraph 1). There are no known antibodies that specifically bind to HER2 S310F but not wild type HER2 in the prior art.
Accordingly absent empirical determination, one skilled in the art would be unable to predict or envision a genus of antibodies that bind to HER2 S310F but not wild type HER2 and further the same epitopes as the clones disclosed in claim 1. Since the disclosure fails to describe a sufficient number of species to describe the claimed genus, it is submitted that the written description requirement of 35 U.S.C. 112(a) has not been met.
Response to Arguments
Applicant's arguments filed December 12, 2025 have been fully considered but they are not persuasive.
Applicant submits: The Patent Office has failed to establish a prima facie case that the claim amendments filed April 10, 2025, constitute new matter.
Applicant respectfully asserts that the new matter rejection is fundamentally flawed because it misinterprets the legal scope and requirements of both 35 U.S.C. § l 12(f) (Means-Plus-Function) and § l 12(a) (Written Description). Assuming that the claim limitation "means for specifically binding" triggers 35 U.S.C. § l 12(f), then the claim scope is automatically limited to the corresponding structures disclosed in the specification (the specific CDRs/VH/VL combinations) that display this binding and their equivalents. The Patent Office errs by then using this legally established scope to argue a lack of 35 U.S.C. § l 12(a) written description.1 The written description standard requires the patent owner to demonstrate possession of the claimed invention, which is sufficiently established for a genus (like an antigen-binding molecule) by disclosing a representative number of species (the specific CDRs/VH/VL). By requiring explicit disclosure for "all the equivalents" that the "means for specifically binding" construction includes, the Patent Office is imposing an impossible burden that exceeds the legal requirements for written description under U.S. patent law.
In response: Applicant submitted remarks on April 10, 2025 that: Amended claim 1 falls under 35 U.S.C,§112(f) and as such, “shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof." That is, the claim is interpreted to cover both the corresponding structure, material, or act described in the Specification, the Specification, as well as equivalents of that structure, material, or act.
Therefore, it is clear that claim 1 falls under 112f interpretation. While this interpretation would include alternative VH/VL/CDRs it would also include antibody mimetics and peptide binders, as they are equivalents in the means for specifically binding HER2 S310F without binding wild type HER2. Therefore this amendment does constitute new matter not included in the instant disclosure.
There are no known antibodies or other binders that bind to HER2 S310F without binding wild type HER2 known in the prior art.
While there is no explicit requirement for the specification to include equivalents thereof in the §112 paragraph 6 language, applicant is still required to meet the written description requirement of the claim. As detailed above, this has not been met.
Applicant submits: Applicant respectfully submits that the specification describes the claimed antibodies in sufficient detail such that one skilled in the art, with the knowledge of what has come before, would reasonably conclude that Applicant had possession of the claimed invention.
On the filing date, it was known that the Serine 310 residue of HER2 resides in Domain II of the extracellular domain - the region known to mediate HER2 dimerization. Additionally, the introduction of a bulky phenylalanine side chain (S310F) was believed to promote constitutive HER2 dimerization into an active state.
The specification describes the isolation and characterization of 12 unrelated structurally diverse antibodies that specifically bind to this mutant (HER2 S310F) without binding to wild type human HER2 (see, e.g., Examples 3 and 4 and Figures 1-2). Each of these antibodies bind an epitope containing or influenced by the large phenylalanine side chain and they are collectively representative of the genus of antibodies encompassed by the claims.
A person skilled in the art, considering the disclosure and guidance of the specification in light of the high level of knowledge and skill in the art would have reasonably concluded that the inventors were in possession of the invention.
In Response: As detailed above the 12 antibodies disclosed would not cover all possible CDRs for epitope binding. All of the antibodies disclosed in the instant specification bind the mutant HER2 as shown in Fig 1. It is unknown which amino acids are essential for binding. Further, the antibodies that show the highest signal in Fig 1 are 7, 9, 10, and 17, which are the most different from the genus of the antibodies tested.
The disclosed HER2 S310F antibody clones are not representative of the other claimed antibodies. In the absence of a representative number of species, the written description requirement for a claimed genus may be satisfied 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.
Allowable Subject Matter
Claims 11, 28-33, 35 and 37 are allowed.
Conclusion
THIS ACTION IS MADE FINAL. 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMBER K FAUST whose telephone number is (703)756-1661. The examiner can normally be reached Monday - Thursday 9:00am-6:00pm EST.
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/AMBER K FAUST/Examiner, Art Unit 1643
/JULIE WU/Supervisory Patent Examiner, Art Unit 1643