DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
The instant application is claiming the benefit as a 35 U.S.C. 371 national phase application from, and claims priority to, International Application No. PCT/US2019/048709 (filing date 08/29/2019), which claims the benefit of the prior-filed United States Provisional Patent Application No. 62/730,701 (filing date 09/13/2018).
Status of Application/Claims
The amendment, filed 01/21/2026, is acknowledged. Claims 11, 13-15, 18, and 22-37 are canceled. Claim 1 is currently amended. Claims 1-10, 12, 16-17, 19-21, and 38 are currently pending and are examined on the merits herein.
Information Disclosure Statement
No new information disclosure statement (IDS) is submitted.
Withdrawn Objections & Rejections
Regarding the drawings objection for figure numbering compliance, applicant amendment has addressed the issue. Thus, the objection is withdrawn. However, upon submission of replacement drawings, there are current issues that must be corrected (see objection below).
Regarding the claim objection for claim 1 for minor informalities, applicant amendment has addressed the issue. Thus, the objection is withdrawn.
Regarding the rejection for claims 1-10, 12, 16-17, 19-21, and 38 under 35 U.S.C. 103 for obviousness, applicant arguments are found persuasive and the rejection is withdrawn. Firstly, applicant argues that Chamberlain does not teach modified PF4 antibodies having reduced Fc binding, which is held not to be persuasive as per examiner response above.
Secondly, applicant argues that while Pongas teaches PF4/LPS complex is immunogenic and can elicit cross-reacting antibodies against PF4/heparin, Pongas does not teach that HIT or the presence of heparin is the cause of symptoms present in sepsis or that PF4/heparin complexes would be present in sepsis patients (see applicant arguments, filed 01/21/2026, p.12, paras.2-3). Regarding the antibody to be administered in a method of treatment, the combination of prior art sufficiently teaches that the KKO antibody and cross-reactive PF4/LPS antibodies generated during sepsis are able to bind PF4/heparin (i.e., both antibodies can bind the same antigen, as taught collectively by Pongas, Cai, and Gollump). And, Chamberlain further contributes the rationale for modifying the Fc region of the antibody for reduced effector binding.
Lastly, applicant argues that the cited art only discusses NETs in the context of HIT (see applicant arguments, filed 01/21/2026, p.13, paras.1-2). It is on this last point that applicant arguments, in the specific context of bacterial sepsis, are found persuasive. While the prior art provides a rationale for why one of ordinary skill would modify a PF4/NET complex-binding antibody for a method of treatment that includes treatment for HIT, and for which the role of “HIT-like” and the KKO antibody is known, the prior art does not provide a clear rationale for one of ordinary skill to use such an antibody in a method of treating bacterial sepsis. While Chamberlain teaches methods of treatment for autoimmune, inflammatory, infectious disease, etc., Chamberlain does not teach treatment of bacterial sepsis, specifically, as is instantly claimed. Therefore, applicant arguments are found persuasive in regards to the obviousness rejection of instant claim 1 on the grounds that the prior art neglects to teach the method of treatment in the specific context of bacterial sepsis; Thus, the rejection for claims 1-10, 12, 16-17, 19-21, and 38 under 35 U.S.C. 103 for obviousness is withdrawn.
Drawings
The drawings were received on 01/21/2026. These replacement drawings are unacceptable and are objected to for the following reasons:
The drawings are objected to because color drawings were filed. Applicant must either submit an appropriate petition under 35 CF$ 1.84(a)(2) or black and white/grayscale figures:
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Figures 1-22 have color drawings.
The drawings are objected to because the labeling of the following figures is not in compliance:
Figs.1A-G lists panel (E) twice and panel (G) is missing (see page 1 of drawings filed 01/21/2026).
The black and white drawings are objected to because of poor resolution in the following figures:
Fig. 14
Figs. 15A-B
Figs. 20A-C
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings.
Figs.15A contains a nucleic acid sequence with no associated SEQ ID NO.
Fig. 15B contains amino acid sequences with no associated SEQ ID NOs.
Figs. A-C contain amino acid sequences with no associated SEQ ID NOs.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-10, 12, and 38 (Maintained) 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.
Claims 2-10, 12, and 38 are dependent on claim 1, which recites the following: “A method of treating a subject having or at risk of developing bacterial sepsis comprising administering to said subject an antibody or fragment thereof that binds immunologically to platelet factor 4 (PF4) complexed to neutrophil extracellular traps (NETs), wherein said administered antibody exhibits reduced binding to FcR and/or complement activation as compared to an unmodified antibody of the same class and isotype.”
The claims are drawn to a genus of antibodies that are limited only by the recited functional limitations. As the claims are drawn to functional limitations without additional structural limitations, the claims are drawn to what the antibody does (function) rather than by what the antibody is (structure). See MPEP 2173.05(g).
The instant specification discloses the use of antibodies or antibody fragments in a method of treating NET associated disease or syndrome by modifying the Fc regions of antibodies that bind NETs or via PF4 bound to NETs in order to reduce binding to FcR and/or complement activation (p.3, [2]).
Regarding antigens that bind applicant antibodies: The disclosure states, “Moreover, antibodies that cross-link NETs are pathogenic in HIT, but if their Fc portions are modified to eliminate cell activation they may be a therapeutic intervention.” Applicant disclosure also states that “Other antibodies that bind directly to DNA as seen with lupus related antibodies may have similar application for therapeutic intervention in sepsis. An example of such a HIT-like antibody with such potential therapeutic use is termed KKO” (p.3, [2]). This suggests that HIT-like antibodies are considered to bind directly to DNA and also “NETs” which contain DNA. Here, the applicant provides one example of such a HIT-like antibody: KKO. Applicant disclosure further states that the Fc-modified antibody or fragment may bind “…to NETs directly or via the PF4 bound to the NETs…” (p3, [2]) and may bind “…to the same PF4 epitope as antibody KKO or other site or directly to the DNA contained within the NET…” and “…may be a monoclonal antibody or may be part of a population of polyclonal antibodies (p.3, [4]). Applicant disclosure also provides that the antibody or antibody fragment can bind PF4 or PF4/heparin (p.4, [1]). Additionally, applicant provides that the antibodies, “also bind specifically with PF4 in a complex with other GAGs (glycosaminoglycans) besides heparin…” Thus, a HIT-like/KKO antibody is interpreted 1) to bind the above underlined antigens and 2) to induce an immune response.
Applicant drawings show assessments of KKO administration on leukocyte/ neutrophil adhesion in vitro and in vivo (Figures 1-3, 6) and KKO-mediated protection from DNaseI treatment (Figure 5). Applicant drawings also show assessments of deglycosylated KKO (DG-KKO) on microbial entrapment (Figure 9, Supp. Figure 5), heparin binding and platelet activation (Figure 10), and survival in mice treated with LPS (Figure 11) and exposed to injury (Figure 13). Further, the schematic overview provided by Figure 14 only mentions DG-KKO as a therapeutic antibody. Additionally, Figure 5D shows the differential effects of KKO-mediated protection from DNaseI digestion compared to a non-KKO anti-PF4 antibody.
The instant disclosure does not provide any examples of other potentially therapeutic HIT-like antibodies that could be modified, other than KKO (DG-KKO), that have the claimed functions and are to be considered for use of treatment in NET associated disease. Further, regarding which HIT-like antibodies are contemplated, all examples (1-7) in the disclosure discuss HIT and NET associated disease only in the context of KKO (and DG-KKO). Thus, there is no clear description regarding antibodies to be considered in a genus of antibodies other than KKO itself. The instant disclosure does not demonstrate an adequate number of species of the claimed genus, nor does it disclose a structure function relationship which would allow an ordinarily skilled artisan to determine which antibodies would have the claimed function. For example, the disclosure does not identify regions, domains, or sequences for the claimed antibodies that would maintain the structure-function relationship of the antibodies.
F. Overall, the disclosure provides only one example of a HIT-like antibody: KKO. This KKO antibody and/or its deglycosylated form are the only antibodies discussed in the disclosure descriptions, examples, and drawings. According to applicant, the HIT-like KKO antibody is considered to bind the following antigens: PF4/heparin, PF4, DNA/NETs, PF4/NETs, or any combination thereof. The specification does not identify how the function is performed or how the result is achieved. Additionally, broad genus claims are presented but the specification only describes a narrow species (i.e., antibody KKO) with no evidence that the genus is contemplated. See MPEP 2163.03 (V).
G. The state of the art around the time of the effective filing date of the claimed invention also does not disclose a representative number of species of the claimed antibodies or a structure function relationship that would allow a person of ordinary skill to predicably determine which antibodies would be able to perform the claimed functions.
Hummer, A.M., et al. Advances in computational structure-based antibody design Current Opinion in Structural Biology (2022), 74:102379, p.1-7, demonstrates ongoing unpredictability between antibody binding and epitopes. Specifically, Hummer teaches that traditional methods for antibody development, such as deriving antibodies from hybridomas of inoculated animals or from library assembly followed by display techniques are not only costly and time consuming but also are not necessarily able to produce antibodies that bind to the desired site (epitope) on an antigen. Hummer teaches that computational antibody design methods offer a way to overcome these limitations, but are held back by the lack of accurate antibody and antigen structures (p.1, col.2, para.2). Hummer provides a review on how advances in protein structure prediction and other areas are bringing us closer to being able to entirely computationally designed antibodies that bind strongly to a defined epitope (p.1, col.2, para.3) demonstrating that in 2022 predictable structure function relationships were still not known. Hummer acknowledges this in their discussion of future directions stating that “Several challenges still remain for true computational structure-based antibody design. While there has been great progress in protein structure prediction, current methods are not yet able to accurately predict the position of the side chain atoms or structural changes on binding. For antibodies, accurately modeling the CDR-H3 loop remains a major obstacle. Additionally, improvements in paratope and epitope prediction, both in terms of accuracy and specificity (predicting the types of binding interactions for residues), will be needed to help improve docking for high-throughput virtual screening.” (p.4, . col.2, para.3). Thus, Hummer teaches the difficulties in predicting the relationship between antibody structure and the epitopes to which they bind demonstrating a lack of predictability in the field between antibody structure and function.
Cai, et al. Atomic description of the immune complex involved in heparin-induced thrombocytopenia. Nature Communications (2015), 6:8277, p.1-10, herein referred to as Cai teaches that PF4 molecules exist in an equilibrium among monomers, dimers, and tetramers and that binding of PF4 to heparin stabilizes the tetrameric form (Figure 5). Cai further teaches that antibody KKO binds to PF4 tetramers to stabilize the tetrameric form which results in sustained activation of FcRs. Whereas, RTO antibody binds PF4 monomers, prevents PF4 oligomerization, and prevents formation of the larger immune complexes (Figure 5). Thus, while KKO and RTO are both antibodies that bind PF4, the epitope binding and resultant functions are different.
The only HIT-like antibody in the art that is described 1) to bind the above listed antigens and 2) to induce an immune response in HIT is KKO:
Arepally, et al. Characterization of a murine monoclonal antibody that mimics heparin-induced thrombocytopenia antibodies. Blood (2000). 95:5, p.1533-1540 (herein referred to as Arepally) describes characterization of the monoclonal IgG2bƘ antibody termed “KKO” as binding human PF4/heparin complexes. Arepally also teaches that the KKO antibody binds PF4 in association with other GAGs (abstract).
Gollomp, et al. A Special Role for Neutrophil Extracellular Traps (NETs) and Neutrophils in the Prothrombotic Nature of Heparin-Induced Thrombocytopenia. Blood (2016). 128:22, p.1023 (herein referred to as Gollomp) teaches that the KKO antibody also, “…bound readily to NETs following PF4 incubation, indicating that PF4-NET complexes are antigenic” (p.1, line 16-p.2, line 1).
H. Overall, it is not evident from the disclosure or the prior art that applicant was in possession of an adequate number of antibodies that bind the same epitope as KKO which would lead to the same function. There is no support providing that applicant had possession nor did applicant provided a sufficient description for antibodies or antibody fragments that are considered to bind the same epitope as antibody KKO. This subject matter was not described in the specification in such a way as to reasonably convey to one of ordinary skill in the art that applicant was in possession of the claimed invention at the time of filing and, therefore, the claims do not meet the written description requirement.
Claim Rejections - 35 USC § 103
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 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 16-17 and 19-21 (Maintained) are rejected under 35 U.S.C. 103 as being unpatentable over Chamberlain, et al. (US 2010/0234575 A1), herein referred to as Chamberlain.
Chamberlain teaches IgG variants for therapeutic purposes (p1, [2]) of treating various disorders including “…but not limited to autoimmune diseases (e.g., systemic lupus erythematosus and antiphospholipid syndrome), immunological diseases, infectious diseases, neurological diseases, and oncological and neoplastic diseases including cancer” (p.20, [181]) in human and non-human mammalian subjects (p.20, [181]). Chamberlain teaches Fc variants that modulate effector function (p.2, [21]), including functions such as ADCC (antibody dependent cell-mediated cytotoxicity; p.4, [49]), and CDC (complement dependent cytotoxicity, p.5, [62]). The variants include modifications that affect interaction with FcγRs and FcR homologs (p15, [141]). Chamberlain teaches that virtually any antigen may be targeted by these IgG variants, including but not limited to proteins, subunits, domains, motifs, and/or epitopes belonging to the following list of target antigens, which includes both soluble factor such as cytokines and membrane-bound factors, including:......PF4... (p.10-11, [124]). Chamberlain also teaches that the IgG variants are optimized to have increased or reduced affinity for FcRn and increased or decreased affinity for a human FcγR, including but not limited to FcγRI, FcγRIla, FcγRIIb, FcγRIlc, FcγRIIIa, and FcγRIIIb including their allelic variations (p.15, [139]). Chamberlain also teaches modification of the Fc region via amino acid variation (i.e., mutation; p.1-2, [6-9]). Additionally, Chamberlain also discusses amino acid substitutions in the context of altering glycosylation (p.9, [109]) and facilitating addition of PEG (p.9, [112]), as well as other modifications that affect affinity of Fc polypeptides to Fc ligands including: “…insertions, deletions, substitutions, other modifications, or combinations of these and other changes” (p.16, [147]). Chamberlain also discusses Fc modification via alteration of antibody glycoforms including addition or removal of oligosaccharides (i.e., deglycosylation) for purposes that include enhancing or reducing effector function (e.g., receptor binding; p.9, [106-111]). Chamberlain teaches that IgG variant can be formulated in a pharmaceutical composition with one or more therapeutically active agents with pharmaceutically acceptable carriers, excipients, or stabilizers (p.20, [184]). Chamberlain also teaches that such pharmaceutical compositions containing the antibodies and other therapeutically active agents can be formulated in aqueous solutions for intravenous (IV) treatment (i.e., via IV fluids; p.20-21, [184-186]). Further, Chamberlain teaches that IgG variant administration may include, but is not limited to oral, subcutaneous, intravenous, parenteral, intranasal, intraotic, intraocular, rectal, vaginal, transdermal, topical, intraperitoneal, intramuscular, or intrapulmonary delivery (p.20-21, [186]).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify a PF4-binding antibody by altering the Fc region of an IgG antibody, via amino acid mutation (including substitution), in order to receive the benefit of producing an IgG variant that exhibits reduced binding to FcR, as taught by Chamberlain. One of ordinary skill in the art would have a reasonable expectation of success because Chamberlain teaches modification of PF4 antibodies. This conclusion of obviousness is further supported by KSR (E) obvious to try. Chamberlain teaches a finite number of antibodies that can be used in the methods disclosed including a PF4 binding antibody. Therefore, one of ordinary skill in the art would have been able to pursue the alternative antibodies disclosed by Chamberlain with a reasonable expectation of success.
Response to Arguments
Regarding the rejections for claims 1-10, 12, and 38 under 35 U.S.C. 112(a) for failing to comply with the written description requirement: Claims 2-10, 12, and 38 are dependent on claim 1. Claim 1 is rejected on the basis that the modified antibody is defined only by functional language and the full scope of the genus of antibodies as claimed is not supported by sufficient written description as there is not a clear structure that would predictably function as claimed. Applicant traverses in arguments submitted 01/21/2026, stating that “the claim only permits other antibodies with the same binding function, namely that it binds to PF4” and that “many commercially available antibodies that bind PF4 exist.” Further, applicant arguments cite “Nor does the Action provide any basis for suggesting that KKO has some additional features for its performance that would be lacking from other anti-PF4 antibodies” (see applicant arguments, filed 01/21/2026, p.8, para.2). While the examiner agrees that antibodies other than KKO are able to bind PF4, the prior art teaches that KKO does, in fact, have an additional feature that is lacking from at least one other PF4-binding antibody (i.e., RTO as taught by Cai, et al.). The claim recites a method of treatment comprising administration of a broad genus of antibodies defined only by the functional language of binding PF4 as stated by applicant (see arguments, p.8, para.2). However, it is not clear which PF4 antibody structures could predictably be used in the claimed method of treatment based on the combination of teachings by the instant disclosure and the prior art. Cai teaches that, while the RTO antibody can bind PF4 monomers, RTO and KKO bind different epitopes and KKO requires an epitope formed by tetramerization of PF4 and that “the KKO binding site on the tetramer is nonexistent or incompletely expressed on the PF4 monomer and dimer” (Cai, p.6, col.2, para.1). Thus, it appears that KKO does possess a unique ability to bind “pathogenic” forms of the PF4 tetramer; whereas, the PF4 antibody RTO binds a monomeric epitope. Thus, it is not clear that an antibody structure, for a genus of “PF4 antibody” as is broadly claimed, would predictably function in the claimed method of treatment as claimed. Thus, applicant arguments are found not to be persuasive and the rejection is maintained.
Regarding the rejection for claims 16-17 and 19-21 under 35 U.S.C. 103 for obviousness: Claims 17, and 19-21 are dependent on claim 16. Claim 16 is rejected on the basis that a modified PF4 antibody that exhibits reduced binding to FcR and/or complement activation is taught by the combination of teachings of the prior art. Applicant traverses in arguments submitted 01/21/2026, stating that Chamberlain 1) does not teach IgG variants with reduced binding, 2) does not provide motivation for combining the different elements taught by Chamberlain, and 3) does not teach how reduced binding to FcRs can be accomplished (see applicant arguments, filed 01/21/2026, p.9-10). The examiner respectfully disagrees. Chamberlain not only teaches all limitations of the claim, but does in fact teach antibodies with reduced FcR binding, including PF4 antibodies. Further, Chamberlain teaches methods of therapeutic treatment for which the Fc region of the antibody is varied to reduce FcR binding. Chamberlain recites, “These embodiments are anticipated to provide IgG polypeptides with enhanced therapeutic properties in humans, for example increased serum half-life and reduced effector function” (see Chamberlain, p.15, [0139]). Further, Chamberlain teaches Fc modifications for reduced FcR binding in the context of autoimmune, inflammatory, infectious, and other diseases (see Chamberlain, p.20, [0181]). Additionally, Chamberlain teaches that Fc regions can be modified for reduced effector function by substituting one or more amino acids in the Fc polypeptide (see Chamberlain, p.16, [0149]). As per MPEP §2121, “When the reference relied on expressly anticipates or makes obvious all of the elements of the claimed invention, the reference is presumed to be operable.” A person of ordinary skill in the art would be enabled to produce a modified antibody that is able to both bind PF4 and exhibit reduced binding to FcR based on the combination of teachings provided by Chamberlain. Not only is a case for obviousness met because Chamberlain provides a motivation of using Fc-modified antibodies for treatment of autoimmune/inflammatory/ infectious diseases, but Chamberlain also teaches that Fcs with reduced effector function provide the additional benefit of increased serum half-life. The obviousness conclusion is further supported by KSR rationale (E) as it would have been “obvious to try” based on the finite number of antibodies taught, which includes PF4, as stated in the previous rejection. Even further, combining the prior art elements of Chamberlain according to known methods yields a predictable result of producing a modified PF4 antibody that has reduced FcR binding as instantly claimed (as per KSR rationale (A)). For all of the above reasons, applicant arguments are found not to be persuasive and the rejection is maintained.
Conclusion
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.
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 Jami M Gurley whose telephone number is (571)272-0117. The examiner can normally be reached Monday - Friday, 8am - 4pm.
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/JAMI MICHELLE GURLEY/Examiner, Art Unit 1647
/JOANNE HAMA/Supervisory Patent Examiner, Art Unit 1647