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 .
DETAILED ACTION
Status of Claims
Applicant's preliminary amendment of the instant application, which was originally submitted on July 27, 2023 and later amended on September 15, 2023, is acknowledged by the Examiner. The cancellation of claims 17, 20, and 22 – 34 pursuant to the amendment on September 15, 2023 is acknowledged. Claims 1 – 16, 18, 19, 21, and 22 were previously examined and restricted in the Office Action mailed on December 29, 2025.
Election/Restrictions
Applicant’s election without traverse of a method for producing a monoclonal antibody with a functional profile directed against a pathogen of interest, i.e., Group V, in the reply filed on February 26, 2026 is acknowledged.
Claim 45 is withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claim 45 reads as a method of treating for Ebola virus infection in a subject, i.e., Group IV, which is a nonelected invention.
Election was made without traverse in the reply filed on February 26, 2026. Claims 21, 22, and 35 – 44 are pending and under review.
Priority
The instant application is a National Stage Entry of International Patent Application No. PCT/US2022/014779 filed on February 1, 2022, which claims priority to United States Provisional Application No. 63144383 filed on February 1, 2021. A certified copy of the Provisional Application No. 63144383 has been filed, but not for the International Patent Application No. PCT/US2022/014779.
Applicant’s claim for the benefit of a prior-filed provisional application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 112(a). The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, United States Provisional Application No. 63144383 filed on February 1, 2021, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. While the VIC16 antibody against Ebola virus has been defined, SEQ ID NOs: 19 – 26, 35 – 95, 97 – 104, and 106 – 160 are not disclosed in the provisional application. Only SEQ ID NOs: 1 – 18 are described in the provisional application. Thus, the written description of the provisional application does not support and enable the subject matter of the instant claims. The provisional application fails to provide support or to provide any suggestion to easily reduce to practice, for an antibody that is reactive against Ebola virus, wherein the CH is any one of SEQ ID NOs: 35 – 95, the heavy chain is any one of SEQ ID NOs: 97 – 104 and 106 – 159, and the light chain is SEQ ID NO: 160. Therefore, the breadth of the instant claims far overreaches the provisional disclosure. Accordingly, claims 39 – 44 are not entitled to the benefit of the provisional application.
Priority is granted to the United States Provisional Application No. 63144383 filed on February 1, 2021 for claims 21, 22, and 35 – 38 of the instant application. Priority is granted to the International Patent Application No. PCT/US2022/014779 filed on February 1, 2022 for claims 39 – 44 of the instant application. Thus, the U.S. effective filing date of claims 21, 22, and 35 – 38 is the provisional filing date, i.e., February 1, 2021, and the effective filing date of claims 39 – 44 is the international filing date, i.e., February 1, 2022.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on November 1, 2023 has been considered by the Examiner. Notably, the listing of references in the specification is not a proper IDS. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Unless the references have been cited by the Examiner on form PTO-892, they have not been considered.
Specification
The use of the terms Q5® on page 15; Tween® on pages 19, 64, and 67; Inmazeb™ on pages 23 and 24; Ebanga™ on page 24; FreeStyle™ on page 63; Pierce™ on page 64, and possibly others in the specification, which are trade names or marks used in commerce, have been noted in this application. The terms should be accompanied by the generic terminology; furthermore, the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, ℠, or ® following the terms. 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. Applicant is required to properly annotate all trade names and/or marks that are present in the specification.
Applicant is reminded of the proper language and format for an abstract of the disclosure. The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details. The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. Also, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which Applicant may become aware in the specification.
Drawings
The instant application contains at least one drawing executed in color. Figures 1, 2A – 2C, 5C, 6A, 6C, 7A, 7B, and 10 have multiple parts that refer to and are differentiated by various colors (see pages 6, 8, and 76 of the instant specification, at a minimum). 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).
The drawings are objected to because the different markers in the legend of Figure 6B are indecipherable, making it difficult to differentiate the data points. Additionally, a figure legend is missing for Figures 8B and 8D and 9A – 9D.
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.
Claim Objections
Claims 21, 22, and 40 are objected to because of the following informalities:
There is a grammatical error in claim 21, line 5. The phrase should read “a Fab binding domain” and not “an Fab binding domain”;
There is a typographical error in claim 22, line 4. The “y” in FcyR binding should be a gamma symbol, wherein the phrase reads “FcγR”;
There is a typographical error in claim 40, line 4. There is a comma after “CH2” that should be removed.
Recommended amendments are underlined. Appropriate correction is required.
Claim Rejections - 35 USC § 112
35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION. — The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the Applicant regards as his invention.
Claims 36 – 44 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the Applicant), regards as the invention.
Claims 36 – 41 are vague and unclear, which renders the claim indefinite. Lines 1 and 2 of claim 36 “the antibody that is reactive against Ebola virus is VIC16”. It is unclear if VIC16 is the start point or end point. In other words, is VIC16 the result of some sort of modification to a different antibody? Or is VIC16 itself modified and a different antibody is the result? The presence of multiple very different interpretations of the same claim language renders the claim indefinite. This rejection affects all claims that are dependent on claim 36, i.e., claims 37 – 41. In the context of this examination, it will be inferred that VIC16 is the starting antibody and is modified with the Fc variants to yield a different antibody. However, an appropriate amendment is required.
Claim 37 recites CDRs from sequence identifiers. This gives the claim multiple structural interpretations as there are several CDR labeling systems. Also, it is unclear if the systems can be mixed and matched for each CDR. For example, is Kabat labeling used for some CDRs, whereas IMGT is used for others? Furthermore, it is unclear if composite CDRs are encompassed, i.e., fusions of Kabat and IMGT CDRs. The presence of multiple very different interpretations of the same claim language renders the claim indefinite.
Claims 42 and 43 refer to sequences that are set forth in tables 6 and 2, respectively, of the specification. Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for Applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted). See MPEP § 608.01(m) and 2173.05(s). All variants encompassed by claims 42 and 43 are rendered indefinite without reference to a sequence identifier in the claims.
Moreover, table 6 is not drawn to different Fab-Fc variants, but rather “FcR binding affinities of downselected VIC16 REFORMabs” (see page 78 of the instant specification), as stated in claim 42, so the sequences of the Fab-Fc variants are not known. In the context of this examination, it will be inferred that claim 42 should read on the VIC16-Fc variant sequences set forth in table 4, which consist of the Fc sequence for the REFORM variants that are set forth in table 3. However, an appropriate amendment is required.
Claim 44 is vague and unclear, which renders the claim indefinite. Lines 2 and 3 recite “from an amino acid sequence that is at least 80% to 99% identical to the Fab binding domain selected from SEQ ID NOs: 1 – 18”. However, SEQ ID NOs: 1 – 18 are all nucleic acid sequences. It is unclear if the Fab binding domain is intended to be encoded by the nucleic acid sequence of SEQ ID NOs: 1 – 18 or the nucleic acid sequence itself. The presence of multiple very different interpretations of the same claim language renders the claim indefinite. For the context of this examination, it will be inferred that the Fab binding domain is encoded by the nucleic acid sequence of SEQ ID NOs: 1 – 18. However, an appropriate amendment is required.
It is noted that any interpretation of the claims set forth above does not relieve Applicant of the responsibility of responding to this Office Action. If the actual interpretation of the claims is different than that posited by the Examiner, additional rejection(s) and art may be applied in a subsequent Office Action.
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.
35 USC § 112(a) – Written Description
Claims 42 and 44 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre–AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre–AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
"The 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"); LizardTech Inc. v. Earth Resource Mapping Inc., 424 F.3d 1336, 1345, 76 USPQ2d 1724, 1732 (Fed. Cir. 2005). This requirement is separate and distinct from the enablement requirement. To satisfy the written description requirement for a claimed genus, 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 at the time of filing. See In re Reiffin v. Microsoft Corp., 214 F.3d 1342, 1345, 54 USPQ2d 1915, 1917 (Fed. Cir. 2000). “Even if a claim is supported by the specification, the language of the specification, to the extent possible, must describe the claimed invention so that one skilled in the art can recognize what is claimed. The appearance of mere indistinct words in a specification or a claim, even an original claim, does not necessarily satisfy that requirement.” See In re Enzo Biochem, Inc. v. Gen–Probe, Inc., 323 F.3d 956, 968, 63 USPQ2d 1609, 1616 (Fed. Cir. 2002). See also MPEP § 2163.
The written description requirement 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. See In re University of California v. Eli Lilly & Co., 119 F.3d 1559, 1566, 43 USPQ2d 1398, 1404 (Fed. Cir. 1997); and Juno Therapeutics, Inc. v. Kite Pharma, Inc., 10 F.4th 1330, 1337, 2021 USPQ2d 893 (Fed. Cir. 2021).
A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, the Applicant must describe a sufficient variety of species to reflect the variation within the genus. See In re AbbVie Deutschland GMBH v. Janssen Biotech, 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure "indicates that the patentee has invented species sufficient to constitute the gen[us]." See In re Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004). "A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed." See In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004).
The Federal Circuit has clarified the application of the written description requirement to inventions in the field of biotechnology. The Court stated that a written description of an invention requires a precise definition, one that defines the structural features of the chemical genus that distinguishes it from other chemical structures. A definition by function does not suffice to define the genus because it is only an indication of what the genus does, rather than what it is. This is because functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description support, especially in technology fields that are highly unpredictable, where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus. Further, the Court held that to adequately describe a claimed genus, an Applicant must describe a representative number of species of the claimed genus, and that one of skill in the art should be able to “visualize or recognize the identity of the members of the genus.” The description needed to satisfy the written description varies depending on the nature and scope of the claims and on the complexity and predictability of the relevant technology. See In re University of California v. Eli Lilly and Co., 119 F.3d 1559, 1568, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997); In re AbbVie Deutschland GMBH v. Janssen Biotech, 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014); In re Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 94 USPQ2d 1161 (Fed. Cir. 2010); and In re Capon v. Eshhar, 418 F.3d at 1357, 76 USPQ2d at 1084.
Claim 42 is drawn to an amino acid sequence that is at least 80% identical to the Fab-Fc variants set forth in table 6, whereas claim 44 is drawn to an amino acid sequence that is at least 80% identical to the Fab binding domain set forth in SEQ ID NOs: 1 – 18. While SEQ ID NOs: 1 – 18 are not amino acid sequences, it has been inferred that they are nucleic acid sequences encoding for a respective amino acid sequence, as stated above in paragraph 20. As presently written, claims 42 and 44 encompass a substantial number of variations of Fab binding domains, which would mean likely mean a modification in the CDR of the Fab. As an example, SEQ ID NO: 1 encodes for a protein that is 106 amino acids in length. The claims encompass any sequence having at least 80% sequence identity to SEQ ID NO: 1. An amino acid sequence sharing only 80% identity relative to SEQ ID NO: 1 could have anywhere from 1 to 21 substitutions, deletions, additions, or any combination thereof, along the length of SEQ ID NO: 1, which corresponds to a massive genus of 2021 = 2.1 x 1021 possible sequence combinations in the genus. This genus grows exponentially larger when expanded to include the different possible sequence combinations of SEQ ID NOs: 2 – 18. Moreover, while sequence information cannot be gleaned from table 6 for claim 42, it is inferred that any variant would have modification in the CDR of the Fab, which would encompass a large amount of sequences similar to claim 44, wherein each sequence would have a large amount of possible combinations and still meet the limitation of being at least 80% identical. In general, this creates a massive genera of sequences for the Fab-Fc variant and Fab binding domain with innumerable modifications in the CDR of the Fab.
When there is substantial variation within the genus, as here, one must describe a sufficient variety of species to reflect the variation within the genus to provide a “representative number” of species. The claims are drawn to several genera that are comprised of innumerable sequences, yet, the specification has only adequately described, and successfully reduced to practice the Fab binding domains encoded by SEQ ID NOs: 1 – 18. This is not representative of the extremely large genus of sequences claimed. One of ordinary skill in the art cannot conclude that Applicant was in possession of the trillions of sequences encompassed by the disclosed genera. Absent the disclosed SEQ ID NOs, the skilled artisan generally would not be able to visualize or otherwise predict, a priori, each individual sequence of the Fab-Fc variant or Fab binding domain, and thus, the modified CDRs. Thus, it is clear that the breadth of the recited genera in the claims far overreaches the Applicant’s contribution.
In the absence of a representative number of examples, the specification must at least describe the structural features that are required for the claim function. In the instant case, the specification should explain what portion, i.e., the structure, of the Fab-Fc variant and/or Fab binding domain that is required to maintain function. However, the specification fails to describe any substantive structural limitations as to establish the criteria necessary the Fab-Fc variant and/or Fab binding domain that will still maintain the function of the VIC16 antibody and has all six parental CDRs. At best, the specification contemplates the use of BLAST to identify functional homologs based on sequence homology. However, this is not sufficient to describe members of the claimed genus because such methods access online databases that are continually being updated as sequencing technology improves. As a result, they are not a static source of information. Therefore, one having ordinary skill in the art would readily appreciate that relying on a non–patent source that is continuously subject to change as a means to identify members of the claimed genus does not sufficiently meet the written description requirement.
The art teaches that protein chemistry is an extremely unpredictable area of biotechnology, wherein even a single substitution can change the biological property of a peptide. For example, Burgess, W. H., et. al., (The Journal of cell biology, 111(5 Pt 1), 2129–2138; Published 11/1990), hereby Burgess, teaches that replacement of a single lysine residue by a glutamic acid residue can lead to substantial loss of receptor binding and biological activity of a protein (page 2129; abstract). Moreover, Friedberg, I., (Briefings in bioinformatics, 7(3), 225–242; Published 01/25/2006), hereby Friedberg, teaches that homology–based transfer is not reliable for functional annotation even with high alignment percentages (page 227, second column). Friedberg also teaches that identification of functionally significant sub–regions is critical to functional annotation, and that often addition, deletion, or re–shuffling of domains can lead to errors in annotation (page 227, second column; page 228, first paragraph). Furthermore, Friedberg teaches that as databased and, thus, diversity of sequences, get larger, sequence–based tools are not sensitive enough to identify functional protein similarity (page 228, first full paragraph). Thornton, J., (Trends in biochemical sciences, 26(2), 88–89; Published 02/01/2001), hereby Thornton, teaches that the same protein structure is often seen in apparently different homologous families with different functions. Thornton further describes examples of little correlation between specific binding function and overall protein structure (page 992, right column, lines 2 – 10). Additionally, it is taught by Rudikoff, S., et. al., (Proceedings of the National Academy of Sciences of the United States of America, 79(6), 1979–1983; Published 03/1982), hereby Rudikoff, that the mutation of a single amino acid in the CDR of a phosphocholine-binding myeloma protein resulted in the loss of antigen-binding specificity (page 1979, title and abstract). Thus, when taken with the teachings of Burgess, Friedberg, Thornton, and Rudikoff one having ordinary skill in the art would readily appreciate that sequence homology alone cannot serve as the basis to describe members of the genus that have the recited function.
In summary, these examples teach that the biological function of peptide variants is unpredictable because even a single mutation can abolish activity or give a different function. It is highly unlikely that any CDR structure will be shared by an entire genus. Additionally, the disclosure of one set of antibody CDRs does not guide one of skill in the art to the next set of CDRs. That is to say that all CDRs are unique and none are obvious. This is because it is well known in the art that the mutation of even a single CDR residue can dramatically impact antibody function, and even lead to the loss of antigen binding. Thus, while Applicant has described a species within the genus recited, and the art may provide more, each genus is very large and would encompass peptide structures, i.e., modified Fab binding domains, and thus, modified CDRs, that cannot be visualized from the prior art or instant disclosure. One having ordinary skill in the art cannot determine the structures encompassed by the claimed genera. Thus, the described species cannot be considered representative of the entire recited genus.
Overall, the claims as currently written are not adequately described and one of ordinary skill in that art would readily appreciate that Applicant was not in possession of the claimed genera at the time of filing. At present, it is recommended that the claims remove the recitation of “at least 80% to 99% identical” in claims 42 and 44. It is also suggested that the claims be amended to recite all parental CDRs of the disclosed species.
35 USC § 112(a) – Enablement
Claims 36 – 41 are rejected under 35 U.S.C. § 112, first paragraph, because the specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention, because the specification does not provide evidence that the claimed biological materials are (1) known and readily available to the public; (2) reproducible from the written description.
It is unclear if the VIC16 antibody, and a cell line that would produce a homogeneous population of the antibody, is known and publicly available, or can be reproducibly isolated without undue experimentation. It is apparent that the claimed antibody, named as VIC16, is required to practice the claimed invention since it is a recited limitation. As a required element, it must be known and readily available to the public or obtained by a repeatable method set forth in the specification. Therefore, a suitable deposit for patent purposes is suggested. Without a publicly available deposit of the above antibody, and a cell line which produces the antibody, one of ordinary skill in the art could not be assured of the ability to practice the invention as claimed.
Exact replication of: (1) the claimed cell line; (2) a cell line which produces the chemically and functionally distinct antibody claimed; and/or (3) the claimed antibody's amino acid or nucleic acid sequence is an unpredictable event. Castan, A., et. al., (Biopharmaceutical Processing: Chapter 7 – Cell Line Development, (Elsevier), 131-146; Published 2018), hereby Castan, teaches that a homogenous cell population derived from a single cell is important towards biopharmaceutical production, wherein a heterogenous pool will have different clones contributing to the product (page 136, second paragraph). It is further taught that a thorough understanding and characterization of the clone used is needed (page 136, third paragraph). Therefore, it would require undue experimentation to reproduce the claimed antibody, i.e., VIC16. Deposit of the cell line which produces the chemically and functionally distinct antibody and the claimed antibody’s amino acid sequence would satisfy the enablement requirements of 35 U.S.C. § 112, first paragraph. See 37 C.F.R. 1.801-1.809.
If the deposit is made under the provisions of the Budapest Treaty, filing of an affidavit or declaration by Applicant or assignees or a statement by an attorney of record who has authority and control over the conditions of deposit over his or her signature and registration number stating that the deposit has been accepted by an International Depository Authority under the provisions of the Budapest Treaty and that all restrictions upon public access to the deposited material will be irrevocably removed upon the grant of a patent on this application. This requirement is necessary when deposits are made under the provisions of the Budapest Treaty as the Treaty leaves this specific matter to the discretion of each State.
If the deposit is not made under the provisions of the Budapest Treaty, then in order to certify that the deposits comply with the criteria set forth in 37 CFR 1.801-1.809 regarding availability and permanency of deposits, assurance of compliance is required. Such assurance may be in the form of an affidavit or declaration by Applicants or assignees or in the form of a statement by an attorney of record who has the authority and control over the conditions of deposit over his or her signature and registration number averring:
during the pendency of this application, access to the deposits will be afforded to the Commissioner upon request;
all restrictions upon the availability to the public of the deposited biological material will be irrevocably removed upon the granting of a patent on this application;
the deposits will be maintained in a public depository for a period of at least thirty years from the date of deposit or for the enforceable life of the patent of or for a period of five years after the date of the most recent request for the furnishing of a sample of the deposited biological material, whichever is longest; and
the deposits will be replaced if they should become nonviable or non-replicable.
Amendment of the specification to recite the date of deposit and the complete name and address of the depository is required. As an additional means for completing the record, Applicant may submit a copy of the contract with the depository for deposit and maintenance of each deposit. The mere indication that a deposit has been made under conditions prescribed by the Budapest Treaty would satisfy all conditions of these regulations except the requirement that all restrictions on access be removed on grant of the patent. Ex parte Hildebrand, 15 USPQ2d 1662 (Bd. Pat. App. & Int. 1990).
If a deposit is made after the effective filing date of the application for patent in the United States, a verified statement is required from a person in a position to corroborate that the biological material described in the specification as filed is the same as that deposited in the depository, stating that the deposited material is identical to the biological material described in the specification and was in the Applicant's possession at the time the application was filed.
35 USC § 112(a) – Scope of Enablement
Claims 42 and 44 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for the specific combinations of the tested Fab-Fc variants and Fab binding domains, all with each parental CDR, shown to function, does not reasonably provide enablement for merely any Fab-Fc variant and Fab binding domain, which reads on modification in the CDR region(s) of the VIC16 antibody. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
In order to determine compliance with the enablement requirement of 35 U.S.C. 112(a), the Federal Circuit has developed a framework of factors in In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), referred to as the Wands factors, to assess whether any necessary experimentation required by the specification is "reasonable" or is "undue." The factors considered include, but are not limited to, (A) the breadth of the claims; (B) the nature of the invention; (C) the state of the prior art; (D) the level of one of ordinary skill in the art; (E) the level of predictability in the art; (F) the amount of direction provided by the inventor; (G) the existence of working examples; and (H) the quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Breadth of the claims and nature of the invention: Claims 42 and 44 of the claimed invention are drawn to the VIC antibody that has been modified with the disclosed Fab-Fc variants and/or Fab binding domains. The claims encompass any amino acid sequence that is at least 80% identical to the defined variants and domains. This reads on modification in the CDR of the Fab.
Those with relevant skill in the art: The level of skill in the art is that of Ph.D.-level scientists and
medical doctors (D.O. and/or M.D.).
Amount of direction and existence of working examples: The instant application teaches a single working example with two generic antibodies, which does not represent an example for the trillions of sequences, as described above in paragraph 25. Thus, the instant application offers no reasonable guidance or direction to make the claimed antibody with the countless Fab variants.
The closest working example is on pages 73 – 83. It is taught that the disclosed VIC16 REFORM antibodies, referred to as REFORMabs, wherein specific sequence modifications resulted in different Ebola virus binding affinities per antibody variant (see table 5). There was a mixed bag of binding affinities as some had decreased affinities, increased affinities, or similar affinities compared to wildtype VIC16. It is taught that only 30 REFORMabs retained neutralization activity with six different groups emerging: one group of non-functional monoclonal antibodies (mAbs), two groups of predominantly monofunctional mAbs, and three groups of polyfunctional antibodies. Of the functional REFORMabs, only five were selected for in vivo analysis, wherein each conferred different levels of protection in mice models. Aside from the REFORMabs disclosed, there is no guidance as to what Fab variants would result in an antibody that has comparable, or even improved, affinity for Ebola virus as the VIC16 antibody. The instant disclosure offers no reasonable guidance or direction to create or use merely any Fab variant. If anything, the instant disclosure reinforces the unpredictability on mutations/modifications of the antibody and how it will function as a result.
State of the prior art and unpredictability in the art: It is taught by Paul, W. E., (Fundamental Immunology, 3, 292-295; Published 1993), hereby Paul, that an intact antigen-binding site of antibodies generally requires the association of the complete heavy and light chain variable regions of a given antibody (page 293, left column, lines 3 – 8; right column, lines 1 – 9 and 27 – 30). It is further taught that both the heavy and light chain variable regions are comprised of three CDRs or hypervariable regions, for a total of six CDRs per antibody, which provide the majority of the contact residues for the binding of the antibody to its target epitope (page 293, left column lines 3 – 8 and 19 – 22). The amino acid sequences and conformations of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity, which is characteristic of the immunoglobulin (page 293, left column, lines 8 – 22). It is expected that all of the heavy and light chain CDRs are required in their proper order in the framework sequences, which maintain their required conformation, in order to produce a protein having antigen-binding function. Moreover, the proper association of the CDRs for both the heavy and light chain variable regions is required in order to form functional antigen-binding sites.
It is further taught by Bendig M. M., (Methods: A Companion to Methods in Enzymology, 8, 83-93; Published 1995), hereby Bendig, teaches that the general strategy for “humanizing” antibodies involves the substitution of all six CDRs from a rodent antibody and grafting these regions into human regions (page 83, abstract and right column, second paragraph; page 84). It is noted that Bendig used Kabat CDRs in their humanization process (page 86, right column, second paragraph). Bendig goes on to teach that the six CDRs of the antibody’s light and heavy chain variable regions form loop-like structures that make direct contact with the antigen, holding it in place (page 84, figure 3).
In light of the Supreme Court decision In re Amgen Inc. et al. v. Sanofi et al., 143 S. Ct. 1243 (2023), hereafter Amgen, updated guidelines were provided regarding the assessment of enablement (Federal Register, pp. 1563–1566; Published 01/10/2024). In Amgen, the Supreme Court unanimously affirmed that a genus of monoclonal antibodies were not enabled because when a range within a genus is claimed, there must be reasonable enablement of the scope of the range. The Court found in Amgen that due to the large number of possible candidates within the scope of the claims and the specification's corresponding lack of structural guidance, it would have required undue experimentation to synthesize and screen each candidate to determine which compounds in the claimed class exhibited the claimed functionality. Collectively, the prior art and Court teach that it is unpredictable whether or not peptide variants will have similar structure and/or function, even when only one amino acid is mutated. It would thus require undue experimentation to screen the many Fab variants as presently claimed.
Quantity of experimentation needed: The recitation of the percent identities in the claims would require undue experimentation due to the unpredictability of mutations and their impacts on structure and/or function. There would be undue experimentation to individually analyze the function and structure for each one of the trillions of sequences disclosed by the recitation of the percent identities. At a minimum, the art teaches that a skilled artisan would consider the predictive function of an antibody if the six CDRs are defined, wherein there are three each for the heavy and light chain variable regions, in the context of the framework sequences with the correct spatial orientation. Thus, one of skill in the art would neither expect nor predict the appropriate function of any Fab-Fc variant or Fab binding domain of the instant claims for a modified VIC16 antibody as broadly as claimed, as the claims read on modification in the CDR of the antibody, and, thus, would not have all six CDRs as defined.
Any and all enablement of the claimed Fab variants and domains must therefore come from the instant disclosure. However, the instant disclosure only teaches the production and usage of the disclosed REFORMabs. The claims are clearly not enabled to their full scope. Moreover, claims not containing elements critical or essential to the practice of the invention, such as antibodies or antibody fragments not having all of the relevant functional CDRs in the proper site on an appropriate antibody heavy or light chain framework, are not enabled by the disclosure. Claims that contain materials demonstrated not to bind to the critical element of the invention are also not enabled by the disclosure. See In re Mayhew, 527 F.2d 1229, 188 USPQ 356 (CCPA 1976).
For the reasons discussed above, undue experimentation would be required to practice
the claimed invention commensurate with the scope of the claims. Reasonable correlation must exist between the scope of the claims and scope of enablement set forth. It would take undue trials and errors to practice the claimed invention in view of the quantity of experimentation necessary, the limited working examples, the unpredictability of the art, the lack of sufficient guidance in the specification, and the breadth of the claims.
Conclusion: The instant disclosure is not enabling for any sequence that has at least 80% identity to the disclosed Fab-Fc variants and/or Fab binding domains as presently written, but rather the tested REFORMabs. It is recommended that all iterations of “at least 80% to 99% identical” be removed from claims 42 and 44 as presently written.
35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS. — Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 37 and 38 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claims 37 requires that the VIC16 antibody be comprised of six CDRs, a VH region, and a VL region. Claim 36, which claims 37 and 38 are dependent upon, recites “the antibody that is reactive against Ebola virus is VIC16”. There are no additional limitations in claims 37 and 38 that are not recited in claim 36. Every enabled portion of the antibody defined in claim 36 will have its six CDRs, a VH region, and a VL region regardless. In other words, the claims as currently written only recite inherent properties of the claimed antibody. Thus, claims 37 and 38 fail to further limit the subject matter of claim 36. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 103
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:
Determining the scope and contents of the prior art.
Ascertaining the differences between the prior art and the claims at issue.
Resolving the level of ordinary skill in the pertinent art.
Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 21, 22, and 35 – 43 are rejected under 35 U.S.C. 103 as being unpatentable over Saphire, E. O., et. al., (Cell, 174(4), 938–952.e13; Published August 21, 2018; Cited in Applicant’s IDS on November 1, 2023 as Other Document Desig. ID 60), hereby Saphire, in view of Wang, J., (US 20200392227 A1; Published December 17, 2020), hereby Wang, as evidenced by Saunders, K. O., (Frontiers in immunology, 10, 1296; Published June 7, 2019; Cited in Applicant’s IDS on November 1, 2023 as Other Document Desig. ID 61), hereby Saunders; Zalevsky, J., et. al., (Nature biotechnology, 28(2), 157–159; Published January 17, 2010; Cited in Applicant’s IDS on November 1, 2023 as Other Document Desig. ID 72), hereby Zalevsky; and Diebolder, C. A., et. al., (Science, 343(6176), 1260–1263; Published March 14, 2014; Cited in Applicant’s IDS on November 1, 2023 as Other Document Desig. ID 23), hereby Diebolder.
Saphire teaches the analysis of 171 IgG class monoclonal antibodies to Ebola virus (EBOV) that were gathered by the Viral Hemorrhagic Fever Immunotherapeutic Consortium (VIC), including VIC 16, which comprises a Fab-Fc structure (page 939, right column, second and third paragraph; figures 1 and SARS-CoV-2; table 1), as defined in instant claims 35 and 36. Every enabled portion of VIC16 will inherently have its six CDRs, VH region, VL region, heavy chain, and light chain and their associated sequences, as required in instant claims 37 – 41. Saphire goes on to teach that recombinant anti-EBOV surface glycoprotein (GP) antibodies were produced in CHO cells following stable transfection with paired expression plasmids carrying heavy and light chains derived from the same B cell or in HEK293 cells as human IgG1s (page e3, monoclonal antibody isolation and purification), as required in instant claim 21. The ability of VIC16 to engage the innate immune system was measured by obtaining four different phagocytosis readouts: antibody-dependent cellular phagocytosis (ADCP) by human and mouse monocytes and antibody dependent neutrophil phagocytosis (ADNP) by human and mouse neutrophils, whereas natural killer (NK) cell activation was measured by surface CD107a expression, secretion of cytokine IFNγ, and secretion of chemokine MIP-1β (page 943, right column, bottom paragraph; page 944, right column, second paragraph), as required in instant claim 22. Here, it is taught that phagocytosis removes pathogen-infected cells and can be mediated by monocytes, macrophages, dendritic cells, and neutrophils; whereas NK cells play a role in antiviral immunity by directly killing infected cells or secreting chemokines and cytokines to activate immune signaling pathways, wherein CD107a is a marker of NK degranulation, i.e., killing of antibody-opsonized cells, and IFNγ and MIP-1β confer antiviral effects (page 943, right column, last paragraph; page 944, right column, second paragraph). Thus, it would have been prima facia obvious to a person having skill in the art to have an antibody that is able to recruit multiple immune factors as it is associated with increased vaccination efficacy (page 943, right column, third paragraph).
Saphire fails to teach the modification of VIC16 with different Fc variants, as defined in instant claims 21, 42, and 43. Saphire does teach that VIC16 is an IgG1 monoclonal antibody that binds to the internal fusion loop of the EBOV GP as its epitope and has consistent neutralization and some cross-reactivity (page 941, left column, epitope characterization; page 941, right column, relationship of epitope to neutralization; page 943, binding to other filovirus GPs and mouse-adapted Ebola Virus; figures 2, S2, 4, and 5; table 2). However, it was found that VIC16 conferred only 40 – 50% protection when given to mice that were challenged with EBOV (page 939, right column, last paragraph; page 942, left column, first three lines; figures 3, s1, and S3; table 3). It is also taught that VIC16 had weak and/or no phagocytic activity and NK cell activation, but a strong neutralization activity (page 945, regression analysis of VIC antibody function correlation network; page 948, right column, first four lines; figure 6).
Wang teaches an antibody, i.e., IgG1, comprising a variant Fc region at any of positions 218 – 329, with Fc numbering according to the EU index, that have enhanced binding to FcγR in comparison to a wildtype parent Fc region (abstract; page 1, paragraphs 0005 – 0008; page 3, paragraph 0028; claims 1 and 10). The Fc variant may comprise an amino acid sequence at least 85% identical to that of the wildtype counterpart (column 8, lines 26 – 29). The Fc variant may comprise one or more amino acid substitutions at one or more of positions 233, 234, 235, and/or 236 and/or at positions involved in interaction with an Fc receptor, including, but not limited to, positions S267, V273, L328, and/or P329 (page 1, paragraph 0008; page 4, paragraphs 0036 and 0037; claims 8 and 9), as disclosed in instant claims 42 and 43. Exemplary IgG1-Fc variants are provided by Wang, wherein several have 100% sequence similarity to the amino acid sequences set forth in instant claims 39 and 40. For example, one of these IgG1-Fc variants, SEQ ID NO: 22, has 100% sequence similarity to instant SEQ ID NO: 36 (page 9, SEQ ID NO: 22; see also the sequence alignment results as reproduced below), as required in instant claims 39 and 40. The Fc variants taught by Wang have altered binding activity to a subtype of Fc receptors known as FcγRIIB, wherein antibodies designed with the Fc variants have enhanced therapeutic index, i.e., high treatment efficacy and low toxicity, in comparison to their wildtype counterparts (page 3, paragraphs 0026 and 0027). Thus, it would have been prima facia obvious to a person having ordinary skill in the art to modify VIC16 with one of the disclosed Fc variants to increase its agonistic effects and activation of immune cells, i.e., T cells and NK cells (page 14, paragraph 0046), as required in instant claims 21, 22, 39, and 40.
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Nonetheless, Fc modification is a technique known in the art that is employed to optimize therapeutic antibodies, wherein numerous research and review articles have been written on the topic. For example, Saunders teaches that the sequence and glycosylation of the Fc domain is often manipulated in antibody engineering to enhance or reduce antibody effector functions and circulating half-life (abstract; page 2, right column, first – third paragraphs). Individual mutations were performed in the solvent exposed amino acid residues on the Fc of IgG1, creating an IgG1 Fc variant library, wherein certain combinations were found to result in either increased or decreased FcγR binding, phagocytosis, complement fixation, and neutralization (whole document), as defined in instant claims 21 and 22. Fc variants taught to enhance effector function, such as through ADCC and ADCP, include: S298A/E333A/K334A; S239D/A330L/I332E; S239D/I332E; G236A/S239D/A330L/I332E; E345R; S267E/H268F/S324T; F243L/R292P/Y300L/V305I/P396L; K236W/E333S; and H268F/S324T, among others (pages 2 – 9, antibody fc mutations for the improvement of effector functions; see also table 1), as defined in instant claims 39, 40, 42, and 43. Variants taught to improve antibody circulation half-life, i.e., extended the antibody’s half-life, include: N434A; M252Y/S254T/T256E; and M428L/N434S, among others (pages 9 and 10, improved antibody half-life circulation; see also table 2), as disclosed in instant claims 39, 40, 42, and 43. Variants taught to decrease effector function by alleviating cytokine induction and, thus, cytotoxicity, include: L234A/L235A; L234A/L235A/P329G; and N297Q, among others (pages 11 – 13, antibody fc engineering for the ablation of effector functions; see also table 3), as required in instant claims 39, 40, 42, and 43. Moreover, it is taught by Saunders that the Fc includes the CH2 and CH3 domains of the heavy chain constant region (page 2, left column, second paragraph), as recited in instant claim 40. Zalevsky teaches that Fc-engineered antibodies had improved antitumor activity in a mouse model (page 157, abstract; figure 1). The Fc variants employed were M252Y/S254 T/T256E and M428L/N434S, among others, wherein M428L/N4343S showed promise in improvement of Fc affinity (page 157, right column, first six lines; table s1), as disclosed in instant claims 39, 40, 42, and 43. Furthermore, Diebolder the design of antibody therapeutics with enhanced efficacy, wherein mutations of the Fc, including E345R, enhance an antibody’s ability to activate complement-dependent cytotoxicity (abstract; page 1690, right column, first full paragraph), as required in instant claims 39, 40, 42, and 43.
Saphire, Wang, Saunders, Zalevsky, and Diebolder are considered to be analogous to the claimed invention because Saphire is drawn to a neutralizing IgG monoclonal antibody against EBOV, i.e., VIC16, that has some cross-protectivity, wherein Wang, Saunders, Zalevsky, and Diebolder provide evidence for modifying the Fc-region of the antibody to increase its function. Based on the prior art teachings, it would have been obvious to a person having ordinary skill in the art to modify the Fc of VIC16 to increase its phagocytic activity and/or NK cell activation, as taught by Saphire, by using one of the Fc variants shown to enhance antibody function, as taught by Wang, Saunders, Zalevsky, and Diebolder. An Fc variant can improve antibody function by decreasing its abilities to bind to Fc receptors, i.e., preventing cellular entry of the virus; increasing phagocytosis to facilitate viral clearance; and/or increasing its half-life (Saphire, page 943, right column, last paragraph; page 944, right column, second paragraph; Wang, page 3, paragraphs 0026 and 0027; Saunders, page 15, conclusions). Thus, it would have been obvious to a person having ordinary skill in the art to have combined the teachings of Saphire, Wang, Saunders, Zalevsky, and Diebolder before the effective filing date of the claimed invention with a reasonable expectation of success to selectively activate innate immune responses to facilitate increased killing of target cells and/or increase the half-life of the antibody (Diebolder, abstract; Wang, page 14, paragraph 0046; Saunders, page 15, conclusions) for therapeutic development against EBOV (Saphire; abstract). All the claimed elements were known in the prior art. The use of a known technique, i.e., Fc modification of IgG1, to improve similar devices (methods or products), i.e., VIC16 – an IgG1 antibody, in the same way is likely to be obvious. See KSR International Co. v. Teleflex Inc., 550 U.S. 398,415–421, 82 USPQ2d 1385, 1395–97 (2007) and MPEP §§ 2143C and 2143.02.
Claim 44 is rejected under 35 U.S.C. 103 as being unpatentable over Saphire, E. O., et. al., (Systematic Analysis of Monoclonal Antibodies against Ebola Virus GP Defines Features that Contribute to Protection. Cell, 174(4), 938–952.e13; Published August 21, 2018; Cited in Applicant’s IDS on November 1, 2023 as Other Document Desig. ID 60), hereby Saphire, in view of Wang, J., (US 20200392227 A1; Published December 17, 2020), hereby Wang, as evidenced by Saunders, K. O., (Conceptual Approaches to Modulating Antibody Effector Functions and Circulation Half-Life. Frontiers in immunology, 10, 1296; Published June 7, 2019; Cited in Applicant’s IDS on November 1, 2023 as Other Document Desig. ID 61), hereby Saunders; Zalevsky, J., et. al., (Enhanced antibody half-life improves in vivo activity. Nature biotechnology, 28(2), 157–159; Published January 17, 2010; Cited in Applicant’s IDS on November 1, 2023 as Other Document Desig. ID 72), hereby Zalevsky; and Diebolder, C. A., et. al., (Complement is activated by IgG hexamers assembled at the cell surface. Science, 343(6176), 1260–1263; Published March 14, 2014; Cited in Applicant’s IDS on November 1, 2023 as Other Document Desig. ID 23), hereby Diebolder, as applied to claims 21, 22, 35, 36, 39, 40, 42, and 43 above, and further in view of Pessi, A., Nicosia, a., and Cortese, R., (WO 2012003995 A1; Published January 12, 2012), hereby Pessi.
Saphire, Wang, Saunders, Zalevsky, and Diebolder fail to teach the amino acid sequence of the Fab binding domain that is encoded by the nucleic acid sequence of instant SEQ ID NOs: 1 – 18, as defined in instant claim 44.
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However, Pessi teaches an antibody for use in the treatment or prevention of a disease, including infectious diseases caused by viruses, like Ebola virus (page 2, last paragraph; page 3, first paragraph; page 10, third paragraph). Exemplary antibodies that can be employed are taught by Pessi (pages 7 and 8, table 2; pages 21 and 22). Pessi does not explicitly teach the nucleic acid sequences taught by instant SEQ ID NOs: 1 – 18. However, as stated above in paragraph 21, it has been inferred that the nucleic acid sequences of SEQ ID NOs: 1 – 18 encode for the amino acid sequence of the Fab binding domain set forth in instant claim 44. Numerous amino acid sequences for the desired antibodies are taught by Pessi, wherein several have 100% sequence similarity to the amino acid sequences set forth in instant claim 44. For example, the Fab palivizumab light chain, i.e., SEQ ID NO: 26, and Fab palivizumab heavy chain, i.e., SEQ ID NO: 27, has 100% sequence similarity to the translated sequence of instant SEQ ID NOs: 1 and 2 (page 8; figure 15; see also the sequence alignment results as reproduced below for instant SEQ ID NOs: 1 and 2 on the top and bottom, correspondingly), as required in instant claim 44.
Saphire, Wang, Saunders, Zalevsky, Diebolder, and Pessi are considered to be analogous to the claimed invention because Saphire and Pessi are drawn to antibodies against EBOV that has some cross-protectivity, wherein Wang, Saunders, Zalevsky, and Diebolder provide evidence for modifying the Fc-region of the antibody to increase its function. Based on the prior art teachings, it would have been obvious to a person having ordinary skill in the art to modify the Fc of VIC16 to increase phagocytic activity and/or NK cell activation, as taught by Saphire, by using one of the Fc variants known to enhance antibody function, as taught by Wang, Saunders, Zalevsky, and Diebolder, with the Fab binding domain with therapeutic activity, as taught by Pessi. The optimization of Fc variants can improve antibody functions by decreasing its abilities to bind to Fc receptors, i.e., preventing cellular entry of the virus; increasing phagocytosis to facilitate viral clearance; and/or increasing its half-life (Saphire, page 943, right column, last paragraph; page 944, right column, second paragraph; Wang, page 3, paragraphs 0026 and 0027; Saunders, page 15, conclusions). Thus, it would have been obvious to a person having ordinary skill in the art to have combined the teachings of Saphire, Wang, Saunders, Zalevsky, Diebolder, and Pessi before the effective filing date of the claimed invention with a reasonable expectation of success to selectively activate innate immune responses to facilitate increased killing of target cells and/or increase the half-life of the antibody for therapeutic development against EBOV (Saphire; abstract). All the claimed elements were known in the prior art. The use of a known technique, i.e., Fc modification of IgG1, to improve similar devices (methods or products), i.e., VIC16 – an IgG1 antibody, in the same way is likely to be obvious. See KSR International Co. v. Teleflex Inc., 550 U.S. 398,415–421, 82 USPQ2d 1385, 1395–97 (2007) and MPEP §§ 2143C and 2143.02.
Conclusion
Claims 21, 22, and 35 – 44 are rejected. No claims are allowed.
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Hallie N. Pennington, Ph.D. whose telephone number is (571)272-6781. The Examiner can normally be reached M-Th 7:30-5:30 ET.
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If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s supervisor, Michael Allen can be reached at (571)270-3497. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/HALLIE N. PENNINGTON, PH.D./Examiner, Art Unit 1671
/Michael Allen/Supervisory Patent Examiner, Art Unit 1671