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 claims priority to prior-filed United States Provisional Patent Application Nos. 63/397,698 (filed 08/12/2022) and 63/369,184 (filed 07/22/2022).
Status of Application/Claims
The preliminary amendment, filed 12/26/2023, is acknowledged. Claims 1, 3, 6, 12, 33-45, 51-56, 60-61, and 66-67 are canceled. Claims 4-5, 7-10, 13-14, 16-24, 29, 31-32, 46-50, 57-59, 62-65, and 68-73 are currently amended. Claims 74-106 are new. Claims 2, 4-5, 7-11, 13-32, 46-50, 57-59, 62-65, and 68-106 are currently pending and are examined on the merits herein.
Information Disclosure Statements
The information disclosure statements (IDSs) submitted on 12/26/2023, 01/29/2024, 10/25/2024, and 01/13/2025 have been fully considered by the examiner.
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 specification are not identified by sequence identifiers in accordance with 37 CFR 1.821(d).
p.50, para.1, lines 6 and 11 contain amino acid sequence “LALAPG” without an associated SEQ ID NO.
p.173, para.1, lines 3, 4, and 10 contain amino acid sequence “TSTGGRQGSHH” without an associated SEQ ID NO.
p.204, para.2, lines 14, 15, and 20 contain amino acid sequence “TSTGGRQGSHH” without an associated SEQ ID NO.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, 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.
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.
Figures 1E-1H, 3D, 4A-4B, 6, 7A-7B, 8A-8B, and 13A-13L contain amino acid sequences without 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.
Specification
The use of the terms Bristol Myers Squibb, American Pharmaceutical Partners, Camptosar, Cytiva, Protein Metrics, Agilent, Sciex, Jackson, Alfa Aesar, Surmodics, Corning, GE Healthcare, Qiagen, Cell Signaling, Cusabio, R&D Systems, Sartorius, Cayman, Cayman Chemical, Nunc, Waters, Rapigest, Biocision, Unchained Labs, Abcam, GraphPad, Bruker, Thermo Fisher Scientific, Coot, Pymol, Phenix, Chimera, Titan, Perkin Elmer, StemCell, Krios, Gatan, cryoSPARC, Novagen, Vitrobot, Envigo, Sigma-Aldrich, Gibco, Lonza, Miltenyi Biotec Inc., Invitrogen, BD Biosciences, Sigma, Beckman, Forte Bio, and Rhone-Poulenc Rorer, which are trade names or marks used in commerce, have been noted in this application. The terms should be in all caps wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , 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.
Claim Objections
Claims 4-5, 7, 16-17, 23, 93, 97-100, and 104 are objected to because of the following informalities:
Claims 4 recites “…wherein the VL of the antibody is at least 95% identical to the amino acid sequence of SEQ ID NO: 70" which should be corrected to "...wherein the VL of the antibody comprises an amino acid sequence that is at least 95% identical to SEQ ID NO: 70”.
Claim 5 recites “…wherein the VH of the antibody is at least 95% identical to the amino acid sequence of SEQ ID NO: 68" which should be corrected to "...wherein the VH of the antibody comprises an amino acid sequence that is at least 95% identical to SEQ ID NO: 70”.
Claim 7 recites “…wherein the VL of the antibody is at least 95% identical to the amino acid sequence of SEQ ID NO: 70" which should be corrected to "...wherein the VL of the antibody comprises an amino acid sequence that is at least 95% identical to SEQ ID NO: 70”.
Claims 16 and 17 each recite “…at least 95% identical to the amino acid sequence..." which should be corrected to "...at least 95% identical to an amino acid sequence…”.
Claim 93 recites: “…wherein the VH of the antibody is at least 95% identical to the amino acid sequence..." which should be corrected to "...wherein the VH of the antibody is at least 95% identical to an amino acid sequence…”; and, “…wherein the VL of the antibody is at least 95% identical to the amino acid sequence…” which should be corrected to "...wherein the VL of the antibody is at least 95% identical to an amino acid sequence…”.
Claims 97 and 98 each recite “…at least 95% identical to the amino acid sequence..." which should be corrected to "...at least 95% identical to an amino acid sequence…”.
Claims 99 and 100 each recite “…compared to the amino acid sequence..." which should be corrected to "...compared to an amino acid sequence…”.
Claims 23 and 104 recite “…an IgG antibody lacking a C-terminal lysine…” which should be corrected to “…an IgG antibody lacking the C-terminal lysine…”. The claims are interpreted to mean that “a/the C-terminal lysine” refers to the last amino acid of the polypeptide encoding the IgG heavy chain constant region. While the instant specification does not provide an explicit definition for the meaning of “a C-terminal lysine,” a comparison of instant SEQ ID NOs, for example SEQ ID NO: 174 (harbors terminal lysine) vs SEQ ID NO: 176 (does not harbor terminal lysine), clarifies that the lysine is at the last amino acid position of the polypeptide. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 32 and 106 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 32 and 106 contain the trademark/trade names Campath®, Rituxan®, Zenapax®, and Epivax. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade names Campath®, Rituxan®, and Zenapax® are used to identify/describe antibodies; and, Epivax is used to identify/describe an antibody immunogenicity scale. Accordingly, the identifications/descriptions are indefinite.
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.
Claim 4 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. THIS IS A WRITTEN DESCRIPTION REJECTION.
In the instant case, the claims are inclusive of a genus of PAD4 antibody that is recited to specifically bind PAD4, and wherein the only structural limitations are as follows: the antibody comprises a VH wherein only HCDR1 and HCDR3 are defined; the antibody comprises a VL wherein only LCDR1 and LCDR3 are defined; an additional requirement that the VL comprises an amino acid sequence at least 95% identical to instant SEQ ID NO: 70.
However, the written description in this case only sets forth only one antibody that harbors the defined HCDR1 and HCDR3 sequences: namely, an antibody wherein the HCDR2 is defined by instant SEQ ID NO: 5 and wherein the LCDR2 is defined by instant SEQ ID NO: 8. The specification does not disclose, and the art does not teach, the genus of PAD4 antibody as is broadly encompassed in the claims.
The state of the prior art is such that it is well established in the art that the formation of an intact antigen-binding site of antibodies generally requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three CDRs or hypervariable regions, which provide the majority of the contact residues for the binding of the antibody to its target epitope (see Paul. Fundamental Immunology, 3rd Edition, 1993, pp. 292-295; herein referred to as Paul). 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. It is expected that all of the heavy and light chain CDRs in their proper order and in the context of framework sequences which maintain their required conformation, are required in order to produce a protein having antigen-binding function and that proper association of heavy and light chain variable regions is required in order to form functional antigen binding sites (p.293, col.1-2, lines 3-8, line 31, and lines 27-30).
Additionally, Bendig M. M. Methods: A Companion to Methods in Enzymology, 1995; 8, p.83-93 (herein referred to as Bendig) reviews that the general strategy for “humanizing” antibodies involves the substitution of all six CDRs from a rodent antibody that binds an antigen of interest, and that all six CDRs are involved in antigen binding (see entire document, but especially Figs.1-3). It is noted that Bendig used Kabat CDRs in their humanization process (p.86, col.2, para.2). Similarly, the skilled artisan recognized a “chimeric” antibody to be an antibody in which both the heavy chain variable region (which comprises the three heavy chain CDRs) and the light chain variable region (which comprises the three light chain CDRs) of a rodent antibody are recombined with constant region sequences from a human antibody of a desired isotype (see entire document, but especially Figs.1-3).
Thus, the state of the art recognized that it would be highly unpredictable that a specific antibody comprising less than all six CDRs would have antigen binding function specific to PAD4. The minimal structure which the skilled artisan would consider predictive of the function of binding the PAD4 antigen of an antibody includes six CDRs (three from the heavy chain variable region and three from the light chain variable region) in the context of framework sequences which maintain their correct spatial orientation and have the requisite binding function. One of skill in the art would neither expect nor predict the appropriate functioning of the antibodies produced according to the claimed methods as broadly as is claimed.
A description of a genus may be achieved by means of a recitation of a representative number of species falling within the scope of the genus or by describing structural features common to that genus that “constitute a substantial portion of the genus.
In regards to claims to a product defined by function, without a correlation between structure and function, the claim does little more than define the claimed invention by function. That is not sufficient to satisfy the written description requirement.
The instant specification fails to provide sufficient descriptive information, such as definitive structural features that are common to the genus. That is, the specification provides neither a representative number of PAD4 antibodies with defined HCDR2 and LCDR2 sequences that encompass the genus of all possible PAD4 sequences that fall within the scope of the claim limitations nor does it provide a description of structural features that are common to the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus. Further, the prior art states that the combination of all six CDRs of an antibody dictate binding specificity; however, the claims as written provide for a broad scope of antibodies that would not predictably and specifically bind PAD4 antigen. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number” of species.
The “claims merely recite a description of the problem to be solved while claiming all solutions to it and . . . cover any compound later actually invented and determined to fall within the claim’s functional boundaries— leaving it to the pharmaceutical industry to complete an unfinished invention.”Ariad Pharmaceuticals, Inc. v. EliLilly and Co.,598 F.3d 1336, 1353 (Fed. Cir. 2010).
Because the disclosure fails to describe common attributes or characteristics that adequately identify members of the genus, and because the genus is highly variant, the disclosure of antibodies that specifically bind PAD4 is insufficient to describe the genus. Thus, one of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genus as broadly claimed.
Claims 4, 65 and 83 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 treatment of rheumatoid arthritis (RA), does not reasonably provide enablement for the treatment for delaying onset of RA. 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 commensurate in scope with these claims. THIS IS AN ENABLEMENT REJECTION.
Enablement is considered in view of the Wands factors (MPEP 2164.01(a)). The court in Wands states: “Enablement is not precluded by the necessity for some experimentation such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is ‘undue,’ not ‘experimentation.’” (Wands, 8 USPQ2d 1404). Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. “Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations.” (Wands, 8 USPQ2d 1404). The factors to be considered in determining whether undue experimentation is required include: The nature of the invention; the breadth of the claims; the amount of direction provided by the inventor; the existence of working examples; the state of the prior art; the level of predictability in the art; the quantity of experimentation needed to make or use the invention based on the content of the disclosure; and, the level of one of ordinary skill. While all of these factors are considered, a sufficient amount for amount for a prima facie case are discussed below.
Regarding claim 4:
The nature of the invention
Claim 4 is drawn to an isolated antibody that specifically binds PAD4 wherein only the CDR1 and CDR3 regions of the VH and VL sequences are defined.
The breadth of the claim
The claim is broad in that it encompasses any PAD4 antibody having the defined VH and VL CDR1 and CDR3 regions so long as the VL sequence shares at least 95% identity to instant SEQ ID NO: 70.
The level of skill in the art
The level of skill of one skilled in this art is high.
The amount or direction provided by the inventor/ the existence of working examples
The instant specification only sets forth only one antibody that harbors the defined HCDR1 and HCDR3 sequences: namely, an antibody wherein the HCDR2 is defined by instant SEQ ID NO: 5 and wherein the LCDR2 is defined by instant SEQ ID NO: 8. The specification does not disclose, and the art does not teach, the genus of PAD4 antibody as is broadly encompassed in the claims. However, these teachings do not enable the full breadth of the claim because an antibody lacking all parental CDRs would not predictably bind antigen.
The state of the prior art/ the level of predictability in the art
The state of the prior art is such that it is well established in the art that the formation of an intact antigen-binding site of antibodies generally requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three CDRs or hypervariable regions, which provide the majority of the contact residues for the binding of the antibody to its target epitope (see Paul. Fundamental Immunology, 3rd Edition, 1993, pp. 292-295; herein referred to as Paul). 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. It is expected that all of the heavy and light chain CDRs in their proper order and in the context of framework sequences which maintain their required conformation, are required in order to produce a protein having antigen-binding function and that proper association of heavy and light chain variable regions is required in order to form functional antigen binding sites (p.293, col.1-2, lines 3-8, line 31, and lines 27-30).
Additionally, Bendig M. M. Methods: A Companion to Methods in Enzymology, 1995; 8, p.83-93 (herein referred to as Bendig) reviews that the general strategy for “humanizing” antibodies involves the substitution of all six CDRs from a rodent antibody that binds an antigen of interest, and that all six CDRs are involved in antigen binding (see entire document, but especially Figs.1-3). It is noted that Bendig used Kabat CDRs in their humanization process (p.86, col.2, para.2). Similarly, the skilled artisan recognized a “chimeric” antibody to be an antibody in which both the heavy chain variable region (which comprises the three heavy chain CDRs) and the light chain variable region (which comprises the three light chain CDRs) of a rodent antibody are recombined with constant region sequences from a human antibody of a desired isotype (see entire document, but especially Figs.1-3).
Thus, the state of the art recognized that it would be highly unpredictable that a specific antibody comprising less than all six CDRs would have antigen binding function. The minimal structure which the skilled artisan would consider predictive of the function of binding the antigen of an antibody includes six CDRs (three from the heavy chain variable region and three from the light chain variable region) in the context of framework sequences which maintain their correct spatial orientation and have the requisite binding function. One of skill in the art would neither expect nor predict the appropriate functioning of the antibodies produced according to the claimed methods as broadly as is claimed.
In view of the lack of the predictability of the art to which the invention pertains as evidenced by Paul, and Bendig, the lack of guidance and direction provided by applicant, and the absence of working examples, undue experimentation would be required to practice the method for producing functional antibodies comprising fewer than all six CDRs with a reasonable expectation of success, absent a specific and detailed description in applicant’s specification of how to effectively practice this and absent working examples providing evidence which is reasonably predictive that the claimed antibodies are functional, commensurate in scope with the claimed invention.
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 complementarity determining regions (CDRs) in the proper site on an appropriate antibody heavy or light chain framework, are not enabled by the disclosure. See In re Mayhew, 527 F.2d 1229, 188 USPQ 356 (CCPA 1976).
Regarding claims 65 and 83:
The nature of the invention
Claims 65 and 83 are drawn to a method wherein the treatment of the PAD4 antibodies is for delaying onset of RA.
The breadth of the claims
The claims encompass all forms of RA, which includes seropositive RA, seronegative RA, and juvenile RA.
The level of skill in the art
The level of skill of one skilled in this art is high.
The amount or direction provided by the inventor/ the existence of working examples
The examples of the instant disclosure studied the effect of methods of PAD4 antibody treatments in vivo models that included LPS-induced acute joint inflammatory (AJI; p.206, Example 21; p.218, Example 26) and acute lung inflammatory models (ALI; p.205, Example 20; p.216, Example 25), chronic joint inflammation model (CJI; p.207, Example 22), pristane-induced inflammatory model (p.207, Example 23), collagen-induced arthritis model (CIA; p.212, Example 24), and breast cancer model (p.224, Example 30). The specification also provides examples of assessments for the effect of therapeutic PAD4 antibody administration in RA patients (p.219, Example 27).
The examples provided do not demonstrate the delayed onset of RA, but rather the examples evaluate the effect of the PAD4 antibodies under inflammatory conditions that are already present. Additionally, the disclosure does not discuss, or demonstrate through working examples, a method that could be used to determine that the onset of RA was delayed using the claimed agents as there is no disclosed method to determine that onset of RA would have predictably occurred earlier without treatment.
The state of the prior art/ the level of predictability in the art
There are no art recognized methods that could be used to establish that the onset of RA was delayed using the claimed therapeutic methods. Additionally, there are no art recognized methods that could be used to identify subjects who would have predictably exhibited onset of RA in order to determine that onset of RA was delayed using the claimed methods.
Higuera. Types of Rheumatoid Arthritis. Healthline, 06/19/2021. Internet – Wayback Machine. p.1-11 (herein referred to as Higuera) teaches that RA is an autoimmune disease that affects men, women, and children; and, that RA is particularly difficult to diagnose and is often confused with other conditions that have overlapping symptoms (p.1-3).
Rath. 11 Risk factors for Rheumatoid Arthritis and what you can do about them. Arthritis Foundation, 12/14/2022. Internet – p.1-4 (herein referred to as Rath) teaches that susceptibility to RA can be inherited and that genetic risk for RA varies among races and ethnicities (p.1, paras.1-2). Rath still maintains that RA is not well understood, but that RA is thought to result from the interplay of genetic susceptibility and environmental and lifestyle factors, as well as epigenetics (p.1, para.3).
The quantity of experimentation needed to make or use the invention based on the content of the disclosure
Studies regarding treatment and prevention of RA are underway that aim to improve earlier detection and better treatments for RA. However, based on the disclosure and the prior art, there is no known or disclosed method through which an ordinarily skilled artisan would have been able to predictably identify subjects who would have predictably developed onset of RA at a particular time in order to determine that onset of RA would have been delayed using the claimed methods. Therefore, in order to practice the invention as claimed, an ordinarily skilled artisan would have to participate in undue experimentation to determine a method that would allow for the delayed onset of RA.
In view of the Wands factors discussed above, a person of ordinary skill in the art would have to engage in undue experimentation to practice the full scope of the claimed invention. As such, instant claims 57-58, 65, 74-75, 78-79 and 83 were determined to not meet the scope of enablement requirement of 35 U.S.C. 112(a).
Allowable Subject Matter
Claims 2, 9-11, 13-15, 18-22, 24-31, 46-49, 57-58, 62-64, 68-73, and 77-79 are allowed. Claim 5 and its dependent claims are allowable, however, claim 5 is objected to (see above objection).
The following is a statement of reasons for the indication of allowable subject matter:
An antibody specifically binding to PAD4 wherein the VH and VL are defined by the following instantly claimed CDR sequences is novel: VH comprises HCDR1 of SEQ ID NO: 62, HCDR2 of SEQ ID NO:5, HCDR3 of SEQ ID NO: 6; and, VL comprises LCDR1 of SEQ ID NO: 7, LCDR2 of SEQ ID NO: 8, LCDR3 of SEQ ID NO: 9.
The closest prior art is provided by Kanazawa, et al.—WO2019131769A1, which teaches anti-PAD4 antibodies for inhibiting citrullination of activated PAD4 for treating RA, but does not teach an antibody with the antigen binding VH and VL CDR structure.
Conclusion
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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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Joanne Hama can be reached at 571-272-2911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JAMI MICHELLE GURLEY/Examiner, Art Unit 1647
/JOANNE HAMA/Supervisory Patent Examiner, Art Unit 1647