DETAILED ACTION
Status of Application, Amendments and/or Claims
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . The preliminary amendment of 12/22/23 has been entered in full. Claim 5 is amended. Claims 1-5 are pending.
Specification
The disclosure is objected to for the following informalities:
---The title is not descriptive because it is directed in part to “use thereof”, which encompasses any use, but the claims are limited to a method of applying the antibody for immunohistochemistry, immunoblotting and intracellular flow cytometry, all forms of detecting HLA-G. A new title is required that is clearly indicative of the invention to which the claims are directed. The following is suggested: “Monoclonal Antibody Against HLA-G Molecules and Use Thereof in Detection”.
---At page 7, line 1, “depositary” should be spelled “depository”.
Appropriate correction is required.
Claim Objections
Claims 1-5 are objected to for the following informalities:
In claim 1, the acronym “HLA” should be accompanied by the full terminology the first time it is used in a series of claims; e.g., “human leukocyte antigen (HLA)". See the specification at page 1.
In each of claims 1-5, “HLA-G1, -G2, -G5 and HLA-G6” should be written as either: “HLA-G1, -G2, -G5 or -G6” or “HLA-G1, HLA-G2, HLA-G5 or HLA-G6”.
In claim 1, lines 3-4 (two instances), “depositary” should be “depository”.
In claim 4, line 2, “G6isoforms” should be “G6 isoforms”.
The remaining claim(s) are objected to for depending from an objected claim.
Appropriate correction is required.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Claim Rejections - 35 USC § 112(a), deposit
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 1 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as containing subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Claim 1 is directed to a monoclonal antibody produced by the hybridoma deposited under CCTCC NO: 202121, where the depository institution is China Center for Type Culture Collection and the depository time is August 11, 2021. Possession of the hybridoma is required to make and use the product of the claims. As a required element, the hybridoma must be known and readily available to the public or obtainable by a repeatable method set forth in the specification. If a required element is not so obtainable or available, the enablement requirements of 35 U.S.C. §112(a), may be satisfied by a deposit of the element; e.g., deposit of the hybridoma expressing the antibody.
The specification at pages 6-7 states that this hybridoma was deposited as deposit number 202120 at the China Center for Type Culture Collection (CCTCC), located at Wuhan University, Wuhan, Hubei Province, P.R. China (postal code: 4030072), on August 11th, 2021. However, Applicants’ reference to this deposit is an insufficient assurance that the required deposit has been made and all the conditions of 37 CFR 1.801-1.809 met.
If the deposits have been made under the provisions of the Budapest Treaty, what is required is the filing of an affidavit or declaration by applicants, assignees or a statement by an attorney of record over his or her signature and registration number stating that,
(1) the deposits have been accepted by an International Depository Authority under the provisions of the Budapest Treaty;
(2) all restrictions upon public access to the deposits will be irrevocably removed upon the grant of a patent on this application; and
(3) the deposit will be replaced if viable samples cannot be dispensed by the depository is required.
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:
(a) during the pendency of this application, access to the deposits will be afforded to the Commissioner upon request:
(b) 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:
(c) 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
(d) the deposits will be replaced if they should become nonviable or non-replicable.
Claim Rejections - 35 USC § 112(a), written description
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.-The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 2-4 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
In making a determination of whether the application complies with the written description requirement of 35 U.S.C. 112(a), it is necessary to understand what Applicants are claiming and what Applicants have possession of.
Independent claim 2 is a product; specifically, a monoclonal antibody (termed YWHG-3) directed against (i.e., binding to) human leukocyte antigen (HLA)-G1, -G2, -G5 and -G6 that is defined by the sequence(s) of its complementarity-determining regions (CDRs) of its light and/or heavy chain. Dependent claim 3 further defines the sequences of framework region sequences of the light and/or heavy chain. Dependent claim 4 further defines the antibody by reference to a nucleotide sequence encoding the light and/or heavy chain.
The Federal Circuit in Amgen v. Sanofi, 872 F.3d 1367 (Fed. Circ. 2017) held that a claim directed to an antibody requires written description of the antibody itself rather than being satisfied solely by a written description of the antigen to which it binds (the so-called "newly characterized antigen" test). Thus, a description of the target protein (e.g. the HLA-G1 isoform) itself is not sufficient to provide a written description of the genus of antibodies that bind to said target. Thus, in the instant case the specification must provide a written description of the structure of the claimed antibodies.
While the general structure of an antibody is well-known in the art, the specific structure of the portion of an antibody that provides its functionality, i.e., the ability to bind to a particular antigen, is not. The prior art recognizes that antibodies bind to epitopes of 5-7 amino acids (Benjamini et al, 1991. Immunology: A Short Course, 2nd edition, page 40 only). The antigen-binding site of the antibody is formed by the association of the heavy and light chain variable regions, which each have three CDRs that provide the majority of the contact residues for the binding of the antibody to its target epitope. 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. Furthermore, the set of CDRs in one antibody is independent of the set found in each other antibody, and thus knowledge of one set of CDRs does not provide any predictable information about other sets of CDRs that provide binding specificity, even with regard to the same antigen. Thus, even knowing the structure (CDRs) of one antibody does not allow the skilled artisan to predict the structure of other antibodies that bind to the same epitope or to the other epitopes in the same protein. The relevant art, Ferrara et al (2015. mAbs. 7(1): 32-41) teaches that there is substantial variation in the structure of antibodies that bind to a single protein, on the order of hundreds of different sequences; specifically, see page 36: "The number of different HCDR3s selected against the test antigens ranges from 74 to 460 (Table 3), with the actual number of different antibodies likely to be significantly higher when different VL chains and additional VH mutations are taken into account” (pg 36).
In the instant case, while independent claim 2 includes reference sequences for each of the six CDRs found in YWHG-3, the claim only requires that one of the six CDRs is so defined. Specifically, lines 2-4 recite that the antibody “at least comprises one or more of light chain hypervariable regions CDR1, CDR2 and CDR3, and/or one or more of heavy chain hypervariable regions CDR1, CDR2, and CDR3”, with the following lines further defining the reference sequences. As such, the claim encompasses a genus of anti-HLA-G antibodies in which only a single CDR (LCDR1, LCDR2, LCDR3, HCDR1, HCDR2 or HCDR3) is defined by reference to a defined amino acid sequence and thus encompasses antibodies in which each of the other CDRs has a different amino acid sequence from the defined reference sequences.
Furthermore, even with respect to the defined reference sequences, the claims also encompass variability in the sequences of the antibodies. First, the claims expressly specify that the reference sequences include “an amino acid sequence with equivalent functions to the sequence of SEQ ID No: [X] formed by substituting, deleting or adding one or more amino acids”. This is an open-ended genus that encompasses CDR variants in which one or more, without limit, of the amino acids are changed with respect to the reference CDR sequence. Second, the claims use language with an indefinite article, “an amino acid sequence of the antibody chain of the monoclonal antibody (YWGH-3) is shown in SEQ ID No: [X]”. The phrases " the amino acid sequence of SEQ ID NO: X" and " an amino acid sequence of SEQ ID NO: X" result in claims of very different scope, because while the former encompasses only sequences that comprise the full length of SEQ ID NO: X, with or without additional amino acids at either or both ends, the latter encompasses sequences that comprise the full-length sequence of SEQ ID NO: X or any portion of SEQ ID NO: X; i.e., fragments of SEQ ID NO: X.
By defining the antibody in such a way that the sequence of only one reference CDR amino acid sequence is required; and further allowing for essentially unlimited variants with respect to the reference CDR sequences, the breadth of the claims is expanded, because the antibodies encompass a large genus of antibodies including changes to essentially every amino acid in the CDRs of the defined anti-HLA-G antibody. However, the specification does not describe which, if any, of these variants will retain the functionality of the antibody in binding to the specified HLA-G isoforms.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111 (Fed. Cir. 1991), clearly states “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed” (pg 1117). The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed” (pg 1116).
MPEP 2163 provides guidance for complying with the written description requirement of 35 U.S.C. 112(a) that the “specification shall contain a written description of the invention…”; this requirement is separate and distinct from the enablement requirement (Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1355 (Fed. Cir. 2010)). Written description for a claimed genus may be satisfied through sufficient description of a relevant number of species. This is dependent on whether one of skill in the art would recognize necessary common attributes or features possessed by the members of the genus. Generally, in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. Written description for a claimed genus can also be satisfied when relevant identifying characteristics are disclosed. Per MPEP 2163, “[d]etermine whether the specification discloses other relevant identifying characteristics sufficient to describe the claimed invention in such full, clear, concise, and exact terms that a skilled artisan would recognize applicant was in possession of the claimed invention. For example, if the art has established a strong correlation between structure and function, one skilled in the art would be able to predict with a reasonable degree of confidence the structure of the claimed invention from a recitation of its function. Thus, the written description requirement may be satisfied through disclosure of function and minimal structure when there is a well-established correlation between structure and function.” However, claiming by function does not necessarily satisfy the written description requirement. “[A] generic statement such as "vertebrate insulin cDNA" or "mammalian insulin cDNA," without more, is not an adequate written description of the genus because it does not distinguish the claimed genus from others, except by function. It does not specifically define any of the genes that fall within its definition. It does not define any structural features commonly possessed by members of the genus that distinguish them from others … A definition by function, as we have previously indicated, does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is. It is only a definition of a useful result rather than a definition of what achieves that result” (Regents of the University of California v. Eli Lilly Co., 119 F.3d 1559 (Fed. Cir. 1997)). Also, “[w]hen a patent claims a genus using functional language to define a desired result, the specification must demonstrate that the applicant has made a generic invention that achieves the claimed result and do so by showing that the applicant has invented species sufficient to support a claim to the functionally-defined genus" (Capon v. Eshhar, 418 F.3d 1349 (Fed. Cir. 2005)). “[A] sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can 'visualize or recognize' the members of the genus” (AbbVie, 759 F.3d at 1297, reiterating Eli Lilly, 119 F.3d at 1568-69).
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111 (Fed. Cir. 1991), clearly states “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed” (pg 1117). The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed” (pg 1116). As discussed above, the skilled artisan cannot envision the detailed chemical structure of the encompassed genus of anti-HLA-G antibodies, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016 (Fed. Cir. 1991). One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483 (BPAI 1993). In Fiddes, claims directed to mammalian FGFs were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovine sequence.
Therefore, only:
A monoclonal antibody (YWHG-3) against HLA-G1, HLA-G2, HLA-G5 and HLA-G6 isoforms, wherein said monoclonal antibody comprises a light chain comprising a CDR1 having the amino acid sequence of SEQ ID NO: 2, a CDR2 having the amino acid sequence of SEQ ID NO: 3 and a CDR3 having the amino acid sequence of SEQ ID NO: 4; and a heavy chain comprising a CDR1 having the amino acid sequence of SEQ ID NO: 6, a CDR2 having the amino acid sequence of SEQ ID NO: 7 and a CDR3 having the amino acid sequence of SEQ ID NO: 8, but not the full breadth of the claims meet the written description provision of 35 U.S.C. §112(a). Applicants are reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (pg 1115).
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.
Claims 4 and 5 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 pre-AIA the applicant regards as the invention.
Claim 4 is indefinite because it limits the monoclonal antibody of claim 2 by means of a further limitation directed to “a nucleotide sequence”, which is not part of the antibody.
Claim 5 is directed to a “method for applying the monoclonal antibody (YWHG-3) against HLA-G1, -G2, -G5 and -HLA-G6 isoforms of claim 1 for immunohistochemistry, immunoblotting and intracellular flow cytometry”. This claim is directed to reciting a list of intended applications for the antibody, but without setting forth any steps of how the method(s) are actually practiced. A claim is indefinite where it merely recites a process of use without any active, positive steps delimiting how this use is actually practiced. See MPEP 2173.05(q), which states:
"Attempts to claim a process without setting forth any steps involved in the process generally raises an issue of indefiniteness under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph. For example, a claim which read: "[a] process for using monoclonal antibodies of claim 4 to isolate and purify human fibroblast interferon" was held to be indefinite because merely recites a use without any active, positive steps delimiting how this use is actually practiced. Ex parte Erlich, 3 USPQ2d 1011 (Bd. Pat. App. & Inter. 1986)."
MPEP 2173.05(q) further states, “It is appropriate to reject a claim that recites a use but fails to recite steps under 35 U.S.C. 101 and 35 U.S.C. 112(b) if the facts support both rejections”. As such, claims 6 are indefinite for reciting a use without any active, positive steps. See also the rejection of the claims below in the section titled "Claim Rejections - 35 USC § 101".
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 5 is rejected under 35 U.S.C. 101 because the claimed invention is directed to nonstatutory subject matter.
Claim 5 is directed to a method of using an antibody but without reciting any specific method steps. This claim does not fall within at least one of the four categories of patent eligible subject matter because, per MPEP 217.05(q): ““Use” claims that do not purport to claim a process, machine, manufacture, or composition of matter fail with 35 U.S.C. 101. In re Moreton, 288 F.2d 708, 709, 129 USPQ 227, 228 (CCPA 1961)(“one cannot claim a new use per se, because it is not among the categories of patentable inventions specified in 35 U.S.C. § 101”).”
Note on Patentability
No prior art has been identified that teaches or suggests a monoclonal antibody against HLA-G1, HLA-G2, HLA-G5 and HLA-G6 that comprises a light chain comprising a CDR1 having the amino acid sequence of SEQ ID NO: 2, a CDR2 having the amino acid sequence of SEQ ID NO: 3 and a CDR3 having the amino acid sequence of SEQ ID NO: 4; and a heavy chain comprising a CDR1 having the amino acid sequence of SEQ ID NO: 6, a CDR2 having the amino acid sequence of SEQ ID NO: 7 and a CDR3 having the amino acid sequence of SEQ ID NO: 8.
Conclusion
No claims are allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ZACHARY C HOWARD whose telephone number is (571)272-2877. The examiner can normally be reached on Monday to Friday from 9 AM to 5 PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Vanessa Ford, can be reached at telephone number (571) 272-0857. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ZACHARY C HOWARD/Primary Examiner, Art Unit 1674
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