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 .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 11-12, 14-16 and 19-20 and species of antibody, 266-280 aa of SEQ ID NO: 1, method of antibody to detect blood brain barrier early injury of cerebral ischemic stroke and detection antibody in the reply filed on 3/9/2026 is acknowledged.
Claims 21-26 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions and species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 3/9/2026.
Claims 11-12, 14-16 and 19-20 are under consideration in the instant Office Action.
Withdrawn Rejections
The rejection of claims 11 and 20 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is withdrawn in view of the newly amended claims.
The rejection of claims 11-12, 14-16 and 19-20 under 35 U.S.C. 101 because the claimed invention is directed to natural correlation (process) without significantly more is withdrawn as applicant’s argument is found persuasive.
Maintained Rejection
Claim Rejections - 35 USC § 112
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 11-12, 14-16, and 19-20 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 claimed invention as a whole may not be adequately described where an invention is described solely in terms of a method of its making coupled with its function and there is no described or art recognized correlation or relationship between the structure of the invention and its function. A biomolecule sequence described only by a functional characteristic, without any known or disclosed correlation between that function and the structure of the sequence, normally is not a sufficient identifying characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence.”
Claims 11-12, 14-16, and 19-20 are directed to a method of specifically detecting blood brain barrier early injury of cerebral ischemic stroke that requires an antibody that is specifically reactive with 266-280 aa of SEQ ID NO: 1 (KTRRKMDRYDKSNIL) and has an activity of specifically detecting blood brain barrier early injury of cerebral ischemic stroke which is identified in claim 11 as XW-OCLN-2 antibody. The claimed antibody is a very specific antibody described by only the antigen it binds and its intended function. It is noted that while the instant claims and specification call their antibody by a specific name, such as XW-OCLN-2 antibody, there is no sequences or hybridomas disclosed to set forth what is encompassed by the instantly claimed XW-OCLN-2 antibody.
The Court of Appeals for the Federal Circuit has held that a “written description of an invention involving a chemical genus, like a description of a chemical species, ‘requires a precise definition, such as by structure, formula [or] chemical name,’ of the claimed subject matter sufficient to distinguish it from other materials.” University of California v. Eli Lilly and Co., 1997 U.S. App. LEXIS 18221, at *23, quoting Fiers v. Revel, 25 USPQ2d 1601, 1606 (Fed. Cir. 1993). To fully describe a genus of genetic material, which is a chemical compound, applicants must (1) fully describe at least one species of the claimed genus sufficient to represent said genus whereby a skilled artisan, in view of the prior art, could predict the structure of other species encompassed by the claimed genus and (2) identify the common characteristics of the claimed molecules, e.g., structure, physical and/or chemical characteristics, functional characteristics when coupled with a known or disclosed correlation between function and structure, or a combination of these (paraphrased from Enzo Biochemical).
The claims are drawn to a method that requires an antibody with a specific, intended use in a method for an immunoassay with any antibody that binds the 266-280 amino acids of SEQ ID NO: 1 as is called XW-OCLN-2 antibody.
The instant specification discloses only 4 antibodies in Table 1 (XW-OCLN-1-4, see page 9, [0066] AND [0068]) without disclosing any specific structure, like the CDRS of the antibody. However, as discussed above, without any way to determine how broad the genus of such antibodies are, there is no way to determine if this antibody represents the full breadth of what is claimed. The disclosure of this specific antibody would not convey to the artisan that Applicant was in possession of the full genus of all antibodies which possess the required functions nor does it allow the skilled artisan to envisage the specific structure of such antibodies.
Further note the decision in Amgen v. Sanofi 2017, where the Court supported previous decisions (Centocor 2011; Abbvie 2014) that defining an antibody solely by what it binds does not satisfy the written description requirement, stating that this would allow patentees to “claim antibodies by describing something that is not the invention, i.e., the antigen”. This decision has precipitated guidance to the Office instructing that the portion of MPEP 2163 regarding the “newly characterized antigen test” (indicating a well-characterized antigen is sufficient to satisfy written description for antibodies which bind that antigen) should no longer be used and that contrary materials should not be relied upon as reflecting the current state of the law.
Claim 11 only requires that the antibody bind against a specific fragment of the occludin protein, only binds an antigen and not the full protein of occludin, does not require any particular structure beyond the function and is capable of being used in a method to measure and identify these fragments in a serum sample to determine a specific patient population.
With respect to the claims, it is recognized that information which is well known in the art need not be described in detail in the specification (MPEP §2163(II)(A)(2)). See, e.g., Hybritech, Inc. v. Monoclonal Antibodies, Inc., 802 F.2d 1367, 1379-80, 231 USPQ 81, 90 (Fed. Cir. 1986). However, sufficient information must be provided to show that the inventor had possession of the invention as claimed. MPEP §2163(II)(A)(3)(a) also discusses Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 927, 69 USPQ2d 1886, 1894-95 (Fed. Cir. 2004), where a method of using a PGHS-2 inhibitor did not meet the written description as the inhibitor itself was not sufficiently described, clearly indicating that written description of the compound is still required in a method of using that compound. In this case, it is clear from the specification that the invention is in a new antibody, or at the least disclosure of a new antibody that could not have been envisaged from the prior art indicates that the prior art was not in possession of all antibodies that bind the fragment of 266-280 aa of SEQ ID NO:1. Thus, the prior art cannot provide sufficient written description of this genus of compounds and the specification as filed, disclosing one antibody, does not sufficiently describe the genus either as there is an unknown amount of structurally distinct antibodies in this genus (see Amgen and Centocor decisions discussed above).
To satisfy the written description requirement, a patent 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. See, e.g., Vas-Cath, Inc., v. Mahurkar, 935 F.2d at 1563, 19 U.S.P.Q.2d at 1116. The claimed invention as a whole may not be adequately described where an invention is described solely in terms of a method of its making coupled with its function and there is no described or art-recognized correlation or relationship between the structure of the invention and its function. An antibody described only by functional characteristic, such as an antibody that binds 266-280 aa of SEQ ID NO: 1 of the claimed epitope, without any known or disclosed correlation between that function and the structure of the sequence, is not a sufficient identifying characteristic for written description purposes, even when accompanied by a method of obtaining the biomolecule of interest. In re Bell, 991 F.2d 781, 26 U.S.P.Q.2d 1529 (Fed. Cir. 1993). In re Deuel, 51 F.3d 1552, 34 U.S.P.Q.2d 1210 (Fed. Cir. 1995). In the instant case, the specification provides insufficient direction or guidance concerning the relationship between the structure of the possible antibody to demonstrate possession of the breadth of the genus claimed antibodies encompassed by the instant claims, especially in view of the unpredictability of such an endeavor. The prior art as evidenced by Edwards et al., 2003 (4/6/2026 PTO-892) teaches there is a substantially huge antibody diversity produced to one single antigen target. Edwards provides evidence that over 1000 antibodies, all different amino acid sequences, were generated towards one single protein antigen target (see abstract). Without a correlation between structure and function, the claims do little more than define the claimed invention by function. That is not sufficient to satisfy the written description requirement. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406 (“definition by function … does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is”).
Without this guidance or direction the skilled artisan would not consider applicant to be in possession of the claimed genus of antibodies because the skilled artisan recognizes that even seemingly minor changes made without guidance or direction as to the relationship between the particular amino acid sequence of the instantly claimed antibody and its ability to bind antigen, can dramatically affect antigen-antibody binding.
Applicant has not described the claimed invention sufficiently to show they had possession of the claimed genus of an antibody that specifically binds 266-280 aa of SEQ ID NO: 1 and nothing else. Possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features. See University of Rochester v. G.D. Searle & Co., 358 F.3d 916, 69 USPQ2d 1886 (Fed. Cir. 2004).
The written description requirement for a claimed genus 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. 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, one must describe a sufficient variety of species to reflect the variation within the genus.
What constitutes a "representative number" is an inverse function of the skill and knowledge in the art. Satisfactory disclosure of a "representative number" depends on whether one of skill in the art would recognize that the applicant was in possession of the necessary common attributes or features of the elements possessed by the members of the genus in view of the species disclosed. For inventions 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.
To provide adequate written description and evidence of possession of the claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof. In the instant case, the only factors present in the claims are a recitation of one generic, broad genus that encompassed a diverse and huge number of possible antibodies that bind the disclosed epitope. The specification does not provide a consistent structure for all of the possible antibodies and fails to provide a representative number of species for the claimed genus. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states that “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.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that they invented what is claimed.” (See Vas-Cath at page 1116).
With the exception of specifically disclosed antibodies with specific CDRs, the skilled artisan cannot envision the detailed chemical structure of all of the encompassed 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 product 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.
One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. In Fiddes, claims directed to mammalian FGF's were found to be unpatentable due to lack of written description for that broad class. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115).
Response to Amendment
The declaration under 37 CFR 1.132 filed 8/5/2026 is insufficient to overcome the rejection of claims 11-12, 14-16 and 19-20 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. as set forth in the last Office action because they fail to disclose the required antibody, and specifically XW-OCLN-2 antibody of claims 11 and 19. Independent claim 11 requires a very specific antibody claimed only by function and no specific structure. The declaration does not alleviate this issue because there is no disclosure for the specific antibody required in the claims, in the specification or support for it in the prior art. The declaration does point to some antibodies and disclose their sequences but these antibodies are not mentioned in the instant specification or the same antibody being claimed. These are not the same antibody as the required XW-OCLN-2 antibody. Therefore, the same issue continues to be present; no description disclosure for the genus of antibodies beyond what is its function and no specific structure for the required antibodies.
Response to Arguments
Applicant's arguments filed 8/5/2026 have been fully considered but they are not persuasive. Applicant argues that the disclosed antibodies set forth in the declaration submitted on 8/5/2026, are sufficient to support written description the antibody called XW-OCLN-2 in the instant claims. This is not found persuasive because the claims call for the specific XW-OCLN-2 which is not disclosed in the instant specification, prior art or even in the declaration. The declaration discloses sequences that are for 1F5E3 and 6F8C8. The 1F5E3 and 6F8C8 antibodies are never mentioned in the instant specification and the instant specification does not provide any antibody examples except the named XW-OCLN-2. Therefore, the claims requiring the XW-OCLN-2 antibody still do not have written description support.
Applicant also argues that the claims are towards methods and not a product like the antibody. This is not found persuasive because the required products in a claimed method still require full disclosure to show possession of the necessary elements to produce the required product of the method. Applicant argues that the antibody is a product by process but this is not found persuasive because a product process needs to be predicable and as already discussed above in the 112 written description rejection:
The prior art as evidenced by Edwards et al., 2003 (4/6/2026 PTO-892) teaches there is a substantially huge antibody diversity produced to one single antigen target. Edwards provides evidence that over 1000 antibodies, all different amino acid sequences, were generated towards one single protein antigen target (see abstract). Without a correlation between structure and function, the claims do little more than define the claimed invention by function. That is not sufficient to satisfy the written description requirement. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406 (“definition by function … does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is”).
Finally, it is pointed out that the claimed method is not method for producing an antibody but rather a method for detection.
Therefore, these arguments are not found persuasive.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Advisory Information
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to AURORA M. FONTAINHAS whose telephone number is 571-272-2952. The examiner can normally be reached on Monday - Friday (8AM - 4PM).
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/AURORA M FONTAINHAS/ Primary Examiner, Art Unit 1675
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