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 .
Status of Claims
This national-stage application was filed 8/22/23 with claims 1-15 and a preliminary amendment canceling those claims and adding new claims 16-34. Claims 16-34 are pending and under examination.
Specification
The disclosure is objected to because it contains embedded hyperlinks and/or other form of browser-executable code. (See, for example, Table 1 at page 15, and list of references starting at page 36.) Applicant is required to delete all embedded hyperlinks and/or other forms of browser-executable code. References to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Objections
Claim 16 is objected to because of the following informalities: It does not end in a period. See MPEP 608.01(m). Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 16-34 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.
Claim 16 refers to an antibody or fragment or derivative thereof that “has a reduced FC[Symbol font/0x67]IIA-receptor binding capacity and/or an increased FC[Symbol font/0x67]IIB-receptor binding capacity.” This limitation is indefinite because the claim provides no basis for the terms “reduced” and “increased.” It is unclear what the comparator is for these limitations. Different antibodies have different binding profiles for the FC[Symbol font/0x67]RII components. See, e.g., Mimoto et al. (NPL reference 30 on 8-page information disclosure statement of 12/11/23), which describes an antibody with enhanced FC[Symbol font/0x67]RIIb binding over binding to certain mutants of FC[Symbol font/0x67]RIIa relative to wild-type IgG1. Reference to an object that is variable renders a claim indefinite when the examiner cannot readily ascertain the relationship between the claim limitation and the comparator. Such is the case here, so the claim is rejected under 35 U.S.C. 112(b). Claims 17-34 depend from claim 16 and do not rectify the indefiniteness, so they are rejected as well under 35 U.S.C. 112(b).
In addition, claim 25 is indefinite because it is unclear which numbering system the mutation limitations are referencing. Claim 25 does not specify that the numbering system is Kabat, EU, or IGMT. (See reference U, demonstrating that numerous numbering conventions are followed in this art.) Reference to an object that is variable renders a claim indefinite when the examiner cannot readily ascertain the relationship between the claim limitation and the comparator. Such is the case here, so the claim is rejected under 35 U.S.C. 112(b).
In addition, claim 28 is indefinite because in option (e), it refers to binding to membrane heparan sulfate proteoglycans “preferably alone.” Examples and preferences render claims indefinite when it is unclear whether they are limitations or not. Here, it is unclear whether the claim’s reference is limited to proteins that bind membrane heparan sulfate proteoglycans alone or not, so the claim is indefinite. See MPEP 2173.05(d).
Claim 32 refers to “self proteins of the subject to be treated.” The specification refers to the word “self” as indicating the patient (page 1, line 30) and as combinations of S267E/L328F mutations (page 13, line 7). It is unclear which of these claim 32 is referencing. Claims 33 and 34 depend from claim 32 and do not rectify the confusion.
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 24 and 25 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 they depend. Claim 16 permits that the claimed antibody can have an increased binding capacity for FC[Symbol font/0x67]RIIB, but claim 24 permits significantly reduced binding to “all FC[Symbol font/0x67]Rs,” which would include FC[Symbol font/0x67]RIIB. Claim 24 therefore appears to broaden the scope of claim 16. Claim 25 depends from claim 24 and does not resolve the issue. Applicant may cancel the claims, amend the claims to place them in proper dependent form, rewrite the claims in independent form, or present a sufficient showing that the dependent claims comply with the statutory requirements.
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 16-34 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 enablement requirement. The claim(s) contains 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.
The factors to be considered in determining whether undue experimentation is required are summarized in In re Wands, 858 F.2d 731, 737, 8 U.S.P.Q.2d 1400, 1404 (Fed. Cir. 1988) (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; (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. While all of these factors are considered, a sufficient number are discussed below so as to create a prima facie case.
Claim 16 is drawn to a method of treating or preventing inflammation by administering an antibody specific for a protein antigen capable of binding to nucleic acids or administering an antigen-binding fragment or derivative of the antibody. The antibody, fragment, or derivative also has reduced affinity for Fc[Symbol font/0x67]RIIA and increased affinity for Fc[Symbol font/0x67]RIIB relative to some unnamed standard. Claim 16 therefore requires that upon administration, inflammation is reduced or prevented from developing.
Around the time of the invention, skilled artisans recognized the utility of IgG1-based antibodies with increased affinity for Fc[Symbol font/0x67]RIIA and reduced affinity for Fc[Symbol font/0x67]RIIB in treating and preventing inflammation. See, e.g., Chamberlain et al. (US 20060173170; reference A) at paragraphs 136 and 140; Lazar et al. (US 20070148171; reference B) at paragraphs 189 and 270. Van Vlijmen et al. (US 20060275283; reference C) contemplates an antibody with reduced affinity for Fc[Symbol font/0x67]RIIA and increased affinity for Fc[Symbol font/0x67]RIIB but does so in the context of tumor therapy. See paragraphs 155 and 383. Skilled artisans also understood that Fc[Symbol font/0x67]RIIA and Fc[Symbol font/0x67]RIIB are distinct subunits of FC[Symbol font/0x67]RII receptor (CD32) that have different cellular effects upon activation. (See Koenig et al., US 20200131265; reference D; at paragraphs 9-11.) They would therefore not have understood these antibodies as being interchangeable for each other in the context of the claimed function.
Skilled artisans were also aware of antibodies that bind influenza proteins and have differential affinity for Fc[Symbol font/0x67]RIIA and Fc[Symbol font/0x67]RIIB; see Bourzanos et al. (2020, Nature 588: 485-514; NPL reference 2 on 4-page IDS of 12/11/23) at Figure 1. These antibodies, however, bind the hemagglutinin coat protein of influenza virus, not one of its nucleic-acid-binding proteins. (Figure 1b.) Mimoto et al. (Protein Engineering: Design and Selection 26: 589-598; NPL reference 30 on 8-page information disclosure statement of 12/11/23) describes an antibody with enhanced FC[Symbol font/0x67]RIIb binding over binding to certain mutants of FC[Symbol font/0x67]RIIa relative to wild-type IgG1 but does not link that antibody to any function in inflammatory processes. The skilled artisan considering the claimed invention in view of the prior art, therefore, would not have been able to make and use antibodies with the claimed binding profile that treat or prevent inflammation without undue experimentation.
The as-filed disclosure fails to provide evidence that the skilled artisan would have expected success in treating or preventing inflammation in a subject by providing an antibody with reduced affinity for Fc[Symbol font/0x67]RIIA and/or increased affinity for Fc[Symbol font/0x67]RIIB in particular. The specification actually does not disclose any antibodies with this property. The working examples are confined to investigations of an antibody that binds nucleoproteins yet does not bind Fc[Symbol font/0x67]R receptors; this antibody induces an inflammatory response in human PBMCs (peripheral blood mononuclear cells). (See, e.g., Example 3 starting at page 24.) Specifically, Example 3 teaches that an antibody with E233P F234V L235A D265A mutations (see claim 25) lacks Fc[Symbol font/0x67]R effector activity. The disclosure speculates that a person of ordinary skill in the art will be able to generate antibodies with Fc domain modified “so as not to bind Fc[Symbol font/0x67]RIIA . . . or even to preferentially bind to Fc[Symbol font/0x67]RIIB,” but there is no evidence in the specification that such antibodies would have been expected to reduce or prevent inflammation upon administration to a subject. (See page 19, lines 26-29.)
While a singular, narrow working embodiment cannot be a sole factor in determining enablement, its limited showing, in light of the unpredictable nature of the art and the lack of direction applicants present, provides additional weight to the lack of enablement in consideration of the Wands factors as a whole. Thus, one of ordinary skill in the art would not have a reasonable expectation of success in using the claimed invention without undue experimentation.
Claims 16-34 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.
M.P.E.P. § 2163 recites, “An applicant shows possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention. . . . One must define a compound by ‘whatever characteristics sufficiently distinguish it.’ A lack of adequate written description issue also arises if the knowledge and level of skill in the art would not permit one skilled in the art to immediately envisage the product claimed from the disclosed process.”
Claim 16 recites “an antibody specific for a protein antigen capable of binding to nucleic acids”—i.e., any antigen capable of binding to any nucleic acid—that “has a reduced FC[Symbol font/0x67]RIIA-receptor binding capacity and/or an increased Fc[Symbol font/0x67]RIIB-receptor binding capacity” relative to some unnamed standard and that treats or prevents inflammation in a subject upon administration. The as-filed disclosure is insufficient for the skilled artisan to conclude that applicants possessed an antibody with these functions. An invention described solely in terms of a method of making and/or its function may lack written descriptive support where there is no described or art-recognized correlation between the disclosed function and the structure(s) responsible for the function. See MPEP 2164(I)(A). Such is the case here.
The art around the time of the invention discloses no structure-function correlation for antibodies that bind nucleic-acid-binding proteins, treat or prevent inflammation, and have the required differential affinities for Fc[Symbol font/0x67]RII receptor subunits. The art recognized IgG1-based antibodies with increased affinity for Fc[Symbol font/0x67]RIIA and reduced affinity for Fc[Symbol font/0x67]RIIB in treating and preventing inflammation. See, e.g., Chamberlain et al. (US 20060173170) at paragraphs 136 and 140; Lazar et al. (US 20070148171) at paragraphs 189 and 270. Van Vlijmen et al. (US 20060275283) contemplates an antibody with reduced affinity for Fc[Symbol font/0x67]RIIA and increased affinity for Fc[Symbol font/0x67]RIIB but does so in the context of tumor therapy and does not reduce the antibody to practice. See paragraphs 155 and 383.
Skilled artisans were also aware of antibodies that bind influenza proteins and have differential affinity for Fc[Symbol font/0x67]RIIA and Fc[Symbol font/0x67]RIIB; see Bourzanos et al. (2020, Nature 588: 485-514; NPL reference 2 on 4-page IDS of 12/11/23) at Figure 1. These antibodies, however, bind the hemagglutinin coat protein of influenza virus, not one of its nucleic-acid-binding proteins. (Figure 1b.) Mimoto et al. (Protein Engineering: Design and Selection 26: 589-598; NPL reference 30 on 8-page information disclosure statement of 12/11/23) describes an antibody with enhanced FC[Symbol font/0x67]RIIb binding over binding to certain mutants of FC[Symbol font/0x67]RIIa relative to wild-type IgG1 but does not link that antibody to any function in inflammatory processes.
The prior and contemporaneous art does not provide a correlation between an ability to treat/prevent inflammation, bind a nucleic-acid-binding protein, and exhibit reduced Fc[Symbol font/0x67]RIIA binding and increased Fc[Symbol font/0x67]RIIB binding. The as-filed disclosure does not teach such a correlation either. There is no reduction to practice of any antibody with the claimed functions and no teachings on what the structure of such an antibody might be. Applicant has not provided a number of species that represents the claimed genus, and the disclosure is therefore inadequate to meet the written-description requirement. See MPEP 2163 (II)(A)(3)(a)(ii).
The disclosure speculates that a person of ordinary skill in the art will be able to generate antibodies with Fc domain modified “so as not to bind Fc[Symbol font/0x67]RIIA . . . or even to preferentially bind to Fc[Symbol font/0x67]RIIB,” but even if this were the case, it would not meet the written-description requirement for a demonstration of possession. (See specification at page 19, lines 26-29.) The enablement requirement and written-description requirement are separate from each other.
Conclusion
No claims are allowed.
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/Lora E Barnhart Driscoll/Primary Examiner, Art Unit 3991