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 .
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 02/12/2026 has been entered.
3. Claims 8-12 are pending and under consideration for their full scope.
4. 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.
5. Claims 8-12 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: a method of administering the PC-61 antibody of SEQ ID Nos 1 and 2 wherein the Fc region of the antibody comprises the single mutation of D265A to a subject, does not reasonably provide enablement for : a method of treating an autoimmune disease in a subject comprising administering to a subject in need an effective amount of an anti-CD25 antibody comprising a Fab region that specifically binds to CD25 on T lymphocytes and a mutated Fc region that does not bind to a Fc receptor, wherein the antibody does not block IL-2 binding to CD25, and wherein the antibody induces activation of integrins αLβ2, α4β1, and α4β7 in CD4+ Foxp3+ T-regulatory cells wherein the antibody comprises a protein sequence selected from the group consisting of SEQ ID NO: 1 and SEQ ID NO: 2, and wherein the mutated Fc region comprises a D265A mutation of claim 8; wherein the autoimmune disease is systemic lupus erythematosus, multiple sclerosis, rheumatoid arthritis, chronic inflammation, or inflammatory bowel disease of claim 9; wherein the transplant rejection is due to pancreatic islet, heart, kidney, liver, lung, intestine, cornea, bone marrow, or connective tissue transplantation or vascularized composite allografts of claim 10; a method of inhibiting an immune response in a subject comprising administering to a subject in need an effective amount of an anti-CD25 antibody comprising a Fab region that specifically binds to CD25 on T lymphocytes and a mutated Fc region that does not bind to a Fc receptor, wherein the antibody does not block IL-2 binding to CD25, and wherein the antibody induces activation of integrins αLβ2, α4β1, and α4β7 in CD4+ Foxp3+ T-regulatory cells wherein the antibody comprises a protein sequence selected from the group consisting of SEQ ID NO: 1 and SEQ ID NO: 2, and wherein the mutated Fc region comprises a D265A mutation of claim 11; and a method of stimulating regulatory T cells (Tregs) in a subject, comprising administering to a subject in need an effective amount of an an anti-CD25 antibody comprising a Fab region that specifically binds to CD25 on T lymphocytes and a mutated Fc region that does not bind to a Fc receptor, wherein the antibody does not block IL-2 binding to CD25, and wherein the antibody induces activation of integrins αLβ2, α4β1, and α4β7 in CD4+ Foxp3+ T-regulatory cells wherein the antibody comprises a protein sequence selected from the group consisting of SEQ ID NO: 1 and SEQ ID NO: 2, and wherein the mutated Fc region comprises a D265A mutation of claim 12.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims. The specification disclosure does not enable one skilled in the art to practice the invention without an undue amount of experimentation.
Factors to be considered in determining whether undue experimentation is required to practice the claimed invention are summarized In re Wands (858 F2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)). The factors most relevant to this rejection are the scope of the claim, the amount of direction or guidance provided, the lack of sufficient working examples, the unpredictability in the art and the amount of experimentation required to enable one of skill in the art to practice the claimed invention.
The specification has disclosed that murinized anti-CD25 antibody PC61 (D265A) does not deplete Tregs and does stimulate T cell suppressive function in vitro.
The specification is not enabled for the genus of antibodies encompassed by the instant claim recitations. The specification has only disclosed one example of an antibody which is encompassed by the claimed invention-the murinized anti-CD25 antibody PC61 having a D265A mutation in the Fc region of IgG1.
The specification is not enabled for making and using antibodies which are 98% identical to SEQ ID NOs 1 or 2. The art of Goel et al. (PTO-892 mailed on 06/17/2025; Page 2; Reference U), Khan et al. (PTO-892 mailed on 06/17/2025; Page 2; Reference V) and Poosarla et al. (PTO-892 mailed on 06/17/2025; Page 2; Reference W), antibody specificity for a particular antigen depends on the 6 CDRs. Antibodies with 98% sequence identity can be changed from the sequences of SEQ ID Nos 1 and 2 within the CDRs that are ciritical for antigen binding and function. As such, the specification is not enabled for making and using 98% sequence identical antibodies to SEQ ID Nos 1 and 2 for use in the claimed invention without undue experimentation. It was well known to those skilled in the art at the time the invention was made that minor structural differences among structurally related antibodies or compositions thereof could result in substantially different binding activities. Given the lack of guidance in the specification, it is unpredictable which antibodies with which structures would exhibit the recited functions.
The art of Arce Vargas et al. (PTO-892 mailed on 06/17/2025; Reference U) teaches that pre-clinical studies in mice have used the anti-CD25 antibody clone PC-61 (rat IgG1, λ), which partially depletes Treg cells in the blood and peripheral lymphoid organs, inhibits tumor growth, and improves survival when administered before or soon after tumor challenge. However, the use of anti-CD25 as a therapeutic intervention against established tumors fails to delay tumor growth or prolong survival. This has been attributed to several factors, including poor T cell infiltration of the tumor and potential depletion of activated effector CD8+ and CD4+ T cells that upregulate CD25. However, recent data demonstrate the contribution of intra-tumoral Treg cell depletion to the activity of immune modulatory antibody-based therapies and the relevance of the antibody isotype in this setting. The authors of the reference demonstrated that the lack of therapeutic activity of the widely used anti-CD25 antibody (PC-61) against established mouse tumors results from a failure to effectively deplete intra-tumoral Treg cells. Optimizing FcγR binding and antibody-dependent cell-mediated cytotoxicity (ADCC) resulted in superior intra-tumoral Treg cell depletion. The efficacy of αCD25 as an anti-tumor therapy depends on Treg cell depletion in the tumor microenvironment, which can be achieved only by using an antibody isotype optimized for engagement of activating FcγRs, capable of inducing ADCC. Our results demonstrated that the limited efficacy observed in pre-clinical studies using the αCD25 PC-61 monoclonal antibody with a rat IgG1 isotype relates to ineffective or suboptimal intra-tumoral Treg cell depletion, a consequence of its low A/I binding ratio and high intra-tumoral expression of inhibitory FcγRIIb. This may also explain the modest results observed in early clinical trials using the anti-human CD25 antibody daclizumab. However, the impact of αCD25 antibodies of varying IgG subclass remains to be evaluated in humans. Local depletion of tumor-infiltrating Treg cells by αCD25 monotherapy mediated only partial tumor control, suggesting that further intervention is necessary to increase the intra-tumoral Teff/Treg cell balance and promote effector T cell activity.
The art of Shields et al. (PTO-892 mailed on 06/17/2025; Reference V) teaches that Fc mutations and groups of mutations have unpredictable effects on Fc binding. The reference teaches in great detail that particular Fc mutations and groups of Fc mutations effect binding to some Fc receptors and not to other Fc receptors. (In particular, whole document). The reference teaches that the single D265A mutation showed decreased binding to all FcgR. The reference teaches that ADCC assays with PBMCs showed that D265A prevented ADCC (p , 0.01; paired t test). (In particular, Figure 3).
The art of Sailer et al. (PTO-892 mailed on 06/17/2025; Reference W) teaches that “proteins exist as ensembles of similar conformations. The effect of a mutation depends on the relative probabilities of conformations in the ensemble, which in turn, depend on the exact amino acid sequence of the protein. Accumulating substitutions alter the relative probabilities of conformations, thereby changing the effects of future mutations. This manifests itself as subtle but pervasive high-order epistasis. Uncertainty in the effect of each mutation accumulates and undermines prediction. Because conformational ensembles are an inevitable feature of proteins, this is likely universal” (In particular, abstract, whole document); and that “a key point from our work is that unpredictability can arise even in this extraordinary simple system. The problem of predicting evolution will only become harder as the complexity and realism of the models increase. Using a larger protein, for example, would increase the number of possible options and degeneracy of trajectories, making predictions more challenging.” (In particular, page 11942, left column, whole document).
The art of Sun et al. (PTO-892 mailed on 06/17/2025; Reference X) teaches that PC61, but not two other anti-CD25 antibodies, induce integrin activation in Tregs, but not Tconvs, and amplify Tregs’ suppressive function. The increased suppressive function required the central relays of the integrin activation pathway, Rap1 and talin1. Surprisingly, PC61-stimulated integrin activation did not use the canonical IL-2 signaling pathway. Instead, PC61 induced formation of a receptor formed by the IL-2-dependent association of CD25 with CCR7. Rather than signaling via JAKs and STAT5, this alternative receptor induces Gai/o-dependent integrin activation. Furthermore, blockade of Gai/o signaling abolished the capacity of PC61 to promote Tregs’ suppressive function, thereby establishing that this alternative IL-2 signaling pathway is responsible for increased suppressive activity. As such, the specification is not enabled for any other anti-CD25 antibodies which can increase suppressive activity other than the PC-61 antibody comprising SEQ ID NOs 1 and 2.
The specification has not adequately disclosed the Fc mutation or groups of Fc mutations that will result in not binding to a Fc receptor other than the D265A mutation in IgG1 of PC-61. The specification has not adequately disclosed which antibodies with which mutations to a particular Fc receptor will result in the recited functions of being able to be used to treat “an autoimmune disease”, systemic lupus erythematosus, multiple sclerosis, rheumatoid arthritis, chronic inflammation, or inflammatory bowel disease; “an immune response” or “stimulating regulatory T cells (Tregs) in a subject”.
The specification also has not adequately disclosed that the PC-61 antibody of SEQ ID Nos 1 and 2 wherein the Fc region of the antibody comprises the single mutation of D265A can be used to treat any disease. The specification fails to provide guidance as to how to treat disease using any of the recited agents. The art is highly unpredictable as to what will be a therapy for any autoimmune disease, inhibit an immune response or stimulate regulatory T cells in vivo, so it would require an undue amount of experimentation for one of ordinary skill in the art to practice the claimed invention commensurate in the scope with the claims.
Since no in vivo studies were used as model system to treat any disorder it is not clear that reliance on the in vitro data accurately reflects the relative animal efficacy of the claimed therapeutic strategy. The specification does not adequately teach how to effectively treat any disorders or reach any therapeutic endpoint in animals by administrating the recited antibody, much less treat any autoimmune disorder, inhibit any immune response and stimulate regulatory T cells as encompassed by the instant claims. The specification does not teach how to extrapolate data obtained from the in vitro studies to the development of effective in vivo animal therapeutic treatment, commensurate in scope with the claimed invention. It is not enough to rely on in vitro studies where, as here, a person having ordinary skill in the art has no basis for perceiving those studies as constituting recognized screening procedures with clear relevance to efficacy in humans or animals (emphasis added). Ex parte Maas, 9 USPQ2d 1746
In view of the absence of a specific and detailed description in Applicant's specification of how to effectively use the genus of compositions claimed, absence of working examples providing evidence which is reasonably predictive that the genus of claimed agents are effective for in vivo use for treatment of disease, and the lack of predictability in the art at the time the invention was made, an undue amount of experimentation would be required to practice the invention with a reasonable expectation of success.
Substantiating evidence may be in the form of animal tests, which constitute recognized screening procedures with clear relevance to efficacy in humans. See Ex parte Krepelka, 231 USPQ 746 (Board of Patent Appeals and Interferences 1986) and cases cited therein. Ex parte Maas, 9 USPQ2d 1746.
Reasonable correlation must exist between the scope of the claims and scope of the enablement set forth. In view on the quantity of experimentation necessary the limited working examples, the nature of the invention, the state of the prior art, the unpredictability of the art and the breadth of the claims, it would take undue trials and errors to practice the claimed invention.
Applicant’s amendment filed on 09/17/2025 has been fully considered, but is not found persuasive.
Applicant argues:
“However, solely to expedite prosecution and without acquiescing to the Examiner's rejections, claims 8, 11 and 12 are amended to require a protein sequence selected from the group consisting of SEQ ID NO. 1 and 2, wherein the Fc region of the antibody comprises the single mutation of D265A. As noted by the Examiner, the instant specification is enabling for such antibodies (see Final Office Action, pages 2-3), and contains sufficient written description of such antibodies (see Final Office Action, page 12).
As such, the instant claims as amended are adequately enabled, and comply with the written description requirement. Applicant respectfully requests that the Examiner withdraw these rejections.”
It is the Examiner’s position that one of ordinary skill in the art would not be able to make and use the invention commensurate in scope with the claims. The claims are not directed to any anti-CD25 antibodies which comprise SEQ ID NO:1 or SEQ ID NO:2. The claims are directed to using anti-CD25 antibodies with particular functions to treat particular diseases without a complete structure recited. The disclosure of a single species that falls within the claimed invention “in combination with the reference cited above, the description of this antibody and the guidance presented in the specification” would not be sufficient for one of ordinary skill in the art to make and use the invention commensurate in scope with the claims.
The art of Sun et al. (PTO-892 mailed on 06/17/2025; Reference X) teaches that PC61, but not two other anti-CD25 antibodies, induce integrin activation in Tregs, but not Tconvs, and amplify Tregs’ suppressive function. The increased suppressive function required the central relays of the integrin activation pathway, Rap1 and talin1. Surprisingly, PC61-stimulated integrin activation did not use the canonical IL-2 signaling pathway. Instead, PC61 induced formation of a receptor formed by the IL-2-dependent association of CD25 with CCR7. Rather than signaling via JAKs and STAT5, this alternative receptor induces Gai/o-dependent integrin activation. Furthermore, blockade of Gai/o signaling abolished the capacity of PC61 to promote Tregs’ suppressive function, thereby establishing that this alternative IL-2 signaling pathway is responsible for increased suppressive activity. The reference teaches “we serendipitously noted that PC61, a rat anti-mouse CD25, induced Treg, but not Tconv, activation of multiple integrins as assessed by binding of soluble ligands for αLβ2 (ICAM-1), α4β1 (VCAM-1), or α4β7 (MAdCAM-1)” and “thus, PC61, but not several other anti-CD25 antibodies, triggers activation of Treg β1, β2, and β7 integrins by inducing Rap1-RIAM/Lpd-mediated talin-dependent integrin activation in Tregs.” As such, the specification is not enabled for any other anti-CD25 antibodies which specifically bind to CD25 on T lymphocytes and a mutated Fc region that does not bind to a Fc receptor, wherein the antibody does not block IL-2 binding to CD25, and wherein the antibody induces activation of integrins αLβ2, α4β1, and α4β7 in CD4+ Foxp3+ T-regulatory cells other than the PC-61 antibody comprising SEQ ID NOs 1 and 2.
The specification also has not adequately disclosed that the PC-61 antibody of SEQ ID Nos 1 and/or 2 wherein the Fc region of the antibody comprises the single mutation of D265A can be used to treat any disease. The specification fails to provide guidance as to how to treat disease using any of the recited agents. The art is highly unpredictable as to what will be a therapy for any autoimmune disease, inhibit an immune response or stimulate regulatory T cells in vivo, so it would require an undue amount of experimentation for one of ordinary skill in the art to practice the claimed invention commensurate in the scope with the claims.
The rejection stands for reasons of record.
6. Claims 8-12 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.
Applicant is in possession of: a method of administering the PC-61 antibody of SEQ ID Nos 1 and 2 wherein the Fc region of the antibody comprises the single mutation of D265A to a subject
Applicant is not in possession of: a method of treating an autoimmune disease in a subject comprising administering to a subject in need an effective amount of an anti-CD25 antibody comprising a Fab region that specifically binds to CD25 on T lymphocytes and a mutated Fc region that does not bind to a Fc receptor, wherein the antibody does not block IL-2 binding to CD25, and wherein the antibody induces activation of integrins αLβ2, α4β1, and α4β7 in CD4+ Foxp3+ T-regulatory cells wherein the antibody comprises a protein sequence selected from the group consisting of SEQ ID NO: 1 and SEQ ID NO: 2, and wherein the mutated Fc region comprises a D265A mutation of claim 8; wherein the autoimmune disease is systemic lupus erythematosus, multiple sclerosis, rheumatoid arthritis, chronic inflammation, or inflammatory bowel disease of claim 9; wherein the transplant rejection is due to pancreatic islet, heart, kidney, liver, lung, intestine, cornea, bone marrow, or connective tissue transplantation or vascularized composite allografts of claim 10; a method of inhibiting an immune response in a subject comprising administering to a subject in need an effective amount of an anti-CD25 antibody comprising a Fab region that specifically binds to CD25 on T lymphocytes and a mutated Fc region that does not bind to a Fc receptor, wherein the antibody does not block IL-2 binding to CD25, and wherein the antibody induces activation of integrins αLβ2, α4β1, and α4β7 in CD4+ Foxp3+ T-regulatory cells wherein the antibody comprises a protein sequence selected from the group consisting of SEQ ID NO: 1 and SEQ ID NO: 2, and wherein the mutated Fc region comprises a D265A mutation of claim 11; and a method of stimulating regulatory T cells (Tregs) in a subject, comprising administering to a subject in need an effective amount of an an anti-CD25 antibody comprising a Fab region that specifically binds to CD25 on T lymphocytes and a mutated Fc region that does not bind to a Fc receptor, wherein the antibody does not block IL-2 binding to CD25, and wherein the antibody induces activation of integrins αLβ2, α4β1, and α4β7 in CD4+ Foxp3+ T-regulatory cells wherein the antibody comprises a protein sequence selected from the group consisting of SEQ ID NO: 1 and SEQ ID NO: 2, and wherein the mutated Fc region comprises a D265A mutation of claim 12.
The claims encompass antibodies that were not actually produced in the specification. The skilled artisan cannot envision all the antibody possibilities recited in the instant claims.
Consequently, conception cannot be achieved until a representative description of the structural and functional properties of the claimed invention has occurred, regardless of the complexity or simplicity of the method.
The specification must set forth the structural features that allow one of ordinary skill in the art to identify and produce the recited antibodies. In the instant case, definition by function does not suffice to define the genus because it is only an indication of what the antibodies do, rather than what they are.
The specification has not adequately described the structure of the recited antibodies which comprise SEQ ID NO:1 or SEQ ID NO:2 as encompassed by the instant claims.
The specification does not correlate the structure of the recited antibodies to the recited functions cited supra.
According to MPEP 2163 (II)(A)(3)(a)(ii) 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 (see i)(A), reduction to drawings (see i)(B), or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus (see i)(C). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1404. 1405 held that:
...To fulfill the written description requirement, a patent specification must describe an invention and does so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines Inc. , 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (1997); In re Gosteli , 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (" [T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d 1966.
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. The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure "indicates that the patentee has invented species sufficient to constitute the gen[us]. "See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004) "[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated."). "A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when ... the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed." In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004).
The specification has not adequately described the structure of the antibodies with the recited functions.
As evidenced by the art of Goel et al. (PTO-892 mailed on 06/17/2025; Page 2; Reference U), Khan et al. (PTO-892 mailed on 06/17/2025; Page 2; Reference V) and Poosarla et al. (PTO-892 mailed on 06/17/2025; Page 2; Reference W), antibody specificity for a particular antigen does not correlate with any particular structure for the antibodies themselves. It was well known to those skilled in the art at the time the invention was made that minor structural differences among structurally related antibodies or compositions thereof could result in substantially different binding activities. Given the lack of guidance in the specification, it is unpredictable which antibodies with which structures would exhibit the recited functions. The specification does not disclose a correlation between the structure of the antibodies themselves and their function of binding to CD25 on T lymphocytes, not binding to a Fc receptor, treating autoimmune disease, SLE, MS, rheumatoid arthritis, chronic inflammation, inflammatory bowel disease, inhibiting any immune response and stimulating any regulatory T cells in vivo such that a skilled artisan would have known what antibody structures possess the claimed functions.
"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" Ex parte Kubin (83 U.S.P.Q.2d 1410 (BPAI 2007)), at page 16. In this instant case, Applicants have not provided the requisite identifying structural features of the antibodies encompassed. "Without a correlation between structure and function, the claim does little more than define the claimed invention by function" supra, at page 17.
U.S. Court of Appeals for the Federal Circuit recently decided Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017) which concerned adequate written description for claims drawn to antibodies. The Federal Circuit explained in Amgen that when an antibody is claimed,
35 U.S.C. § 112(a) requires adequate written description of the antibody itself. Amgen, 872 F.3d at 1378-79. The Amgen court expressly stated that the so-called "newly characterized antigen" test, which had been based on an example in USPTO-issued training materials and was noted in dicta in several earlier Federal Circuit decisions, should not be used in determining whether there is adequate written description under 35 U.S.C. § 112(a) for a claim drawn to an antibody. Citing its decision in Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co. , the court also stressed that the "newly characterized antigen" test could not stand because it contradicted the quid pro quo of the patent system whereby one must describe an invention in order to obtain a patent. Amgen, 872 F.3d at 1378-79, quoting Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1345 (Fed. Cir. 2010). In view of the Amgen decision, adequate written description of a newly characterized antigen alone should not be considered adequate written description of a claimed antibody to that newly characterized antigen, even when preparation of such an antibody is routine and conventional. Id.
The specification does not provide adequate written description of the claimed invention.
The legal standard for sufficiency of a patent's (or a specification's) written description is whether that description "reasonably conveys to the artisan that the inventor had possession at that time of the. . .claimed subject matter", Vas-Cath, Inc. V. Mahurkar, 19 U.S.P.Q.2d 1111
(Fed. Cir. 1991). In the instant case, the specification does not convey to the artisan that the applicant had possession at the time of invention of the claimed invention.
Adequate written description requires more than a mere statement that it is part of the invention and a reference to a potential method of isolating it. In the instant application, the amino acid sequence itself or isolated protein is required. See Fiers v. Revel, 25 USPQ 2d 1601 at 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Lts., 18 USPQ2d 1016. In view of the aforementioned problems regarding description of the claimed invention, the specification does not provide an adequate written description of the invention claimed herein.
See The Regents of the University of California v. Eli Lilly and Company, 43 USPQ2d 1398, 1404-7 (Fed. Cir. 1997). In University of California v. Eli Lilly and Co., 39 U.S.P.Q.2d 1225 (Fed. Cir. 1995) the inventors claimed a genus of DNA species encoding insulin in different vertebrates or mammals, but had only described a single species of cDNA which encoded rat insulin. The court held that only the nucleic acids species described in the specification (i.e. nucleic acids encoding rat insulin) met the description requirement and that the inventors were not entitled to a claim encompassing a genus of nucleic acids encoding insulin from other vertebrates, mammals or humans, id. at 1240. The Federal Circuit has held that if an inventor is "unable to envision the detailed constitution of a gene so as to distinguish it from other materials. .conception has not been achieved until reduction to practice has occurred", Amgen, Inc. v. Chugai Pharmaceutical Co, Ltd., 18 U.S.P.Q.2d 016 (Fed. Cir. 1991). Attention is also directed to the decision of The Regents of the University of California v. Eli Lilly and Company (CAFC, July 1997) wherein is stated: "The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 222 USPQ 369, 372-373 (Fed. Cir. 1984) (affirming rejection because the specification does "little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.").
Accordingly, naming a type of material generally known to exist, in the absence of knowledge as to what that material consists of, is not a description of that material. Thus, as we have previously held, a cDNA is not defined or described by the mere name "cDNA," even if accompanied by the name of the protein that it encodes, but requires a kind of specificity usually achieved by means of the recitation of the sequence of nucleotides that make up the cDNA." See
Fiers, 984 F.2d at 1171, 25 USPQ2d at 1606.
As such, there is insufficient written description of the required kind of structure identifying information about the corresponding makeup of the claimed antibodies to demonstrate possession.
Applicant’s amendment filed on 02/12/2026 has been fully considered, but is not found persuasive.
Applicant argues:
However, solely to expedite prosecution and without acquiescing to the Examiner's rejections, claims 8, 11 and 12 are amended to require a protein sequence selected from the group consisting of SEQ ID NO. 1 and 2, wherein the Fc region of the antibody comprises the single mutation of D265A. As noted by the Examiner, the instant specification is enabling for such antibodies (see Final Office Action, pages 2-3), and contains sufficient written description of such antibodies (see Final Office Action, page 12).
As such, the instant claims as amended are adequately enabled, and comply with the written description requirement. Applicant respectfully requests that the Examiner withdraw these rejections.
It remains the Examiner’s position that the specification does not disclose a correlation between the structure of the antibodies themselves and their function of binding to CD25 on T lymphocytes, not binding to a Fc receptor, wherein the antibody does not block IL-2 binding to CD25, and wherein the antibody induces activation of integrins αLβ2, α4β1, and α4β7 in CD4+ Foxp3+ T-regulatory cells in addition to being able to treat transplant rejection, autoimmune disease, SLE, MS, rheumatoid arthritis, chronic inflammation, inflammatory bowel disease, inhibiting any immune response and stimulating any regulatory T cells in vivo such that a skilled artisan would have known what antibody structures possess the claimed functions. The claims encompass antibodies which comprise SEQ ID NO:1 or SEQ ID NO:2 rather than SEQ ID NO:1 and SEQ ID NO:2.
"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" Ex parte Kubin (83 U.S.P.Q.2d 1410 (BPAI 2007)), at page 16. In this instant case, Applicants have not provided the requisite identifying structural features of the antibodies encompassed. "Without a correlation between structure and function, the claim does little more than define the claimed invention by function" supra, at page 17.
The rejection stands for reasons of record.
7. In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
8. The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
9. Claims 8-12 are rejected under 35 U.S.C. 103 as being unpatentable over Huss et al. in view of Baudino et al. (PTO-892; Reference V) and Pfender et al. (PTO-892; Reference W).
Huss et al. teaches the PC61.5.3 antibody which are 100% identical over length and sequence to instant SEQ ID NOs 1 and 2 (In particular, Table 2). Huss et al. teaches that the in vivo impact of a therapeutic monoclonal antibody is determined by both its epitope specificity (e.g. blocking or non‐blocking of ligand interactions) and heavy‐chain constant region (Fc) effector function (e.g. depleting or non‐depleting). Varying the Fc properties of an antibody can significantly affect the biological impact in vivo. The reference teaches engineering the heavy‐chain constant region of PC61 to alter Fc‐mediated effector function without changing antibody specificity. By comparing Fc variants with highly divergent effector function we are able to demonstrate in mouse models the differential effects of actively depleting CD25+ Treg cells through only blockade of CD25 signalling. Our results demonstrate that immune homeostasis can be maintained during CD25 blockade but aberrant immune activation prevails when CD25+ Treg cells are actively depleted. These results should inform the design of monoclonal antibodies that therapeutically target the high‐affinity IL‐2R. The reference teaches the construction of Fc variants of the PC61.5.3 antibody. The reference teaches the antibody daclizumab. (In particular, Table 2, supplemental materials, whole document).
The claimed invention differs from the prior art in the recitation of “wherein the mutated Fc region comprises a D265A mutation” of claims 8-12; and treating transplant rejection and autoimmune diseases such as multiple sclerosis.
Baudino et el teaches that “In conclusion, our present study revealed the loss of Fc-associated effector functions of IgG when aspartic acid at position 265 was substituted with alanine. Because this substitution did not affect the Ag-binding ability of IgG, the D265A variant may present an advantage for therapeutic applications in which Ab is required to bind to Ag, but must not trigger Fc-mediated effector activities.” (In particular, final paragraph, whole document).
Pfender et al. teaches that Daclizumab is an anti-CD25 antibody which treats multiple sclerosis and renal transplant. (In particular, whole document).
It would have been obvious to one of ordinary skill in the art at the time of invention to have used a D265A mutation in the PC61.5.3 antibody of Huss et al. because Huss et al. teaches that the in vivo impact of a therapeutic monoclonal antibody is determined by both its epitope specificity (e.g. blocking or non‐blocking of ligand interactions) and heavy‐chain constant region (Fc) effector function (e.g. depleting or non‐depleting) and that varying the Fc properties of an antibody can significantly affect the biological impact in vivo. The reference further teaches engineering the heavy‐chain constant region of PC61 to alter Fc‐mediated effector function without changing antibody specificity resulted in immune homeostasis during CD25 blockade instead of aberrant immune activation which occurs when CD25+ Treg cells are actively depleted. These results should inform the design of monoclonal antibodies that therapeutically target the high‐affinity IL‐2R. The reference teaches the construction of Fc variants of the PC61.5.3 antibody. It would have been obvious to have treated patients with renal transplants and multiple sclerosis using the antibody of the combined reference teaching because daclizumab, which is an example of an anti-CD25 antibody taught by Huss et al. has been demonstrated to treat multiple sclerosis and renal transplants as taught by Pfender et al.
From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the reference, especially in the absence of evidence to the contrary.
10. No claim is allowed.
11. Any inquiry concerning this communication or earlier communications from the examiner should be directed to NORA MAUREEN ROONEY whose telephone number is (571)272-9937. The examiner can normally be reached on M-F from 8:00am to 4:30pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner' s supervisor, Misook Yu, can be reached at telephone number (571) 272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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February 21, 2026
/Nora M Rooney/
Primary Examiner, Art Unit 1641
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