DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
The amendments and remarks filed 1/2/26 are acknowledged. Claim 1 has been amended. Claims 2, 19, and 22 have been canceled. Claims 1, 4-18, and 20-21 are pending.
Claims 4-18, and 20-21 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 9/17/25.
Claim 1 is under examination.
Withdrawn Objections and Rejections
The rejection of claims 1-2 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112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement, is withdrawn in light of Applicant’s amendment thereto. See paragraph 7, page 3 of the previous Office action.
The rejection of claim 2 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or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention, is withdrawn in light of Applicant’s cancelation of the claims. See paragraph 9, page 10 of the previous Office action.
Maintained Rejection
Claim Rejections - 35 USC § 102
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.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Rondon et al. (US Patent Application Publication 2017/0114130 A1, published April 27, 2017).
The claim recites a composition comprising anIL-2:anti-IL-2 antibody (Ab) complex (IL-2C), wherein the anti-IL-2 antibody bind to the IL-2 at the R46 residue of IL-2 thereby simultaneously sterically blocking IL-2 from binding to the CD122 subunit of the IL-2 receptor and remaining bioavailable to the CD25 subunit of the IL-2 receptor, wherein the antibody comprises the anti-IL-2 antibody clone F5111.2 or JES6-1A12 (JES6).
Rondon et al. teach a composition comprising an anti-IL-2:IL-2 complex comprising an anti-IL-2 antibody and IL-2 (See paragraph 0114 and claim 27). Rondon et al. teach that the antibody is anti-IL-2 antibody F5111.2 (See paragraphs 0133-0142 and 0224 and table 7). With regards to the limitation “the antibody binds to the R46 residue of IL-2”, the prior art teaches the same antibody (F5111.2) as disclosed by Applicant, and therefore, the prior art antibody would have the same properties taught by Applicant. "Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id. Thus, Rondon et al. anticipate the claims.
Applicant’s Arguments
Applicant argues that Rondon's reference teaches a particular sequence defined antibody, not merely an outcome defined antibody. Rondon reference expressly discloses that F5.1.11.02 is an affinity-matured variant derived from parental clone F5.1.11 and provides the variable region sequences by SEQ ID NO: 71 and the light chain variable region as SEQ ID NO: 72. Rondon reference asserts the specific in vitro signaling outcomes in human Tregs and CD8 T cells and in vivo effects for F5.1.11.02:IL 2 complexes. See, Rondon reference page 40, paragraph [0448]. Rondon further explains that the amino acid sequences of the VH and VL domains of the IL-2 antibodies are summarized by sequence identification number in Table 7. In contrast, the current application teaches CD25-targeted IL-2 compositions for increasing CD4 T cell formation and treatment of infections (see current application page 34, lines 9-17; page 35, Example 1). The current application also describes the human IL-2 antibody F5111.2 or its mouse equivalent JES6-1A12 in the context of an IL-2:anti-IL-2 complex that is designed for CD25-biased signaling in vivo, and alleges the functional features, including binding at IL-2 residue R46, blocking CD122 binding, and remaining bioavailable to CD25. See, current application page 14, lines 8-27. Further, the current application refers to F5111.2 as the human anti-IL-2 antibody or JES6-1A12 as the mouse its mouse anti-IL-2 antibody used in IL-2 complex experiments. Moreover, a clone name, standing alone, does not establish that two antibodies are identical at the sequence level, particularly where the later filing describes an engineered or optimized construct used for in vivo IL-2 complexing. The Office effectively assumes that the currently claimed F5111.2 antibody is the same as the F5.1.11.02 antibody described in the Rondon reference, or at least that any differences are inconsequential. That assumption is not supported by Rondon and is contrary to routine antibody engineering practice, where affinity maturation, humanization, framework optimization, and Fc engineering commonly alter biological properties even when the epitope and intended function are generally similar. Rondon further underscores that sequence-level differences matter. Rondon describes an affinity maturation campaign starting from F5.1.11 and generating higher affinity variants, including F5.1.11.02, and reports that these variants were characterized for binding affinity and receptor binding profile. See, Rondon page 40, paragraph [0443], Example 1 and Table 3. Importantly, Rondon alleges that F5.1.11 occludes the IL-2Rβ binding site but not the CD25 binding site, and further states that a perturbation affecting the IL-2 A-B loop may explain decreased affinity of the antibody IL-2 complex for CD25. See, Rondon page 46, paragraph [0498].
Applicant argues that the Rondon reference does not disclose the specific antibody designation F5111.2 as disclosed in the current application, nor does it disclose the functional features that as described in the current application that the F5111.2 antibody drives CD25 biased signaling, including the combination of (i) binding to IL-2 at R46, (ii) blocking CD122 binding, and (iii) remaining bioavailable to CD25 (See, currently amended Claim 1). The Rondon reference instead emphasizes on reduction of receptor binding to IL-2Rβ and IL-2R complex and further explains that conformational effects may decrease affinity for CD25. See, Rondon page 13, paragraph [0215]. Thus, the antibody alleged in the Rondon reference is materially different from the F5111.2 antibody of the current application based on CD25 biased availability and signaling.
Response to Arguments
Applicant’s arguments have been fully considered but they are not persuasive.
In response to Applicant’s argument that the prior art does not teach the claimed antibody, the claims have been amended to recite wherein the antibody is comprises the anti-IL-2 antibody clone F5111.2 or JES6-1A12 (JES6). Rondon et al. disclose the human anti-IL-2 antibody F5.1.11, and teach that this antibody is also referred to as antibody F5111, 5.1.11, 5111 (See paragraph 0224). Rondon et al. teach that these terms are interchangeable, and variants of this parental antibody may be referred to by this nomenclature with an additional number, e.g., antibody F5111.2, 5.1.11.2, F5.1.11.02, or 5111.2 (See paragraph 0224). Thus, the antibody clone names F5.1.11.02 and F5111.2 are name variations, and refer to the same antibody.
Rondon et al. teach a complex comprising IL-2 and an anti-IL-2 antibody, wherein the antibody is the anti-IL-2 antibody F5.1.11.02 (also known as antibody F5111.2). Thus, the prior art discloses a complex comprising IL-2 and an anti-IL-2 antibody having the same clone name as required by the instant claims.
Applicant is reminded that where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Therefore, the prima facie case can be rebutted by evidence showing that the prior art products do not necessarily possess the characteristics of the claimed product. In re Best, 562 F.2d at 1255, 195 USPQ at 433.
In response to Applicant’s argument that the prior art does not teach that the anti-IL-2 antibody possesses the same properties disclosed by Applicant, as noted above, the prior art complex comprises the same antibody recited in the instant claims. Since the prior art antibody is structurally identical to the claimed antibody, the prior art antibody would have the same chemical property of binding the IL-2 at the R46 residue of IL-2 thereby simultaneously sterically blocking IL-2 from binding to the CD122 subunit of the IL-2 receptor and remaining bioavailable to the CD25 subunit of the IL-2 receptor. "Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id.
Furthermore, there is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003) (rejecting the contention that inherent anticipation requires recognition by a person of ordinary skill in the art before the critical date and allowing expert testimony with respect to post-critical date clinical trials to show inherency); see also Toro Co. v. Deere & Co., 355 F.3d 1313, 1320, 69 USPQ2d 1584, 1590 (Fed. Cir. 2004) ("[T]he fact that a characteristic is a necessary feature or result of a prior-art embodiment (that is itself sufficiently described and enabled) is enough for inherent anticipation, even if that fact was unknown at the time of the prior invention."); Abbott Labs v. Geneva Pharms., Inc., 182 F.3d 1315, 1319, 51 USPQ2d 1307, 1310 (Fed. Cir. 1999) ("If a product that is offered for sale inherently possesses each of the limitations of the claims, then the invention is on sale, whether or not the parties to the transaction recognize that the product possesses the claimed characteristics."); Atlas Powder Co. v. IRECO, Inc., 190 F.3d 1342, 1348-49, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999) ("Because ‘sufficient aeration’ was inherent in the prior art, it is irrelevant that the prior art did not recognize the key aspect of [the] invention.... An inherent structure, composition, or function is not necessarily known."); SmithKline Beecham Corp. v. Apotex Corp., 403 F.3d 1331, 1343-44, 74 USPQ2d 1398, 1406-07 (Fed. Cir. 2005) (holding that a prior art patent to an anhydrous form of a compound "inherently" anticipated the claimed hemihydrate form of the compound because practicing the process in the prior art to manufacture the anhydrous compound "inherently results in at least trace amounts of" the claimed hemihydrate even if the prior art did not discuss or recognize the hemihydrate); In re Omeprazole Patent Litigation, 483 F.3d 1364, 1373, 82 USPQ2d 1643, 1650 (Fed. Cir. 2007) (The court noted that although the inventors may not have recognized that a characteristic of the ingredients in the prior art method resulted in an in situ formation of a separating layer, the in situ formation was nevertheless inherent. "The record shows formation of the in situ separating layer in the prior art even though that process was not recognized at the time. The new realization alone does not render that necessary [sic] prior art patentable."). Accordingly, even if Rondon et al. do not teach that the antibody binds to IL-2 at the R46 residue, the prior art teaches this feature because the manner of binding is inherent to the antibody itself.
New Rejection Necessitated by Applicant’s Amendment
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.
Claim 1 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 1 recites the terms “F5111.2” and “JES6-1A12(JES6)”. The term F5111.2 and JES6-1A12(JES6) are indefinite because the terms are merely laboratory designations and do not clearly define the claimed product, since difference laboratories may use the same designation to define completely distinct molecules. Claiming biochemical molecules by a particular laboratory designation fails to distinctly claim what the biochemical molecule is. Clarification and/or correction is required.
Applicant’s Arguments
Applicants argues that the current application describes the human IL-2 antibody "F5111.2" in the context of an IL-2:anti-IL-2 complex that is designed for CD25-biased signaling in vivo, and alleges the functional features, including binding at IL-2 residue R46, blocking CD122 binding, and remaining bioavailable to CD25. Thus, the term "F5111.2" is not indefinite.
Response to Arguments
Applicant’s arguments have been fully considered but they are not persuasive. Although the specification provides the function of the claimed complex, this is not a description of what the antibody is. One of skill in the art would not be apprised of the structure of “F5111.2” and “JES6-1A12(JES6)” by simply knowing the names of the antibodies because multiple labs can use the same designation for different biological molecules. This is particularly relevant given that Applicant is arguing that a prior art antibody having the name F5111.2 is different from the claimed antibody (i.e., F5111.2), which shares the same name.
Claim 1 indefinite because of the use of parentheses. Although parenthesis may be appropriate when defining an abbreviation or acronym, the inclusion of parentheses for anything else, raises uncertainty as to whether the feature in the parentheses is optional or always present. The recitation of “JES6-1A12(JES6)” introduces ambiguity to the scope of the claims because it is unclear if the limitation in parentheses (i.e., JES6) is required or exemplary. Do both names refer to the same antibody clone, or does the name in parentheses reference a distinct antibody clone. Thus, clarification of the claim is required to ascertain their metes and bounds. The Office suggest deleting the limitation in parentheses to overcome the rejection. Clarification and/or correction is required.
Claim Rejections - 35 USC § 102
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.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Trotta et al. (Nature Medicine volume 24, pages1005–1014 (2018).
The instant claims are drawn to a composition comprising an IL-2:anti-IL-2 antibody (Ab) complex (IL-2C), wherein the anti-IL-2 antibody binds to the IL-2 at the R46 residue of IL-2 thereby simultaneously sterically blocking IL-2 from binding to the CD122 subunit of the IL-2 receptor and remaining bioavailable to the CD25 subunit of the IL-2 receptor, wherein the antibody comprises the anti-IL-2 antibody clone F5111.2 or JES6-1A12 (JES6).
Trotta et al. teach a composition comprising a complex comprising human IL-2 complexed to human anti-IL-2 antibody F5111.2 (…mice were treated daily for 5 days with PBS, 25,000 U hIL-2 (Proleukin), 8000 U hIL-2 complexed with 25µg of F5111.2) (See abstract and pages 1007 and 1015-1016). Trotta et al. teach a composition comprising a complex comprising antibody JES6-1A12 complexed with mouse IL-2 (…The antibody JES6-1A12 was pre-complexed with mouse IL-2 in RPMI 0.1% BSA) (See page 1015).
With regards to the limitation “wherein the anti-IL2 antibody binds to the IL-2 at the R46 residue of the IL-2 thereby simultaneously sterically clocking IL-2 from binding to the CD122 subunit of the IL-2 receptor and remaining bioavailable to the CD25 subunit of the IL-2 receptor, the prior art teaches the same antibody (F5111.2 and JES6-1A12) as disclosed by Applicant, and therefore, the prior art antibody would have the same binding properties taught by Applicant. "Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id. Thus, Trotta et al. anticipate the claims.
Claim Status
No claims are allowed.
Conclusion
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.
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/SANDRA CARTER/Examiner, Art Unit 1674
/VANESSA L. FORD/Supervisory Patent Examiner, Art Unit 1674
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