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 (i.e., claims 1-9 and 14 drawn to a fusion protein) in the reply filed on November 21, 2025, is acknowledged. Additionally, Applicant’s election without traverse of Species A (i.e., a single and specific fusion protein as an antibody comprising SEQ ID NOs: 1-3 as the HCDRs, SEQ ID NOs: 5-7 as the LCDRs; two IL-2 proteins that are variants having the amino acid sequence of SEQ ID NO: 20; and a linker having the amino acid sequence of SEQ ID NO: 19) in the reply filed on November 21, 2025, is acknowledged.
Please note that a single and specific linker as it pertains to Species A is hereby removed in light of the Examiner’s search.
Status of Claims
Claims 1-18 were originally filed on December 22, 2022.
The amendment received on December 22, 2022, canceled claims 15-17; amended claims 10, 14, and 18; and added new claim 19. The amendment received on November 21, 2025, amended claim 6. The amendment received on 4/3/26, canceled claims 2 and 5-6; and amended claims 1 and 7-8.
Claims 1, 3-4, 7-14 and 18-19 are currently pending and claims 1, 3-4, 7-9, and 14 are under consideration as claims 10-13 and 18-19 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on November 21, 2025.
Priority
The present application claims status as a 371 (National Stage) of PCT/KR2021/008198 filed June 29, 2021, and claims priority under 119(a)-(d) to Korean Application No. 10-2020-0079978 filed on June 30, 2020.
Receipt is acknowledged of papers submitted under 35 U.S.C. 119(a)-(d) for Korean Application No. 10-2020-0079978, which papers have been placed of record in the file. The English language translation of Korean application no. 10-2020-0079978 received on 4/3/26 is acknowledged.
Claim/Sequence Interpretation
For claim 1, with respect to the antibody, please note that the Examiner is interpreting the scope as open-ended requiring 100% identity to each recited sequence with any N- and/or C-terminal additions. With respect to the IL-variant, please note that the Examiner is interpreting the scope as closed-ended (i.e., “is” as the transitional phrase) requiring 100% identity and the same length to SEQ ID NO: 22 except with one or more of the recited substitutions.
For claim 3, please note that the Examiner is interpreting the scope as open-ended requiring 100% identity to each recited sequence with any N- and/or C-terminal additions.
For claim 7, please note that the Examiner is interpreting the scope as open-ended requiring 100% identity to either SEQ ID NO: 20 or 21 with any N- and/or C-terminal additions.
Response to Arguments
Applicant’s arguments, see Response, filed 4/3/26, with respect to the objection to the specification have been fully considered and are persuasive. The objection of the specification has been withdrawn.
Applicant’s arguments, see Response, filed 4/3/26, with respect to the claim objection have been fully considered and are persuasive. The objection of claim 1 has been withdrawn.
Applicant’s arguments, see Response, filed 4/3/26, with respect to the 112(a), written description, rejection have been fully considered and are persuasive. The rejection of claims 1, 4-9, and 14 as failing to comply with the written description requirement has been withdrawn.
Applicant’s arguments, see Response, filed 4/3/26, with respect to the 112(a), written description, rejection have been fully considered and are persuasive. The rejection of claims 1-5, 8-9 and 14 as failing to comply with the written description requirement has been withdrawn.
Applicant’s arguments, see Response, filed 4/3/26, with respect to the 102(a)(1) rejection have been fully considered and are persuasive. The rejection of claims 1, 5, 8-9, and 14 as being anticipated by Timmer et al. WO 2020/146221 A1 published on July 16, 2020 (effective filing date of January 7, 2019) (cited in the IDS received on 4/11/24) has been withdrawn.
Applicant’s arguments, see Response, filed 4/3/26, with respect to the 103(a) rejection have been fully considered and are persuasive. The rejection of claims 1-4 as being unpatentable over Timmer et al. WO 2020/146221 A1 published on July 16, 2020 (effective filing date of January 7, 2019) (cited in the IDS received on 4/11/24), and further in view of Lee et al. WO 2020/005003 A1 published on January 2, 2020 (effective filing date of June 28, 2019) (note: US 2021/0238283 A1 as English language equivalent and will be cited in the rejection below) (US 2021/0238283 A1 cited in the IDS received on 12/22/22) has been withdrawn.
Applicant’s arguments, see Response, filed 4/3/26, with respect to the 103(a) rejection have been fully considered and are persuasive. The rejection of claims 1 and 5-7 as being unpatentable over Timmer et al. WO 2020/146221 A1 published on July 16, 2020 (effective filing date of January 7, 2019) (cited in the IDS received on 4/11/24), and further in view of Li et al. WO 2020/088459 A1 published on May 7, 2020, and Keane et al., Blood Adv. 4:1367-1377 (April 2020) has been withdrawn.
New Rejections Necessitated by Amendment
Claim Rejections - 35 USC § 103
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.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
103 - KSR Examples of 'Rationales' Supporting a Conclusion of Obviousness(Consistent with the "Functional Approach" of Graham)
Further regarding 35 USC 103(a) rejections, the Supreme Court in KSR International Co. v. Teleflex Inc., 550 U.S. 398, 127 S. Ct. 1727, 82 USPQ2d 1385, 1395-97 (2007) (KSR) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper "functional approach" to the determination of obviousness as laid down in Graham. The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. The Supreme Court in KSR noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit.
Exemplary rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) "Obvious to try" - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Note that the list of rationales provided is not intended to be an all-inclusive list. Other rationales to support a conclusion of obviousness may be relied upon by Office personnel.
Also, a reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings. (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976).
Claims 1, 3-4, 7-9, and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Timmer et al. WO 2020/146221 A1 published on July 16, 2020 (effective filing date of January 7, 2019) (cited in the IDS received on 4/11/24) in view of Lee et al. WO 2020/005003 A1 published on January 2, 2020 (effective filing date of June 28, 2019) (cited in the Action mailed on 1/5/26) (note: US 2021/0238283 A1 as English language equivalent and will be cited in the rejection below) (US 2021/0238283 A1 cited in the IDS received on 12/22/22), Li et al. WO 2020/088459 A1 published on May 7, 2020 (cited in the Action mailed on 1/5/26), and Keane et al., Blood Adv. 4:1367-1377 (April 2020) (cited in the Action mailed on 1/5/26).
For claims 1, 3, and 7-9, with respect to a fusion protein comprising (a) an antibody that specifically binds to LAG-3 comprising a heavy chain variable region comprising HCDR1 of SEQ ID NO: 1, HCDR2 of SEQ ID NO: 2, and HCDR3, and a light chain variable region comprising LCDR1 of SEQ ID NO: 5, LCDR2 of SEQ ID NO: 6, and LCDR3 of SEQ ID NO: 7; and (b) an IL-2 variant that is substituted at position R38A and F42A of SEQ ID NO: 22 as recited in instant claim 1; with respect to where the antibody that specifically binds to LAG-3 comprises a heavy chain variable region comprising SEQ ID NO: 4 and a light chain variable region comprising SEQ ID NO: 8 as recited in instant claim 3; with respect to where the IL-2 variant comprises SEQ ID NO: 20 or SEQ ID NO: 21 as recited in instant claim 7; with respect to where the antibody that specifically binds to LAG-3 and the IL-2 variant are attached to each other via a linker as recited in instant claim 8; and with respect to where the linker is a peptide linker as recited in instant claim 9:
Timmer et al. teaches that a modified IL-2 polypeptide is fused to the C-terminus of a Fc region or heavy chain constant region via a peptide linker where the polypeptide further comprises at least one antigen binding domain where the antigen binding domain specifically binds to LAG3 (See Timmer, [0006], embodiments 30, 50, 55-56, 62, 78; [00112]). The at least one antigen binding domain comprises a VH domain and a VL domain (See Timmer, [0006], embodiment 68). Timmer et al. teaches a specific embodiment of a fusion protein comprising an antibody specific for LAG3 (i.e., LAG3-Mab xELL-Knob Fc) and a IL-2 variant amino acid sequence where the antibody and the IL-2 variant are linked via a GGSGGS peptide linker (See Timmer, pg. 71; SEQ ID NO: 95). Thus, the teachings of Timmer suggest a fusion protein comprising an antibody that specifically binds to LAG-3 and an IL-2 variant that are fused together via a peptide linker, i.e., GGSGGS, as recited in instant claims 1 and 8-9.
With respect to the antibody amino acid sequences, Timmer et al. teaches that the modified IL-2 polypeptide comprises a heavy chain constant region where the VH domain is fused to the heavy chain constant region and where the VL domain is associated with the VH domain (See Timmer, [0006], embodiment 71). As discussed supra, Timmer teaches a specific fusion of a LAG-3 antibody and an IL-2 variant. However, Timmer et al. does not expressly teach the specific amino acid sequences for the VL and VH domains, which necessarily contain the CDRs for each region, for the antibody.
Lee et al. teaches an antibody for LAG-3 or an antigen-binding fragment thereof (See Lee, [0008]). Lee teaches that the heavy chain variable region comprises SEQ ID NO: 1 or 27 as HCDR1, SEQ ID NO: 2 as HCDR2, and SEQ ID NO: 3 as HCDR3 (See Lee, [0012], [0040]). Moreover, the light chain variable region comprises SEQ ID NOs: 8, 53, or 57 as LCDR1, DAS as LCDR2, and SEQ ID NO: 10, 33, or 60 as LCDR3 (See Lee, [0012], [0040]). Lee teaches that a heavy chain variable region comprises SEQ ID NO: 114, 116 or 118; and a light chain variable region comprises SEQ ID NOs: 115, 117, or 119 (See Lee, [0042]). When comparing Lee’s SEQ ID NO: 114 with instant SEQ ID NO: 4, there is 100% identity. When comparing Lee’s SEQ ID NO: 115 with instant SEQ ID NO: 8, there is 100% identity. As such, Lee et al. suggests an antibody that specifically binds to LAG-3 and comprises a VH domain comprising instant SEQ ID NO: 4 and a VL domain comprising instant SEQ ID NO: 8, each necessarily containing instant SEQ ID NOs: 1-3 as HCDRs1-3 and instant SEQ ID NOs: 5-7 as LCDRs1-3, respectively, as recited in instant claims 1 and 3. Therefore, the combination of Timmer et al. and Lee et al. suggests the antibody that specifically binds to LAG-3 of the instant fusion protein as recited in instant claims 1 and 3.
With respect to the IL-2 variant amino acid sequence, Timmer et al. teaches a modified IL-2 polypeptide comprising at least one substitution at, at least one amino acid position (See Timmer, [0006]). Timmer et al. also teaches that the modified IL-2 and at least one antigen binding domain (e.g., anti-LAG-3 antibody), enhances anti-tumor T cell responses or natural killer cell responses while avoiding Tregs, peripheral T cells, and endothelial cells (See Timmer, [00111]). Plus, Timmer et al. teaches that the modified IL-2 binds and modulates an IL-2R only when the IL-2R is on the same cell as the antigen bound by the at least one antigen binding domain, but would not bind or activate an IL-2R when the IL-2R is on a different cell than the cell expressing the antigen bound by the at least one antigen binding domain (See Timmer, [00111]). Thus, the IL-2 variant taught by Timmer et al. encompasses where the IL-2 variant enhances anti-tumor T cell responses or NK cell responses but not Tregs, peripheral and endothelial cells. However, Timmer et al. does not expressly teach where the at least one substitution at, at least one amino acid position is a combination of R38A and F42A.
Li et al. teaches fusion proteins comprising an anti-checkpoint antibody or fragment thereof and a mutant IL-2 polypeptide (See Li, [0008]-[0009]). The fusion protein compositions can simultaneously enhance anti-tumor immunity or depress tumor-associated immunosuppression along with direct activation of effector cells by IL2 without activating Treg (See Li, [0008]). Moreover, Li et al. teaches that the IL-2 variant has one or both of the following features that can increase the anti-tumor capability of the fusion protein: (a) reduce ability to activate CTLL2 and human and mouse Treg while retaining its ability to activate effector T cells or NK cells, and (b) a up to 10-fold to over 1000-fold increase in its relative ability to activate Teff/Treg compared to wild type IL2 (See Li, [00012]). Even though Li et al. teaches that the IL2 mutant is less selective towards the high affinity IL-2R, the IL-2 mutant is maintains it’s ability to activated effector T cells or NK cells whereby such activation increases the anti-tumor capability of the fusion protein. These mutant IL-2 polypeptide sequences are selected from SEQ ID NOs: 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, or 57 (See Li, [00012]). These mutant polypeptide sequences include the following substitutions: K35E; R38A; F42K, F42A; Y45R; E62R, E62K; L72G; and C125S (See Li, [000155]-[000205]). Thus, the teachings of Li et al. suggests a fusion protein comprising an anti-checkpoint antibody fused to a IL-2 variant amino acid sequence that comprises one or more substitutions selected from: K35E; R38A; F42K, F42A; Y45R; E62R, E62K; L72G; and C125S, where the IL-2 variant increases the anti-tumor capability of the fusion protein by (a) reduce ability to activate CTLL2 and human and mouse Treg while retaining its ability to activate effector T cells or NK cells, and/or (b) a up to 10-fold to over 1000-fold increase in its relative ability to activate Teff/Treg compared to wild type IL2.
Keane et al. teaches that LAG3 is a novel immune checkpoint that was most highly expressed on CD4+ Tregs and CD8+ TILs and typically co-expressed with PD1 and TIM3 (See Keane, pg. 1373, col. 2, last paragraph). Thus, Keane et al. demonstrates that an antibody that specifically targets LAG3 would constitute an anti-checkpoint antibody. Therefore, the combination of Timmer et al., Li et al., and Keane et al. suggest the IL-2 variant amino acid sequence as recited in instant claims 1 and 7.
Thus, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant application to modify the teachings of Timmer et al. and utilize a fusion protein comprising (a) an antibody comprising a heavy chain constant region where the VH domain is fused to the heavy chain constant region and where the VL domain is associated with the VH domain such that the VH and VL domains comprise instant SEQ ID NOs: 4 and 8, respectively, in order for the antibody to specifically bind to LAG-3, and (b) instant SEQ ID NO: 20 as a modified IL-2 polypeptide that has R38A and F42A substitutions where the fusion protein enhances anti-tumor T cell responses or natural killer cell responses while avoiding Tregs. One of ordinary skill in the art at the time the invention was made would have been motivated to do so because an antibody comprising a VH domain of instant SEQ ID NO: 4 and a VL domain of instant SEQ ID NO: 8 was known to specifically bind to LAG-3 as taught by Lee et al.; a modified IL-2 polypeptide fused to an anti-checkpoint antibody was known to have the amino acid sequence of instant SEQ ID NO: 20, which was known to simultaneously enhance anti-tumor immunity or depress tumor-associated immunosuppression along with direct activation of effector cells by IL2 without activating Treg as taught by Lee et al.; and because an antibody that specifically targets LAG-3 was known to constitute an anti-checkpoint antibody as taught by Keane et al.
One of ordinary skill in the art at the time the invention was made would have had a reasonable expectation of success given that the fusion protein of Timmer et al. comprised a modified IL-2 polypeptide that enhances anti-tumor T cell responses or natural killer cell responses while avoiding Tregs and an antibody that specifically binds to LAG-3 comprising a heavy chain constant region where the VH domain is fused to the heavy chain constant region and where the VL domain is associated with the VH domain. Therefore, substituting instant SEQ ID NO: 4 as the VH domain and instant SEQ ID NO: 8 as the VL domain, and substituting instant SEQ ID NO: 20 as the modified IL-2 polypeptide would support the enhancement of anti-tumor T cell responses or natural killer cell responses while avoiding Tregs by constituting a simple substitution of one known element for another to obtain predictable results and/or some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention pursuant to KSR.
For claim 4, with respect to where the fusion protein comprises two IL-2 proteins:
Timmer et al. teaches that the modified IL-2 polypeptide forms a homodimer under physiological conditions (See Timmer, [0006], embodiment 79). By forming a homodimer necessarily constitutes where Timmer’s fusion protein contains two IL-2 proteins. Furthermore, Timmer et al. depicts a fusion protein comprising an antibody containing Fab and Fc regions where each Fc region each is fused to an IL-2 protein thereby constituting two IL-2 proteins. Thus, the teachings of Timmer et al. satisfy the claim limitation as recited in instant claim 4.
For claim 14, with respect to a pharmaceutical composition comprising the fusion protein of claim 1:
Timmer et al. teaches pharmaceutical compositions comprising modified IL-2 polypeptides in combination with a pharmaceutically acceptable carriers (See Timmer, [00146]-[00147]). Thus, the teachings of Timmer satisfies the claim limitation as recited in instant claim 14.
From the 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 before the effective filing date of the instant application, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant’s arguments with respect to claims 1, 3-4, 7-9, and 14 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
However, the Examiner would like to respond to Applicants’ arguments as they pertain to the Timmer reference; more specifically, Applicant contends that the binding properties of the IL-2 variant described in Timmer differ from the binding properties of the IL-2 variant of the instantly claimed fusion protein (See Applicant’s Response received on 4/3/26, pg. 9). Applicant asserts that Timmer’s IL-2 variant exhibits reduced activity on resting or activated T cells and has a reduced binding affinity for IL-2R including CD122 compared to the wild-type IL-2 whereas the claimed IL-2 variant maintains activity equivalent or similar to wild-type IL-2, specifically, the activity to bind specifically to the IL-2 receptor while simultaneously exhibiting lower in vivo toxicity compared to wild-type IL-2 due to its selectively reduced binding affinity for IL-2α (See Applicant’s Response received on 4/3/26, pg. 9).
In response to Applicant’s argument, it is noted that the features upon which applicant relies (i.e., the binding properties of the IL-2 variant) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). However, even if the functional property is recited in the claim, it would not per se render the claimed invention nonobvious over the cited art. Pursuant to MPEP 2111.02(II),
[i]f the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. Shoes by Firebug LLC v. Stride Rite Children’s Grp., LLC, 962 F.3d 1362, 2020 USPQ2d 10701 (Fed. Cir. 2020). See also Rowe v. Dror, 112 F.3d 473, 478, 42 USPQ2d 1550, 1553 (Fed. Cir. 1997) ("where a patentee defines a structurally complete invention in the claim body and uses the preamble only to state a purpose or intended use for the invention, the preamble is not a claim limitation"); Kropa v. Robie, 187 F.2d at 152, 88 USPQ2d at 480-81 (preamble is not a limitation where claim is directed to a product and the preamble merely recites a property inherent in an old product defined by the remainder of the claim); STX LLC. v. Brine, 211 F.3d 588, 591, 54 USPQ2d 1347, 1350 (Fed. Cir. 2000) (holding that the preamble phrase "which provides improved playing and handling characteristics" in a claim drawn to a head for a lacrosse stick was not a claim limitation).
During examination, statements in the preamble reciting the purpose or intended use of the claimed invention must be evaluated to determine whether or not the recited purpose or intended use results in a structural difference (or, in the case of process claims, manipulative difference) between the claimed invention and the prior art. To satisfy an intended use limitation which is limiting, a prior art structure which is capable of performing the intended use as recited in the preamble meets the claim. See, e.g., In re Schreiber, 128 F.3d 1473, 1477, 44 USPQ2d 1429, 1431 (Fed. Cir. 1997) (anticipation rejection affirmed based on Board’s factual finding that the reference dispenser (a spout disclosed as useful for purposes such as dispensing oil from an oil can) would be capable of dispensing popcorn in the manner set forth in appellant’s claim 1 (a dispensing top for dispensing popcorn in a specified manner)) (emphasis added).
In the instant case, as discussed in the rejection supra, Timmer and Li both teach IL-2 variants that exhibit similar modified binding properties, i.e., reduced binding to Tregs but enhanced binding to effector T cells or NK cells. As such, the cited art, which includes two of the claimed substitutions (i.e., R38A and F42A), suggests the claimed IL-2 variant structure. Thus, the combination of Timmer and Li suggest the instantly claimed IL-2 variant structure.
In light of the MPEP, the question is whether a functional property imparts structure to the claimed IL-2 variant. As discussed in the rejection supra, Timmer expressly teaches an IL-2 variant that enhances anti-tumor T cell responses or natural killer cell responses while avoiding Tregs, peripheral T cells, and endothelial cells (See Timmer, [00111]). Timmer also teaches that the IL-2 variant binds and modulates IL-2R only when the IL-2R is on the same cell as the antigen bound by the at least one antigen binding domain. Similarly, Li teaches the IL-2 variant comprising one or more of the following substitutions: K35E; R38A; F42K, F42A; Y45R; E62R, E62K; L72G; and C125S, exhibits one or both of the following features that can increase the anti-tumor capability of the fusion protein: (a) reduce ability to activate CTLL2 and human and mouse Treg while retaining its ability to activate effector T cells or NK cells, and (b) a up to 10-fold to over 1000-fold increase in its relative ability to activate Teff/Treg compared to wild type IL2 (See Li, [00012]). Even though Li et al. teaches that the IL2 mutant is less selective towards the high affinity IL-2R, the IL-2 mutant maintains its ability to activated effector T cells or NK cells whereby such activation increases the anti-tumor capability of the fusion protein. Thus, the combination of Timmer and Li are consistent with one another with respect to the functional binding properties of the IL-2 variant comprising instant SEQ ID NO: 20. As such, the combination of Timmer and Li suggest the required IL-2 variant structure claimed. The binding properties of the IL-2 variant would not impart a structural limitation for the claimed labeled peptide, and thus, are of no structural significance in determining whether Timmer/Li’s IL-2 variant renders obvious the claimed invention. However, even if the functional IL-2 variant binding properties are considered limiting, as discussed in the MPEP supra, the question is whether a prior art structure is capable of performing the function. Given that the structure of the suggested IL-2 variant of Timmer and Li is encompassed by the scope of the claimed IL-2 variant, it would then follow that the suggested IL-2 variant is capable of performing the claimed functional binding IL-2 properties.
Furthermore, pursuant to MPEP 2112(I),
the claiming of a new use, new function or unknown property which is necessarily present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). The discovery of a previously unappreciated property of a prior art composition, or a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer. Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999).
Moreover, pursuant to MPEP 2112.01(I),
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.
Pursuant to MPEP 2112.01(II), “[p]roducts of identical chemical composition cannot 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. In the instant case, as discussed supra, the combination of Timmer and Li suggest the claimed structural limitations of an IL-2 variant comprising an amino acid sequence of SEQ ID NO: 20. Thus, given that the teachings of Timmer and Li render the claimed structure of the IL-2 variant obvious, the combined teachings of Timmer and Li would also necessarily render the claimed function obvious. Therefore, contrary to Applicant’s argument, the combined teachings of Timmer and Li regarding the functional binding IL-2 properties would necessarily be present because the IL-2 variant structure must exhibit the same properties.
Furthermore, pursuant to MPEP 2111, the pending claims must be "given their broadest reasonable interpretation consistent with the specification." The Federal Circuit’s en banc decision in Phillips v. AWH Corp., 415 F.3d 1303, 1316, 75 USPQ2d 1321, 1329 (Fed. Cir. 2005) expressly recognized that the USPTO employs the "broadest reasonable interpretation" standard:
The Patent and Trademark Office ("PTO") determines the scope of claims in patent applications not solely on the basis of the claim language, but upon giving claims their broadest reasonable construction "in light of the specification as it would be interpreted by one of ordinary skill in the art." In re Am. Acad. of Sci. Tech. Ctr., 367 F.3d 1359, 1364[, 70 USPQ2d 1827, 1830] (Fed. Cir. 2004). Indeed, the rules of the PTO require that application claims must "conform to the invention as set forth in the remainder of the specification and the terms and phrases used in the claims must find clear support or antecedent basis in the description so that the meaning of the terms in the claims may be ascertainable by reference to the description." 37 CFR 1.75(d)(1).
Here, it is noted that the instant specification does NOT teach that the IL-2 variant must have activity equivalent or similar to the wild-type IL-2. Rather, the instant specification teaches that the IL-2 variant “may” have activity equivalent or similar to the wild-type IL-2 where IL-2 activity “may” refer to specific binding to an IL-2 receptor (See instant, pg. 6, 6th paragraph). In fact, as acknowledged by Applicants in their Response, the instant specification teaches that the IL-2 variants have low binding ability for the IL-2Rα, and thus have lower in vivo toxicity than the wild-type IL-2 (See instant, pg. 10, 2nd paragraph). Thus, Applicants and the instant specification admit that the claimed IL-2 variant may have reduced affinity for a IL-2R, albeit, IL-2Rα. Moreover, it is contradictory to state that the claimed IL-2 variant maintains activity equivalent or similar to wild-type IL-2, specifically, the activity to bind specifically to the IL-2R, and then assert that it exhibits lower in vivo toxicity due to reduced binding affinity to a specific IL-2R. In other words, the two assertions cannot be true at the same time. Either the claimed IL-2 variant exhibits improved properties relative to the wild-type IL-2, i.e., lower in vivo toxicity via reduced binding affinity to a specific IL-2R, or it maintains activity equivalent or similar to wild-type IL-2. Given that the claimed invention does not recite a specific binding IL-2 variant binding property, the broadest reasonable interpretation of the claimed invention encompasses where the IL-2 variant may or may not maintain activity equivalent or similar to wild-type IL-2, or it may exhibit lower in vivo toxicity due to reduced binding affinity to a specific IL-2R. Therefore, contrary to Applicant’s argument, the teachings of Timmer do not contradict the inherent functional binding IL-2 properties claimed.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to THEA D' AMBROSIO whose telephone number is (571)270-1216. The examiner can normally be reached M-F 11:00 to 8:00 pm.
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/THEA D' AMBROSIO/Primary Examiner, Art Unit 1654
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