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 .
Claims Status
The Amendment filed on 20Jan2026 is acknowledged in which claim(s) 2, 4, 7-10, 12, 14-20, 22-23, 25-32, 34-43, 45, 48-51, 55-56, 58-81, 83, 85-89, 91, 94-99, 101-106, 114, 119-120, and 124-125 are canceled by Applicant.
Applicant’s election without traverse of The Invention of Group I and Species of rheumatoid arthritis in the reply filed on 20Jan2026 is acknowledged.
Claim(s) 44, 46-47, 52-54, 57, 82, 84, 90, 92-93, 100, 107-113, and 115-116 is/are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Invention, there being no allowable generic or linking claim.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 20Jan2026.
Claim(s) 1, 3, 5-6, 11, 13, 21, 24, 33, 117-118 and 121-123 is/are currently pending and presented for examination on the merits.
Specification
The use of trade name(s) or mark(s) used in commerce (e.g., FlowJo, BioLegend, GeneWiz, FastQC, NextFlow), has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Interpretation
Claim(s) 5-6 recite the phrase “natural killer cell activation assay as described in Example 7”. According to the instant disclosure [e.g., ¶ 0345], the NK assay of Example 7 is an NK cell degranulation assay. Therefore, for the purposes of compact prosecution, any NK cell degranulation assay will be considered to meet the limitations of the phrase “natural killer cell activation assay as described in Example 7”.
Claim(s) 33 recites specific KDs and/or binding affinity ratios relative to modified Fc domain characteristics of the anti-PD1 antibody. The instant disclosure provides that the Fc domain of the antibody comprises a sequence that has at least 80% sequence identity to instant SEQ ID NO: 17. Therefore, any Fc domain sequence comprising at least 80% sequence identity to SEQ ID NO: 17 is considered to meet the recited KD and/or binding affinity limitations of the instant claim.
Claim Objections
Claim 117 is objected to because of the following informalities: “any one of claims” should be “claim”. Appropriate correction is required.
Claim 33 is objected to because of the following informalities: “the antibody” in sections (i) - (iv) should be “the Fc domain of the antibody”. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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 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.
Claim(s) 5-6, 21, 33, 117-118, and 121-123 is/are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 5 recites the limitation “the ADCC” in line 1. There is insufficient antecedent basis for this limitation in the claim. This rejection may be overcome by amending claim 5 to provide antecedent basis.
Claim(s) 5-6, are rejected for making reference to an example within the specification. Where possible, claims are to be complete in themselves. Incorporation by reference to a specific section of the specification “is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim.” See MPEP 2173.05(s). In the instant case, there is a practical way to define the invention in words. Incorporation by reference is a necessity doctrine, not for applicant' s convenience.
Claim 6 recites the limitation “with 0 to 3 amino acid modifications” in lines 9 and 10-11, rendering the claim indefinite. Specifically, it is unclear if the phrase “with 0 to 3 amino acid modifications” means (1) there are 0 to 3 amino acid modifications per each individual CDR, or (2) o to 3 amino acid modifications amongst all 3 CDRs (e.g., HCDR1-3 or LCDR1-3) claimed. For the purposes of compact prosecution, the phrase “with 0 to 3 amino acid modifications” is considered to mean per each individual CDR. This rejection may be overcome by deleting the phrase “with 0 to 3 amino acid modifications” in lines 9 and 10-11.
Claims 21, 33 does not recite a conjunction between (ii) and (iii), rendering the claim indefinite. Specifically, without a conjunction it is unclear if (1) i-iii are required, (2) only one of i-iii are required, or (3) something else. In the interest of compact prosecution, the conjunction is considered to be “or”. This rejection may be overcome by amending claim 21 to recite a conjunction between (ii) and (iii). Dependent claim 33 can overcome this rejection by amending claim 21 as described above.
Claims 117-118, 121-123 recites the limitation “the antibody of claim 57”, but claim 57 was withdrawn (non-elected invention, see details in “claim Status” above). There is insufficient antecedent basis for this limitation in the claim. For the purposes of compact prosecution, claims 117, 121, and 122 are considered to depend from claim 1. This rejection may be overcome by amending claims 117, 121, 122 to depend from a claim of the elected invention (e.g., claim 1). Dependent claims 118, 123 can overcome this rejection by amending claims 117 and 122 as described above.
Claim Rejections - 35 USC § 112(a)
Claim(s) 1, 3, 5-6, 11, 13, 21, 24, 33, 117-118 and 121-123 is/are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claimed Invention
Claim(s) 1, 3, 5-6, 11, 13, 21, 24, 33, 117-118, and 121-123 are drawn to an antibody that binds PD1 antigen.
Breadth of Claims
The invention as disclosed in claim(s) 1, 3, 5-6, 11, 13, 21, 24, 33, 117-118 and 121-123 recite(s) “…agonizes PD-1 signaling in the immune cell…” and “…enhances interaction of the PD-1 on the surface of the immune cell with PD-L1…”. One of ordinary skill in the art would understand that the 6 CDRs of an antibody are responsible for antigen binding characteristics, including target agonism and antibody-mediated interactions (e.g., enhancing interaction between PD-1 and PD-L1). The claim does not disclose the structure associated with the claimed function. The instant disclosure does not provide a structure-function correlation that would allow for a person of ordinary skill in the art to envision light and heavy chain sequences, particularly in the CDR regions, such that the obtained structure would result in the claimed function(s).
The invention as disclosed in claim(s) 6, 11, 13 are readable to fewer than 6CDRs (e.g., HCDR1-3 and/or LCDR1-3), which is effectively less than a full antibody binding site, as being sufficient for a functional antibody binding region. Specifically, the claim limitations as written (e.g., “…one or more of SEQ ID NOs:…”) require only one LCDR (e.g., LCDR3) and/or only one HCDR (e.g., HCDR2), which is effectively less than a full antibody binding site missing the additional LCDRs (e.g., LCDR1-2) and/or HCDRs (e.g., HCDR1 and HCDR3) that would create the full antibody binding site (e.g., 6 CDRs). One of ordinary skill in the art would understand that one cannot use only a fraction antibody binding domain (e.g., LCDR3 and HCDR2 only) and reasonably expect to maintain PD1 antigen binding function.
The invention as disclosed in claim(s) 6, 11, 13 recite(s) “…with 0 to 3 amino acid modifications….”; and claim(s) 13 recite(s) “…[a VH or VL sequence comprising] at least 80%, 85%, 90%, 95%, or 99%, or 100% identity…”. The claim(s) encompass a genus of heavy and/or light chain variable regions comprising variability (e.g., 80% identical, 2 amino acid substitution in CDRs) in the heavy and/or light chain variable regions which are claimed as having the function of specifically binding to PD1 antigen. This means that the variability in sequence identity can also occur in the CDRs, the domains that are critical for the antibody binding to its target, which one of ordinary skill in the art would understand to result in unpredictable binding characteristics with no reasonable expectation of maintaining PD1 antigen binding. Additionally, the instant disclosure does not provide an adequate number of species of the claimed genus nor does the disclosure provide a structure-function correlation that would allow for a person of ordinary skill in the art to envision what variation can occur to the light and heavy chains, particularly in the CDR regions, such that the obtained structure would result in the claimed functions.
Scope of Disclosed Species
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The anti-PD1 antibody in the Applicant disclosure (see summary table above for details) with 100% sequence identity in the CDR regions of the heavy and light chain variable regions represents the anti-PD1 antibody that the applicant was in possession of at the time of filing.
State of the Prior Art
At the time of filing, antibody functionality were known to depend on the entire structure, particularly a full complement of six CDRs. It is understood by one of ordinary skill in the art that that mutation to CDRs is unpredictable and that each construct requires function testing.
Sela-Culang, Kunik, and Ofran (Fron. Immuno., Vol. 4, Article 302, Oct. 2013), hereinafter “Sela-Culang”, reviews the structural basis of antibody-antigen recognition in the state of the art. Naturally occurring antibodies have six hypervariable loops are commonly termed complementary determining regions (CDRs) and are widely assumed to be responsible for antigen recognition [e.g., pg. 1, abstract; pg. 3, “The Role of CDRs and their Definition”]. A person of ordinary skill in the art would understand that although the above basics of antibody-antigen binding are known, that the specifics of antibody structure (e.g., within the CDRs) that underlie the antigen recognition are not well characterized [e.g., pg. 1, “The Motivations for…”].
Further, Herold et al. (Nature Scientific Reports, 7:12276, 25 Sep 2017), hereinafter “Herold”, teaches that it should be emphasized that there is no correlation between experimentally determined change in antibody binding affinity and a given mutation and additionally that no such correlation is expected because antigen binding is “affected by each CDR loop differently” and changes thereto “can in principle affect antigen binding affinity in an unpredictable way” [e.g., pg. 14, ¶ 2]. Further, Herold asserts that multiple determinants regulate antigen affinity and the interactions with CDRs are complex [e.g., pg. 14, ¶ 3].
At the time of filing, US 2017/0007693 A1 (hereinafter “US693”) taught anti-PD1 antibodies were recognized in the art as therapeutic for autoimmune disease [e.g., ¶ 0078]. US693 taught various separate species of anti-PD1 antibodies [e.g., ¶ 0075]. Therefore, the prior art demonstrates that the binding of PD1 is possible by various anti-PD1 antibodies. The prior art does not teach a known structure activity relationship for HCDR1-3 and LCDR1-3 in anti-PD1 antibody that would allow prediction of CDR residues that specifically bind to PD1 antigen, and maintain the claimed function(s).
Thus, making changes to the CDR sequence of an antibody sequence is a highly unpredictable process and one skilled in the art could not a priori make any predications regarding such mutations with any reasonable expectation of success nor envisage the breadth of structurally unrelated CDR combinations that would still possess the required function(s).
Conclusion
As indicated by the art, a full complement of 6 CDRs are required for antigen binding and one cannot predict which CDR residues may be changed and still result in an antibody that binds PD1. Written description can be met if the claims recite the minimal structure that is needed to perform the function recited in the claims. Above, the art indicates that the 6 CDRs in an antibody antigen-binding domain are the minimal structure that binds to a target antigen. Specifically, Applicant claim(s) 1, 6, 11, 13 would need to recite the 6 CDRs (e.g., HCDR1-3 and LCDR1-3) in the antibody that bind PD1 antigen, without variability in the sequences thereof, with the claimed function(s). Dependent claim(s) 3, 5, 21, 24, 33, 117-118, and 121-123 can overcome this rejection by amending claim 1 as described above.
Claim(s) 21 and 33 is/are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claimed Invention
Claim(s) 21 and 33, are drawn to an anti-PD1 antibody comprising an Fc domain that selectively binds to FcyR2b.
Breadth of Claims
Further the invention as disclosed in claim(s) 21, 33 recite(s) “…the antibody binds to human FcyR2B with a KD of less than 5 μM, 4 μM, 3 μM, or 2 μM…”; and claim(s) 33 recite(s) “….(i) the antibody binds to human FcyR2A (131R allotype) with a Ko of more than 5 μM or 10 μM, or at least 15 μM, as determined by surface plasmon resonance at 3 7 °C; (ii) the antibody binds to human FcyR2A (131H allotype) with a KD of at least 50 μM or at least 80 μM, as determined by surface plasmon resonance at 37 °C; (iii) a ratio of binding affinity of the antibody to human FcyR2B versus binding affinity of the antibody to human FcyR2A (13 IR allotype) is at least 2: 1, 3: 1, 4: 1, 5: 1, or 6: 1, or at least 6: 1, or about 6: 1, as determined by surface plasmon resonance at 37 °C; and/or (iv) a ratio of binding affinity of the antibody to human FcyR2B versus binding affinity of the antibody to human FcyR2A (13 IH allotype) is at least 10: 1, 15: 1, 20: 1, 40: 1, or 50: 1, or at least 40: 1, or about 40: 1…”. The specification defines KD as “the equilibrium dissociation constant of an antibody-antigen interaction.” and further that the binding affinity “may be characterized by Ka, Kd, or KD”. One of ordinary skill in the art would understand that the amino acid sequence of the portion(s) of the Fc domain of the antibody that interact with FcyRs are responsible for binding characteristics, including binding affinity and KD. The claim does not disclose the structure of the Fc domain associated with the claimed function(s). The instant disclosure does not provide a structure-function correlation that would allow for a person of ordinary skill in the art to envision Fc domain variants, particularly in the FcyR binding regions, such that the obtained structure would result in the claimed functions.
Scope of Disclosed Species
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The anti-PD1 antibody comprising hIgG1 Fc domain variants in the Applicant disclosure (see summary table above for details) with 100% sequence identity in the Fc region represents the anti-PD1 antibody-Fc variants that the applicant was in possession of at the time of filing.
State of the Prior Art
At the time of filing, Fc domain variant interaction(s) with FcyRs were known to depend on the entire structure. It is understood by one of ordinary skill in the art that that mutation to the Fc domain in region(s) that bind to FcyR may result in unpredictable changes in FcyR binding characteristics and that each new Fc variant requires function testing.
Mimoto et al. (Protein Engineering, Design & Selection vol. 26 no. 10 pp. 589–598, 2013; hereinafter “Mimoto”) taught human IgG1 Fc variants were recognized in the art, as were the therapeutic potentials thereof [e.g., title, abstract]. Mimoto taught various separate species of Fc domain variants with different relative binding characteristics to FcyRs [e.g., figs. 1-2, 4, tbl. 1]. Therefore, the prior art demonstrates that various human IgG1 Fc variants result in altered FcyR (e.g., FcyR2b vs. FcyR2a) binding characteristics. The prior art does not teach a known structure activity relationship human IgG1 Fc domain variants that would allow prediction of each and every Fc variant that would result in the instant claimed function(s).
US 2014/294812 A1 (hereinafter “US812”) taught human IgG1 Fc variants were recognized in the art, as were the therapeutic potentials thereof include treating autoimmune disease [e.g., title, abstract; fig. 82U, ¶ 0342, 0351]. Mimoto taught various separate species of Fc domain variants with different relative binding characteristics to FcyRs [e.g., figs. 78, 80]. Therefore, the prior art demonstrates that various human IgG1 Fc variants result in altered FcyR (e.g., FcyR2b vs. FcyR2a) binding characteristics. The prior art does not teach a known structure activity relationship human IgG1 Fc domain variants that would allow prediction of each and every Fc variant that would result in the instant claimed function(s).
Thus, making changes to the hIgG1 Fc domain sequence of an antibody is an unpredictable process and one skilled in the art could not envisage the breadth of structurally unrelated hIgG1 Fc domain variants that would still possess the required function(s).
Conclusion
As indicated by the art, hIgG1 Fc domain variants may alter FcyRs binding characteristics and one cannot predict which specific variants will result in the instant claimed KD and/or binding affinity function(s). Written description can be met if the claims recite the specific Fc variant(s) that are known to perform the function(s) recited in the claims. Specifically, Applicant claim(s) 21, 33 would need to recite the specific Fc variant(s) of the antibody that possess the instant claimed function(s).
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim(s) 1, 6, 13, 24, 117-118, and 122-123 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US 9,181,342 B2 (hereinafter “US342”).
Regarding instant claim(s) 1, 13, 121-123, US342 teaches methods of reducing the immune responses mediated by activated lymphocytes in a subject comprising the administration of disclosed anti-PD1 antibodies [e.g., col. 5, lines 63-67]. US342 further teaches the anti-PD1 antibodies down regulate the immune response by reducing the proliferation of activated T cells, and are used to treat or prevent immune disorders by reducing the T cell response [e.g., col. 6, lines 13-34]. US342 further teaches that the disclosed provides anti-PD1 antibodies that act as PD1 agonists, specifically capable of binding and inhibiting immune cells expressing PD1 [e.g., abstract; col. 1, lines 22-24; col. 4, lines 25-38]. US342 further teaches the anti-PD1 antibody comprises a heavy chain and light chain (e.g., scFv), and Fc region [e.g., col. 7, line 45- col. 8, line 59], and that the Fc domain comprises IgG1 [e.g., fig. 8].
Regarding instant claim(s) 6, 13, US342 further teaches the antibody is anti-PD1 antibody is clone 19 and comprises a VH of SEQ ID NO: 14 and a VL of SEQ ID NO: 12 [e.g., col. 8, lines 10-34], which are the same as the instant claimed HCDR1-3 and LCDR1-3 (SEQ ID NOs: 1-3 and 4-6, with 0 to 3 amino acid modifications; see alignments below).
Alignment of anti-PD1 antibody HCDR1-3 (SEQ ID NOs: 1-3, respectively) with US432 (Mouse PD-1 antibody clone 19 VH protein sequence SEQ ID NO:14):
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Alignment of anti-PD1 antibody LCDR1-3 (SEQ ID NOs: 4-6, respectively) with US432 (Mouse PD-1 antibody clone 19 VK protein sequence SEQ ID NO:12):
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Regarding instant claim(s) 24, US342 further teaches the antibody is humanized [e.g., col. 8, lines 10-18].
Regarding instant claim(s) 117, US342 further teaches a therapeutically effective amount of the antibody is administered [e.g., col. 4, lines 8-14; col. 6, lines 53-64].
Regarding instant claim(s) 118, US342 further teaches the disease treated is rheumatoid arthritis [e.g., col. 1, lines 32-48; col. 6, lines 1-34].
Claim Rejections - 35 USC § 103
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 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 for establishing a background for determining obviousness under 35 U.S.C. 103 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 the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 3, 5, 11, 21, 33 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 9,181,342 B2 (hereinafter “US342”) as applied to claim(s) 1 and 6 above, and further in view of Mimoto et al. (Protein Engineering, Design & Selection vol. 26 no. 10 pp. 589–598, 2013; hereinafter “Mimoto”), as evidenced by US 2014/294812 A1 (hereinafter “US812”).
The teachings of US432 as recited above for claims 1 and 6 are applied.
US432 does not expressly teach that the antibody Fc domain comprises SEQ ID NO: 17.
Regarding claims 3, 5, 11, 21, 33, Mimoto teaches engineered antibody Fc variants for selectively enhanced FcyR2b binding over FcyR2a binding improved antibody therapy efficacy [e.g., title, abstract]. Mimoto further teaches that the IgG1 Fc and variants thereof tested comprise human IgG1 [e.g., pg. 590, col. 1, ¶ 3], FcyR2b selectivity was achieved by IgG1 Fc domain 238D substitution [e.g., abstract; pgs. 592-595 ], and summarizes that the IgG1 Fc 238D variant is expected to have significant therapeutic potential [e.g., pg. 597 “Conclusion”]. The human IgG1 Fc domain comprising a 238D substitution is the same as the instant claimed Fc of SEQ ID NO: 17, as evidenced by US812 (see alignment below; e.g., claim 9; fig. 78) and instant disclosure [e.g., pg. 83 “SEQ ID NO: 17”].
Alignment of instant FC domain (SEQ ID NO: 17) with US812 (Human IgG1 constant heavy chain mutant P238D):
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It would have been prima facie obvious to a person having ordinary skill in the art (PHOSITA) before the effective filing date of the claimed invention to substitute the FC domain of the anti-PD1 antibody comprising an IgG1 Fc domain as taught by US432, with the IgG1 Fc domain comprising a 238D substitution as taught by Mimoto, in the context of designing and developing an anti-PD1 antibody therapy. A PHOSITA would have been motivated to substitute the FC domain of the anti-PD1 antibody comprising an IgG1 Fc domain as taught by US432, with the IgG1 Fc domain comprising a 238D substitution as taught by Mimoto, because US432 teaches the method comprising administering an anti-PD1 antibody comprising an IgG1 Fc domain, and Mimoto teaches that IgG1 Fc 238D substitution increases RcyR2b selectivity, reduces ADCC, and is a promising modification for antibody therapeutics. The instant disclosure teaches that the anti-PD1 antibody comprising an IgG1 Fc with a 238D substitution (1) resulted in no NK cell degranulation or NK cell death [e.g., Example 7], and (2) resulted in the instant claimed KD and binding affinity characteristics [e.g., Example 3, tbl. 3]. Therefore, the teaching of the IgG1 Fc with a 238D substitution is considered to necessarily teach (1) that ADCC against regulatory T cells is reduced as determined by NK degranulation assay, and (2) the instant claimed KD and/or binding characteristics. There would have been a reasonable expectation of success for a PHOSITA to substitute FC domain of the anti-PD1 antibody comprising an IgG1 Fc domain as taught by US432, with the IgG1 Fc domain comprising a 238D substitution as taught by Mimoto, because US432 teaches the anti-PD1 antibody structure comprises an IgG1 Fc region, and Mimoto teaches the IgG1 Fc 238D mutation is a promising substitution for antibody therapies. This rationale aligns with the principle of simple substitution of one known element for another to obtain predictable results, supporting a conclusion of obviousness (see MPEP § 2141).
Thus, the invention as a whole is prima facie obvious over the references, especially in the absence of evidence to the contrary.
Free From the Prior Art
During the course of examination, the anti-PD1 antibodies or antigen binding fragments thereof comprising HCDR1-3 and LCDR1-3 of SEQ ID NOs: 1-3 and 4-6 (see table below for ease of reference) were found to nonobvious over the prior art. Briefly, a sequence search of the prior art returned no 100% matches to the instant claimed HCDR1-3 (see closest prior art alignments below).
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Alignment of anti-PD1 antibody HCDR1-3 (SEQ ID NOs: 1-3, respectively) with over US 9,181,342 B2 (Mouse PD-1 antibody clone 19 VH protein sequence SEQ ID NO:14):
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Conclusion
No claims are currently allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMY M CHATTIN whose telephone number is (571)270-0646. The examiner can normally be reached T-F 0600-1600 PST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Julie Wu can be reached at (571) 272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/AMY M. CHATTIN/Examiner, Art Unit 1643
/JULIE WU/Supervisory Patent Examiner, Art Unit 1643