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 .
DETAILED ACTION
The amendment filed September 24, 2026, is acknowledged. Claim 2 has been amended.
Claims 1-11 are pending and are under examination.
Grounds of Rejection Withdrawn
The 35 U.S.C. 103 rejection as being unpatentable over Chu et al (US 2009/0136485 A1, IDS), Anonymous 3: (Antibodies by Design: Xencor R&D Day welcome, 6/26/2015; 154 pages, IDS) and Stone, John (SDP, 29(4):177-190, 2012, abstract only, IDS) has been withdrawn in view of the 1.130 declaration that the Anonymous 3: (Antibodies by Design: Xencor R&D Day welcome, 6/26/2015; 154 pages, IDS) art is a grace period disclosure by the inventors.
The double patenting rejection over US Patent 11,365,256 has been obviated by filing of a TD. The other double patenting rejections have been obviated in view of Applicant’s remarks filed September 24, 2026.
Rejections Maintained
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 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.
Claims 1-11 are rejected under 35 U.S.C. 103 as being unpatentable over Chu et al (US 2009/0136485 A1, IDS), Anonymous: (Press Release, 1/2015; pages 1-2, IDS), Anonymous 2: (Press Release, 10/2014; pages 1-3) and Stone, John (SDP, 29(4):177-190, 2012, abstract only, IDS).
Chu et al teach treating B cell disorders, including autoimmune disorders, such as autoimmune hepatitis with the HuAM4G7 antibody which binds to CD19 and comprises the amino acids sequences of instant SEQ ID NO:7 and 9 by intravenous or subcutaneous administration (see entire document, e.g., alignments and pages 2, 32, 41, 51 and 53). Chu et al teach dosing the antibody at a range from 1 to 10 mg/kg about 2 weeks apart which would treat patients within the range of 125 mg and 375 mg depending on the patient weight (see page 36).
RESULT 3
US-12-156-183A-7
; Sequence 7, Application US/12156183A
; Publication No. US20090136485A1
; GENERAL INFORMATION
; APPLICANT: CHU, Seung Yup
; APPLICANT:DESJARLAIS, John R
; APPLICANT:KARKI, Sher Bahadur
; APPLICANT:LAZAR, Gregory Alan
; APPLICANT:MOORE, Gregory L.
; APPLICANT:VOSTIAR, Igor
; TITLE OF INVENTION: Methods and Compositions for Inhibiting CD32B Expressing Cells
; FILE REFERENCE: 190323/US/8
; CURRENT APPLICATION NUMBER: US/12/156,183A
; CURRENT FILING DATE: 2009-01-21
; PRIOR APPLICATION NUMBER: 60/940,776
; PRIOR FILING DATE: 2007-05-30
; PRIOR APPLICATION NUMBER: 60/953,174
; PRIOR FILING DATE: 2007-07-31
; PRIOR APPLICATION NUMBER: 60/970,413
; PRIOR FILING DATE: 2007-09-06
; PRIOR APPLICATION NUMBER: 60/976,279
; PRIOR FILING DATE: 2007-09-28
; PRIOR APPLICATION NUMBER: 60/990,509
; PRIOR FILING DATE: 2007-11-27
; PRIOR APPLICATION NUMBER: 61/012,035
; PRIOR FILING DATE: 2007-12-06
; PRIOR APPLICATION NUMBER: 61/013,775
; PRIOR FILING DATE: 2007-12-14
; PRIOR APPLICATION NUMBER: 61/019,395
; PRIOR FILING DATE: 2008-01-07
; PRIOR APPLICATION NUMBER: 61/032,059
; PRIOR FILING DATE: 2008-02-27
; PRIOR APPLICATION NUMBER: 61/043,585
; PRIOR FILING DATE: 2008-04-09
; PRIOR APPLICATION NUMBER: 61/046,397
; PRIOR FILING DATE: 2008-04-18
; NUMBER OF SEQ ID NOS: 40
; SOFTWARE: PatentIn version 3.5
; SEQ ID NO 7
; LENGTH: 219
; TYPE: PRT
; ORGANISM: Artificial Sequence
; FEATURE:
; OTHER INFORMATION: Synthesized HuAM4G7 light chain (VH-C )
US-12-156-183A-7
Query Match 100.0%; Score 1138; DB 8; Length 219;
Best Local Similarity 100.0%;
Matches 219; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIVMTQSPATLSLSPGERATLSCRSSKSLQNVNGNTYLYWFQQKPGQSPQLLIYRMSNLN 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DIVMTQSPATLSLSPGERATLSCRSSKSLQNVNGNTYLYWFQQKPGQSPQLLIYRMSNLN 60
Qy 61 SGVPDRFSGSGSGTEFTLTISSLEPEDFAVYYCMQHLEYPITFGAGTKLEIKRTVAAPSV 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 SGVPDRFSGSGSGTEFTLTISSLEPEDFAVYYCMQHLEYPITFGAGTKLEIKRTVAAPSV 120
Qy 121 FIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSL 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 FIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSL 180
Qy 181 SSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 219
|||||||||||||||||||||||||||||||||||||||
Db 181 SSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 219
RESULT 2
US-12-156-183A-9
; Sequence 9, Application US/12156183A
; Publication No. US20090136485A1
; GENERAL INFORMATION
; APPLICANT: CHU, Seung Yup
; APPLICANT:DESJARLAIS, John R
; APPLICANT:KARKI, Sher Bahadur
; APPLICANT:LAZAR, Gregory Alan
; APPLICANT:MOORE, Gregory L.
; APPLICANT:VOSTIAR, Igor
; TITLE OF INVENTION: Methods and Compositions for Inhibiting CD32B Expressing Cells
; FILE REFERENCE: 190323/US/8
; CURRENT APPLICATION NUMBER: US/12/156,183A
; CURRENT FILING DATE: 2009-01-21
; PRIOR APPLICATION NUMBER: 60/940,776
; PRIOR FILING DATE: 2007-05-30
; PRIOR APPLICATION NUMBER: 60/953,174
; PRIOR FILING DATE: 2007-07-31
; PRIOR APPLICATION NUMBER: 60/970,413
; PRIOR FILING DATE: 2007-09-06
; PRIOR APPLICATION NUMBER: 60/976,279
; PRIOR FILING DATE: 2007-09-28
; PRIOR APPLICATION NUMBER: 60/990,509
; PRIOR FILING DATE: 2007-11-27
; PRIOR APPLICATION NUMBER: 61/012,035
; PRIOR FILING DATE: 2007-12-06
; PRIOR APPLICATION NUMBER: 61/013,775
; PRIOR FILING DATE: 2007-12-14
; PRIOR APPLICATION NUMBER: 61/019,395
; PRIOR FILING DATE: 2008-01-07
; PRIOR APPLICATION NUMBER: 61/032,059
; PRIOR FILING DATE: 2008-02-27
; PRIOR APPLICATION NUMBER: 61/043,585
; PRIOR FILING DATE: 2008-04-09
; PRIOR APPLICATION NUMBER: 61/046,397
; PRIOR FILING DATE: 2008-04-18
; NUMBER OF SEQ ID NOS: 40
; SOFTWARE: PatentIn version 3.5
; SEQ ID NO 9
; LENGTH: 451
; TYPE: PRT
; ORGANISM: Artificial Sequence
; FEATURE:
; OTHER INFORMATION: Synthesized HuAM4G7 S267E/L328F heavy chain
US-12-156-183A-9
Query Match 100.0%; Score 2418; DB 8; Length 451;
Best Local Similarity 100.0%;
Matches 451; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLVKPGGSLKLSCAASGYTFTSYVMHWVRQAPGKGLEWIGYINPYNDGTKY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVESGGGLVKPGGSLKLSCAASGYTFTSYVMHWVRQAPGKGLEWIGYINPYNDGTKY 60
Qy 61 NEKFQGRVTISSDKSISTAYMELSSLRSEDTAMYYCARGTYYYGTRVFDYWGQGTLVTVS 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 NEKFQGRVTISSDKSISTAYMELSSLRSEDTAMYYCARGTYYYGTRVFDYWGQGTLVTVS 120
Qy 121 SASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQS 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 SASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQS 180
Qy 181 SGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLG 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 SGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLG 240
Qy 241 GPSVFLFPPKPKDTLMISRTPEVTCVVVDVEHEDPEVKFNWYVDGVEVHNAKTKPREEQY 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 GPSVFLFPPKPKDTLMISRTPEVTCVVVDVEHEDPEVKFNWYVDGVEVHNAKTKPREEQY 300
Qy 301 NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAFPAPIEKTISKAKGQPREPQVYTLPPSRE 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAFPAPIEKTISKAKGQPREPQVYTLPPSRE 360
Qy 361 EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 EMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSR 420
Qy 421 WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 451
|||||||||||||||||||||||||||||||
Db 421 WQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 451
Anonymous teaches using the XMAb5871 antibody that inhibits B cells to treat RA and starting a clinical trial with the antibody to treat IgG4-RD. Anonymous 2 teaches administering the antibody biweekly for 12 weeks (see entire document).
Anonymous 2 teaches using the XMAb5871 antibody that inhibits B cells to treat RA and starting clinical testing with the antibody to treat IgG4-RD, an autoimmune disease where B-cell inhibition shows promise (see entire document).
Stone teaches that glucocorticoids and B-cell depletion both appear effective in treating IgG4-RD (see entire document).
Accordingly, it would have been prima facie obvious to treat IgG4-RD with the HuAM4G7 antibody which binds to CD19 and comprises the amino acids sequences of instant SEQ ID NO:7 and 9 with S267E/L328F mutations of Chu et al i.e., the XmAB5871 antibody of Anonymous 1 and 2, by IV or subcutaneous administration at therapeutically effective amount between 125 mg and 375 mg, such as 125 mg for a 125 kg patient (1 mg/kg) or 350 mg for a 70 kg patient (5 mg/kg) because the HuAM4G7 antibody was taught as treating B-cell disorders and IgG4-RD is a known B cell disorder which was disclosed as starting a clinical trial with the XmAB5871 antibody. Notably, B-cell depletion appeared effective in treating IgG4-RD, and such that one could have predictably treated IgG4-RD with such an antibody that binds and inhibits B cells by binding CD19 on the B cells like the XmAB5871 antibody. In this case, the XmAB5871 antibody, which appears to be the same antibody as the HuAM4G7 antibody, absent a showing otherwise, was in clinical testing for treating IgG4-RD, so one of skill in the art would have reasonably expected success in treating IgG4-RD when considering the art as a whole with such an antibody. Furthermore, it was already known in the art that B cell depletion treated IgG4-RD and inhibiting B cells instead of depleting them would have the advantage of being a less extreme reduction of the immune system which would be reversible faster than B-cell depletion.
Then with respect to the other limitations of claims 5-10, it is noted that the limitations which recite intended results would be met by such methods which would necessarily occur in the methods suggested in the prior art absent a showing otherwise. Applicant is reminded that products of identical composition cannot have mutually exclusive properties. A chemical composition and its properties are inseparable. In re Spada 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). See MPEP 2112.01. Accordingly, as the same antibody is administered at doses within the range, the results claimed necessarily must occur. The claims do not recite that each patient achieves the result and it is known that different patients respond differently to the same treatment such that it would be understood that the result would be reached in some patients and not all patients. Furthermore, with respect to the subjects of claim 11, IgG4-RD subjects to be treated necessarily include subject between 18 and 44 so the prior art subjects meet this limitation.
Furthermore, with respect to the doses of treatment, one of skill in the art would administer the antibody in amounts and schedules to treat the disease as the antibody is a results effective variable. Here, doses of 1-10 mg/kg were taught in the art and biweekly administration was known in the art, so one of skill would not have found it inventive to administer the antibody at a dose of 5mg/kg, absent a showing otherwise, which gives a 350 mg dose in a 70 kg patient. In this case, optimizing the amount of the antibody administered and the dosing schedule of the antibody, would be seen as routine optimization of a results effective variable. See MPEP 2144.05.
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made, absent a showing otherwise.
Applicant has traversed the rejection and argues that “A proper "Obvious to Try" rationale under MPEP § 2143 applies only when (1) there are a finite number of identified, predictable solutions and (2) a person of ordinary skill in the art (POSA) would have had a reasonable expectation of success. Moreover, MPEP § 2143 explicitly clarifies that "even when only a small number of possible choice exist, the obvious to try line of reasoning is not appropriate when, upon consideration of all the evidence, the outcome would not have been reasonably predictable and the inventor would not have had a reasonable expectation of success." Applicant respectfully submits that Applicant's claimed invention cannot be obvious because:
i. The Examiner has used impermissible hindsight, relying on the instant specification to
connect the teachings of Chu with Anonymous 1 and Anonymous 2 in selecting the
claimed antibody amongst hundreds of possible candidates; and
ii. A POSA would not have had a reasonable expectation that the claimed antibody could successfully treat IgG4-RD.
Applicant believes that the remarks herein overcome the obviousness rejections asserted against claim 1. For the sake of efficient prosecution, without conceding to the Examiner's characterization of the remaining claims, Applicant submits that dependent claims 2-11 are patentable for at least the same reasons.
For the sake of clarity and to avoid confusion, Applicant would like to first remark on the difference between the terms "XmAB5871" and "HuAM4G7." XmAb5871 (also known as obexelimab) is a bifunctional monoclonal antibody that binds both anti-CD19 and FcyRIIb. As described in both Chu and the present specification, HuAM4G7 is a variable domain (Fv region) that binds CD19. See, e.g., Chu at paras. [0061] and [0299]. In contrast with the Examiner's description that XmAb5871 is "the same antibody as the HuAM4G7 antibody" (Office Action at p. 6), XmAb5871 refers to an anti-CD19 antibody that incorporates the HuAM4G7 Fv region with an Fc region that possesses S267E and L328F mutations. HuAM4G7 can be used to describe different anti-CD19 antibody variants, including those that do not possess S267E and L328F mutations. See, e.g., Chu, at FIG. 54 (describing a heavy chain with wild-type IgGI Fc as "HuAM4G7 IgGI heavy chain"). Herein, Applicant uses HuAM4G7 to refer to the Fv region, while XmAb5871 refers to the antibody as a whole.”
In response, as a first point Chu et al (US 2009/0136485 A1, IDS), discloses the sequences of HuAM4G7 with the either light and heavy chain as set forth above and characterizes them as the Synthesized HuAM4G7 light chain and the Synthesized HuAM4G7 S267E/L328F heavy chain (see alignments above and Applicant states that XmAb5871 refers to an anti-CD19 antibody that possesses S267E and L328F mutations, so the antibody comprising HuAM4G7 S267E/L328F heavy chain and HuAM4G7 light chain of Chu appear to be identical to the XmAb5871 anti-CD19 antibody that possesses S267E and L328F mutations as evidenced by Applicant’s response.
Applicant further submits that “the only possible evidence (that the CD19 antibody comprising HuAM4G7 S267E/L328F heavy chain and HuAM4G7 light chain of Chu appear to be identical to the XmAb5871 anti-CD19 antibody that possesses S267E and L328F mutations) comes from Applicant's own disclosure in the present specification which describes the claimed antibody as both XmAb5871 and HuAM4G7 with S267E and L328F mutations. See US 2026-0250393 A1, at paras. [0317]-[0318] (specification as published). However, this disclosure cannot be used to evidence obviousness. In re Kahn, 441 F.3d 977, at 988.
In response, the instant disclosure was not used to evidence obviousness, the CD19 antibody comprising HuAM4G7 S267E/L328F heavy chain and HuAM4G7 light chain of Chu and the XmAb5871 antibody either inherently are identical or not. Based on Applicant’s response, the CD19 antibody comprising HuAM4G7 S267E/L328F heavy chain and HuAM4G7 light chain of Chu appear to be identical to the XmAb5871 anti-CD19 antibody that possesses S267E and L328F mutations. In further response, and as further evidence that the CD19 antibody comprising HuAM4G7 S267E/L328F heavy chain and HuAM4G7 light chain of Chu is identical to the XmAb5871 anti-CD19 antibody that possesses S267E and L328F mutations Horton et al (JI, 186:4223-4233, 2011, IDS) discloses that XmAb5871 anti-CD19 antibody has an Fc domain with greater than 400-fold increased FcγRIIb affinity compared to native IgG1 Fc and is disclosed in Chu et al (MI:45:3926-3933, 2008) (see pages 4223). Chu et al (MI:45:3926-3933, 2008) does not refer to an antibody designated mAb5871, it instead discloses a 4G7 CD19 antibody and a variant with an Fc domain with S267E and L328F mutations with greater than 400-fold increased FcγRIIb affinity compared to native IgG1 Fc (see Table 1). Accordingly, the prior art evidence supports that the CD19 antibody comprising HuAM4G7 S267E/L328F heavy chain and HuAM4G7 light chain of Chu is identical to the XmAb5871 anti-CD19 antibody that possesses S267E and L328F mutations even though they have different names.
With respect to Applicant’s second argument that a POSA would not have had a reasonable expectation that the claimed antibody could successfully treat IgG4-RD, Applicant further submits Stone discloses B-cell depletion, not B cell inhibition and that “It is well-known in the art that the treatment of autoimmune diseases, such as IgG4-RD, is highly unpredictable, and that even antibodies sharing the same mechanism of action can produce divergent clinical outcomes. For example, the anti-CD20 antibody rituximab was known to be a safe and efficacious treatment of rheumatoid arthritis. See Chi Chiu Mok, Rituximab for the treatment of rheumatoid arthritis: an update, 8 DRUG DESIGN, DEVELOPMENT THERAPY 87 (2014) (provided as Exhibit A). Further studies in rheumatoid arthritis using others that were known to also deplete B-cells were unsuccessful. Ocrelizumab, ofatumumab, belimumab, and atacicept shared the same B-cell depletion mechanism as rituximab, but were either ineffective in treating rheumatoid arthritis or possessed an unfavorable safety profile. See id., at p. 88.
As such, a POSA would appreciate that simply because two antibodies share a similar mechanism of action does not mean that they would achieve similar clinical results, or could even successfully treat the same diseases. See id. The Office Action asserts that because "B cell depletion appeared effective in treating IgG4-RD,. one could have predictably treated IgG4-RD with such an antibody that binds and inhibits B cells See Office Action, p. 6. This reasoning assumes, without evidentiary support, that efficacy achieved through a mechanism of action (B-cell depletion) necessarily predicts efficacy through a distinct mechanism of action (B cell inhibition) in the same disease.”
In response, the argument relating to Stone individually was not found persuasive because Anonymous and Anonymous 2 both disclose using the CD19 XMAb5871 antibody that inhibits B cells for use in a clinical trial to treat IgG4-RD. There was clear motivation in Anonymous and Anonymous 2 to use the CD19 antibody comprising HuAM4G7 S267E/L328F heavy chain and HuAM4G7 light chain of Chu , i.e. the XmAb5871 anti-CD19 antibody that possesses S267E and L328F mutations to treat IgG4-RD and a reasonable expectation of success because Anonymous and Anonymous 2 would not have disclosed clinical trials to treat IgG4-RD with the antibody, without a reasonable expectation that the antibody would treat IgG4-RD.
Accordingly, after careful and complete consideration of the record as a whole, the rejection is being maintained.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. 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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Brad Duffy whose telephone number is (571) 272-9935. The examiner works a flexible schedule.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Julie Wu can be reached on (571) 272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Respectfully,
Brad Duffy
571-272-9935
/Brad Duffy/
Primary Examiner, Art Unit 1643
October 5, 2026
