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
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Claims 1, 3-10, 21, 23, 26, 30-33, 35, 37-38, 40, and 42 have an effective filing date of 15 FEB 2019.
Election/Restriction
In the response filed 10/23/2024, Applicant elected:
Group I, claims 1-10
Species
Systemic lupus erythematosus (SLE)
Status of Claims
Claims 1, 3-10, 21, 23, 26, 30-33, 35, 37-38, 40, and 42 are currently pending and presented for examination on the merits.
Claims 8, 21, 23, 26, 30-33, 35, 37-38, 40, and 42 are withdrawn from further consideration by Examiner under 37 CFR 1.142(b) as being drawn to non-elected inventions.
Claims 1, 4, 6, and 9-10 are amended.
Claims 2, 11-20, 22, 24-25, 27-29, 34, 36, 39, 41, and 43 are canceled.
Rejections Withdrawn
The rejection filed under 35 U.S.C. 112(a) is withdrawn in view of Applicant’s amendment to claim.
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.
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 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.
Claims 1, 3-7, and 9-10 are rejected under 35 U.S.C. 103 as being unpatentable over Furie et al (Anifrolumab, an Anti–Interferon-a Receptor Monoclonal Antibody, in Moderate-to-Severe Systemic Lupus Erythematosus, Vol. 69, No. 2, pgs. 376-386, 2017, IDS 1/25/2022), James et al (US 20180364229 A1), Rai et al (RNA-seq Analysis Reveals Unique Transcriptome Signatures in Systemic Lupus Erythematosus Patients with Distinct Autoantibody Specificities, PLos One, 11(11): e0166312., 2016), Wong et al (Elevated Production of B Cell Chemokine CXCL13 is Correlated with Systemic Lupus Erythematosus Disease Activity, J Clin Immunol (2010) 30:45–52), and further in view of Yu et al (Increased concentration of serum soluble LAG3 in systemic lupus erythematosus, Kazuhiko Yamamoto Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, 113-0033, Japan Arthritis Research & Therapy, 2012).
In regards to claims 1 and 9, Furie et al teaches administering anifrolumab to treat patients with SLE [Objective, pg. 376]. Furie et al further teaches treating SLE patients resulting in an improvement of SLE Disease Activity Index (SLEDAI) score [Left column, pg. 382].
Furie et al does not specifically teach detecting the level of EPHB2 in SLE patients. However, this deficiency is made up in the teachings of Rai et al.
Rai et al teaches antigens of SLE that are elevated in SLE patients [S4 Fig, pg. 28]. Rai et al further teaches the elevation of EPHB2 in SLE patients [S4 Fig, pg. 28].
Furie et al does not specifically teach detecting BLC (CXCL13) in SLE patients. However, this deficiency is made up in the teachings of Wong et al.
Wong et al teaches the chemokines in SLE patients [Abstract, pg. 45]. Wong et al further teaches that CXCL13 is a disease marker for SLE [Right column, pg. 50].
Furie et al does not specifically teach detecting the level of LAG-3 in SLE patients. However, this deficiency is made up in the teachings of Yu et al.
Yu et al teaches measuring serum LAG-3 in SLE patients [Background, P16]. Yu et al further teaches the elevation of LAG-3 in SLE patients [Results, P16].
Furie et al does not specifically teach detecting the level of IP-10 in SLE patients. However, this deficiency is made up in the teachings of James et al.
James et al teaches the increase of IP-10 in SLE patients [Table 4, pg. 19].
With respect to claims 1 and 9, one of ordinary skill, before the effective filing date, would have been motivated to combine Furie’s method of treating SLE patients comprising administering anifrolumab, with Rai’s method of detecting elevated EPHB2 in SLE patients, with Wong’s method of detecting elevated BLC in SLE patients, with Yu’s method of detecting elevated LAG-3 in SLE patients, with James method of detecting elevated IP-10 in SLE patients. The idea of combining them flows logically from their having been individually taught in the prior art (MPEP 2144.06). Combining prior art elements according to known methods to yield predictable results is an exemplary rationale for a prima facie case of obviousness. MPEP2143. It would have been prima facie obvious to combine Furie, James, Rai, Wong, and Yu’s methods for a method of treating SLE comprising anifrolumab in patients identified as having SLE by elevated EPHB2, BLC, LAG-3, and IP-10. One of ordinary skill in the art would be motivated by known methods of identifying SLE patients by elevated EPHB2, BLC, LAG-3, and IP-10, and treating SLE using known method comprising administering anifrolumab.
In regards to claim 3, Furie et al teaches administering anifrolumab at dosages of 300 or 1000 mg [Objective, pg. 376].
In regards to claims 4 and 10, James et al teaches treating SLE patients has been shown to normalize IFN-regulated gene expression and reduce downstream levels [0127]. James et al further teaches that treating SLE patients reduced gene expression and downstream levels of IP-10 [0127].
In regards to claim 5, Furie et al teaches treating SLE patients [Objective, pg. 376].
In regards to claim 6, Furie et al teaches treating SLE patients resulting in an improvement of SLE Disease Activity Index (SLEDAI) score [Left column, pg. 382].
In regards to claim 7, Furie et al teaches administering anifrolumab every 4 weeks [Figure 2].
Applicant’s Arguments
Obviousness rejections under 35 U.S.C. 103 are traversed
To cure the deficiency of Furie et al, the Examiner has cited the other four references
A person skilled in the art would understand that the claim element "an elevated interferon protein signature (IFNPS) characterized by elevated protein expression of EPHB2, BLC, LAG-3 and IP-10 in the serum" should be considered as a whole, and the cited references, even when combined, fail to teach at least this element.
Wong et al only teaches upregulation of various RNA transcripts in different SLE subsets (e.g., upregulation of EPHB2 transcripts in the anti-dsDNA*ENA* subgroup) but does not teach elevated "protein expression" which is the required element in the instant claims. A person skilled in the art would understand that elevated mRNA transcript expression does not necessarily translate into elevated protein expression.
The cited references still fail to teach at least one element in the instant claims, namely, "an elevated interferon protein signature (1FNPS) characterized by elevated protein expression of EPHB2, BLC, LAG-3 and IP-10 in the serum."
In view of Rai et al, a person skilled in the art would not have had a reason to select EPHB2 as part of the elevated IFNPS panel since its elevated expression was limited to one of the SLE subgroups.
The cited references did not study comparable SLE populations.
Some of the cited references only showed the elevated mRNA transcripts expression, which doesn't necessarily translate into elevated protein expression.
Examiner’s Response
Applicant states, “Examiner has cited the other four references”.
In Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 82 USPQ2d 1321 (Fed. Cir. 2007),
Pfizer argued that the results of forming amlodipine besylate would have been unpredictable and therefore nonobvious. The court rejected the notion that unpredictability could be equated with nonobviousness here, because there were only a finite number (53) of pharmaceutically acceptable salts to be tested for improved properties.
The court found that one of ordinary skill in the art having problems with the machinability of amlodipine would have looked to forming a salt of the compound and would have been able to narrow the group of potential salt-formers to a group of 53 anions known to form pharmaceutically acceptable salts, which would be an acceptable number to form "a reasonable expectation of success."
Applicant states, “different SLE subsets”
Applicant elected the species “Systemic lupus erythematosus (SLE)” which would include all subsets and different population of patients having SLE.
Applicant states, “Wong et al only teaches upregulation of various RNA transcripts” vs. the claim element "an elevated interferon protein signature (IFNPS) characterized by elevated protein expression”.
Wong et al teaches serum CXCL13 concentrations correlated with dsDNA in SLE patients with active disease.
One of ordinary skill would recognize elevated levels of RNA transcripts correlates with increase protein expression.
Applicant states, “In view of Rai et al, a person skilled in the art would not have had a reason to select EPHB2 as part of the elevated IFNPS panel”.
Rai et al teaches the elevation of EPHB2 in SLE patients [S4 Fig, pg. 28]. Rai et al further teaches EPHB2 is upregulated in anti-dsDNA+/anti-ENA+/anti-dsDNA+ENA+ patients [1st paragraph, pg. 10]. Rai et al further teaches this ability of EPHB2 to be upregulated in anti-dsDNA+ and/or ENA+ patients, or all three subtypes, compared to healthy individuals [Fig. 3, pg. 9].
One of ordinary skill would recognize EPHB2 being upregulated in both/all subtypes compared to healthy individuals makes it an ideal candidate. Furthermore, Rai et al does not teach away from EPHB2 or the fact EPHB2 is upregulated in SLE patients.
One of ordinary skill, before the effective filing date, would have been motivated to combine Furie’s method of treating SLE patients comprising administering anifrolumab, with Rai’s method of detecting elevated EPHB2 in SLE patients, with Wong’s method of detecting elevated BLC in SLE patients, with Yu’s method of detecting elevated LAG-3 in SLE patients, with James method of detecting elevated IP-10 in SLE patients. The idea of combining them flows logically from their having been individually taught in the prior art (MPEP 2144.06). Combining prior art elements according to known methods to yield predictable results is an exemplary rationale for a prima facie case of obviousness. MPEP2143. It would have been prima facie obvious to combine Furie, James, Rai, Wong, and Yu’s methods for a method of treating SLE comprising anifrolumab in patients identified as having SLE by elevated EPHB2, BLC, LAG-3, and IP-10. One of ordinary skill in the art would have been motivated by known methods of identifying SLE patients by elevated EPHB2, BLC, LAG-3, and IP-10, and treating SLE using known method comprising administering anifrolumab. Furthermore, each elevated interferon protein is taught as upregulated in SLE patients.
Conclusion
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 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 DENNIS JOHN SULLIVAN whose telephone number is (571)272-0509. The examiner can normally be reached Mon - Fri: 7:30AM - 4:30PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis can be reached at (571) 270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/DENNIS J SULLIVAN/Examiner, Art Unit 1642
/NELSON B MOSELEY II/Primary Examiner, Art Unit 1642