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 .
Election/Restrictions
Applicant’s election of ianalumab having CDRs of SEQ ID NO:3-8 in the reply filed on 7/8/26 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claim Status
The amendments filed 7/8/26 are acknowledged. Claims 1-15 are pending. Claims 1-15 are amended. Claims 1-15 are currently under consideration for patentability under 37 CFR 1.104.
Information Disclosure Statement
The information disclosure statements filed on 12/18/23, 6/13/24, 1/18/25, 7/9/25, 1/27/26, 4/10/26, 4/30/26 have been considered. Signed copies are enclosed.
Notably, the disclosure statement filed lists a Search Report. The listing of the references cited in a Search Report itself is not considered to be an information disclosure statement (IDS) complying with 37 CFR 1.98. 37 CFR 1.98(a)(2) requires a legible copy of: (1) each foreign patent; (2) each publication or that portion which caused it to be listed; (3) for each cited pending U.S. application, the application specification including claims, and any drawing of the application, or that portion of the application which caused it to be listed including any claims directed to that portion, unless the cited pending U.S. application is stored in the Image File Wrapper (IFW) system; and (4) all other information, or that portion which caused it to be listed. In addition, each IDS must include a list of all patents, publications, applications, or other information submitted for consideration by the Office (see 37 CFR 1.98(a)(1) and (b)), and MPEP § 609.04(a), subsection I. states, "the list ... must be submitted on a separate paper." Therefore, the references cited in the Search Report have not been considered. Applicant is advised that the date of submission of any item of information or any missing element(s) will be the date of submission for purposes of determining compliance with the requirements based on the time of filing the IDS, including all "statement" requirements of 37 CFR 1.97(e). See MPEP § 609.05(a).
Note: If copies of the individual references cited on the Search Report are also cited separately on the IDS (and these references have not been lined-through) they have been considered.
Claim Objections
Claim 1 is objected to because of the following informalities: the term “thereofby” should contain a space, to read “thereof by”. Appropriate correction is required.
Claim Rejections - 35 USC § 112(a)
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 the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
Claims 1 and 4-15 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.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed. The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include “level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention.”
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, disclosure of drawings, or by disclosure of relevant identifying characteristics, for example, structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the Applicants were in possession of the claimed genus.
The instant claims are directed to a method of treating systemic lupus erythematosus (SLE) in a subject comprising administering a therapeutically effective dose of an anti-BAFFR antibody or a binding fragment thereof. The rejected dependent claims recite dosing and administration regimens.
The recited antibody genus is not adequately described. The instant specification has provided an example of ianalumab, which comprises CDRs of SEQ ID NO:3-6. However, the rejected claims are not limited to this single species, and instead encompass treatment with any anti-BAFFR antibody or binding fragment thereof. The genus of antibodies must perform the functions of binding BAFFR and treating SLE. Applicant has not provided adequate description of a structure that would correlate with this function, and a single species is not representative of a broad genus of antibodies defined only by function.
The claimed methods require an antibody that has not been adequately described, and therefore the method is necessarily inadequately described. The claimed antibody genus has no correlation between the antibodies’ structure and function. The claim requires that the antibody exhibit anti-BAFFR binding activity and treat SLE, but the specification provides no guidance regarding which antibodies or fragments are capable of the required function. Therefore, the specification provides insufficient written description to support the genus encompassed by the claim. Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that
"applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116.)
With the exception of ianalumab or binding fragments thereof, the skilled artisan cannot envision the detailed chemical structure of the encompassed antibodies, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. In Fiddes v. Baird, 30 USPQ2d 1481, 1483, claims directed to mammalian FGF's were found unpatentable due to lack of written description for the broad class. The specification provided only the bovine sequence.
University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1404. 1405 held that:
...To fulfill the written description requirement, a patent specification must describe an invention and does so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines Inc. , 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (1997); In re Gosteli , 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (" [T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2datl966.
Protein chemistry is one of the most unpredictable areas of biotechnology. This unpredictability prevents prediction of the effects that a given number or location of mutation will have on a protein (such as TNF or a cytokine) As taught by Skolnick et al (Trends Biotechnol. 2000 Jan;18(1):34-9), sequence based methods for predicting protein function are inadequate because of the multifunctional nature of proteins (see e.g. abstract). Further, just knowing the structure of the protein is also insufficient for prediction of functional sites (see e.g. abstract). Sequence to function methods cannot specifically identify complexities for proteins, such as gain and loss of function during evolution, or multiple functions possible within a cells (see e.g. page 34, right column). Skolnick advocates determining the structure of the protein, then identifying the functionally important residues since using the chemical structure to identify functional sites is more in line with how a protein actually works (see e.g. page 34, right column).
The sensitivity of proteins to alterations of even a single amino acid in a sequence are exemplified by Burgess et al. (J. Cell Biol. 111:2129-2138, 1990) who teach that replacement of a single lysine reside at position 118 of acidic fibroblast growth factor by glutamic acid led to the substantial loss of heparin binding, receptor binding and biological activity of the protein and by Lazar et al. (Mol. Cell. Biol., 8:1247-1252, 1988) who teach that in transforming growth factor alpha, replacement of aspartic acid at position 47 with alanine or asparagine did not affect biological activity while replacement with serine or glutamic acid sharply reduced the biological activity of the mitogen. These references demonstrate that even a single amino acid substitution will often dramatically affect the biological activity and characteristics of a protein.
Further, Miosge (Proc Natl Acad Sci U S A. 2015 Sep 15;112(37):E5189-98) teach that Short of mutational studies of all possible amino acid substitutions for a protein, coupled with comprehensive
functional assays, the sheer number and diversity of missense mutations that are possible for proteins means that their functional importance must presently be addressed primarily by computational inference (see e.g. page E5189, left column). However, in a study examining some of these methods, Miosge shows that there is potential for incorrect calling of mutations (see e.g. page E5196, left column, top paragraph). The authors conclude that the discordance between predicted and actual effect of missense mutations creates the potential for many false conclusions in clinical settings where sequencing is performed to detect disease-causing mutations (see e.g. page E5195, right column, last paragraph). The findings in their study show underscore the importance of interpreting variation by direct experimental measurement of the consequences of a candidate mutation, using as sensitive and specific an assay as possible (see e.g. page E5197, left column, top paragraph). Additionally, Bork (Genome Research, 2000,10:398-400) clearly teaches the pitfalls associated with comparative sequence analysis for predicting protein function because of the known error margins for high-throughput computational methods. Bork specifically teaches that computational sequence analysis is far from perfect, despite the fact that sequencing itself is highly automated and accurate (p. 398, column 1). One of the reasons for the inaccuracy is that the quality of data in public sequence databases is still insufficient. This is particularly true for data on protein function. Protein function is context dependent, and both molecular and cellular aspects have to be considered (p. 398, column 2). Conclusions from the comparison analysis are often stretched with regard to protein products (p. 398, column 3). Further, although gene annotation via sequence database searches is already a routine job, even here the error rate is considerable (p. 399, column 2). Most features predicted with an accuracy of greater than 70% are of structural nature and, at best, only indirectly imply a certain functionality (see legend for table 1, page 399). As more sequences are added and as errors accumulate and propagate it becomes more difficult to infer correct function from the many possibilities revealed by database search (p. 399, paragraph bridging columns 2 and 3). The reference finally cautions that although the current methods seem to capture important features and explain general trends, 30% of those features are missing or predicted wrongly. This has to be kept in mind when processing the results further (p. 400, paragraph bridging cols 1 and 2).
One key issue is the prediction of protein function based on sequence similarity, which could be one way to identify the functional antibodies and binding fragments that are useful in the instant claims. Kulmanov et al (Bioinformatics, 34(4), 2018, 660–668), teach that there are key challenges for protein function prediction methods (see e.g. page 661, left column). These challenges arise from the difficulty identifying and accounting for the complex relationship between protein sequence structure and function (see e.g. page 661, left column). Despite significant progress in the past years in protein structure prediction, it still requires large efforts to predict protein structure with sufficient quality to be useful in function prediction (see e.g. page 661, left column). Another challenge is that proteins do not function in isolation. In particular higher level physiological functions that go beyond simple molecular interactions will require other proteins and cannot usually be predicted by considering a single protein in isolation (see e.g. page 661, left column). Due to these challenges it is not obvious what kinds of features should be used to predict the functions of a protein and whether they can be generated efficiently for a large number of proteins, such as the vast genus of antibodies and binding fragments encompassed by the instant claims (see e.g. page 661, left column).
The functional characteristics of antibodies (including binding specificity and affinity are dictated on their structure. Amino acid sequence and conformation of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity which is characteristic of the parent immunoglobulin. For example, Vajdos et al. (J Mol Biol. 2002 Jul 5;320(2):415-28 at 416) teaches that, “ … Even within the Fv, antigen binding is primarily mediated by the complementarity determining regions (CDRs), six hypervariable loops (three each in the heavy and light chains) which together present a large contiguous surface for potential antigen binding. Aside from the CDRs, the Fv also contains more highly conserved framework segments which connect the CDRs and are mainly involved in supporting the CDR loop conformations, although in some cases, framework residues also contact antigen. As an important step to understanding how a particular antibody functions, it would be very useful to assess the contributions of each CDR side-chain to antigen binding, and in so doing, to produce a functional map of the antigen-binding site." The art shows an unpredictable effect when making single versus multiple changes to any given CDR. For example, Brown et al. (J Immunol. 1996 May;156(9):3285-91 at 3290 and Tables 1 and 2), describes how the VH CDR2 of a particular antibody was generally tolerant of single amino acid changes, however the antibody lost binding upon introduction of two amino changes in the same region.
The claims encompass an extremely large number of antibodies and binding fragments thereof that have specific required functions. The specification discloses a single species within the instant claims scope and does not provide any guidance as to which amino acids can be varied while retaining the appropriate functionality.
Recently, the U.S. Court of Appeals for the Federal Circuit (Federal Circuit) decided Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017), which concerned adequate written description for claims drawn to antibodies. The Federal Circuit explained in Amgen that when an antibody is claimed, 35 U.S.C. § 112(a) requires adequate written description of the antibody itself even when preparation of such an antibody would be routine and conventional. Amgen, 872 F.3d at 1378-79. A key role played by the written description requirement is to prevent “attempt[s] to preempt the future before it has arrived.” Ariad at 1353, (quoting Fiers v. Revel, 984 F.2d at 1171). Upholding a patent drawn to a genus of antibodies that includes members not previously characterized or described could negatively impact the future development of species within the claimed genus of antibodies. In the instant application, neither the art nor the specification provide a sufficient representative number of antibodies or a sufficient structure-function correlation to meet the written description requirements.
Therefore, neither the art nor the specification provide a sufficient representative number of antibodies or a sufficient structure-function correlation to meet the written description requirements.
Adequate written description requires more than a mere statement that is part of the invention. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. v. Chungai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. In Fiddes v. Baird, 30 USPQ2d 1481, 1483, claims directed to mammalian FGF's were found unpatentable due to lack of written description for the broad class. The specification provided only the bovine sequence.
The University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1404, 1405 held that: …To fulfill the written description requirement, a patent specification must describe an invention and does so in sufficient detail that one skilled in the art can clearly conclude that “the inventor invented the claimed invention.” Lockwood v. American Airlines Inc. 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (1997); In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) ("[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus an Applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2dat1966.
MPEP § 2163.02 states, “[a]n objective standard for determining compliance with the written description requirement is, 'does the description clearly allow person of ordinary skill in the art to recognize that he or she invented what is claimed’”. The courts have decided: the purpose of the "written description" requirement is broader than to merely explain how to "make and use"; the Applicant must convey with reasonable clarity to those skilled in the art, that as of the filing date sought, he or she was in possession of the invention. The invention is for purposes of the “written description” inquiry, whatever is now claimed. See Vas-Cath, Inc v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Federal Circuit, 1991).
Furthermore, the written description provision of 35 USC §112 is severable from its enablement provision; and adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993). And Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. Moreover, an adequate written description of the claimed invention must include sufficient description of at least a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics sufficient to show that Applicant was in possession of the claimed genus. However, factual evidence of an actual reduction to practice has not been disclosed by Applicant in the specification; nor has Applicant shown the invention was “ready for patenting” by disclosure of drawings or structural chemical formulas that show that the invention was complete; nor has the Applicant described distinguishing identifying characteristics sufficient to show that Applicant were in possession of the claimed invention at the time the application was filed.
Therefore for all these reasons the specification lacks adequate written description, and one of skill in the art cannot reasonably conclude that Applicant had possession of the claimed invention at the time the instant application was filed.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 11-12 and 14-15 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.
Regarding claims 11 and 12, the phrase "e.g." that appears in several places renders the claims indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
In claim 11, the phrase “a steroid…or with disease modifying anti-rheumatic drug (DMARD)…or mycophenolic acid derivatives” renders the claim indefinite. It is unclear if the named drugs are alternatives in a Markush grouping, or if administration of multiple drugs is required.
In claim 11, the recitation of plural terms in “a steroid…or with disease modifying anti-rheumatic drug (DMARD)…or mycophenolic acid derivatives” renders the claim indefinite. It is unclear if a single DMARD and a single mycophenolic acid derivative must be administered, or if the plural terms indicate administration of more than one of each of these drugs simultaneously.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 11 recites the broad recitation steroid, DMARD, and myophenolic acid derivatives, and the claim also recites specific species of each genus of compound, which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 12 recites the broad recitation glucocorticoid, and the claim also recites specific species of each genus of compound, which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claims 11-12 and 14-15 contain terms or phrases that are referenced parenthetically. It is unclear, due to the presence of the parentheses, if the terms/phrases are intended as limitations of the claims, or are merely exemplary.
In claims 14 and 15, the scope of the regimen time is indefinite. It is unclear whether the scope requires 4 and 12 weeks, and whether the +/- 3 days is applied to the overall number of days, or to each week individually.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1-4 and 8-11 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by NCT03656562 (version published 8/31/18; downloaded from: https://clinicaltrials.gov/study/NCT03656562?tab=history&a=1#version-content-panel) as evidenced by Gladman et al (J Rheumatol. 2002 Feb;29(2):288-91).
Regarding the limitations of instant claims 1-4, the NCT03656562 study measures the Efficacy and Safety of VAY736 and CFZ533 in SLE Patients (see entire reference). The instant specification indicates that VAY736, also called ianalumab, is a preferred anti-BAFFR antibody (see e.g. page 5 of the instant specification).
Regarding the limitations of instant claims 8-10, the inclusion criteria for the NCT03656562 study indicate that subjects are “Currently receiving corticosteroids and/or anti-malarials and/or another DMARD on a stable dose according to protocol requirements” (see e.g. “Inclusion Criteria” section, and entire reference). This language indicates that patients can have received corticosteroids or DMARDs prior to treatment. Further, the cohort is required to have a SLEDAI-2K score of 6 or greater at screening (see e.g. entire reference, particularly the “Inclusion Criteria” section). As evidenced by Gladman, a SLEDAI-2K score of 4 or more indicates a flare of disease (see e.g. Gladman, page 289). The instant specification defines “inadequate” response as referring to “SLE patient still has one or more pathological symptoms of SLE” (see e.g. instant specification page 19). The SLEDAI-2K score of the NCT03656562 study indicates that prior treatments are not preventing pathological symptoms, which would meet the limitations of the instant claims’ “inadequate response.”
Regarding the limitations of instant claims 11, the NCT03656562 study states “response status at Week 29 (reduced steroid dose maintained between Weeks 17 and 29)” indicating that the patients concomitantly receive steroids (see e.g. entire reference, particularly “Primary Outcome Measures.”).
Claim(s) 1-4, 9, 11-12, and 14-15 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Heusser et al (US 9,340,620 B2; filed 12/15/11; published 5/17/16).
Regarding the limitations of instant claims 1-4, Heusser et al teach a method of treating an autoimmune disease comprising administering an antibody or antigen binding fragment thereof that binds BAFFR (see e.g. claim 1). The antibodies can comprise a light chain comprising the sequence of SEQ ID NO:45, which comprises an identical sequence to instant SEQ ID NO:1, and a heavy chain comprising the sequence of SEQ ID NO: 52, which comprises an identical sequence to instant SEQ ID NO:2 (see e.g. claim 4). The disease treated can comprise systemic lupus erythematosus (see e.g. claim 2).
Regarding the limitations of instant claims 9 and 11-12, Heusser teaches administering the anti-BAFFR antibody or binding fragment thereof with an additional agent such as a corticosteroid (see e.g. column 39, line 55 to column 40, line 5) or glucocorticoid (see e.g. column 39, lines 55-67, and column 30, line 29-55).
Regarding the limitations of instant claims 14-15, Heusser teaches that the administration can comprise administration once every four weeks, once every three months, or other schedules (see e.g. column 36, lines 25-40). The dosing can comprise 3 mg/kg, 5 mg/kg, or 10 mg/kg (see e.g. column 36, lines 25-40).
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) 1-7, 9, and 11-15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Heusser et al (US 9,340,620 B2; filed 12/15/11; published 5/17/16) and in view of Nair et al (J Basic Clin Pharm. 2016 Mar;7(2):27-31).
Heusser et al teach a method of treating an autoimmune disease comprising administering an antibody or antigen binding fragment thereof that binds BAFFR (see e.g. claim 1). The antibodies can comprise a light chain comprising the sequence of SEQ ID NO:45, which comprises an identical sequence to instant SEQ ID NO:1, and a heavy chain comprising the sequence of SEQ ID NO: 52, which comprises an identical sequence to instant SEQ ID NO:2 (see e.g. claim 4). The disease treated can comprise systemic lupus erythematosus (see e.g. claim 2). The administration can comprise administration once every four weeks, once every three months, or other schedules (see e.g. column 36, lines 25-40). The dosing can comprise 3 mg/kg, 5 mg/kg, or 10 mg/kg (see e.g. column 36, lines 25-40). Heusser also teaches administering the anti-BAFFR antibody or binding fragment thereof with an additional agent such as a corticosteroid (see e.g. column 39, line 55 to column 40, line 5) or glucocorticoid (see e.g. column 39, lines 55-67, and column 30, line 29-55).
Heusser et al do not teach the specific total dosing of the instant claims of about 150 mg to about 300 mg.
Nair teaches that the average human body weight is 60 kg (see e.g. page 28, right column, “Dose Calculations and Examples, paragraph beginning with “Dose is equally related to body weight…”
It would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to combine the teachings of Heusser and Nair to arrive at the dosing regimens of the instant claims. The Supreme Court set forth in KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), that if the scope and content of the prior art included a similar or analogous product, with differences between the claimed invention and prior art that were encompassed in known variation or in a principle known in the art, and one of ordinary skill in the art could have combined the elements as claimed by known methods, the claimed variation would have been predictable in to one of ordinary skill in the art. Heusser teaches administering the same antibody to SLE patients to treat SLE. Heusser provides specific guidance for treating SLE with the 3, 5, or 10 mg/kg. It would have been obvious as a known variation or principle to administer the dose between 150 and 300 mg (about 3 mg/kg and 5 mg/kg, respectively) in light of Nair et al, and recognizing that there is some weight variation between humans. It further would have been within a known variation in the art to administer the antibody every 4 weeks or every 12 weeks as described by Heusser. One of skill in the art would have been motivated to apply a known variation on the dosing regimen to a known treatment for SLE to maximize benefit to the treated patients. Thus, the combination of prior art references as combined provided a prima facie case of obviousness, absent convincing evidence to the contrary.
Claim(s) 1-15 is/are rejected under 35 U.S.C. 103 as being unpatentable over NCT03656562 (version published 8/31/18; downloaded from: https://clinicaltrials.gov/study/NCT03656562?tab=history&a=1#version-content-panel) as evidenced by Gladman et al (J Rheumatol. 2002 Feb;29(2):288-91), in view of Heusser et al (US 9,340,620 B2; filed 12/15/11; published 5/17/16) and further in view of Nair et al (J Basic Clin Pharm. 2016 Mar;7(2):27-31).
Regarding the limitations of instant claims 1-4, the NCT03656562 study measures the Efficacy and Safety of VAY736 and CFZ533 in SLE Patients (see entire reference). The instant specification indicates that VAY736, also called ianalumab, is a preferred anti-BAFFR antibody (see e.g. page 5 of the instant specification).
Regarding the limitations of instant claims 8-10, the inclusion criteria for the NCT03656562 study indicate that subjects are “Currently receiving corticosteroids and/or anti-malarials and/or another DMARD on a stable dose according to protocol requirements” (see e.g. “Inclusion Criteria” section, and entire reference). This language indicates that patients can have received corticosteroids or DMARDs prior to treatment. Further, the cohort is required to have a SLEDAI-2K score of 6 or greater at screening (see e.g. entire reference, particularly the “Inclusion Criteria” section). As evidenced by Gladman, a SLEDAI-2K score of 4 or more indicates a flare of disease (see e.g. Gladman, page 289). The instant specification defines “inadequate” response as referring to “SLE patient still has one or more pathological symptoms of SLE” (see e.g. instant specification page 19). The SLEDAI-2K score of the NCT03656562 study indicates that prior treatments are not preventing pathological symptoms, which would meet the limitations of the instant claims’ “inadequate response.”
Regarding the limitations of instant claims 11, the NCT03656562 study states “response status at Week 29 (reduced steroid dose maintained between Weeks 17 and 29)” indicating that the patients concomitantly receive steroids (see e.g. entire reference, particularly “Primary Outcome Measures.”).
The NCT03656562 study does not teach the exact dosing amount or dosing regimen of the instant claims.
Heusser et al teach a method of treating an autoimmune disease comprising administering an antibody or antigen binding fragment thereof that binds BAFFR (see e.g. claim 1). The antibodies can comprise a light chain comprising the sequence of SEQ ID NO:45, which comprises an identical sequence to instant SEQ ID NO:1, and a heavy chain comprising the sequence of SEQ ID NO: 52, which comprises an identical sequence to instant SEQ ID NO:2 (see e.g. claim 4). The disease treated can comprise systemic lupus erythematosus (see e.g. claim 2). The administration can comprise administration once every 4 weeks, once every three months, or other schedules (see e.g. column 36, lines 25-40). The dosing can comprise 3 mg/kg, 5 mg/kg, or 10 mg/kg (see e.g. column 36, lines 25-40). Heusser also teaches administering the anti-BAFFR antibody or binding fragment thereof with an additional agent such as a corticosteroid (see e.g. column 39, line 55 to column 40, line 5) or glucocorticoid (see e.g. column 39, lines 55-67, and column 30, line 29-55).
Nair teaches that the average human body weight is 60 kg (see e.g. page 28, right column, “Dose Calculations and Examples, paragraph beginning with “Dose is equally related to body weight…”
It would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to combine the teachings of the NCT03656562 study with Heusser and Nair to arrive at the dosing regimens of the instant claims. The Supreme Court set forth in KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), that if the scope and content of the prior art included a similar or analogous product, with differences between the claimed invention and prior art that were encompassed in known variation or in a principle known in the art, and one of ordinary skill in the art could have combined the elements as claimed by known methods, the claimed variation would have been predictable in to one of ordinary skill in the art. Both the NCT03656562 study and Heusser teach administering the same antibody to SLE patients to treat SLE. Heusser provides specific guidance for treating SLE with the 3, 5, or 10 mg/kg. It would have been obvious as a known variation or principle to administer the dose between 150 and 300 mg (about 3 mg/kg and 5 mg/kg, respectively) in light of Nair et al, and recognizing that there is some weight variation between humans. It further would have been within a known variation in the art to administer the antibody every 4 weeks or every 12 weeks as described by Heusser. One of skill in the art would have been motivated to apply a known variation of the dosing regimen to a known treatment for SLE to maximize benefit to the treated patients. The combination of the methods would not alter the steps, treatments or functions of either the NCT03656562 study or Heusser. Thus, the combination of prior art references as combined provided a prima facie case of obviousness, absent convincing evidence to the contrary.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-4 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. US 9,340,620 B2.
Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding the limitations of instant claims 1-4, the ‘620 patent teaches a method of treating an autoimmune disease comprising administering an antibody or antigen binding fragment thereof that binds BAFFR (see e.g. claim 1). The antibodies can comprise a light chain comprising the sequence of SEQ ID NO:45, which comprises an identical sequence to instant SEQ ID NO:1, and a heavy chain comprising the sequence of SEQ ID NO: 52, which comprises an identical sequence to instant SEQ ID NO:2 (see e.g. claim 4). The disease treated can comprise systemic lupus erythematosus (see e.g. claim 2).
The ’620 patent anticipates the rejected claims, but differs in scope, because the instant claims are directed to treatment with the entire genus of anti-BAFFR antibodies and binding fragments thereof, or treatment with a single species from those identified in the ‘620 patent claims. Therefore the subject matter of the ‘620 patent and the instant claims overlaps but is not identical in scope.
Claims 1-7, 9, and 11-15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. US 9,340,620 B2, in view of Heusser et at (US 2012/0183529 A1; filed 12/15/11; published 7/19/12).
Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding the limitations of instant claims 1-4, the ‘620 patent teaches a method of treating an autoimmune disease comprising administering an antibody or antigen binding fragment thereof that binds BAFFR (see e.g. claim 1). The antibodies can comprise a light chain comprising the sequence of SEQ ID NO:45, which comprises an identical sequence to instant SEQ ID NO:1, and a heavy chain comprising the sequence of SEQ ID NO: 52, which comprises an identical sequence to instant SEQ ID NO:2 (see e.g. claim 4). The disease treated can comprise systemic lupus erythematosus (see e.g. claim 2).
Heusser et al teach a method of treating an autoimmune disease comprising administering an antibody or antigen binding fragment thereof that binds BAFFR (see e.g. claim 1). The antibodies can comprise a light chain comprising the sequence of SEQ ID NO:45, which comprises an identical sequence to instant SEQ ID NO:1, and a heavy chain comprising the sequence of SEQ ID NO: 52, which comprises an identical sequence to instant SEQ ID NO:2 (see e.g. claims 7-10). The disease treated can comprise systemic lupus erythematosus (see e.g. claim 2). The administration can comprise administration once every four weeks, once every three months, or other schedules (see e.g. paragraphs [0226]-[0227]). The dosing can comprise 3 mg/kg, 5 mg/kg, or 10 mg/kg (see e.g. paragraphs [0226]-[0227]). Heusser also teaches administering the anti-BAFFR antibody or binding fragment thereof with an additional agent such as a corticosteroid (see e.g. paragraphs [0192], [0246]) or glucocorticoid (see e.g. paragraphs [0192], [0246]).
Neither the ‘620 patent nor Heusser et al teach the specific total dosing of the instant claims of about 150 mg to about 300 mg.
Nair teaches that the average human body weight is 60 kg (see e.g. page 28, right column, “Dose Calculations and Examples, paragraph beginning with “Dose is equally related to body weight…”)
It would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to combine the teachings of the ‘620 patent, Heusser and Nair to arrive at the dosing regimens of the instant claims. The Supreme Court set forth in KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), that if the scope and content of the prior art included a similar or analogous product, with differences between the claimed invention and prior art that were encompassed in known variation or in a principle known in the art, and one of ordinary skill in the art could have combined the elements as claimed by known methods, the claimed variation would have been predictable in to one of ordinary skill in the art. The ‘620 patent and Heusser teach administering the same antibody to SLE patients to treat SLE. Heusser provides specific guidance for treating SLE with the 3, 5, or 10 mg/kg. It would have been obvious as a known variation or principle to administer the dose between 150 and 300 mg (about 3 mg/kg and 5 mg/kg, respectively) in light of Nair et al, and recognizing that there is some weight variation between humans. It further would have been within a known variation in the art to administer the antibody every 4 weeks or every 12 weeks as described by Heusser. One of skill in the art would have been motivated to apply a known variation on the dosing regimen to a known treatment for SLE to maximize benefit to the treated patients. Thus, the combination of prior art references as combined provided a prima facie case of obviousness, absent convincing evidence to the contrary.
Claim(s) 1-15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. US 9,340,620 B2, in view of Heusser et at (US 2012/0183529 A1; filed 12/15/11; published 7/19/12), and further in view of NCT03656562 (version published 8/31/18; downloaded from: https://clinicaltrials.gov/study/NCT03656562?tab=history&a=1#version-content-panel) as evidenced by Gladman et al (J Rheumatol. 2002 Feb;29(2):288-91), and further in view of Nair et al (J Basic Clin Pharm. 2016 Mar;7(2):27-31).
Regarding the limitations of instant claims 1-4, the ‘620 patent teaches a method of treating an autoimmune disease comprising administering an antibody or antigen binding fragment thereof that binds BAFFR (see e.g. claim 1). The antibodies can comprise a light chain comprising the sequence of SEQ ID NO:45, which comprises an identical sequence to instant SEQ ID NO:1, and a heavy chain comprising the sequence of SEQ ID NO: 52, which comprises an identical sequence to instant SEQ ID NO:2 (see e.g. claim 4). The disease treated can comprise systemic lupus erythematosus (see e.g. claim 2).
Heusser et al teach a method of treating an autoimmune disease comprising administering an antibody or antigen binding fragment thereof that binds BAFFR (see e.g. claim 1). The antibodies can comprise a light chain comprising the sequence of SEQ ID NO:45, which comprises an identical sequence to instant SEQ ID NO:1, and a heavy chain comprising the sequence of SEQ ID NO: 52, which comprises an identical sequence to instant SEQ ID NO:2 (see e.g. claims 7-10). The disease treated can comprise systemic lupus erythematosus (see e.g. claim 2). The administration can comprise administration once every four weeks, once every three months, or other schedules (see e.g. paragraphs [0226]-[0227]). The dosing can comprise 3 mg/kg, 5 mg/kg, or 10 mg/kg (see e.g. paragraphs [0226]-[0227]). Heusser also teaches administering the anti-BAFFR antibody or binding fragment thereof with an additional agent such as a corticosteroid (see e.g. paragraphs [0192], [0246]) or glucocorticoid (see e.g. paragraphs [0192], [0246]).
Neither the ‘620 patent nor Heusser et al teach the specific total dosing of the instant claims of about 150 mg to about 300 mg.
Nair teaches that the average human body weight is 60 kg (see e.g. page 28, right column, “Dose Calculations and Examples, paragraph beginning with “Dose is equally related to body weight…”)
The ‘620 patent, Heusser, and Nair do not teach response to prior treatments.
The NCT03656562 study measures the Efficacy and Safety of VAY736 and CFZ533 in SLE Patients (see entire reference). The instant specification indicates that VAY736, also called ianalumab, is a preferred anti-BAFFR antibody (see e.g. page 5 of the instant specification). Regarding the limitations of instant claims 8-10, the inclusion criteria for the NCT03656562 study indicate that subjects are “Currently receiving corticosteroids and/or anti-malarials and/or another DMARD on a stable dose according to protocol requirements” (see e.g. “Inclusion Criteria” section, and entire reference). This language indicates that patients can have received corticosteroids or DMARDs prior to treatment. Further, the cohort is required to have a SLEDAI-2K score of 6 or greater at screening (see e.g. entire reference, particularly the “Inclusion Criteria” section). As evidenced by Gladman, a SLEDAI-2K score of 4 or more indicates a flare of disease (see e.g. Gladman, page 289). The instant specification defines “inadequate” response as referring to “SLE patient still has one or more pathological symptoms of SLE” (see e.g. instant specification page 19). The SLEDAI-2K score of the NCT03656562 study indicates that prior treatments are not preventing pathological symptoms, which would meet the limitations of the instant claims’ “inadequate response.” Regarding the limitations of instant claims 11, the NCT03656562 study states “response status at Week 29 (reduced steroid dose maintained between Weeks 17 and 29)” indicating that the patients concomitantly receive steroids (see e.g. entire reference, particularly “Primary Outcome Measures.”).
It would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to combine the teachings of the ‘620 patent with the NCT03656562 study, Heusser, and Nair to arrive at the dosing regimens of the instant claims. The Supreme Court set forth in KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), that if the scope and content of the prior art included a similar or analogous product, with differences between the claimed invention and prior art that were encompassed in known variation or in a principle known in the art, and one of ordinary skill in the art could have combined the elements as claimed by known methods, the claimed variation would have been predictable in to one of ordinary skill in the art. Both the NCT03656562 study and Heusser teach administering the same antibody to SLE patients to treat SLE. Heusser provides specific guidance for treating SLE with the 3, 5, or 10 mg/kg. It would have been obvious as a known variation or principle to administer the dose between 150 and 300 mg (about 3 mg/kg and 5 mg/kg, respectively) in light of Nair et al, and recognizing that there is some weight variation between humans. It further would have been within a known variation in the art to administer the antibody every 4 weeks or every 12 weeks as described by Heusser. One of skill in the art would have been motivated to apply a known variation on the dosing regimen to a known treatment for SLE, including in patients that have had inadequate response to standard therapies such as steroids, to maximize benefit to the treated patients. The combination of the methods would not alter the steps, treatments or functions of the NCT03656562 study or Heusser. Thus, the combination of prior art references as combined provided a prima facie case of obviousness, absent convincing evidence to the contrary.
Claims 1-4 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. US 9,751,951 B2.
Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding the limitations of instant claims 1-4, the ‘951 patent teaches a method of treating an autoimmune disease comprising administering an antibody or antigen binding fragment thereof that binds BAFFR (see e.g. claim 1). The antibodies can comprise a heavy chain variable region comprising the sequence of SEQ ID NO:1, which comprises an identical sequence to instant SEQ ID NO:1, and a light chain variable region comprising the sequence of SEQ ID NO: 2, which comprises an identical sequence to instant SEQ ID NO:2 (see e.g. claim 3). The disease treated can comprise systemic lupus erythematosus (see e.g. claim 2).
The ’951 patent anticipates the rejected claims, but differs in scope, because the instant claims are directed to treatment with the entire genus of anti-BAFFR antibodies and binding fragments thereof, or treatment with a single species from those identified in the ‘951 patent claims. Therefore the subject matter of the ‘951 patent and the instant claims overlaps but is not identical in scope.
Claims 1-7, 9, and 11-15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. US 9,751,951 B2, in view of Heusser et at (US 2012/0183529 A1; filed 12/15/11; published 7/19/12).
Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding the limitations of instant claims 1-4, the ‘951 patent teaches a method of treating an autoimmune disease comprising administering an antibody or antigen binding fragment thereof that binds BAFFR (see e.g. claim 1). The antibodies can comprise a heavy chain variable region comprising the sequence of SEQ ID NO:1, which comprises an identical sequence to instant SEQ ID NO:1, and a light chain variable region comprising the sequence of SEQ ID NO: 2, which comprises an identical sequence to instant SEQ ID NO:2 (see e.g. claim 3). The disease treated can comprise systemic lupus erythematosus (see e.g. claim 2).
Heusser et al teach a method of treating an autoimmune disease comprising administering an antibody or antigen binding fragment thereof that binds BAFFR (see e.g. claim 1). The antibodies can comprise a light chain comprising the sequence of SEQ ID NO:45, which comprises an identical sequence to instant SEQ ID NO:1, and a heavy chain comprising the sequence of SEQ ID NO: 52, which comprises an identical sequence to instant SEQ ID NO:2 (see e.g. claims 7-10). The disease treated can comprise systemic lupus erythematosus (see e.g. claim 2). The administration can comprise administration once every four weeks, once every three months, or other schedules (see e.g. paragraphs [0226]-[0227]). The dosing can comprise 3 mg/kg, 5 mg/kg, or 10 mg/kg (see e.g. paragraphs [0226]-[0227]). Heusser also teaches administering the anti-BAFFR antibody or binding fragment thereof with an additional agent such as a corticosteroid (see e.g. paragraphs [0192], [0246]) or glucocorticoid (see e.g. paragraphs [0192], [0246]).
Neither the ‘951 patent nor Heusser et al teach the specific total dosing of the instant claims of about 150 mg to about 300 mg.
Nair teaches that the average human body weight is 60 kg (see e.g. page 28, right column, “Dose Calculations and Examples, paragraph beginning with “Dose is equally related to body weight…”)
It would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to combine the teachings of the ‘951 patent, Heusser and Nair to arrive at the dosing regimens of the instant claims. The Supreme Court set forth in KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), that if the scope and content of the prior art included a similar or analogous product, with differences between the claimed invention and prior art that were encompassed in known variation or in a principle known in the art, and one of ordinary skill in the art could have combined the elements as claimed by known methods, the claimed variation would have been predictable in to one of ordinary skill in the art. The ‘951 patent and Heusser teach administering the same antibody to SLE patients to treat SLE. Heusser provides specific guidance for treating SLE with the 3, 5, or 10 mg/kg. It would have been obvious as a known variation or principle to administer the dose between 150 and 300 mg (about 3 mg/kg and 5 mg/kg, respectively) in light of Nair et al, and recognizing that there is some weight variation between humans. It further would have been within a known variation in the art to administer the antibody every 4 weeks or every 12 weeks as described by Heusser. One of skill in the art would have been motivated to apply a known variation on the dosing regimen to a known treatment for SLE to maximize benefit to the treated patients. Thus, the combination of prior art references as combined provided a prima facie case of obviousness, absent convincing evidence to the contrary.
Claim(s) 1-15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. US 9,751,951 B2, in view of Heusser et at (US 2012/0183529 A1; filed 12/15/11; published 7/19/12), and further in view of NCT03656562 (version published 8/31/18; downloaded from: https://clinicaltrials.gov/study/NCT03656562?tab=history&a=1#version-content-panel) as evidenced by Gladman et al (J Rheumatol. 2002 Feb;29(2):288-91), and further in view of Nair et al (J Basic Clin Pharm. 2016 Mar;7(2):27-31).
Regarding the limitations of instant claims 1-4, the ‘951 patent teaches a method of treating an autoimmune disease comprising administering an antibody or antigen binding fragment thereof that binds BAFFR (see e.g. claim 1). The antibodies can comprise a heavy chain variable region comprising the sequence of SEQ ID NO:1, which comprises an identical sequence to instant SEQ ID NO:1, and a light chain variable region comprising the sequence of SEQ ID NO: 2, which comprises an identical sequence to instant SEQ ID NO:2 (see e.g. claim 3). The disease treated can comprise systemic lupus erythematosus (see e.g. claim 2).
Heusser et al teach a method of treating an autoimmune disease comprising administering an antibody or antigen binding fragment thereof that binds BAFFR (see e.g. claim 1). The antibodies can comprise a light chain comprising the sequence of SEQ ID NO:45, which comprises an identical sequence to instant SEQ ID NO:1, and a heavy chain comprising the sequence of SEQ ID NO: 52, which comprises an identical sequence to instant SEQ ID NO:2 (see e.g. claims 7-10). The disease treated can comprise systemic lupus erythematosus (see e.g. claim 2). The administration can comprise administration once every four weeks, once every three months, or other schedules (see e.g. paragraphs [0226]-[0227]). The dosing can comprise 3 mg/kg, 5 mg/kg, or 10 mg/kg (see e.g. paragraphs [0226]-[0227]). Heusser also teaches administering the anti-BAFFR antibody or binding fragment thereof with an additional agent such as a corticosteroid (see e.g. paragraphs [0192], [0246]) or glucocorticoid (see e.g. paragraphs [0192], [0246]).
Neither the ‘951 patent nor Heusser et al teach the specific total dosing of the instant claims of about 150 mg to about 300 mg.
Nair teaches that the average human body weight is 60 kg (see e.g. page 28, right column, “Dose Calculations and Examples, paragraph beginning with “Dose is equally related to body weight…”)
The ‘951 patent, Heusser, and Nair do not teach response to prior treatments.
The NCT03656562 study measures the Efficacy and Safety of VAY736 and CFZ533 in SLE Patients (see entire reference). The instant specification indicates that VAY736, also called ianalumab, is a preferred anti-BAFFR antibody (see e.g. page 5 of the instant specification). Regarding the limitations of instant claims 8-10, the inclusion criteria for the NCT03656562 study indicate that subjects are “Currently receiving corticosteroids and/or anti-malarials and/or another DMARD on a stable dose according to protocol requirements” (see e.g. “Inclusion Criteria” section, and entire reference). This language indicates that patients can have received corticosteroids or DMARDs prior to treatment. Further, the cohort is required to have a SLEDAI-2K score of 6 or greater at screening (see e.g. entire reference, particularly the “Inclusion Criteria” section). As evidenced by Gladman, a SLEDAI-2K score of 4 or more indicates a flare of disease (see e.g. Gladman, page 289). The instant specification defines “inadequate” response as referring to “SLE patient still has one or more pathological symptoms of SLE” (see e.g. instant specification page 19). The SLEDAI-2K score of the NCT03656562 study indicates that prior treatments are not preventing pathological symptoms, which would meet the limitations of the instant claims’ “inadequate response.” Regarding the limitations of instant claims 11, the NCT03656562 study states “response status at Week 29 (reduced steroid dose maintained between Weeks 17 and 29)” indicating that the patients concomitantly receive steroids (see e.g. entire reference, particularly “Primary Outcome Measures.”).
It would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to combine the teachings of the ‘951 patent with the NCT03656562 study, Heusser, and Nair to arrive at the dosing regimens of the instant claims. The Supreme Court set forth in KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), that if the scope and content of the prior art included a similar or analogous product, with differences between the claimed invention and prior art that were encompassed in known variation or in a principle known in the art, and one of ordinary skill in the art could have combined the elements as claimed by known methods, the claimed variation would have been predictable in to one of ordinary skill in the art. Both the NCT03656562 study and Heusser teach administering the same antibody to SLE patients to treat SLE. Heusser provides specific guidance for treating SLE with the 3, 5, or 10 mg/kg. It would have been obvious as a known variation or principle to administer the dose between 150 and 300 mg (about 3 mg/kg and 5 mg/kg, respectively) in light of Nair et al, and recognizing that there is some weight variation between humans. It further would have been within a known variation in the art to administer the antibody every 4 weeks or every 12 weeks as described by Heusser. One of skill in the art would have been motivated to apply a known variation on the dosing regimen to a known treatment for SLE, including in patients that have had inadequate response to standard therapies such as steroids, to maximize benefit to the treated patients. The combination of the methods would not alter the steps, treatments or functions of the ‘951 method, the NCT03656562 study or Heusser. Thus, the combination of prior art references as combined provided a prima facie case of obviousness, absent convincing evidence to the contrary.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ANDREA MCCOLLUM whose telephone number is (571)272-4002. The examiner can normally be reached 9:00 AM to 6:00 PM EST.
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, VANESSA FORD can be reached at (571)272-0857. 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.
/ANDREA K MCCOLLUM/Examiner, Art Unit 1674
Prosecution Insights