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 without traverse of Group I and a composition comprising histidine, sucrose, arginine, NaCl, and polysorbate 20, in the reply filed on 8/8/25 is acknowledged.
Claim Status
Claims 1-38 are pending.
Claim 37 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claims 13-15 and 33 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 8/8/25.
Claims 1-12, 16-32, 34-36, and 38 are currently under consideration for patentability under 37 CFR 1.104.
Information Disclosure Statement
The information disclosure statements filed on 8/2/23, 3/22/24, 10/21/24, 4/17/25, and 4/24/25 have been considered. Signed copies are enclosed.
The references lined through were not considered because the references were not properly cited including date and author (if any) (see 37 CFR 1.98(b)) and/or a copy of the reference was not provided (see 37 CFR 1.98(a)).
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.
Specification
Abstract
The abstract of the disclosure is objected to because the term “IL” contains an acronym and/or abbreviation that should be spelled out upon first occurrence. Correction is required. See MPEP § 608.01(b).
Lengthy Specification
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Trademarks
The use of numerous trademarks have been noted in this application. They should be capitalized wherever they appear and be accompanied by the generic terminology.
Although the use of trademarks is permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as trademarks. It is noted that any cited occurrences of improper use are only exemplary and applicant should review the specification to correct any other use of trademarks.
Claim Objections
Claims 1 and 24 are objected to because of the following informalities: the claims contain “IL-36R” and “CEX” which contains an acronym and/or abbreviation that should be spelled out upon first occurrence. Appropriate correction is required.
Claims 1, 12, 34, and 38 are objected to because of the following informalities: the claim subparts are designated with a period. Each claim begins with a capital letter and ends with a period. Periods may not be used elsewhere in the claims except for abbreviations. See Fressola v. Manbeck, 36 USPQ2d 1211 (D.D.C. 1995). It is recommended that the claim subparts be designated with parentheses, such as “(a)” or “a)”. Appropriate correction is required.
Claims 1, 2, 12, and 38 are objected to because of the following informalities: the claim recites “wherein the anti-IL-36R antibody or antigen binding fragment thereof comprising a light chain”, which should be amended to read “wherein the anti-IL-36R antibody or antigen binding fragment thereof comprises a light chain” occurrence. Appropriate correction is required.
Claims 4, 8, and 12 are objected to because of the following informalities: the claims recite “concentration of within”, which should be amended to read “concentration [[of]] within”. Appropriate correction is required.
Claim 23 is objected to because of the following informalities: the claim recites “(i) Increased shelf life” which should not be capitalized and should contain appropriate punctuation, such as ““(i) increased shelf life,”. Appropriate correction is required.
Claim 24 is objected to because of the following informalities: the claim recites “wherein the formulation having at least” which should be amended to read “wherein the formulation has at least”. Appropriate correction is required.
Claim 31 is objected to because of the following informalities: the claim recites “comprising at least” which should be amended to read “comprising . Appropriate correction is required.
Claim 34 is objected to because of the following informalities: subpart (a) recites “SEQ ID NO:127; and” which should be amended to recite “SEQ ID NO:127; 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.
Written Description
Claims 17, 19, 23, 24, and 34 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 pharmaceutical composition comprising an anti-IL36R antibody or antigen binding fragments thereof comprising a light chain variable region of SEQ ID NO:80 and a heavy chain variable region of SEQ ID NO:89; combined with a buffer at a concentration of about 20-80mM, wherein the buffer comprises acetate, histidine, or citrate; and a tonicifying agent at a concentration of about 100-250mM comprising one or more sugar and/or polyol comprising sucrose, trehalose, sorbitol, glycerol, mannitol or dextrose, wherein the formula has a pH from about 5 to about 8. The dependent claims define various agents that can be used for the tonicifying agent and buffer, as well as salts, surfactants and providing specific concentrations of components.
The antibody of claim 34 is not adequately described. The claim names SEQ ID NO:118 and 127, but the claims are not limited to polypeptides with the entire sequence. It is possible, given the language of the claim which includes "an amino acid sequence described in SEQ ID NO:118", that any two amino acids in sequence would suffice to meet the limitations of the claims. Because function of protein is dependent on the presence of each specific amino acid residue, and with the possibility of added or deleted amino acids, a wide variety of polypeptides, is encompassed by the instant claim. In addition the phrase “an amino acid sequence” allows any fragment, including any two amino acids in sequence, to be encompassed in the instant claim. This would in theory encompass any possible protein on earth. These peptides have no correlation between their structure and function. The claim requires that the antibody possess specific binding functions, but the specification provides no guidance to which peptides encompassed by the claim are capable of the required function.
The claims that do not recite additional functions for the formulation are therefore not rejected However, claims 17, 19, 23, and 24 require specific functions of the claimed formulation, for which a corresponding structure is not adequately described. The functions include having less than 5% of the antibody present in the aggregate form, being stable upon freezing and thawing and/or having one or more of the functions of increased shelf life, better temperature stability, decreased formation of aggregates, better chemical stability, decreased viscosity, decreased percentage of aggregates or higher percentage of monomers as measured by HP-SEC, higher percentage of main peak by CEX, lower percentage of subvisible particles, and lower turbidity value in FNU, all after storage at about 40 deg C as compared to a reference formulation. The specification presents example formulations that all share common components, but do not represent the breadth of the genus of claimed formulations, for which any buffer and any other agent or component may be present. Thus, the specification fails to adequately describe a structure for the formulation genus that correlates with the required functions, and does not present representative species for the breadth of the claimed genera that would provide adequate written description to allow one of skill in the art to immediately envisage the encompassed antibodies and formulations.
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.
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.
The claimed invention as a whole may not be adequately described where an invention is described solely in terms of a method of its making coupled with its function and there is no described or art-recognized correlation or relationship between the structure of the invention and its function (see MPEP 2163). A patent specification must set forth enough detail to allow a person of ordinary skill in the art to understand what is claimed and to recognize that the inventor invented what is claimed. In the case of DNA, an adequate written description requires a precise definition, such as by structure, formula, chemical name, or physical properties, not a mere wish or plan for obtaining the claimed chemical invention (see Lilly, 119 F.3d at 1566 (quoting Fiers, 984 F.2d 15 1171 ).
The demonstration that a limited number of specific antibody formulations can achieve the required stability features of the rejected claims does not correlate to, generally, the ability of all anti-IL-36R antibody and antigen binding fragment formulations, including those of varying isotypes, to achieve the required stability parameters set forth in the instant claims just from being solubilized in any buffer, any tonicifying agent, or any other component or agent within a wide range of pH values, or in the presence of any number of other active ingredients or excipients. The functional characteristics of a particular formulation of antibodies (including stability and ability to remain stable at specific temperatures) are dictated by both the antibody that is subject of the formulation, as well as the components of the formulation itself. As taught in Walsh et al (US 2013/0186797 A1; filed 1/22/13; published 7/25/13), therapeutic antibodies in liquid solution are prone to degradation, aggregation, or undesired chemical modifications unless the solution is formulated properly. The stability of an antibody in liquid formulation depends not only on the kinds of excipients used in the formulation, but also on the amounts and proportions of the excipients relative to one another. Furthermore, other considerations aside from stability must be taken into account when preparing a liquid antibody formulation. Examples of such additional considerations include the viscosity of the solution and the concentration of antibody that can be accommodated by a given formulation, and the visual quality or appeal of the formulation. Thus, when formulating a therapeutic antibody, great care must be taken to arrive at a formulation that remains stable, contains an adequate concentration of antibody, and possesses a suitable viscosity as well as other properties which enable the formulation to be conveniently administered to patients (see paragraph [0006]).
As taught by Chang et al, proteins typically have a wide range of stability issues as a result of their complexity and delicate structural stability. See Chang et al, page 1, first paragraph (Chang, B.S. and Hershenson, S. 2002. Practical approaches to protein formulation development in "Rationale Design of stable protein formulations-theory and practice" (J.F. Carpenter and M.C. Manning eds.) Kluwer Academic/Plenum publishers, New York. pp. 1-25.) Chang also states that because proteins are complex molecules composed of numerous reactive chemical groups and delicate three-dimensional structures, identifying a set of conditions to keep all components stable is virtually impossible. See Chang, page 1, paragraph 1. The instant specification does not provide substantive evidence that the claimed formulation would comprise a stable antibody formulation for the entire genus of anti-IL-36R antibodies, or that all of the claimed excipients, buffers, and other agents would result in a formulation that meets the required functional characteristics of the claims. Without demonstration that a representative number of formulations within the broad genus of encompassed formulations that can include any one of the vast number of possible anti-IL-36R antibody/antigen binding species, the skilled artisan would not be able to reasonably predict the outcome of the claimed formulation, i.e. would not be able to accurately predict if the claimed composition would result in stable formulations for each claimed antibody species, which may have widely divergent physical and biological properties depending on the composition itself, antibody isotype, and/or antibody/antigen binding fragment amino acid sequence(s).
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 12, 21-24, 34 and 38 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.
In claims 12 and 34, there are several instances of two alternatives that are presented with the conjunction “and/or” which renders the scope indefinite. For example, “acetate and/or histidine buffer present at a concentration within the range from about 20 mM to about 80 mM” is indefinite because it is not clear if the concentrations apply to each of acetate and histidine buffers separately (i.e. for a total of about 40 mM to about 160 mM), or if the concentrations represent the total combined concentration. This is only one of several instances of this language in the two claims, and all instances should be addressed to overcome the rejection.
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, claims 21-22 recites the broad recitation “liquid”, and the claim also recites “when reconstituted with water” which is the narrower statement of the range/limitation because water is a liquid. 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.
In claim 23, the phrase “decreased viscosity, and as compared to a reference formulation” renders the claim indefinite. It is unclear whether the “and as compared to a reference formulation” is intended to be a member of the Markush grouping, or is a condition of the other group alternatives.
The term “better” in claim 23 is a relative term which renders the claim indefinite. The term “better” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
In claim 24, part (c), terms or phrases 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.
Regarding claim24, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 24 recites the limitation "the reference formulation". There is insufficient antecedent basis for this limitation in the claim.
Claim 34 recites “an amino acid sequence” in two separate instances. It is unclear if the term “an amino acid sequence refers to the entire sequence of the named SEQ ID NOs, or if “an amino acid sequence refers only to any two amino acids connected in sequence that appear within the SEQ ID NO.
Claim 38 does not recite a conjunction between parts (b) and (c). It is unclear if the listed subparts are alternatives or if they are all required in the formulation.
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 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.
Claims 1-12, 16-32, 34-36, and 38 is/are rejected under 35 U.S.C. 103 as being unpatentable over Brown et al (US 9,023,995 B2; filed 11/14/12; published 5/5/15) in view of Brige et al (US 2012/0244158 A1; filed 9/3/10; published 9/27/12).
The instant claims are directed to an antibody formulation comprising an anti-IL-36R antibody or antigen binding fragment thereof, a buffer at a concentration of 20mM to about 80mM, and a tonicifying agent at a concentration of 100-250 mM, where the composition has a pH in the range of about 5 to about 8. The formulation can be in a liquid or powder form, and the concentration can be 20, 60, or 150 mg/ml. The buffer can be an acetate buffer. The tonicifying agent can be sucrose. The formulation can comprise a stabilizer at a concentration of 0-80 mM, wherein the stabilizer can be L-arginine. It is noted that the requirement for “0 mM” of stabilizer means that the stabilizer may not be present in the formulation. Therefore the claim is interpreted to read on formulations that lack L-arginine. The formulation can have a salt of about 0-about 150 mM. As indicated for the salt, the presence of a requirement for “0 mM” salt means that the salt does not have to be present in the formulation. The formulation can comprise a surfactant such as polysorbate 20, at around 0.4 g/L. The formulation will have specific functional characteristics as outlined in the claims. The formulation can be sterile, and can be reconstituted with water. The pharmaceutical product can be in a pre-assembled injection device, or in a kit, which can be administered for intramuscular, subcutaneous, self-administration. The antibody can have the sequences as shown in in the instant claims.
Brown et al describe the anti-IL-36R antibodies of the instant claims, where the antibodies have identical SEQ ID NO: to the instant claims (see entire reference, e.g. claims 1-36). The antibody can be in a sterile formulation that are in isotonic aqueous buffer (see e.g. column 74). The formulation can be supplied as a lyophilized powder or mixed with water or saline to form a pharmaceutical formulation (see e.g. column 74). The antibody can be found in a kit with multiple containers (see e.g. column 74). The package can contain instructions (see e.g. column 22). The pharmaceutical formulation can be administered by intramuscular, intravenous, subcutaneous and other administration methods (see e.g. column 73). The administration can be in prefilled syringes (see e.g. column 73).
Brown et al do not describe the specific formulation components and concentrations of the instant claims.
Brige et al teach a formulation comprising an aqueous carrier having a pH of 5.5 to 8 and comprising one or more single variable domains at a concentration of 1 mg/ml to 200 mg/ml, with several examples showing a concentration of 10 mg/ml (see e.g. paragraph [0257]-[0281]). the formulation being formulated for human administration (see e.g. claim 1-28). The term “variable domain” can refer to part of an immunoglobulin or antibody that is responsible for antigen binding (see e.g. paragraphs [0148]-[0159]). The formulation can be liquid (see e.g. paragraph [0167]). The formulation can have components including a buffer at a concentration of 10 to 100 mM, such as an acetate buffer at pH 5.5-6.0, or a histidine buffer at pH 6.0-6.5, an excipient at 1-20% (w/v), a surfactant of 0.001%-1% that can be Tween 20, which is the trade name for polysorbate 20, and an inorganic salt concentration of 150mM or lower (see e.g. claim 1). The excipient can be arginine (see e.g. paragraph [0147]). The formulation allows for a polypeptide stability and solubility with several functional characteristics (see e.g. claim 6). The inorganic salt can be NaCl (see e.g. paragraph [0015]). The formulation can comprise an excipient that is sucrose (see e.g. claim 11-12). There can be more than one excipient and/or tonifiers, indicating that both sucrose and arginine could be present (see e.g. paragraph [0022]). The sucrose can be at a concentration of 1-10% (w:v). The osmolality can be about osmolality of about 290±60 mOsm/kg, such as about 240 or higher, 250 or higher or 260 or higher (see e.g. paragraph [0022]). The formulation can be sterile (see e.g. paragraph [0475]). The liquid carrier can be water (see e.g. paragraph [0018]). The formulation can be formatted for intramuscular or subcutaneous administration (see e.g. paragraph [0081]). Since the molecular weight of sucrose is 342.3 g/mol, this would be a concentration of 30-300 mM. The composition can be in a container, pharmaceutical unit dosage form, kit or other administration forms (see e.g. claims 21-28).
It would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to use the formulation of Brige to provide known stabilized effects for the antibodies of Brown. As indicated by Brige, the formulations provide good stability under different storage, transportation and stress conditions (see e.g. abstract). Brige teaches that proteins such as therapeutic antibodies are often transported and stored, and it is therefore important that such proteins are preserved in terms of stability and biological activities under the various conditions such as different temperature and mechanical stress conditions (see paragraph [0005]). This stability prevents degradation due to short shelf life, and loss of biological activity resulting from chemical and/or physical stability (see e.g. paragraph [0006]). The advantage of increased stability provides the motivation to make the aforementioned modification of the antibody of Brown et al, based on the teachings of Brige et al, with a reasonable expectation of success.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that if a technique has been used to improve one method, and a person of ordinary skill would recognize that it would be used in similar methods in the same way, using the technique is obvious unless its application is beyond that person’s skill. It would be obvious to apply a known technique to a known product to be used in a known method that is ready for improvement to yield predictable results. Thus, the combination of prior art references as combined provided a prima facie case of obviousness, absent convincing evidence to the contrary.
Regarding the concentrations of the formulation components, one of ordinary skilled in the art would have been motivated to optimize the concentrations of various buffers, excipients and other components in the composition, since “it is the normal desire of scientists or artisans to improve upon what is already generally known”. The MPEP states the following: Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller. 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson. 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc, v. Biocraft Laboratories Inc.. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert, denied, 493 U.S. 975 (1989); In re Kulling. 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler. 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997).
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
1. Claims 1-12, 16-32, 34-36, and 38 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of copending Application No. 18/815,907 (reference application) in view of Brige et al (US 2012/0244158 A1; filed 9/3/10; published 9/27/12). Although the claims at issue are not identical, they are not patentably distinct from each other.
The instant claims are directed to an antibody formulation comprising an anti-IL-36R antibody or antigen binding fragment thereof, a buffer at a concentration of 20mM to about 80mM, and a tonicifying agent at a concentration of 100-250 mM, where the composition has a pH in the range of about 5 to about 8. The formulation can be in a liquid or powder form, and the concentration can be 20, 60, or 150 mg/ml. The buffer can be an acetate buffer. The tonicifying agent can be sucrose. The formulation can comprise a stabilizer at a concentration of 0-80 mM, wherein the stabilizer can be L-arginine. It is noted that the requirement for “0 mM” of stabilizer means that the stabilizer may not be present in the formulation. Therefore the claim is interpreted to read on formulations that lack L-arginine. The formulation can have a salt of about 0-about 150 mM. As indicated for the salt, the presence of a requirement for “0 mM” salt means that the salt does not have to be present in the formulation. The formulation can comprise a surfactant such as polysorbate 20, at around 0.4 g/L. The formulation will have specific functional characteristics as outlined in the claims. The formulation can be sterile, and can be reconstituted with water. The pharmaceutical product can be in a pre-assembled injection device, or in a kit, which can be administered for intramuscular, subcutaneous, self-administration. The antibody can have the sequences as shown in in the instant claims.
The copending claims are directed to the anti-IL-36R antibodies of the instant claims, where the antibodies have identical SEQ ID NO: to the instant claims (see entire reference, e.g. claims 1-18).
The copending claims do not describe the specific formulation components and concentrations of the instant claims.
Brige et al teach a formulation comprising an aqueous carrier having a pH of 5.5 to 8 and comprising one or more single variable domains at a concentration of 1 mg/ml to 200 mg/ml, with several examples showing a concentration of 10 mg/ml (see e.g. paragraph [0257]-[0281]). the formulation being formulated for human administration (see e.g. claim 1-28). The term “variable domain” can refer to part of an immunoglobulin or antibody that is responsible for antigen binding (see e.g. paragraphs [0148]-[0159]). The formulation can be liquid (see e.g. paragraph [0167]). The formulation can have components including a buffer at a concentration of 10 to 100 mM, such as an acetate buffer at pH 5.5-6.0, or a histidine buffer at pH 6.0-6.5, an excipient at 1-20% (w/v), a surfactant of 0.001%-1% that can be Tween 20, which is the trade name for polysorbate 20, and an inorganic salt concentration of 150mM or lower (see e.g. claim 1). The excipient can be arginine (see e.g. paragraph [0147]). The formulation allows for a polypeptide stability and solubility with several functional characteristics (see e.g. claim 6). The inorganic salt can be NaCl (see e.g. paragraph [0015]). The formulation can comprise an excipient that is sucrose (see e.g. claim 11-12). There can be more than one excipient and/or tonifiers, indicating that both sucrose and arginine could be present (see e.g. paragraph [0022]). The sucrose can be at a concentration of 1-10% (w:v). The osmolality can be about osmolality of about 290±60 mOsm/kg, such as about 240 or higher, 250 or higher or 260 or higher (see e.g. paragraph [0022]). The formulation can be sterile (see e.g. paragraph [0475]). The liquid carrier can be water (see e.g. paragraph [0018]). The formulation can be formatted for intramuscular or subcutaneous administration (see e.g. paragraph [0081]). Since the molecular weight of sucrose is 342.3 g/mol, this would be a concentration of 30-300 mM. The composition can be in a container, pharmaceutical unit dosage form, kit or other administration forms (see e.g. claims 21-28).
It would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to use the formulation of Brige to provide known stabilized effects for the antibodies of the copending claims. As indicated by Brige, the formulations provide good stability under different storage, transportation and stress conditions (see e.g. abstract). Brige teaches that proteins such as therapeutic antibodies are often transported and stored, and it is therefore important that such proteins are preserved in terms of stability and biological activities under the various conditions such as different temperature and mechanical stress conditions (see paragraph [0005]). This stability prevents degradation due to short shelf life, and loss of biological activity resulting from chemical and/or physical stability (see e.g. paragraph [0006]). The advantage of increased stability provides the motivation to make the aforementioned modification of the antibody of the copending claims, based on the teachings of Brige et al, with a reasonable expectation of success.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that if a technique has been used to improve one method, and a person of ordinary skill would recognize that it would be used in similar methods in the same way, using the technique is obvious unless its application is beyond that person’s skill. It would be obvious to apply a known technique to a known product to be used in a known method that is ready for improvement to yield predictable results. Thus, the combination of prior art references as combined provided a prima facie case of obviousness, absent convincing evidence to the contrary.
Regarding the concentrations of the formulation components, one of ordinary skilled in the art would have been motivated to optimize the concentrations of various buffers, excipients and other components in the composition, since “it is the normal desire of scientists or artisans to improve upon what is already generally known”. The MPEP states the following: Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller. 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson. 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc, v. Biocraft Laboratories Inc.. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert, denied, 493 U.S. 975 (1989); In re Kulling. 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler. 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
2. Claims 1-12, 16-32, 34-36, and 38 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 3-4, 6-7, and 37-41 of copending Application No. 17/101,126 (reference application) in view of Brige et al (US 2012/0244158 A1; filed 9/3/10; published 9/27/12). Although the claims at issue are not identical, they are not patentably distinct from each other.
The instant claims are directed to an antibody formulation comprising an anti-IL-36R antibody or antigen binding fragment thereof, a buffer at a concentration of 20mM to about 80mM, and a tonicifying agent at a concentration of 100-250 mM, where the composition has a pH in the range of about 5 to about 8. The formulation can be in a liquid or powder form, and the concentration can be 20, 60, or 150 mg/ml. The buffer can be an acetate buffer. The tonicifying agent can be sucrose. The formulation can comprise a stabilizer at a concentration of 0-80 mM, wherein the stabilizer can be L-arginine. It is noted that the requirement for “0 mM” of stabilizer means that the stabilizer may not be present in the formulation. Therefore the claim is interpreted to read on formulations that lack L-arginine. The formulation can have a salt of about 0-about 150 mM. As indicated for the salt, the presence of a requirement for “0 mM” salt means that the salt does not have to be present in the formulation. The formulation can comprise a surfactant such as polysorbate 20, at around 0.4 g/L. The formulation will have specific functional characteristics as outlined in the claims. The formulation can be sterile, and can be reconstituted with water. The pharmaceutical product can be in a pre-assembled injection device, or in a kit, which can be administered for intramuscular, subcutaneous, self-administration. The antibody can have the sequences as shown in in the instant claims.
The copending claims are directed to a method for treatment of a patient with generalized pustular psoriasis, which is an inflammatory disease and type of psoriasis, comprising administering an anti-IL-36R antibody (see e.g. claims 3-4, 6-7, and 37-41). The IL-36R antibodies are identical in sequence to the instant antibodies, and each SEQ ID NO corresponds to the same SEQ ID NO: as the antibodies in the instant specification.
The copending claims do not describe the specific formulation components and concentrations of the instant claims.
Brige et al teach a formulation comprising an aqueous carrier having a pH of 5.5 to 8 and comprising one or more single variable domains at a concentration of 1 mg/ml to 200 mg/ml, with several examples showing a concentration of 10 mg/ml (see e.g. paragraph [0257]-[0281]). the formulation being formulated for human administration (see e.g. claim 1-28). The term “variable domain” can refer to part of an immunoglobulin or antibody that is responsible for antigen binding (see e.g. paragraphs [0148]-[0159]). The formulation can be liquid (see e.g. paragraph [0167]). The formulation can have components including a buffer at a concentration of 10 to 100 mM, such as an acetate buffer at pH 5.5-6.0, or a histidine buffer at pH 6.0-6.5, an excipient at 1-20% (w/v), a surfactant of 0.001%-1% that can be Tween 20, which is the trade name for polysorbate 20, and an inorganic salt concentration of 150mM or lower (see e.g. claim 1). The excipient can be arginine (see e.g. paragraph [0147]). The formulation allows for a polypeptide stability and solubility with several functional characteristics (see e.g. claim 6). The inorganic salt can be NaCl (see e.g. paragraph [0015]). The formulation can comprise an excipient that is sucrose (see e.g. claim 11-12). There can be more than one excipient and/or tonifiers, indicating that both sucrose and arginine could be present (see e.g. paragraph [0022]). The sucrose can be at a concentration of 1-10% (w:v). The osmolality can be about osmolality of about 290±60 mOsm/kg, such as about 240 or higher, 250 or higher or 260 or higher (see e.g. paragraph [0022]). The formulation can be sterile (see e.g. paragraph [0475]). The liquid carrier can be water (see e.g. paragraph [0018]). The formulation can be formatted for intramuscular or subcutaneous administration (see e.g. paragraph [0081]). Since the molecular weight of sucrose is 342.3 g/mol, this would be a concentration of 30-300 mM. The composition can be in a container, pharmaceutical unit dosage form, kit or other administration forms (see e.g. claims 21-28).
It would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to use the formulation of Brige to provide known stabilized effects for the antibodies of the copending claims. As indicated by Brige, the formulations provide good stability under different storage, transportation and stress conditions (see e.g. abstract). Brige teaches that proteins such as therapeutic antibodies are often transported and stored, and it is therefore important that such proteins are preserved in terms of stability and biological activities under the various conditions such as different temperature and mechanical stress conditions (see paragraph [0005]). This stability prevents degradation due to short shelf life, and loss of biological activity resulting from chemical and/or physical stability (see e.g. paragraph [0006]). The advantage of increased stability provides the motivation to make the aforementioned modification of the antibody of the copending claims, based on the teachings of Brige et al, with a reasonable expectation of success.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that if a technique has been used to improve one method, and a person of ordinary skill would recognize that it would be used in similar methods in the same way, using the technique is obvious unless its application is beyond that person’s skill. It would be obvious to apply a known technique to a known product to be used in a known method that is ready for improvement to yield predictable results. Thus, the combination of prior art references as combined provided a prima facie case of obviousness, absent convincing evidence to the contrary.
Regarding the concentrations of the formulation components, one of ordinary skilled in the art would have been motivated to optimize the concentrations of various buffers, excipients and other components in the composition, since “it is the normal desire of scientists or artisans to improve upon what is already generally known”. The MPEP states the following: Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller. 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson. 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc, v. Biocraft Laboratories Inc.. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert, denied, 493 U.S. 975 (1989); In re Kulling. 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler. 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997).
The Federal Circuit held in Sun Pharmaceutical Industries v. Eli Lilly and Co., 611 F.3d 1381, 1389 (2010) that claims of a later patent can be held invalid for obviousness-type double patenting where an earlier patent claimed a compound, disclosing its utility in the specification, and a later patent claimed a method of using the compound for a use described in the specification of the earlier patent. See Pfizer, 518 F.3d at 1363; Geneva, 349 F.3d at 1385-86. In this case, U.S. 4,808,614 (‘614) patent claimed gemcitabine and methods of using gemcitabine for treating viral infections. The patent also disclosed (but did not claim) using these compounds to fight cancer. U.S. 5,464,826 (‘826) patent claimed methods of using gemcitabine for treating cancer. The Federal Circuit found that “The asserted claims of the later '826 patent simply claim the anticancer use disclosed in the specification of the '614 patent as a method of use claim. See Pfizer, 518 F.3d at 1363; Geneva, 349 F.3d at 1385. Therefore, we affirm the district court's judgment that the asserted claims, claims 2, 6, and 7, of the '826 patent are invalid for obviousness-type double patenting over the '614 patent.” Sun Pharmaceutical Industries v. Eli Lilly and Co., 611 F.3d 1381, 1389 (2010). This is similar to the instant application as compared to the copending application. The copending application claims the use of the product of the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
3. Claims 1-12, 16-32, 34-36, and 38 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-36 of U.S. Patent No. 9,023,995 (referred to as “Brown;” filed 11/14/12; published 5/5/15) in view of Brige et al (US 2012/0244158 A1; filed 9/3/10; published 9/27/12). Although the claims at issue are not identical, they are not patentably distinct from each other.
The instant claims are directed to an antibody formulation comprising an anti-IL-36R antibody or antigen binding fragment thereof, a buffer at a concentration of 20mM to about 80mM, and a tonicifying agent at a concentration of 100-250 mM, where the composition has a pH in the range of about 5 to about 8. The formulation can be in a liquid or powder form, and the concentration can be 20, 60, or 150 mg/ml. The buffer can be an acetate buffer. The tonicifying agent can be sucrose. The formulation can comprise a stabilizer at a concentration of 0-80 mM, wherein the stabilizer can be L-arginine. It is noted that the requirement for “0 mM” of stabilizer means that the stabilizer may not be present in the formulation. Therefore the claim is interpreted to read on formulations that lack L-arginine. The formulation can have a salt of about 0-about 150 mM. As indicated for the salt, the presence of a requirement for “0 mM” salt means that the salt does not have to be present in the formulation. The formulation can comprise a surfactant such as polysorbate 20, at around 0.4 g/L. The formulation will have specific functional characteristics as outlined in the claims. The formulation can be sterile, and can be reconstituted with water. The pharmaceutical product can be in a pre-assembled injection device, or in a kit, which can be administered for intramuscular, subcutaneous, self-administration. The antibody can have the sequences as shown in in the instant claims.
Brown et al describe the anti-IL-36R antibodies of the instant claims, where the antibodies have identical SEQ ID NO: to the instant claims (see entire reference, e.g. claims 1-36). The antibody can be in a sterile formulation that are in isotonic aqueous buffer (see e.g. column 74). The formulation can be supplied as a lyophilized powder or mixed with water or saline to form a pharmaceutical formulation (see e.g. column 74). The antibody can be found in a kit with multiple containers (see e.g. column 74). The package can contain instructions (see e.g. column 22). The pharmaceutical formulation can be administered by intramuscular, intravenous, subcutaneous and other administration methods (see e.g. column 73). The administration can be in prefilled syringes (see e.g. column 73).
Brown et al do not describe the specific formulation components and concentrations of the instant claims.
Brige et al teach a formulation comprising an aqueous carrier having a pH of 5.5 to 8 and comprising one or more single variable domains at a concentration of 1 mg/ml to 200 mg/ml, with several examples showing a concentration of 10 mg/ml (see e.g. paragraph [0257]-[0281]). the formulation being formulated for human administration (see e.g. claim 1-28). The term “variable domain” can refer to part of an immunoglobulin or antibody that is responsible for antigen binding (see e.g. paragraphs [0148]-[0159]). The formulation can be liquid (see e.g. paragraph [0167]). The formulation can have components including a buffer at a concentration of 10 to 100 mM, such as an acetate buffer at pH 5.5-6.0, or a histidine buffer at pH 6.0-6.5, an excipient at 1-20% (w/v), a surfactant of 0.001%-1% that can be Tween 20, which is the trade name for polysorbate 20, and an inorganic salt concentration of 150mM or lower (see e.g. claim 1). The excipient can be arginine (see e.g. paragraph [0147]). The formulation allows for a polypeptide stability and solubility with several functional characteristics (see e.g. claim 6). The inorganic salt can be NaCl (see e.g. paragraph [0015]). The formulation can comprise an excipient that is sucrose (see e.g. claim 11-12). There can be more than one excipient and/or tonifiers, indicating that both sucrose and arginine could be present (see e.g. paragraph [0022]). The sucrose can be at a concentration of 1-10% (w:v). The osmolality can be about osmolality of about 290±60 mOsm/kg, such as about 240 or higher, 250 or higher or 260 or higher (see e.g. paragraph [0022]). The formulation can be sterile (see e.g. paragraph [0475]). The liquid carrier can be water (see e.g. paragraph [0018]). The formulation can be formatted for intramuscular or subcutaneous administration (see e.g. paragraph [0081]). Since the molecular weight of sucrose is 342.3 g/mol, this would be a concentration of 30-300 mM. The composition can be in a container, pharmaceutical unit dosage form, kit or other administration forms (see e.g. claims 21-28).
It would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to use the formulation of Brige to provide known stabilized effects for the antibodies of Brown. As indicated by Brige, the formulations provide good stability under different storage, transportation and stress conditions (see e.g. abstract). Brige teaches that proteins such as therapeutic antibodies are often transported and stored, and it is therefore important that such proteins are preserved in terms of stability and biological activities under the various conditions such as different temperature and mechanical stress conditions (see paragraph [0005]). This stability prevents degradation due to short shelf life, and loss of biological activity resulting from chemical and/or physical stability (see e.g. paragraph [0006]). The advantage of increased stability provides the motivation to make the aforementioned modification of the antibody of Brown et al, based on the teachings of Brige et al, with a reasonable expectation of success.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that if a technique has been used to improve one method, and a person of ordinary skill would recognize that it would be used in similar methods in the same way, using the technique is obvious unless its application is beyond that person’s skill. It would be obvious to apply a known technique to a known product to be used in a known method that is ready for improvement to yield predictable results. Thus, the combination of prior art references as combined provided a prima facie case of obviousness, absent convincing evidence to the contrary.
Regarding the concentrations of the formulation components, one of ordinary skilled in the art would have been motivated to optimize the concentrations of various buffers, excipients and other components in the composition, since “it is the normal desire of scientists or artisans to improve upon what is already generally known”. The MPEP states the following: Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller. 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson. 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc, v. Biocraft Laboratories Inc.. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert, denied, 493 U.S. 975 (1989); In re Kulling. 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler. 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997).
4. Claims 1-12, 16-32, 35-36, and 38 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-40 of U.S. Patent No. 11,730,812. Although the claims at issue are not identical, they are not patentably distinct from each other.
The instant claims are directed to an antibody formulation comprising an anti-IL-36R antibody or antigen binding fragment thereof, a buffer at a concentration of 20mM to about 80mM, and a tonicifying agent at a concentration of 100-250 mM, where the composition has a pH in the range of about 5 to about 8. The formulation can be in a liquid or powder form, and the concentration can be 20, 60, or 150 mg/ml. The buffer can be an acetate buffer. The tonicifying agent can be sucrose. The formulation can comprise a stabilizer at a concentration of 0-80 mM, wherein the stabilizer can be L-arginine. It is noted that the requirement for “0 mM” of stabilizer means that the stabilizer may not be present in the formulation. Therefore the claim is interpreted to read on formulations that lack L-arginine. The formulation can have a salt of about 0-about 150 mM. As indicated for the salt, the presence of a requirement for “0 mM” salt means that the salt does not have to be present in the formulation. The formulation can comprise a surfactant such as polysorbate 20, at around 0.4 g/L. The formulation will have specific functional characteristics as outlined in the claims. The formulation can be sterile, and can be reconstituted with water. The pharmaceutical product can be in a pre-assembled injection device, or in a kit, which can be administered for intramuscular, subcutaneous, self-administration. The antibody can have the sequences as shown in in the instant claims.
The reference claims are directed to an antibody formulation comprising an anti-IL-36R antibody or antigen binding fragment thereof at a concentration of 10-200 mg/ml, an acetate buffer at a concentration of about 45 mM, sucrose at 150 mM, L-arginine at 25 mM, polysorbate 20 at 0.4 g/L, wherein the formulation in liquid form or when reconstituted in water is characterized by a pH of 5-6, and wherein the antibody has the sequence of SEQ ID NO:80 and 89, which are identical in sequence to instant SEQ ID NO:80 and 89 (see e.g. claim 1). The formulation can be in a liquid or powder form, and the concentration can be 20, 60, or 150 mg/ml (see e.g. claim 2). The formulation can comprise a surfactant such as polysorbate 20, at around 0.4 g/L (see e.g. claim 26). The formulation will have specific functional characteristics as outlined in the instant claims (see e.g. reference claims 11-14, 19-22, 34-37). The formulation can be sterile, and can be reconstituted with water (see e.g. claim 12, 14, 36 and 38). The pharmaceutical product can be in a pre-assembled injection device, or in a kit, which can be administered for intramuscular, subcutaneous, self-administration (see e.g. claims 10, 15-16, 19, 24-25, 34, and 39-40). The antibody can have the sequences as shown in in the instant claims, and the SEQ ID NO of the reference patent are identical to the SEQ ID NO: of the instant claims (see e.g. claim 1).
The reference claims anticipate the instant claims, but differ in scope because the reference claims are directed to a species of the instant claims that recite a specific group of components with specific concentrations that are encompassed within the instant claims. Therefore, the scope of the two claim sets is overlapping, but not identical.
5. Claims 1-12, 16-32, 34-36, and 38 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 3-9 of copending Application No. 17/376,233 (reference application) in view of Brige et al (US 2012/0244158 A1; filed 9/3/10; published 9/27/12). Although the claims at issue are not identical, they are not patentably distinct from each other.
The instant claims are directed to an antibody formulation comprising an anti-IL-36R antibody or antigen binding fragment thereof, a buffer at a concentration of 20mM to about 80mM, and a tonicifying agent at a concentration of 100-250 mM, where the composition has a pH in the range of about 5 to about 8. The formulation can be in a liquid or powder form, and the concentration can be 20, 60, or 150 mg/ml. The buffer can be an acetate buffer. The tonicifying agent can be sucrose. The formulation can comprise a stabilizer at a concentration of 0-80 mM, wherein the stabilizer can be L-arginine. It is noted that the requirement for “0 mM” of stabilizer means that the stabilizer may not be present in the formulation. Therefore the claim is interpreted to read on formulations that lack L-arginine. The formulation can have a salt of about 0-about 150 mM. As indicated for the salt, the presence of a requirement for “0 mM” salt means that the salt does not have to be present in the formulation. The formulation can comprise a surfactant such as polysorbate 20, at around 0.4 g/L. The formulation will have specific functional characteristics as outlined in the claims. The formulation can be sterile, and can be reconstituted with water. The pharmaceutical product can be in a pre-assembled injection device, or in a kit, which can be administered for intramuscular, subcutaneous, self-administration. The antibody can have the sequences as shown in in the instant claims.
The copending claims are directed to a method for treatment of a patient with pyoderma gangrenosum, comprising administering an anti-IL-36R antibody (see e.g. claims 1 and 3-9). The IL-36R antibodies are identical in sequence to the instant antibodies, and each SEQ ID NO corresponds to the same SEQ ID NO: as the antibodies in the instant specification.
The copending claims do not describe the specific formulation components and concentrations of the instant claims.
Brige et al teach a formulation comprising an aqueous carrier having a pH of 5.5 to 8 and comprising one or more single variable domains at a concentration of 1 mg/ml to 200 mg/ml, with several examples showing a concentration of 10 mg/ml (see e.g. paragraph [0257]-[0281]). the formulation being formulated for human administration (see e.g. claim 1-28). The term “variable domain” can refer to part of an immunoglobulin or antibody that is responsible for antigen binding (see e.g. paragraphs [0148]-[0159]). The formulation can be liquid (see e.g. paragraph [0167]). The formulation can have components including a buffer at a concentration of 10 to 100 mM, such as an acetate buffer at pH 5.5-6.0, or a histidine buffer at pH 6.0-6.5, an excipient at 1-20% (w/v), a surfactant of 0.001%-1% that can be Tween 20, which is the trade name for polysorbate 20, and an inorganic salt concentration of 150mM or lower (see e.g. claim 1). The excipient can be arginine (see e.g. paragraph [0147]). The formulation allows for a polypeptide stability and solubility with several functional characteristics (see e.g. claim 6). The inorganic salt can be NaCl (see e.g. paragraph [0015]). The formulation can comprise an excipient that is sucrose (see e.g. claim 11-12). There can be more than one excipient and/or tonifiers, indicating that both sucrose and arginine could be present (see e.g. paragraph [0022]). The sucrose can be at a concentration of 1-10% (w:v). The osmolality can be about osmolality of about 290±60 mOsm/kg, such as about 240 or higher, 250 or higher or 260 or higher (see e.g. paragraph [0022]). The formulation can be sterile (see e.g. paragraph [0475]). The liquid carrier can be water (see e.g. paragraph [0018]). The formulation can be formatted for intramuscular or subcutaneous administration (see e.g. paragraph [0081]). Since the molecular weight of sucrose is 342.3 g/mol, this would be a concentration of 30-300 mM. The composition can be in a container, pharmaceutical unit dosage form, kit or other administration forms (see e.g. claims 21-28).
It would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to use the formulation of Brige to provide known stabilized effects for the antibodies of the copending claims. As indicated by Brige, the formulations provide good stability under different storage, transportation and stress conditions (see e.g. abstract). Brige teaches that proteins such as therapeutic antibodies are often transported and stored, and it is therefore important that such proteins are preserved in terms of stability and biological activities under the various conditions such as different temperature and mechanical stress conditions (see paragraph [0005]). This stability prevents degradation due to short shelf life, and loss of biological activity resulting from chemical and/or physical stability (see e.g. paragraph [0006]). The advantage of increased stability provides the motivation to make the aforementioned modification of the antibody of the copending claims, based on the teachings of Brige et al, with a reasonable expectation of success.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that if a technique has been used to improve one method, and a person of ordinary skill would recognize that it would be used in similar methods in the same way, using the technique is obvious unless its application is beyond that person’s skill. It would be obvious to apply a known technique to a known product to be used in a known method that is ready for improvement to yield predictable results. Thus, the combination of prior art references as combined provided a prima facie case of obviousness, absent convincing evidence to the contrary.
Regarding the concentrations of the formulation components, one of ordinary skilled in the art would have been motivated to optimize the concentrations of various buffers, excipients and other components in the composition, since “it is the normal desire of scientists or artisans to improve upon what is already generally known”. The MPEP states the following: Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller. 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson. 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc, v. Biocraft Laboratories Inc.. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert, denied, 493 U.S. 975 (1989); In re Kulling. 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler. 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997).
The Federal Circuit held in Sun Pharmaceutical Industries v. Eli Lilly and Co., 611 F.3d 1381, 1389 (2010) that claims of a later patent can be held invalid for obviousness-type double patenting where an earlier patent claimed a compound, disclosing its utility in the specification, and a later patent claimed a method of using the compound for a use described in the specification of the earlier patent. See Pfizer, 518 F.3d at 1363; Geneva, 349 F.3d at 1385-86. In this case, U.S. 4,808,614 (‘614) patent claimed gemcitabine and methods of using gemcitabine for treating viral infections. The patent also disclosed (but did not claim) using these compounds to fight cancer. U.S. 5,464,826 (‘826) patent claimed methods of using gemcitabine for treating cancer. The Federal Circuit found that “The asserted claims of the later '826 patent simply claim the anticancer use disclosed in the specification of the '614 patent as a method of use claim. See Pfizer, 518 F.3d at 1363; Geneva, 349 F.3d at 1385. Therefore, we affirm the district court's judgment that the asserted claims, claims 2, 6, and 7, of the '826 patent are invalid for obviousness-type double patenting over the '614 patent.” Sun Pharmaceutical Industries v. Eli Lilly and Co., 611 F.3d 1381, 1389 (2010). This is similar to the instant application as compared to the copending application. The copending application claims the use of the product of the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
6. Claims 1-12, 16-32, 34-36, and 38 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of copending Application No. 17/819,327(reference application) in view of Brige et al (US 2012/0244158 A1; filed 9/3/10; published 9/27/12). Although the claims at issue are not identical, they are not patentably distinct from each other.
The instant claims are directed to an antibody formulation comprising an anti-IL-36R antibody or antigen binding fragment thereof, a buffer at a concentration of 20mM to about 80mM, and a tonicifying agent at a concentration of 100-250 mM, where the composition has a pH in the range of about 5 to about 8. The formulation can be in a liquid or powder form, and the concentration can be 20, 60, or 150 mg/ml. The buffer can be an acetate buffer. The tonicifying agent can be sucrose. The formulation can comprise a stabilizer at a concentration of 0-80 mM, wherein the stabilizer can be L-arginine. It is noted that the requirement for “0 mM” of stabilizer means that the stabilizer may not be present in the formulation. Therefore the claim is interpreted to read on formulations that lack L-arginine. The formulation can have a salt of about 0-about 150 mM. As indicated for the salt, the presence of a requirement for “0 mM” salt means that the salt does not have to be present in the formulation. The formulation can comprise a surfactant such as polysorbate 20, at around 0.4 g/L. The formulation will have specific functional characteristics as outlined in the claims. The formulation can be sterile, and can be reconstituted with water. The pharmaceutical product can be in a pre-assembled injection device, or in a kit, which can be administered for intramuscular, subcutaneous, self-administration. The antibody can have the sequences as shown in in the instant claims.
The copending claims are directed to a method for treatment of a patient with a fibrotic condition, comprising administering an anti-IL-36R antibody (see e.g. claims 1-18). The IL-36R antibodies are identical in sequence to the instant antibodies, and each SEQ ID NO corresponds to the same SEQ ID NO: as the antibodies in the instant specification.
The copending claims do not describe the specific formulation components and concentrations of the instant claims.
Brige et al teach a formulation comprising an aqueous carrier having a pH of 5.5 to 8 and comprising one or more single variable domains at a concentration of 1 mg/ml to 200 mg/ml, with several examples showing a concentration of 10 mg/ml (see e.g. paragraph [0257]-[0281]). the formulation being formulated for human administration (see e.g. claim 1-28). The term “variable domain” can refer to part of an immunoglobulin or antibody that is responsible for antigen binding (see e.g. paragraphs [0148]-[0159]). The formulation can be liquid (see e.g. paragraph [0167]). The formulation can have components including a buffer at a concentration of 10 to 100 mM, such as an acetate buffer at pH 5.5-6.0, or a histidine buffer at pH 6.0-6.5, an excipient at 1-20% (w/v), a surfactant of 0.001%-1% that can be Tween 20, which is the trade name for polysorbate 20, and an inorganic salt concentration of 150mM or lower (see e.g. claim 1). The excipient can be arginine (see e.g. paragraph [0147]). The formulation allows for a polypeptide stability and solubility with several functional characteristics (see e.g. claim 6). The inorganic salt can be NaCl (see e.g. paragraph [0015]). The formulation can comprise an excipient that is sucrose (see e.g. claim 11-12). There can be more than one excipient and/or tonifiers, indicating that both sucrose and arginine could be present (see e.g. paragraph [0022]). The sucrose can be at a concentration of 1-10% (w:v). The osmolality can be about osmolality of about 290±60 mOsm/kg, such as about 240 or higher, 250 or higher or 260 or higher (see e.g. paragraph [0022]). The formulation can be sterile (see e.g. paragraph [0475]). The liquid carrier can be water (see e.g. paragraph [0018]). The formulation can be formatted for intramuscular or subcutaneous administration (see e.g. paragraph [0081]). Since the molecular weight of sucrose is 342.3 g/mol, this would be a concentration of 30-300 mM. The composition can be in a container, pharmaceutical unit dosage form, kit or other administration forms (see e.g. claims 21-28).
It would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to use the formulation of Brige to provide known stabilized effects for the antibodies of the copending claims. As indicated by Brige, the formulations provide good stability under different storage, transportation and stress conditions (see e.g. abstract). Brige teaches that proteins such as therapeutic antibodies are often transported and stored, and it is therefore important that such proteins are preserved in terms of stability and biological activities under the various conditions such as different temperature and mechanical stress conditions (see paragraph [0005]). This stability prevents degradation due to short shelf life, and loss of biological activity resulting from chemical and/or physical stability (see e.g. paragraph [0006]). The advantage of increased stability provides the motivation to make the aforementioned modification of the antibody of the copending claims, based on the teachings of Brige et al, with a reasonable expectation of success.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that if a technique has been used to improve one method, and a person of ordinary skill would recognize that it would be used in similar methods in the same way, using the technique is obvious unless its application is beyond that person’s skill. It would be obvious to apply a known technique to a known product to be used in a known method that is ready for improvement to yield predictable results. Thus, the combination of prior art references as combined provided a prima facie case of obviousness, absent convincing evidence to the contrary.
Regarding the concentrations of the formulation components, one of ordinary skilled in the art would have been motivated to optimize the concentrations of various buffers, excipients and other components in the composition, since “it is the normal desire of scientists or artisans to improve upon what is already generally known”. The MPEP states the following: Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller. 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson. 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc, v. Biocraft Laboratories Inc.. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert, denied, 493 U.S. 975 (1989); In re Kulling. 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler. 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997).
The Federal Circuit held in Sun Pharmaceutical Industries v. Eli Lilly and Co., 611 F.3d 1381, 1389 (2010) that claims of a later patent can be held invalid for obviousness-type double patenting where an earlier patent claimed a compound, disclosing its utility in the specification, and a later patent claimed a method of using the compound for a use described in the specification of the earlier patent. See Pfizer, 518 F.3d at 1363; Geneva, 349 F.3d at 1385-86. In this case, U.S. 4,808,614 (‘614) patent claimed gemcitabine and methods of using gemcitabine for treating viral infections. The patent also disclosed (but did not claim) using these compounds to fight cancer. U.S. 5,464,826 (‘826) patent claimed methods of using gemcitabine for treating cancer. The Federal Circuit found that “The asserted claims of the later '826 patent simply claim the anticancer use disclosed in the specification of the '614 patent as a method of use claim. See Pfizer, 518 F.3d at 1363; Geneva, 349 F.3d at 1385. Therefore, we affirm the district court's judgment that the asserted claims, claims 2, 6, and 7, of the '826 patent are invalid for obviousness-type double patenting over the '614 patent.” Sun Pharmaceutical Industries v. Eli Lilly and Co., 611 F.3d 1381, 1389 (2010). This is similar to the instant application as compared to the copending application. The copending application claims the use of the product of the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
7. Claims 1-12, 16-32, 34-36, and 38 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8, 15, 19-38 of copending Application No. 18/363,875 (reference application) in view of Brige et al (US 2012/0244158 A1; filed 9/3/10; published 9/27/12). Although the claims at issue are not identical, they are not patentably distinct from each other.
The instant claims are directed to an antibody formulation comprising an anti-IL-36R antibody or antigen binding fragment thereof, a buffer at a concentration of 20mM to about 80mM, and a tonicifying agent at a concentration of 100-250 mM, where the composition has a pH in the range of about 5 to about 8. The formulation can be in a liquid or powder form, and the concentration can be 20, 60, or 150 mg/ml. The buffer can be an acetate buffer. The tonicifying agent can be sucrose. The formulation can comprise a stabilizer at a concentration of 0-80 mM, wherein the stabilizer can be L-arginine. It is noted that the requirement for “0 mM” of stabilizer means that the stabilizer may not be present in the formulation. Therefore the claim is interpreted to read on formulations that lack L-arginine. The formulation can have a salt of about 0-about 150 mM. As indicated for the salt, the presence of a requirement for “0 mM” salt means that the salt does not have to be present in the formulation. The formulation can comprise a surfactant such as polysorbate 20, at around 0.4 g/L. The formulation will have specific functional characteristics as outlined in the claims. The formulation can be sterile, and can be reconstituted with water. The pharmaceutical product can be in a pre-assembled injection device, or in a kit, which can be administered for intramuscular, subcutaneous, self-administration. The antibody can have the sequences as shown in in the instant claims.
The copending claims are directed to a method for treatment of a patient with inflammatory bowel disease, comprising administering an anti-IL-36R antibody (see e.g. claims 1-8, 15, 19-38). The IL-36R antibodies are identical in sequence to the instant antibodies, and each SEQ ID NO corresponds to the same SEQ ID NO: as the antibodies in the instant specification.
The copending claims do not describe the specific formulation components and concentrations of the instant claims.
Brige et al teach a formulation comprising an aqueous carrier having a pH of 5.5 to 8 and comprising one or more single variable domains at a concentration of 1 mg/ml to 200 mg/ml, with several examples showing a concentration of 10 mg/ml (see e.g. paragraph [0257]-[0281]). the formulation being formulated for human administration (see e.g. claim 1-28). The term “variable domain” can refer to part of an immunoglobulin or antibody that is responsible for antigen binding (see e.g. paragraphs [0148]-[0159]). The formulation can be liquid (see e.g. paragraph [0167]). The formulation can have components including a buffer at a concentration of 10 to 100 mM, such as an acetate buffer at pH 5.5-6.0, or a histidine buffer at pH 6.0-6.5, an excipient at 1-20% (w/v), a surfactant of 0.001%-1% that can be Tween 20, which is the trade name for polysorbate 20, and an inorganic salt concentration of 150mM or lower (see e.g. claim 1). The excipient can be arginine (see e.g. paragraph [0147]). The formulation allows for a polypeptide stability and solubility with several functional characteristics (see e.g. claim 6). The inorganic salt can be NaCl (see e.g. paragraph [0015]). The formulation can comprise an excipient that is sucrose (see e.g. claim 11-12). There can be more than one excipient and/or tonifiers, indicating that both sucrose and arginine could be present (see e.g. paragraph [0022]). The sucrose can be at a concentration of 1-10% (w:v). The osmolality can be about osmolality of about 290±60 mOsm/kg, such as about 240 or higher, 250 or higher or 260 or higher (see e.g. paragraph [0022]). The formulation can be sterile (see e.g. paragraph [0475]). The liquid carrier can be water (see e.g. paragraph [0018]). The formulation can be formatted for intramuscular or subcutaneous administration (see e.g. paragraph [0081]). Since the molecular weight of sucrose is 342.3 g/mol, this would be a concentration of 30-300 mM. The composition can be in a container, pharmaceutical unit dosage form, kit or other administration forms (see e.g. claims 21-28).
It would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to use the formulation of Brige to provide known stabilized effects for the antibodies of the copending claims. As indicated by Brige, the formulations provide good stability under different storage, transportation and stress conditions (see e.g. abstract). Brige teaches that proteins such as therapeutic antibodies are often transported and stored, and it is therefore important that such proteins are preserved in terms of stability and biological activities under the various conditions such as different temperature and mechanical stress conditions (see paragraph [0005]). This stability prevents degradation due to short shelf life, and loss of biological activity resulting from chemical and/or physical stability (see e.g. paragraph [0006]). The advantage of increased stability provides the motivation to make the aforementioned modification of the antibody of the copending claims, based on the teachings of Brige et al, with a reasonable expectation of success.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that if a technique has been used to improve one method, and a person of ordinary skill would recognize that it would be used in similar methods in the same way, using the technique is obvious unless its application is beyond that person’s skill. It would be obvious to apply a known technique to a known product to be used in a known method that is ready for improvement to yield predictable results. Thus, the combination of prior art references as combined provided a prima facie case of obviousness, absent convincing evidence to the contrary.
Regarding the concentrations of the formulation components, one of ordinary skilled in the art would have been motivated to optimize the concentrations of various buffers, excipients and other components in the composition, since “it is the normal desire of scientists or artisans to improve upon what is already generally known”. The MPEP states the following: Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller. 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson. 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc, v. Biocraft Laboratories Inc.. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert, denied, 493 U.S. 975 (1989); In re Kulling. 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler. 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997).
The Federal Circuit held in Sun Pharmaceutical Industries v. Eli Lilly and Co., 611 F.3d 1381, 1389 (2010) that claims of a later patent can be held invalid for obviousness-type double patenting where an earlier patent claimed a compound, disclosing its utility in the specification, and a later patent claimed a method of using the compound for a use described in the specification of the earlier patent. See Pfizer, 518 F.3d at 1363; Geneva, 349 F.3d at 1385-86. In this case, U.S. 4,808,614 (‘614) patent claimed gemcitabine and methods of using gemcitabine for treating viral infections. The patent also disclosed (but did not claim) using these compounds to fight cancer. U.S. 5,464,826 (‘826) patent claimed methods of using gemcitabine for treating cancer. The Federal Circuit found that “The asserted claims of the later '826 patent simply claim the anticancer use disclosed in the specification of the '614 patent as a method of use claim. See Pfizer, 518 F.3d at 1363; Geneva, 349 F.3d at 1385. Therefore, we affirm the district court's judgment that the asserted claims, claims 2, 6, and 7, of the '826 patent are invalid for obviousness-type double patenting over the '614 patent.” Sun Pharmaceutical Industries v. Eli Lilly and Co., 611 F.3d 1381, 1389 (2010). This is similar to the instant application as compared to the copending application. The copending application claims the use of the product of the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
8. Claims 1-12, 16-32, 34-36, and 38 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-43 of copending Application No. 18/599,267 (reference application) in view of Brige et al (US 2012/0244158 A1; filed 9/3/10; published 9/27/12). Although the claims at issue are not identical, they are not patentably distinct from each other.
The instant claims are directed to an antibody formulation comprising an anti-IL-36R antibody or antigen binding fragment thereof, a buffer at a concentration of 20mM to about 80mM, and a tonicifying agent at a concentration of 100-250 mM, where the composition has a pH in the range of about 5 to about 8. The formulation can be in a liquid or powder form, and the concentration can be 20, 60, or 150 mg/ml. The buffer can be an acetate buffer. The tonicifying agent can be sucrose. The formulation can comprise a stabilizer at a concentration of 0-80 mM, wherein the stabilizer can be L-arginine. It is noted that the requirement for “0 mM” of stabilizer means that the stabilizer may not be present in the formulation. Therefore the claim is interpreted to read on formulations that lack L-arginine. The formulation can have a salt of about 0-about 150 mM. As indicated for the salt, the presence of a requirement for “0 mM” salt means that the salt does not have to be present in the formulation. The formulation can comprise a surfactant such as polysorbate 20, at around 0.4 g/L. The formulation will have specific functional characteristics as outlined in the claims. The formulation can be sterile, and can be reconstituted with water. The pharmaceutical product can be in a pre-assembled injection device, or in a kit, which can be administered for intramuscular, subcutaneous, self-administration. The antibody can have the sequences as shown in in the instant claims.
The copending claims are directed to a method for treatment of a patient with hidradenitis suppurativa, comprising administering an anti-IL-36R antibody (see e.g. claims 1-43). The IL-36R antibodies are identical in sequence to the instant antibodies, and each SEQ ID NO corresponds to the same SEQ ID NO: as the antibodies in the instant specification.
The copending claims do not describe the specific formulation components and concentrations of the instant claims.
Brige et al teach a formulation comprising an aqueous carrier having a pH of 5.5 to 8 and comprising one or more single variable domains at a concentration of 1 mg/ml to 200 mg/ml, with several examples showing a concentration of 10 mg/ml (see e.g. paragraph [0257]-[0281]). the formulation being formulated for human administration (see e.g. claim 1-28). The term “variable domain” can refer to part of an immunoglobulin or antibody that is responsible for antigen binding (see e.g. paragraphs [0148]-[0159]). The formulation can be liquid (see e.g. paragraph [0167]). The formulation can have components including a buffer at a concentration of 10 to 100 mM, such as an acetate buffer at pH 5.5-6.0, or a histidine buffer at pH 6.0-6.5, an excipient at 1-20% (w/v), a surfactant of 0.001%-1% that can be Tween 20, which is the trade name for polysorbate 20, and an inorganic salt concentration of 150mM or lower (see e.g. claim 1). The excipient can be arginine (see e.g. paragraph [0147]). The formulation allows for a polypeptide stability and solubility with several functional characteristics (see e.g. claim 6). The inorganic salt can be NaCl (see e.g. paragraph [0015]). The formulation can comprise an excipient that is sucrose (see e.g. claim 11-12). There can be more than one excipient and/or tonifiers, indicating that both sucrose and arginine could be present (see e.g. paragraph [0022]). The sucrose can be at a concentration of 1-10% (w:v). The osmolality can be about osmolality of about 290±60 mOsm/kg, such as about 240 or higher, 250 or higher or 260 or higher (see e.g. paragraph [0022]). The formulation can be sterile (see e.g. paragraph [0475]). The liquid carrier can be water (see e.g. paragraph [0018]). The formulation can be formatted for intramuscular or subcutaneous administration (see e.g. paragraph [0081]). Since the molecular weight of sucrose is 342.3 g/mol, this would be a concentration of 30-300 mM. The composition can be in a container, pharmaceutical unit dosage form, kit or other administration forms (see e.g. claims 21-28).
It would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to use the formulation of Brige to provide known stabilized effects for the antibodies of the copending claims. As indicated by Brige, the formulations provide good stability under different storage, transportation and stress conditions (see e.g. abstract). Brige teaches that proteins such as therapeutic antibodies are often transported and stored, and it is therefore important that such proteins are preserved in terms of stability and biological activities under the various conditions such as different temperature and mechanical stress conditions (see paragraph [0005]). This stability prevents degradation due to short shelf life, and loss of biological activity resulting from chemical and/or physical stability (see e.g. paragraph [0006]). The advantage of increased stability provides the motivation to make the aforementioned modification of the antibody of the copending claims, based on the teachings of Brige et al, with a reasonable expectation of success.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that if a technique has been used to improve one method, and a person of ordinary skill would recognize that it would be used in similar methods in the same way, using the technique is obvious unless its application is beyond that person’s skill. It would be obvious to apply a known technique to a known product to be used in a known method that is ready for improvement to yield predictable results. Thus, the combination of prior art references as combined provided a prima facie case of obviousness, absent convincing evidence to the contrary.
Regarding the concentrations of the formulation components, one of ordinary skilled in the art would have been motivated to optimize the concentrations of various buffers, excipients and other components in the composition, since “it is the normal desire of scientists or artisans to improve upon what is already generally known”. The MPEP states the following: Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller. 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson. 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc, v. Biocraft Laboratories Inc.. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert, denied, 493 U.S. 975 (1989); In re Kulling. 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler. 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997).
The Federal Circuit held in Sun Pharmaceutical Industries v. Eli Lilly and Co., 611 F.3d 1381, 1389 (2010) that claims of a later patent can be held invalid for obviousness-type double patenting where an earlier patent claimed a compound, disclosing its utility in the specification, and a later patent claimed a method of using the compound for a use described in the specification of the earlier patent. See Pfizer, 518 F.3d at 1363; Geneva, 349 F.3d at 1385-86. In this case, U.S. 4,808,614 (‘614) patent claimed gemcitabine and methods of using gemcitabine for treating viral infections. The patent also disclosed (but did not claim) using these compounds to fight cancer. U.S. 5,464,826 (‘826) patent claimed methods of using gemcitabine for treating cancer. The Federal Circuit found that “The asserted claims of the later '826 patent simply claim the anticancer use disclosed in the specification of the '614 patent as a method of use claim. See Pfizer, 518 F.3d at 1363; Geneva, 349 F.3d at 1385. Therefore, we affirm the district court's judgment that the asserted claims, claims 2, 6, and 7, of the '826 patent are invalid for obviousness-type double patenting over the '614 patent.” Sun Pharmaceutical Industries v. Eli Lilly and Co., 611 F.3d 1381, 1389 (2010). This is similar to the instant application as compared to the copending application. The copending application claims the use of the product of the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
9. Claims 1-12, 16-32, 34-36, and 38 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-44 of copending Application No. 18/736,586 (reference application) in view of Brige et al (US 2012/0244158 A1; filed 9/3/10; published 9/27/12). Although the claims at issue are not identical, they are not patentably distinct from each other.
The instant claims are directed to an antibody formulation comprising an anti-IL-36R antibody or antigen binding fragment thereof, a buffer at a concentration of 20mM to about 80mM, and a tonicifying agent at a concentration of 100-250 mM, where the composition has a pH in the range of about 5 to about 8. The formulation can be in a liquid or powder form, and the concentration can be 20, 60, or 150 mg/ml. The buffer can be an acetate buffer. The tonicifying agent can be sucrose. The formulation can comprise a stabilizer at a concentration of 0-80 mM, wherein the stabilizer can be L-arginine. It is noted that the requirement for “0 mM” of stabilizer means that the stabilizer may not be present in the formulation. Therefore the claim is interpreted to read on formulations that lack L-arginine. The formulation can have a salt of about 0-about 150 mM. As indicated for the salt, the presence of a requirement for “0 mM” salt means that the salt does not have to be present in the formulation. The formulation can comprise a surfactant such as polysorbate 20, at around 0.4 g/L. The formulation will have specific functional characteristics as outlined in the claims. The formulation can be sterile, and can be reconstituted with water. The pharmaceutical product can be in a pre-assembled injection device, or in a kit, which can be administered for intramuscular, subcutaneous, self-administration. The antibody can have the sequences as shown in in the instant claims.
The copending claims are directed to a method for treatment of a patient with generalized pustular psoriasis, comprising administering an anti-IL-36R antibody (see e.g. claims 1-44). The IL-36R antibodies are identical in sequence to the instant antibodies, and each SEQ ID NO corresponds to the same SEQ ID NO: as the antibodies in the instant specification.
The copending claims do not describe the specific formulation components and concentrations of the instant claims.
Brige et al teach a formulation comprising an aqueous carrier having a pH of 5.5 to 8 and comprising one or more single variable domains at a concentration of 1 mg/ml to 200 mg/ml, with several examples showing a concentration of 10 mg/ml (see e.g. paragraph [0257]-[0281]). the formulation being formulated for human administration (see e.g. claim 1-28). The term “variable domain” can refer to part of an immunoglobulin or antibody that is responsible for antigen binding (see e.g. paragraphs [0148]-[0159]). The formulation can be liquid (see e.g. paragraph [0167]). The formulation can have components including a buffer at a concentration of 10 to 100 mM, such as an acetate buffer at pH 5.5-6.0, or a histidine buffer at pH 6.0-6.5, an excipient at 1-20% (w/v), a surfactant of 0.001%-1% that can be Tween 20, which is the trade name for polysorbate 20, and an inorganic salt concentration of 150mM or lower (see e.g. claim 1). The excipient can be arginine (see e.g. paragraph [0147]). The formulation allows for a polypeptide stability and solubility with several functional characteristics (see e.g. claim 6). The inorganic salt can be NaCl (see e.g. paragraph [0015]). The formulation can comprise an excipient that is sucrose (see e.g. claim 11-12). There can be more than one excipient and/or tonifiers, indicating that both sucrose and arginine could be present (see e.g. paragraph [0022]). The sucrose can be at a concentration of 1-10% (w:v). The osmolality can be about osmolality of about 290±60 mOsm/kg, such as about 240 or higher, 250 or higher or 260 or higher (see e.g. paragraph [0022]). The formulation can be sterile (see e.g. paragraph [0475]). The liquid carrier can be water (see e.g. paragraph [0018]). The formulation can be formatted for intramuscular or subcutaneous administration (see e.g. paragraph [0081]). Since the molecular weight of sucrose is 342.3 g/mol, this would be a concentration of 30-300 mM. The composition can be in a container, pharmaceutical unit dosage form, kit or other administration forms (see e.g. claims 21-28).
It would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to use the formulation of Brige to provide known stabilized effects for the antibodies of the copending claims. As indicated by Brige, the formulations provide good stability under different storage, transportation and stress conditions (see e.g. abstract). Brige teaches that proteins such as therapeutic antibodies are often transported and stored, and it is therefore important that such proteins are preserved in terms of stability and biological activities under the various conditions such as different temperature and mechanical stress conditions (see paragraph [0005]). This stability prevents degradation due to short shelf life, and loss of biological activity resulting from chemical and/or physical stability (see e.g. paragraph [0006]). The advantage of increased stability provides the motivation to make the aforementioned modification of the antibody of the copending claims, based on the teachings of Brige et al, with a reasonable expectation of success.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that if a technique has been used to improve one method, and a person of ordinary skill would recognize that it would be used in similar methods in the same way, using the technique is obvious unless its application is beyond that person’s skill. It would be obvious to apply a known technique to a known product to be used in a known method that is ready for improvement to yield predictable results. Thus, the combination of prior art references as combined provided a prima facie case of obviousness, absent convincing evidence to the contrary.
Regarding the concentrations of the formulation components, one of ordinary skilled in the art would have been motivated to optimize the concentrations of various buffers, excipients and other components in the composition, since “it is the normal desire of scientists or artisans to improve upon what is already generally known”. The MPEP states the following: Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller. 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson. 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc, v. Biocraft Laboratories Inc.. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert, denied, 493 U.S. 975 (1989); In re Kulling. 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler. 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997).
The Federal Circuit held in Sun Pharmaceutical Industries v. Eli Lilly and Co., 611 F.3d 1381, 1389 (2010) that claims of a later patent can be held invalid for obviousness-type double patenting where an earlier patent claimed a compound, disclosing its utility in the specification, and a later patent claimed a method of using the compound for a use described in the specification of the earlier patent. See Pfizer, 518 F.3d at 1363; Geneva, 349 F.3d at 1385-86. In this case, U.S. 4,808,614 (‘614) patent claimed gemcitabine and methods of using gemcitabine for treating viral infections. The patent also disclosed (but did not claim) using these compounds to fight cancer. U.S. 5,464,826 (‘826) patent claimed methods of using gemcitabine for treating cancer. The Federal Circuit found that “The asserted claims of the later '826 patent simply claim the anticancer use disclosed in the specification of the '614 patent as a method of use claim. See Pfizer, 518 F.3d at 1363; Geneva, 349 F.3d at 1385. Therefore, we affirm the district court's judgment that the asserted claims, claims 2, 6, and 7, of the '826 patent are invalid for obviousness-type double patenting over the '614 patent.” Sun Pharmaceutical Industries v. Eli Lilly and Co., 611 F.3d 1381, 1389 (2010). This is similar to the instant application as compared to the copending application. The copending application claims the use of the product of the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
10. Claims 1-12, 16-32, 34-36, and 38 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of copending Application No. 18/755,744(reference application) in view of Brige et al (US 2012/0244158 A1; filed 9/3/10; published 9/27/12). Although the claims at issue are not identical, they are not patentably distinct from each other.
The instant claims are directed to an antibody formulation comprising an anti-IL-36R antibody or antigen binding fragment thereof, a buffer at a concentration of 20mM to about 80mM, and a tonicifying agent at a concentration of 100-250 mM, where the composition has a pH in the range of about 5 to about 8. The formulation can be in a liquid or powder form, and the concentration can be 20, 60, or 150 mg/ml. The buffer can be an acetate buffer. The tonicifying agent can be sucrose. The formulation can comprise a stabilizer at a concentration of 0-80 mM, wherein the stabilizer can be L-arginine. It is noted that the requirement for “0 mM” of stabilizer means that the stabilizer may not be present in the formulation. Therefore the claim is interpreted to read on formulations that lack L-arginine. The formulation can have a salt of about 0-about 150 mM. As indicated for the salt, the presence of a requirement for “0 mM” salt means that the salt does not have to be present in the formulation. The formulation can comprise a surfactant such as polysorbate 20, at around 0.4 g/L. The formulation will have specific functional characteristics as outlined in the claims. The formulation can be sterile, and can be reconstituted with water. The pharmaceutical product can be in a pre-assembled injection device, or in a kit, which can be administered for intramuscular, subcutaneous, self-administration. The antibody can have the sequences as shown in in the instant claims.
The copending claims are directed to a method for treatment of a patient with generalized pustular psoriasis, comprising administering an anti-IL-36R antibody (see e.g. claims 1-15). The IL-36R antibodies are identical in sequence to the instant antibodies, and each SEQ ID NO corresponds to the same SEQ ID NO: as the antibodies in the instant specification.
The copending claims do not describe the specific formulation components and concentrations of the instant claims.
Brige et al teach a formulation comprising an aqueous carrier having a pH of 5.5 to 8 and comprising one or more single variable domains at a concentration of 1 mg/ml to 200 mg/ml, with several examples showing a concentration of 10 mg/ml (see e.g. paragraph [0257]-[0281]). the formulation being formulated for human administration (see e.g. claim 1-28). The term “variable domain” can refer to part of an immunoglobulin or antibody that is responsible for antigen binding (see e.g. paragraphs [0148]-[0159]). The formulation can be liquid (see e.g. paragraph [0167]). The formulation can have components including a buffer at a concentration of 10 to 100 mM, such as an acetate buffer at pH 5.5-6.0, or a histidine buffer at pH 6.0-6.5, an excipient at 1-20% (w/v), a surfactant of 0.001%-1% that can be Tween 20, which is the trade name for polysorbate 20, and an inorganic salt concentration of 150mM or lower (see e.g. claim 1). The excipient can be arginine (see e.g. paragraph [0147]). The formulation allows for a polypeptide stability and solubility with several functional characteristics (see e.g. claim 6). The inorganic salt can be NaCl (see e.g. paragraph [0015]). The formulation can comprise an excipient that is sucrose (see e.g. claim 11-12). There can be more than one excipient and/or tonifiers, indicating that both sucrose and arginine could be present (see e.g. paragraph [0022]). The sucrose can be at a concentration of 1-10% (w:v). The osmolality can be about osmolality of about 290±60 mOsm/kg, such as about 240 or higher, 250 or higher or 260 or higher (see e.g. paragraph [0022]). The formulation can be sterile (see e.g. paragraph [0475]). The liquid carrier can be water (see e.g. paragraph [0018]). The formulation can be formatted for intramuscular or subcutaneous administration (see e.g. paragraph [0081]). Since the molecular weight of sucrose is 342.3 g/mol, this would be a concentration of 30-300 mM. The composition can be in a container, pharmaceutical unit dosage form, kit or other administration forms (see e.g. claims 21-28).
It would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to use the formulation of Brige to provide known stabilized effects for the antibodies of the copending claims. As indicated by Brige, the formulations provide good stability under different storage, transportation and stress conditions (see e.g. abstract). Brige teaches that proteins such as therapeutic antibodies are often transported and stored, and it is therefore important that such proteins are preserved in terms of stability and biological activities under the various conditions such as different temperature and mechanical stress conditions (see paragraph [0005]). This stability prevents degradation due to short shelf life, and loss of biological activity resulting from chemical and/or physical stability (see e.g. paragraph [0006]). The advantage of increased stability provides the motivation to make the aforementioned modification of the antibody of the copending claims, based on the teachings of Brige et al, with a reasonable expectation of success.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that if a technique has been used to improve one method, and a person of ordinary skill would recognize that it would be used in similar methods in the same way, using the technique is obvious unless its application is beyond that person’s skill. It would be obvious to apply a known technique to a known product to be used in a known method that is ready for improvement to yield predictable results. Thus, the combination of prior art references as combined provided a prima facie case of obviousness, absent convincing evidence to the contrary.
Regarding the concentrations of the formulation components, one of ordinary skilled in the art would have been motivated to optimize the concentrations of various buffers, excipients and other components in the composition, since “it is the normal desire of scientists or artisans to improve upon what is already generally known”. The MPEP states the following: Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller. 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson. 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc, v. Biocraft Laboratories Inc.. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert, denied, 493 U.S. 975 (1989); In re Kulling. 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler. 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997).
The Federal Circuit held in Sun Pharmaceutical Industries v. Eli Lilly and Co., 611 F.3d 1381, 1389 (2010) that claims of a later patent can be held invalid for obviousness-type double patenting where an earlier patent claimed a compound, disclosing its utility in the specification, and a later patent claimed a method of using the compound for a use described in the specification of the earlier patent. See Pfizer, 518 F.3d at 1363; Geneva, 349 F.3d at 1385-86. In this case, U.S. 4,808,614 (‘614) patent claimed gemcitabine and methods of using gemcitabine for treating viral infections. The patent also disclosed (but did not claim) using these compounds to fight cancer. U.S. 5,464,826 (‘826) patent claimed methods of using gemcitabine for treating cancer. The Federal Circuit found that “The asserted claims of the later '826 patent simply claim the anticancer use disclosed in the specification of the '614 patent as a method of use claim. See Pfizer, 518 F.3d at 1363; Geneva, 349 F.3d at 1385. Therefore, we affirm the district court's judgment that the asserted claims, claims 2, 6, and 7, of the '826 patent are invalid for obviousness-type double patenting over the '614 patent.” Sun Pharmaceutical Industries v. Eli Lilly and Co., 611 F.3d 1381, 1389 (2010). This is similar to the instant application as compared to the copending application. The copending application claims the use of the product of the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
11. Claims 1-12, 16-32, 34-36, and 38 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of copending Application No. 18/798,981 (reference application) in view of Brige et al (US 2012/0244158 A1; filed 9/3/10; published 9/27/12). Although the claims at issue are not identical, they are not patentably distinct from each other.
The instant claims are directed to an antibody formulation comprising an anti-IL-36R antibody or antigen binding fragment thereof, a buffer at a concentration of 20mM to about 80mM, and a tonicifying agent at a concentration of 100-250 mM, where the composition has a pH in the range of about 5 to about 8. The formulation can be in a liquid or powder form, and the concentration can be 20, 60, or 150 mg/ml. The buffer can be an acetate buffer. The tonicifying agent can be sucrose. The formulation can comprise a stabilizer at a concentration of 0-80 mM, wherein the stabilizer can be L-arginine. It is noted that the requirement for “0 mM” of stabilizer means that the stabilizer may not be present in the formulation. Therefore the claim is interpreted to read on formulations that lack L-arginine. The formulation can have a salt of about 0-about 150 mM. As indicated for the salt, the presence of a requirement for “0 mM” salt means that the salt does not have to be present in the formulation. The formulation can comprise a surfactant such as polysorbate 20, at around 0.4 g/L. The formulation will have specific functional characteristics as outlined in the claims. The formulation can be sterile, and can be reconstituted with water. The pharmaceutical product can be in a pre-assembled injection device, or in a kit, which can be administered for intramuscular, subcutaneous, self-administration. The antibody can have the sequences as shown in in the instant claims.
The copending claims are directed to a method for treatment of a patient with Netherton syndrome, comprising administering an anti-IL-36R antibody (see e.g. claims 1-8). The IL-36R antibodies are identical in sequence to the instant antibodies, and each SEQ ID NO corresponds to the same SEQ ID NO: as the antibodies in the instant specification.
The copending claims do not describe the specific formulation components and concentrations of the instant claims.
Brige et al teach a formulation comprising an aqueous carrier having a pH of 5.5 to 8 and comprising one or more single variable domains at a concentration of 1 mg/ml to 200 mg/ml, with several examples showing a concentration of 10 mg/ml (see e.g. paragraph [0257]-[0281]). the formulation being formulated for human administration (see e.g. claim 1-28). The term “variable domain” can refer to part of an immunoglobulin or antibody that is responsible for antigen binding (see e.g. paragraphs [0148]-[0159]). The formulation can be liquid (see e.g. paragraph [0167]). The formulation can have components including a buffer at a concentration of 10 to 100 mM, such as an acetate buffer at pH 5.5-6.0, or a histidine buffer at pH 6.0-6.5, an excipient at 1-20% (w/v), a surfactant of 0.001%-1% that can be Tween 20, which is the trade name for polysorbate 20, and an inorganic salt concentration of 150mM or lower (see e.g. claim 1). The excipient can be arginine (see e.g. paragraph [0147]). The formulation allows for a polypeptide stability and solubility with several functional characteristics (see e.g. claim 6). The inorganic salt can be NaCl (see e.g. paragraph [0015]). The formulation can comprise an excipient that is sucrose (see e.g. claim 11-12). There can be more than one excipient and/or tonifiers, indicating that both sucrose and arginine could be present (see e.g. paragraph [0022]). The sucrose can be at a concentration of 1-10% (w:v). The osmolality can be about osmolality of about 290±60 mOsm/kg, such as about 240 or higher, 250 or higher or 260 or higher (see e.g. paragraph [0022]). The formulation can be sterile (see e.g. paragraph [0475]). The liquid carrier can be water (see e.g. paragraph [0018]). The formulation can be formatted for intramuscular or subcutaneous administration (see e.g. paragraph [0081]). Since the molecular weight of sucrose is 342.3 g/mol, this would be a concentration of 30-300 mM. The composition can be in a container, pharmaceutical unit dosage form, kit or other administration forms (see e.g. claims 21-28).
It would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to use the formulation of Brige to provide known stabilized effects for the antibodies of the copending claims. As indicated by Brige, the formulations provide good stability under different storage, transportation and stress conditions (see e.g. abstract). Brige teaches that proteins such as therapeutic antibodies are often transported and stored, and it is therefore important that such proteins are preserved in terms of stability and biological activities under the various conditions such as different temperature and mechanical stress conditions (see paragraph [0005]). This stability prevents degradation due to short shelf life, and loss of biological activity resulting from chemical and/or physical stability (see e.g. paragraph [0006]). The advantage of increased stability provides the motivation to make the aforementioned modification of the antibody of the copending claims, based on the teachings of Brige et al, with a reasonable expectation of success.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that if a technique has been used to improve one method, and a person of ordinary skill would recognize that it would be used in similar methods in the same way, using the technique is obvious unless its application is beyond that person’s skill. It would be obvious to apply a known technique to a known product to be used in a known method that is ready for improvement to yield predictable results. Thus, the combination of prior art references as combined provided a prima facie case of obviousness, absent convincing evidence to the contrary.
Regarding the concentrations of the formulation components, one of ordinary skilled in the art would have been motivated to optimize the concentrations of various buffers, excipients and other components in the composition, since “it is the normal desire of scientists or artisans to improve upon what is already generally known”. The MPEP states the following: Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller. 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson. 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc, v. Biocraft Laboratories Inc.. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert, denied, 493 U.S. 975 (1989); In re Kulling. 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler. 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997).
The Federal Circuit held in Sun Pharmaceutical Industries v. Eli Lilly and Co., 611 F.3d 1381, 1389 (2010) that claims of a later patent can be held invalid for obviousness-type double patenting where an earlier patent claimed a compound, disclosing its utility in the specification, and a later patent claimed a method of using the compound for a use described in the specification of the earlier patent. See Pfizer, 518 F.3d at 1363; Geneva, 349 F.3d at 1385-86. In this case, U.S. 4,808,614 (‘614) patent claimed gemcitabine and methods of using gemcitabine for treating viral infections. The patent also disclosed (but did not claim) using these compounds to fight cancer. U.S. 5,464,826 (‘826) patent claimed methods of using gemcitabine for treating cancer. The Federal Circuit found that “The asserted claims of the later '826 patent simply claim the anticancer use disclosed in the specification of the '614 patent as a method of use claim. See Pfizer, 518 F.3d at 1363; Geneva, 349 F.3d at 1385. Therefore, we affirm the district court's judgment that the asserted claims, claims 2, 6, and 7, of the '826 patent are invalid for obviousness-type double patenting over the '614 patent.” Sun Pharmaceutical Industries v. Eli Lilly and Co., 611 F.3d 1381, 1389 (2010). This is similar to the instant application as compared to the copending application. The copending application claims the use of the product of the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claim is allowed.
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/ANDREA K MCCOLLUM/Examiner, Art Unit 1674