Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Claims 1-13 are pending and under examination.
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 8 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of inhibiting naïve T cell proliferation in a subject having a T cell mediated autoimmune disease or disorder comprising administering to the patient the composition of claim 7, or for a method for inhibiting T cell proliferation in a patient, wherein the patient has a disease or disorder selected from the group consisting of psoriasis, rheumatoid arthritis, multiple sclerosis, transplant rejection, graft-versus-host disease, type-1 diabetes, cutaneous T cell lymphoma, thyroiditis, autoimmune encephalomyelitis comprising administering to the patient the composition of claim 7, does not reasonable provide enablement for a method for inhibiting any type of T cell proliferation in any patient, comprising administering to the patient the composition of claim 7.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
Factors to be considered in determining whether undue experimentation is required to practice the claimed invention are summarized In re Wands (858 F2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)). The factors most relevant to this rejection are the scope of the claim, the amount of direction or guidance provided, the lack of sufficient working examples, the unpredictability in the art and the amount of experimentation required to enable one of skill in the art to practice the claimed invention.
MPEP § 2111 instructs:
“The Federal Circuit’s en banc decision in Phillips v. AWH Corp., 415 F.3d 1303, 75 USPQ2d 1321 (Fed. Cir. 2005) expressly recognized that the USPTO employs the ‘broadest reasonable interpretation’ standard:
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The Patent and Trademark Office (‘PTO’) determines the scope of claims in patent applications not solely on the basis of the claim language, but upon giving claims their broadest reasonable construction ‘in light of the specification as it would be interpreted by one of ordinary skill in the art.’ In re Am. Acad. of Sci. Tech. Ctr., 367 F.3d 1359, 1364[, 70 USPQ2d 1827] (Fed. Cir. 2004). Indeed, the rules of the PTO require that application claims must ‘conform to the invention as set forth in the remainder of the specification and the terms and phrases used in the claims must find clear support or antecedent basis in the description so that the meaning of the terms in the claims may be ascertainable by reference to the description.’ 37 CFR 1.75(d)(1).”
Likewise, MPEP § 2164.08 instructs:
“All questions of enablement are evaluated against the claimed subject matter. The focus of the examination inquiry is whether everything within the scope of the claim is enabled. Accordingly, the first analytical step requires that the examiner determine exactly what subject matter is encompassed by the claims.”
(emphasis added)
Claim 8 encompasses in its breadth a method for inhibiting any type of T cell proliferation in any patient, comprising administering to the patient the composition of claim 7; however, neither the instant specification nor the prior art provide any reason the ordinarily skilled artisan would want to inhibit any type of T cell proliferation in any patient by administering a monoclonal anti-CD6 antibody, merely for the sake of doing so.
Rather, the person of skill in the art considering inhibiting T cell proliferation by administering a monoclonal anti-CD6 antibody to a patient would look to the teachings of the instant specification to determine in which scenarios one would want to inhibit T cell proliferation in a recipient of the claimed anti-CD6 antibody.
In so doing the skilled artisan would understand from the instant specification that conditions involving naïve T cell proliferation that would allegedly benefit from anti-CD6 antibody treatment include, e.g., psoriasis, rheumatoid arthritis, multiple sclerosis, transplant rejection, graft-versus-host disease, type-1 diabetes, psoriasis, cutaneous T cell lymphoma and thyroiditis (see page 5, 1st paragraph and page 39, 2nd paragraph1).
At the same time, it would be apparent to the skilled artisan that any method of inhibiting T cell proliferation with the anti-CD6 antibody of the instant claims could not be considered effective unless such treatment were to lead to an overall improvement in the patient's well-being. In other words, if a treatment were to inhibit T cell proliferation in a patient without otherwise ameliorating disease in the treated patient then the skilled artisan would not consider this to be successfully practicing the invention.
According to the teachings of the instant specification at page 24, 2nd paragraph, “From these experiments it is clear that T1h causes inhibition of naive T cell proliferation and this is mediated by substantial decrease in pro inflammatory cytokines and also reduction in CD25 and CD4 counts.” (emphasis added).
Similarly, at page 26-27 bridging paragraph, “…[i]n an allogeneic (Antigen Presenting Cells taken from one individual and the PBMCs taken from another individual) Mixed Lymphocyte Reaction, wherein mature Dendritic cells (Antigen Presenting Cells) cause proliferation of naive PBMCs, T1h inhibits this proliferation in a dose dependent manner. The data showed that the mode of action involved down regulation of at least two major pro-inflammatory cytokines, namely IL6 and IFNγ.” (emphasis added).
The instant specification further teaches an anti-CD6 antibody comprising SEQ ID NOs: 1 and 2 does not inhibit memory T cell proliferation in response to antigen-presenting cells displaying a memory T cell stimulatory antigen, see, e.g., Example 10. Lastly, the specification teaches anti-CD6 receptor density on the surface of T cells is ten-fold more than on the surface of B cells (see, e.g., Section 4 on page 19 and Example 3 on page 31).
In conclusion, the teachings of the instant specification would suggest to the skilled artisan that the T1h antibody may be acting by changing CD6 signaling in a way that inhibits naive T cell proliferation by decreasing the production of certain pro-inflammatory cytokines.
Note in this regard that the U.S. Patent Nos. 8524233 and 10000573, which were based on U.S. Application Nos. 12/921544 and 15/609625, respectively, said applications occurring within the priority chain from which the instant application is the latest continuation (see above), include the following claims:
Claims 2 and 5 of the ‘233 patent:
2. A monoclonal anti-CD6 antibody comprising heavy and light chain variable regions as set forth in Sequence ID No 1 and 2, respectively, wherein the monoclonal antibody treats a disorder selected from a group consisting of multiple sclerosis, transplant rejection, rheumatoid arthritis, and psoriasis and exhibits at least one of the following functions: inhibits proliferation of naive PBMCs induced by tethered anti-CD3; inhibits one way MLR where Raji cells are Antigen Presenting Cells and PBMCs proliferate; inhibits one way autologous MLR mediated by PBMCs; inhibits T cell proliferation by mediating suppression of IL2; and inhibits naive T cell proliferation by reducing CD25 and CD4 counts.
5. A therapeutically effective composition comprising a monoclonal anti-CD6 antibody, wherein the monoclonal antibody comprises heavy and light chain variable regions as set forth in Sequence ID No. 1 and 2, respectively, and in an amount to deliver a dose of 0.1-25 mg/Kg/week to a subject in need thereof, wherein the monoclonal antibody treats an auto-immune disorder in the subject selected from a group consisting of multiple sclerosis, transplant rejection, rheumatoid arthritis, and psoriasis and exhibits at least one of the following characteristics selected form the group consisting of: i does not induce complement dependent cytotoxicity (CDC), antibody dependent cytotoxicity or apoptosis in-vitro; ii inhibits naive T-cell proliferation by decreasing pro-inflammatory cytokines; and iii does not inhibit Memory-T-cell proliferation.
Claim 1 of the ‘573 patent:
1. A method of inhibiting naïve T cell proliferation in a subject having a T cell mediated autoimmune disease or disorder, the method comprising administering a therapeutically effective amount of a monoclonal anti-CD6 antibody that comprises heavy and light chain variable regions comprising amino acid sequences as set forth in SEQ ID NOs: 1 and 2.
Claim 8 given its broadest reasonable interpretation consistent with the instant specification encompass in its breadth using an anti-CD6 antibody comprising SEQ ID NO: 2 to “inhibit T cell proliferation” in any patient thereby treating any disease, including any “T-cell mediated autoimmune disease.”
Note that the instant specification does not define what is meant by a “T-cell mediated autoimmune disease.” This phrase, given its broadest reasonable interpretation consistent with the teachings of the instant specification and the knowledge in the prior art would be understood to include in its breadth any disease wherein T-cells have a role in pathogenesis, even if said T-cells are not the primary mediators of immune dysfunction.
The genus of “autoimmune diseases” is enormous, and includes, e.g., autoimmune hemolytic anemia, autoimmune neonatal thrombocytopenia, idiopathic thrombocytopenia purpura, autoimmunocytopenia, hemolytic anemia, antiphospholipid syndrome, dermatitis, allergic encephalomyelitis, myocarditis, relapsing polychondritis, rheumatic heart disease, glomerulonephritis (e.g., IgA nephropathy), Multiple Sclerosis, Neuritis, Uveitis Ophthalmia, Polyendocrinopathies, Purpura (e.g., Henloch-Scoenlein purpura), Reiter's Disease, Stiff-Man Syndrome, Autoimmune Pulmonary Inflammation, Guillain-Barre Syndrome, insulin dependent diabetes mellitis, and autoimmune inflammatory eye, autoimmune thyroiditis, hypothyroidism (i.e., Hashimoto's thyroiditis, systemic lupus erythematosus, Goodpasture's syndrome, Pemphigus, Receptor autoimmunities such as, for example, (a) Graves' Disease, (b) Myasthenia Gravis, and (c) insulin resistance, autoimmune hemolytic anemia, autoimmune thrombocytopenic purpura, rheumatoid arthritis, schleroderma with anti-collagen antibodies, mixed connective tissue disease, polymyositis/dermatomyositis, pernicious anemia, idiopathic Addison's disease, infertility, glomerulonephritis such as primary glomerulonephritis and IgA nephropathy, bullous pemphigoid, Sjogren's syndrome, diabetes millitus, and adrenergic drug resistance (including adrenergic drug resistance with asthma or cystic fibrosis), chronic active hepatitis, primary biliary cirrhosis, other endocrine gland failure, vitiligo, vasculitis, post-MI, cardiotomy syndrome, urticaria, atopic dermatitis, asthma, inflammatory myopathies, and other inflammatory, granulamatous, degenerative, and atrophic disorders), see e.g., Ruben et al., US 20020187526, at claims 25-27, cited herewith.
Thus, the instant claims encompass in their breadth the treatment of an enormous genus of diseases with diverse etiologies and pathologies.
For example, while a defining feature of an autoimmune disease is reactivity to an autoantigen(s) (often of unknown identity), this autoantigen reactivity is not only mediated by Th1-type inflammatory cytokine driven cell mediated immune response but also, for some diseases, by Th2-type driven humoral immune response. Furthermore, additional types of T cells, such as Th17, NKT and γδ T cells are also relevant for some autoimmune diseases.
While the teachings of the instant specification and the knowledge in the art are sufficient to enable the ordinarily skilled artisan to practice a method of treating a disease or disorder selected from the group consisting of psoriasis, rheumatoid arthritis, multiple sclerosis, transplant rejection, graft-versus-host disease, type-1 diabetes, cutaneous T cell lymphoma, thyroiditis, autoimmune encephalomyelitis by administering a therapeutically effective amount of the claimed antibody, they do not provide the ordinarily skilled artisan with sufficient direction or guidance for inhibiting any type of T cell proliferation in any patient, comprising administering to the patient the composition of claim 7.
The specification discloses the anti-CD6 antibody comprising SEQ ID NOs: 1 and 2 inhibits T cell proliferation by decreasing the production of pro-inflammatory cytokines. The skilled artisan would consider most of the cytokines reduced by the claimed antibody to be of the Th1 type. Moreover, the skilled artisan knows that decreases in Th1-type cytokine production upon αβ-T cell receptor antigen engagement tend to tip the immune system balance to favor the production of Th2 type cytokines, e.g., IL-4 and IL-13 (see, e.g., Goldsby et al., Immunology, 2002, Freeman Press, pages 290-291, cited herewith).
Thus, an uncertainty with respect to treating the breadth of diseases encompassed by the instant claims by administering an antibody comprising SEQ ID NO: 2 is that for many diseases it would not at all be clear to the skilled that one could have an ameliorative effect on the disease by inhibiting production of Th1 type cytokines thereby allowing immunomodulation toward Th2 type cytokines.
This is because some T cell mediated autoimmune diseases are known to have both Th1 and Th2 elements, and was not clear to the ordinarily skilled artisan as of applicant’s effective priority date what the effect of inhibiting one over the other might be.
For example, the skilled artisan would consider the treatment of the granulomatous experimental autoimmune thyroiditis species of thyroiditis by administering a monoclonal antibody comprising SEQ ID NO: 2 to be a highly unpredictable endeavor given that while T-cell infiltration of the thyroid is a recognized component of the disease, and said infiltrating T-cell produce both Th1 and Th2 type cytokines, the role of particular subsets of thyroid-infiltrating inflammatory cells in the development of fibrosis is unknown (see Chen et al., J Immunol. 2002 Dec 1;169(11):6530-8, Abstract and page 6530, cited herewith).
As another example, systemic lupus erythematosus is an autoimmune disease with a mixed Th1/Th2 type phenotype (see, e.g., Horwitz et al., Arthritis Rheum. 1998 May;41(5):838-44, Introduction, paragraph bridging pages 841-42 and Discussion, cited herewith).
Moreover yet other autoimmune diseases, such as ulcerative colitis, are believed to be mediated primarily by Th2-type cytokines produced by non-canonical CD4+ T cells, i.e., CD4+ NKT cells having certain invariant TCR chains in mice and humans (see Fuss et al., The Journal of Clinical Investigation, Volume 113 Number 10 May 2004, page 1490-1497, especially Introduction and Discussion, cited herewith).
As another example, systemic sclerosis is an autoimmune disease characterized by lymphocyte infiltration into the skin and a variety of internal organs. According to at least one reference the most common type of systemic sclerosis manifests by fibrotic changes of the skin (scleroderma) where infiltrating CD4+ T cells of the Th2 type, i.e., IL-4 producing cells dominate (see Mavilia et al., Am J Pathol. 1997 Dec;151(6):1751-8, Introduction, cited herewith). This reference further teaches SSc patients exhibit reduced levels of IFN-γ in the blood as well as defective production of IFN-γ by both peripheral blood mononuclear cells and bronchoalveolar lavage cells, which is consistent with the notion that Th1- Th2-type cytokines are mutually antagonistic in that a paucity of a prototypical Th1 cytokine, such as IFN-γ, allows for the CD4+ Th2 type T-cells, and hence the Th2 type cytokines, to dominate (see Discussion, especially the last paragraph). Given these teachings the skilled artisan would be quite uncertain how an SSC patient might react to anti-CD6 antibody that comprises SEQ ID NO:2 and could find out only with undue trial and error experimentation.
However, while the etiologies of ulcerative colitis and systemic sclerosis may be well studied, many other members of the vast genus of autoimmune diseases are not so well characterized, and likewise, which other members of the vast genus of autoimmune diseases could be treated with an anti-CD6 antibody that comprises SEQ ID NO:2 would not be at all clear to the skilled artisan.
Furthermore, as would be immediately evident to the skilled artisan, most patients with autoimmune diseases have had a prior autoimmune response to an autoantigen, or have an ongoing immune response to an autoantigen when they present clinically. Therefore, such patients may already have, e.g., memory T cell and/or memory B cells and/or antibody secreting plasma B cells, which the teachings of the instant specification would suggest are likely to be unaffected by anti-CD6 antibody that comprises SEQ ID NO:2.
In conclusion, the instant claims encompass a method of tremendous breadth, and essentially call for trial and error by the skilled artisan to begin discovering how to practice the claimed method without assisting the skilled artisan in such an endeavor, which is insufficient to constitute adequate enablement.
As put forth in Rasmusson v. SmithKline Beecham Corp., 75 USPQ2d 1297-1303 (CAFC 2005), “[i]f mere plausibility were the test for enablement under section 112, applicants could obtain patent rights to ‘inventions’ consisting of little more than respectable guesses as to the likelihood of their success. When one of the guesses later proved true, the ‘inventor’ would be rewarded the spoils instead of the party who demonstrated that the method actually worked. That scenario is not consistent with the statutory requirement that the inventor enable an invention rather than merely proposing an unproved hypothesis.”
Similarly, a patent is granted for a completed invention, not the general suggestion of an idea and how that idea might be developed into the claimed invention. In the decision of Genentech, Inc, v. Novo Nordisk, 42 USPQ 2d 1001,(CAFC 1997), the court held: “[p]atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable” and that “[t]ossing out the mere germ of an idea does not constitute enabling disclosure”. Further, “[i]t is the specification, not the knowledge of one skilled in the art, that must supply the novel aspects of an invention in order to constitute adequate enablement”.
The instant specification is not enabling because the skilled artisan cannot follow the guidance presented therein to practice the claims without first making a substantial inventive contribution, which is hardly a matter of routine experimentation.
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.
In the rejections set forth below U.S. Patent Nos. 11981743, 10000573, 10669346, 9670285, 9217037 and 8524233 (all cited herewith) are set forth as ‘743, ‘573, ‘346, ‘285, ‘037 and ‘233, respectively.
Claims 1-2 and 7-9 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. ‘233.
The reference claims refer to antibodies comprising SEQ ID NOs: 1 and 2, and to methods of treatment of various disorders.
For example, representative claim 1 of the ‘233 recites “A monoclonal anti-CD6 antibody that binds to domain 1 (D1) of CD6 and inhibits T cell proliferation without interfering with ALCAM binding, wherein the monoclonal antibody comprises heavy and light chain variable regions comprising amino acid sequences as set forth in Sequence ID No. 1 and 2, respectively, encoded by nucleotide sequences as set forth in Sequence ID Nos. 3 and 4 respectively, and effectively treats a disorder selected from a group consisting of multiple sclerosis, transplant rejection, rheumatoid arthritis, and psoriasis.”
Moreover, representative claim 3 of the ‘233 recites “A method of treatment of a disorder selected from a group consisting of multiple sclerosis, transplant rejection rheumatoid arthritis, and psoriasis, said method comprising the step of administering the monoclonal anti-CD6 antibody according to claim 1, in an effective dose from 0.1-25 mg/Kg/week,”
while representative claim 5 recites, “A therapeutically effective composition comprising a monoclonal anti-CD6 antibody, wherein the monoclonal antibody comprises heavy and light chain variable regions as set forth in Sequence ID No. 1 and 2, respectively, and in an amount to deliver a dose of 0.1-25 mg/Kg/week to a subject in need thereof, wherein the monoclonal antibody treats an auto-immune disorder in the subject selected from a group consisting of multiple sclerosis, transplant rejection, rheumatoid arthritis, and psoriasis and exhibits at least one of the following characteristics selected form the group consisting of: i does not induce complement dependent cytotoxicity (CDC), antibody dependent cytotoxicity or apoptosis in-vitro; ii inhibits naive T-cell proliferation by decreasing pro-inflammatory cytokines; and iii does not inhibit Memory-T-cell proliferation.”
Insofar as representative claim 5 does not explicitly state that the claimed “therapeutically effective composition” which comprises a monoclonal anti-CD6 antibody “…wherein the monoclonal antibody treats an auto-immune disorder in the subject selected from a group consisting of multiple sclerosis, transplant rejection, rheumatoid arthritis, and psoriasis…” includes “a physiologically acceptable carrier,” in order for a therapeutically effective composition to function as claimed it must necessarily include “a physiologically acceptable carrier” in order for it to be administered to a multiple sclerosis, transplant rejection, rheumatoid arthritis or psoriasis patient.
Likewise, for essentially the same reasons the “method of treatment of a disorder selected from a group consisting of multiple sclerosis, transplant rejection rheumatoid arthritis, and psoriasis, said method comprising the step of administering the monoclonal anti-CD6 antibody according to claim 1, in an effective dose from 0.1-25 mg/Kg/week” as recited in reference claim 6 will necessarily need to performed with a “therapeutically effective composition” as recited in reference claim 5, said “therapeutically effective composition” necessarily including “a physiologically acceptable carrier” in order for it to be administered to a multiple sclerosis, transplant rejection, rheumatoid arthritis or psoriasis patient.
Thus, the instant claims are obvious variants of the reference claims.
Claims 1-2 and 7 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 2 of U.S. Patent No. ‘037.
Representative reference claim 2 is drawn to “[a] composition comprising a monoclonal antibody comprising a heavy chain polypeptide and a light chain polypeptide as set forth in Sequence ID No 1 and 2 in a pharmaceutically effective dose of 0.1-25 mg/Kg/week and further comprising at least one antigen capable of eliciting an anti-inflammatory immune response selected from a group comprising Glutamic acid decarboxylase (GAD) and Heat Shock Protein 60 (HSP60), Myelin Basic Protein (MBP) and Myelin oligodendrocyte glycoprotein (MOG).”
Insofar as the representative claim 2 does not explicitly state that the claimed composition includes “a physiologically acceptable carrier,” in order for the reference composition to be useful as “a pharmaceutically effective dose of 0.1-25 mg/Kg/week and further comprising at least one antigen capable of eliciting an anti-inflammatory immune response selected from…” it must necessarily include “a physiologically acceptable carrier.”
Claims 8-9 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. ‘285.
The reference claims refer to an antibody comprising SEQ ID NOs: 1 and 2 for the treatment of various disorders.
For example, representative reference claim 2 recites “A method of treatment for an inflammatory disorder, the method comprising administering to a patient a therapeutically effective amount of a monoclonal anti-CD6 antibody that binds to domain 1 (D1) of CD6 without interfering with ALCAM binding, wherein the monoclonal antibody comprises heavy and light chain variable regions comprising amino acid sequences as set forth in SEQ ID NOs: 1 and 2, wherein the inflammatory disorder is multiple sclerosis, transplant rejection, rheumatoid arthritis or psoriasis, wherein the therapeutically effective amount is a dose of 0.1 to 25 mg/Kg/week.”
Insofar as the representative claim 2 does not explicitly state that the method of treatment is performed with administering the antibody via a composition comprising said antibody “and a physiologically acceptable carrier,” to practice a method of treatment wherein an antibody is administered at a “therapeutically effective amount is a dose of 0.1 to 25 mg/Kg/week,” it must necessarily be administered via a composition comprising said antibody and a physiologically acceptable carrier.
Claims 1-7 and 11-12 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. ‘346.
Reference claims 1-1 2 are drawn to:
1. An anti-CD6 monoclonal antibody, or an antigen-binding fragment thereof, comprising a light chain variable region comprising the amino acid sequence of SEQ ID NO:2.
2. The antibody, or antigen-binding fragment thereof, of claim 1 further comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:1.
3. The antibody, or antigen-binding fragment thereof, of claim 1, wherein the antibody is a whole antibody.
4. The antibody, or antigen-binding fragment thereof, of claim 1, wherein the antibody comprises a human constant region.
5. The antibody, or antigen-binding fragment thereof, of claim 4, wherein the antibody comprises a human IgG1 constant region.
6. A recombinant polynucleotide comprising a polynucleotide sequence encoding the amino acid sequence of SEQ ID NO:1.
7. A composition comprising the antibody, or antigen-binding fragment thereof, of claim 1 and a physiologically acceptable carrier.
8. The recombinant polynucleotide of claim 6, wherein said polynucleotide sequence encoding the amino acid sequence of SEQ ID NO:1 comprises a sequence as set forth in SEQ ID NO: 3.
9. The recombinant polynucleotide of claim 6, further comprising a polynucleotide sequence encoding the amino acid sequence of SEQ ID NO: 2.
10. The recombinant polynucleotide of claim 8, further comprising a polynucleotide sequence encoding the amino acid sequence of SEQ ID NO: 2.
11. The recombinant polynucleotide of claim 9, wherein said polynucleotide sequence encoding the amino acid sequence of SEQ ID NO: 2 comprises a sequence as set forth in SEQ ID NO: 4.
12. The recombinant polynucleotide of claim 10, wherein said polynucleotide sequence encoding the amino acid sequence of SEQ ID NO: 2 comprises a sequence as set forth in SEQ ID NO: 4.
Said reference claims plainly anticipate instant claims 1,2, 4-7 and 11-12.
Claim 13 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 8 and 11 of U.S. Patent No. ‘346 in view of in view of Casimiro et al. (6,572,857)(cited herewith).
Reference claim 8 is drawn to:
“A recombinant polynucleotide comprising a polynucleotide sequence encoding the amino acid sequence of SEQ ID NO:1, wherein said polynucleotide sequence encoding the amino acid sequence of SEQ ID NO:1 comprises a sequence as set forth in SEQ ID NO: 3.”
Reference claim 11 is drawn to:
“A recombinant polynucleotide comprising a polynucleotide sequence encoding the amino acid sequence of SEQ ID NO:1, said recombinant polynucleotide
further comprising a polynucleotide sequence encoding the amino acid sequence of SEQ ID NO: 2, wherein said polynucleotide sequence encoding the amino acid sequence of SEQ ID NO: 2 comprises a sequence as set forth in SEQ ID NO: 4.”
It would have been obvious to one of ordinary skill in the art wishing to make the SEQ ID NOs: 1 and 2 recombinant polynucleotides of the reference claims making using the polynucleotide sequences of SEQ ID NOs: 3 and 4 that encode said polypeptides to make use of genetic engineering techniques well known the ordinarily skilled artisan prior to applicant’s first filing date, such as transfection of a cell line (see, e.g., Casimiro at cols. 4-5 bridging paragraph), to introduce the polynucleotide sequences of SEQ ID NOs: 3 and 4 into a cell line that could be used to produce the heavy and light chain polypeptides of SEQ ID NOs: 1 and 2 so as to make a Fv domain capable of binding CD6.
In view of the reference teachings it was apparent that one of ordinary skill in the art would have had a reasonable expectation of success in arriving at the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made.
Claims 8-11 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. ‘573.
The reference claims refer to an antibody comprising SEQ ID NOs: 1 and 2 for the treatment of various disorders, including a method of inhibiting naïve T cell proliferation in a subject having a T cell mediated autoimmune disease or disorder, and a method of inhibiting naïve T cell proliferation in a subject having a T cell mediated autoimmune disease or disorder, wherein the T cell mediated autoimmune disease or disorder is selected from the group consisting of psoriasis, rheumatoid arthritis, an adverse T cell autoimmune responses associated with multiple sclerosis or transplant rejection, graft-versus-host disease, type-1 diabetes, psoriasis, cutaneous T cell lymphoma, thyroiditis, and autoimmune encephalomyelitis, and further drawn to a method of inhibiting naïve T cell proliferation in a subject having a T cell mediated autoimmune disease or disorder, said method further comprising administering an immunosuppressant.
Thus, the reference claims plainly anticipate the instant claims.
Claim 8 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 11028168 (cited herewith) as evidenced by Nair et al. (J Immunol April 1, 2011, 186 (1 Supplement) 52.27, cited herewith).
Although the claims at issue are not identical, they are not patentably distinct from each other because the “itolizumab” antibody of the reference claims has the Vh and Vl domains of SEQ ID NOs: 1 and 2 as evidenced by Nair et al. which refers to “Itolizumab (T1h),” wherein the instant specification also refers to T1h as an antibody comprising SEQ ID NOs: 1 and 2 (see Fig. 1b,“description of accompanying sequence listings” at page 10, paragraphs 0011-0013).
Thus, the reference claims anticipate the instant claims.
Claims 8-9 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 3-6 of U.S. Patent No. 10189899 (cited herewith) as evidenced by Nair et al. (J Immunol April 1, 2011, 186 (1 Supplement) 52.27, cited herewith).
Although the claims at issue are not identical, they are not patentably distinct from each other because the “itolizumab” antibody of the reference claims has the Vh and Vl domains of SEQ ID NOs: 1 and 2 as evidenced by Nair et al. which refers to “Itolizumab (T1h),” wherein the instant specification also refers to T1h as an antibody comprising SEQ ID NOs: 1 and 2 (see Fig. 1b,“description of accompanying sequence listings” at page 10, paragraphs 0011-0013).
Thus, the reference claims anticipate the instant claims.
No claims are allowed.
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/ZACHARY S SKELDING/Primary Examiner, Art Unit 1644
1 The instant application is a continuing application of 12921544. All page and paragraph citations set forth in the instant office action refer to the pages and paragraphs of the ‘544 application.
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