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 .
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.
Priority
The instant application 18/073,663, filed on 12/02/2022, claims priority to the US Provisional application 63/287,344, filed on 12/08/2021. The instant application will be examined with a priority date of 12/08/2021.
Status of the Claims
Claims 1-55 are currently pending and are under examined on the merits herein.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 01/12/2024, has been considered, is acknowledged and is in compliance with the provisions of 37 CRF 1.97.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-4, 7-12, 15-16, 20-27, 30-34, 37-40, 44-51 and 54-55 are rejected under 35 U.S.C. 103 as being unpatentable over US20210317199A1, and further in view of Kanagaratham et al. IgE and IgG Antibodies as Regulators of Mast Cell and Basophil Functions in Food Allergy. Front Immunol. 2020 Dec 11;11:603050, James LK, Till SJ. Potential Mechanisms for IgG4 Inhibition of Immediate Hypersensitivity Reactions. Curr Allergy Asthma Rep. 2016 Mar;16(3):23, Greg T. Hermanson, Bioconjugate Techniques (Third Edition) Ch 1 and 20, Academic Press, 2013., and Kent SP, Ryan KH, Siegel AL. Steric hindrance as a factor in the reaction of labeled antibody with cell surface antigenic determinants. J Histochem Cytochem. 1978 Aug;26(8):618-21, further herein referred to as US’199, Kanagaratham, James, Hermanson and Kent.
Regarding claims 1, 2, 7-8, 15-16, 20-21, 24-25, 30, 39-40 and 44-45, US’199 teaches a pharmaceutical composition and a method for treating allergies comprising administering to a subject the composing of an antibody that specifically binds an epitope on an allergen (US’199 pg. 2 para 0021). US’199 also teaches that the antibody can be a monoclonal IgG4 due to its antigen blocking characteristics (allergen reactivity and early allergen exposure) (US’199 pg. 9 para 0194). US’199 also teaches that the antibody are IgE blocking antibodies, by outcompeting IgE to bind to the allergen thereby preventing IgE-mediated crosslinking and degranulation of mast cells and/or basophil. US’199 further teaches a method for treating allergies by administering the composition comprising the composition (US’199 pg. 44 para 0713).
US’199 does not teach of the composition comprising a steric inhibitor coupled to the antibody where it prevents IgE-mediated crosslinking and degranulation of mast cell and/or basophil.
Kanagaratham teaches that allergen specific IgG antibodies counter the effects of IgE in two ways through receptor mediated inhibition and through steric blockade. In steric blockage, IgG antibodies bind the allergen before it reaches receptor-bound IgE and masking the IgE masking epitope, thereby preventing the receptor-bound IgE from complexing with the allergen and thereby preventing FcεRI-mediated mast cell activation (Kanagaratham pg. 5 Fig 1).
James teaches that IgG4 antibody can inhibit IgE-facilitated allergen presentation (IgE-FAP), the immune complex formed when allergen and specific IgE binds to low affinity IgE receptor CD23 (FcεRII). James also teaches that the ability of IgG4 to inhibit this complex is entirely reliant on the affinity, specificity and quantity of the blocking antibody (James pg. 3 col 2 para 2). James also teaches that IgG4 also blocks the effects of IgE signaling through FcεRI, which in turn inhibits immediate hypersensitivity caused by IgE-mediated basophil degranulation that depends on crosslinking of high affinity IgE receptor (FcεRI)-bound IgE. James also teaches that the ability of IgG4 to inhibit the FcεRI-dependent activity of IgE is either through direct competition for allergen with the receptor-bound IgE and/or through simultaneous binding of IgG4 to the inhibitory FcγRIIb (James pg. 4 col 1 para 2).
Hermanson teaches that antibodies can be conjugated to a second molecule having another desirable property to form a hybrid complex where both properties can be exploited for use in when the antibody binds to its target (Hermanson Ch. 20 Introduction). Hermanson further teaches that the second molecule can be a ligand having a specific affinity for a receptor molecule in the body such as a molecule on the surface of a tumor cell (Hermanson Ch. 20 pg. 897 col 1 para 4). Hermanson teaches several bioconjugates including antibody conjugate design where the antibody can be conjugated to a ligand or haptens (having specificity to a receptor in the body) through a linker or spacer for targeting tumor (Hermanson Ch. 1 pg. 8 Tab 1.1).
Kent teaches that the size of an antibody may interfere with the reactions of the antibody molecule with the surface antigenic determinant, particularly to those that are closely spaced. And that steric hindrance is likely to be compounded when the antibodies have been labeled with large molecules (macromolecules) (Kent pg. 618 col 1 para 1).
Therefore, it would have been obvious before the effective filing date for one with ordinary skill in the art to modify the teachings of US’199 in view of Kanagaratham, James, Hermanson and Kent with a reasonable high degree of predictable success so as to obtain an antibody coupled to a ligand that is capable of binding to another molecule that is present in the body to create a large complex that sterically prevents IgE-mediated crosslinking and degranulation of mast cell and/or basophils. Therefore, a skill artisan will have been able to conjugate a ligand (that has a binding affinity or specificity to another molecule in the body as thought by Hermanson) to an antibody such as the IgG4 antibody of US’199 that can out compete IgE to bind to a specific epitope on an allergen, thereby forming a large complex molecule that would bind to a specific epitope on an allergen. Once the antibody portion of the large complex is bound to the allergen or to it Fcγ receptors and the ligand binds to its receptors in the body, the large complex creates a steric effect due to its size and potentially blocks the other epitopes on the allergen from binding to another antibody that may be close by, as well as prevents crosslinking of the allergen to the receptor-bound IgE thereby preventing IgE-mediated crosslinking and degranulation of mast and/or basophils.
Regarding claims 3-4, 22-23, 26-27 and 46-47, and incorporating the analysis to claims 1, 15, 24 and 39 above, US’991 teaches of an antibody that is IgG4 (US’991 pg. 2 para 0028-0030 and pg. 50 para 0756) that binds to Ara h 2 and Ara h 3). US’781 teaches that IgG4 are antibodies known to have high affinity for allergens of interest (US’991 pg. 10 para 0196) and exhibit cross-reactivity to different allergens. IgG4 isotype are also of growing interest due to their potential role in mediating the reduced clinical allergen reactivity that accompanies immunotherapy and early allergen exposure through antigen blocking (US’991 pg. 9 para 0194). US’991 further teaches that the allergen-specific antibodies of the invention can be prepared using recombinant methods known in the arts (US’991 pg. 17 para 0277).
Regarding claims 9-11, 31-33 and 48-50 and incorporating the analysis of claims 1, 24 and 39, US’991 teaches that the antibody of the invention can be generated from sample from a human subject having an allergy including to a food allergen, animal allergen and dust mite allergen.
Regarding claims 12, 34 and 51, and incorporating the analysis of claims 1, 24, 39 US’991 further teaches the composition can be formulated for intranasal, transdermal, oral or intravenous delivery.
Regarding claims 37 and 54, an incorporating the analysis of claims 24 and 39 above, US’991 further teaches a composition comprising a diluent (US’991 pg. 362 claim 8).
Regarding claims 38 and 55, and incorporating the analysis of claims 24 and 39 above, US’991 further teaches the administration of a therapeutic amount of the composition for treating a subject with allergy (US’991 pg. 44 para 0713-0714).
Claims 5 and 28 are rejected under 35 U.S.C. 103 as being unpatentable over US’199, Kanagaratham, James, Hermanson and Kent as applied to claims 1 and 24 above, and further in view of Chapman AP. PEGylated antibodies and antibody fragments for improved therapy: a review. Adv Drug Deliv Rev. 2002 Jun 17;54(4):531-45, herein further referred to as Chapman respectively.
Regarding claims 5 and 28, and incorporating the analysis of claims 1 and 24 above, US’199, Kanagaratham, James, Hermanson and Kent teach the limitations of the claims as described, it does not specifically teach of polyethylene glycol as a steric inhibitor.
Chapman teaches that PEGylation of an antibody can inhibit the antibody’s effector functions. Chapman all teaches an exemplary conjugation of a rabbit immunoglobulin with 5-kDa PEG (polyethylene glycol) showed that Fc receptor binding was completely inhibited when greater than 15% of the antibody’s amino groups had been modified and that PEGylation to an antibody substantially compromises the complement fixation and Fc receptor binding (Chapman Sec 3.2). Chapman further teaches of the conjugation of antibodies to PEG that leads to a reduction of the antibody binding to their target antigen or antigen receptors due to steric hindrance as a result of the PEG-antibody conjugate (PEGylation reaction) occurring at or close to the antigen binding domain (Chapman pg. 536 col 1 para 3 and col 2 para 1).
Therefore, it would have been obvious before the effective filing date for one with ordinary skills in the art to modify the teachings of US’199, Kanagaratham, James, Hermanson and Kent in view of Chapman with a reasonable degree of predictable success so as to obtain an allergen-specific IgG4 (a known blocking antibody) as thought by US’199 that can be conjugated or coupled to a PEG as thought by Chapman. It is common in the art to PEGylate antibodies for several reasons and as indicated by Chapman, a skilled artisan would have been motivated to design such antibody-steric inhibitor complex wherein the antibody portion will outcompete IgE for the specific allergen of interest by binding to an epitope on the allergen and the antibody-steric inhibitor-allergen complex will sterically inhibit other epitopes of the allergen to be able to bind to another binding site of the same antibody or another antibody, thereby preventing the allergen to be bound to free or receptor-bound IgE and preventing IgE-mediated crosslinking and degranulation of mast cells and/or basophils and therefore treating the subject with allergy.
Claims 6, 18, 29 and 42 are rejected under 35 U.S.C. 103 as being unpatentable over US’199, Kanagaratham, James, Hermanson and Kent as applied to claims 1, 16, 24 and 39 above, and further in view of Patterson Human Serum Albumin Domain I Fusion Protein for Antibody Conjugation. Bioconjug. Chem. 2016 Oct 19;27(10):2271-2275, and Dong D, Xia G, Li Z, Li Z. Human Serum Albumin and HER2-Binding Affibody Fusion Proteins for Targeted Delivery of Fatty Acid-Modified Molecules and Therapy. Mol Pharm. 2016 Oct 3;13(10):3370-3380, herein further referred to as Patterson and Dong respectively.
Regarding claims 6, 18, 29 and 42, an incorporating the analysis of claims 1, 16, 24 and 39 above, US’199, Kanagaratham, James, Hermanson and Kent teach the limitations of the claims as described, it does not specifically teach of albumin or human serum albumin as a steric inhibitor or binding moiety that is a ligand.
Patterson teaches that human serum albumin (HSA) a macromolecule can be conjugated to antibodies for improving targeting capacities or enhance cytotoxicity (Patterson Abstract). Patterson also teaches that HSA-antibody conjugates are useful so improving pharmacokinetics and pharmacodynamics of the antibody (Patterson pg. 2 para 1). Patterson also teaches that HSA can be conjugated to the antibody through a linker (Patterson pg. 2 Fig).
Dong teaches that HAS can bind to fatty acids for targeted delivery of therapeutics (Dong Abstract).
Therefore, it would have been obvious before the effective filing date for one with ordinary skills in the art to modify the teachings of US’199, Kanagaratham, James, Hermanson and Kent in view of Patterson and Dong with a reasonable high degree of predictable success so as to conjugate HAS to the IgG4 antibody as a ligand (binding moiety) that can bind to fatty acids in the body creating a bulky antibody-HSA complex that can sterically prevent IgE-mediated crosslinking and degranulation of mast cells and/or basophils. As indicated by Patterson HSA can be conjugated with antibodies to effectuate a desired pharmacodynamic outcome effectuated by the antibody at a specific target site. Therefore, a skilled artisan would have been able to conjugated the antibody to an HSA as a steric inhibitor to obtain a bulky complex in the composition as claimed.
Claims 17 and 41 are rejected under 35 U.S.C. 103 as being unpatentable over US’199, Kanagaratham, James, Hermanson and Kent as applied to claims 16 and 39 above, and further in view of Baird et al. Highly Effective Poly(Ethylene Glycol) Architectures for Specific Inhibition of Immune Receptor Activation. Biochemistry 2003 Oct 14; 42, 44; 12738-12748 herein further referred to as Baird et al.
Regarding claims 17 and 41, and incorporating the analysis of claims 16 ad 39 above, US’199, Kanagaratham, James, Hermanson and Kent does not teach if the ligand is and albumin-binding ligand.
Baird et al. teaches of a PEG based DNP ligands (Baird et al. Table 1) that can be conjugated to antibodies (anti-DNP IgE) for the use of preventing IgE-mediated cross-linking and degranulation of mast cells and/or basophils (Baird et al. Abstract). Baird et al. also teaches that DNP2-PEG3350-DNP2 a DNP ligand was able to inhibit degranulation (Baird et al. pg. 12747 col 2 para 1). Baird et al also teaches that DNP is a hapten which is a type of ligand (Baird et al. Abstract).
Therefore, it would have been obvious before the effective filing date for one with ordinary skill in the art to modify the teachings of US’199, Kanagaratham, James, Hermanson and Kent in view of Baird et al with a high degree of predictable success so as to obtain a composition where the ligand as claimed in this claim is an albumin binding ligand such as DNP to create ligands such as DNP2-PEG3350-DNP2 that is capable of inhibiting degranulation of mast cell. As indicated by Baird et al. DNP2-PEG3350-DNP2forms stables intramolecular cross-links between the two antigen binding sites of IgE thus preventing the clustering of Ige-FcεRI complexes on the cell surface and can be tuned vis changes in ligand length, overall valency and end-valency (Baird et al et al. 12747 col 1 para 2). Therefore, an ordinary skilled artisan would have been motivated to use a molecule such as DNP for the production of a composition, that wherein the DNP ligand is able to act as a steric hindrance for the IgE-FcεRI complex and therefore prevents the IgE-mediating complex from degranulation of the mast cells and/or basophils.
Claims 19 and 43 are rejected under 35 U.S.C. 103 as being unpatentable over US’199, Kanagaratham, James, Hermanson and Kent as applied to claims 16 and 39 above, and further in view of Toshiro et al. Galectin-9 is a high affinity IgE-binding lectin with anti-allergic effect by blocking IgE-antigen complex formation. J Biol Chem. 2009 Nov 20;284(47):32344-52, herein further referred to as Toshiro et al.
Regarding claims 19 and 43, and incorporating the analysis of claims 16 and 39 above, US’199, Kanagaratham, James, Hermanson and Kent does not teach that the ligand is a lectin.
Toshiro et al. teaches a lectin (galectin-9 -with anti-allergic effect) that can bind with antibody (IgE) that has been stimulated by an antigen to form a complex that prevents the IgE-antigen (allergen) complex from forming and hence prevent degranulation of mast cells (Toshiro et al Abstract). Toshiro also teaches galectin is an IgE binding protein (Toshiro et al. pg. 32348 col 2 para 2).
Therefore, it would have been obvious before the effective filing date for one with ordinary skill in the art to modify the teachings of US’199, Kanagaratham, James, Hermanson and Kent in view of Toshiro et al. with a reasonable high degree of predictable success so as to use a lectin (galectin-9) as a ligand in the composition given that galectin 9 can bind to IgE or an antibody similar to IgE and thus inhibits the binding of the IgE-allergen complex and therefore prevents the IgE from binding to FcεRI as exemplified in galectin 9 binding to IR162 and causing steric hindrance (Toshiro et al. pg. 32351 col 2 para 1).. Therefore, it would have been obvious for an ordinary artisan to modify the teachings of US’199, Kanagaratham, James, Hermanson and Kent in view of Toshiro et al. to use a galectin 9 that can bind to IgE or similar antibody or surface of mast cells and/or basophils and elucidating a conformation change due to steric hindrance whereby it prevents IgE-mediated cross-linking and degranulation of mast cells and/or basophils.
Claims 13-14, 35-36 and 52-53 are rejected under 35 U.S.C. 103 as being unpatentable over US’199, Kanagaratham, James, Hermanson and Kent as applied to claims 1, 24 and 39 above, and further in view of WO2006048781 A2, herein further referred to as WO’781 respectively.
Regarding claims 13-14, 35-36 and 52-53 and incorporating the analysis of claims 1, 24 and 39 above, US’199, Kanagaratham, James, Hermanson and Kent does not teach of a composition encapsulated in a microparticle or a lipid nanoparticle.
WO’781 teaches of an IgE retarding, Function-Altering Molecule that is used for treating allergies by preventing IgE-mediated crosslinking and degranulation of mast cells (WO’781 Abstract). WO’781 teaches that the active component (composition) are prepared with carriers that will protect the composition against rapid elimination from the body, such as controlled release formulation including microencapsulated delivery systems (WO’781 pg. 20 ln 25-29). WO’781 teaches that the composition can be entrapped in microcapsules in colloidal drug delivery systems such as liposomes, microemulsions, nanoparticles and nanocapsules for sustain released preparations (WO’781 pg. 18 ln 1-6).
Therefore, it would have been obvious before the effective filing date for one with ordinary skills in the art to modify the teachings of US’199, Kanagaratham, James, Hermanson and Kent in view of WO’781 with a reasonable degree of predictable success so as to obtain a composition that is encapsulated in a microparticle in order to design a sustained-release composition. Composition that are sustain-release are commonly applied in the art to reduce dosing frequency. Therefore, a skilled artisan would have been able to modify US’991 in view of WO’781 to make the composition as claimed.
Conclusion
No claims allowed.
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/EMMANUEL LED YOUTCHOM PENDIE/Examiner, Art Unit 1647
/JOANNE HAMA/
Supervisory Patent Examiner, Art Unit 1647