DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Response to Amendment
Applicant’s amendments to the claims filed 4/29/2024 are acknowledged. Claim 1 is now canceled. Claims 2-21 are pending.
Priority
Applicant claims domestic benefit under 35 U.S.C. 199(e) to: U.S. Patent Application No. 17/143731, filed 1/7/2021, now Patent No. 11,884,721, which is a continuation of U.S. Patent Application No. 16/523877, filed 7/26/2019 now Patent No. 10,919,963, issued 2/16/2021, which is a continuation of U.S. Patent Application No. 15/357999, filed 11/21/2016, now Patent No. 10,392,437, issued 8/27/2019, which is a continuation of U.S. Patent Application No. 13/206,034, filed 8/9/2011, now Patent No. 9,518,087, issued 12/13/2016, which claims priority to U.S. Provisional Application No. 61/372,181 filed 8/10/2010.
Applicant’s claim for the benefit of the prior-filed applications under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 4/29/2024 and 2/27/2024 are acknowledged. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements have been considered by the examiner.
Due to the large number (approximately 800) of references cited, the references have been afforded a cursory review (e.g. title, Abstract, and keyword search), in accordance with the time provided for considering IDS submissions. If there are any particular references that the Applicant deems relevant to patentability, the Applicant is respectfully asked to further point out and/or provide a brief description of such references.
Specification
The disclosure is objected to because of at least the following informalities:
In [0030], the phrase “that that” should be “that”.
In [0037], the phrase “the a” should be “a”.
In [0048], the term “polymerosomes” appears to be a typo for “polymersomes”.
In [0055], the term “biocompatbile" should be “biocompatible”.
In [0055], the term “polyethylyene”, should be “polyethylene”.
In [0055], the term “polycyanoacylates” should be “polycyanoacrylates”.
In [0085], the term “mutatuions” appears to be a typo for “mutations”.
In [0087], the term “β-gluco cerebrosidase” should be “β-glucocerebrosidase”.
In [0087], the term “idursuphase” should be “idursulphase”.
In [0087], the term “galsulphase,” should be “galsulfase,”.
In [0090], the term “caboxypeptidase” should be “carboxypeptidase”.
In [0090], the term “perplakin” should be “periplakin”.
In [0091], the term “cerials” should be “cereals”.
In [0101], the term “biotinlyated” should be “biotinylated”.
In [0110], the term “xylasine” should be “xylazine”.
In [0126], the term “measureable” should instead say “measurable”.
In [0137], the term “PerSpective” should instead say “PerSeptive”.
In [0140], the term “ADVIVA” should instead say “ADVIA”.
In [0174], the phrase “protein, s a portion”, should be “protein, a portion”.
Please note the above are considered necessary grammatical corrections; however, is not exhaustive of all possible informalities, as examination is not made for the purpose of securing grammatical perfection. (See MPEP 601.01(g)). Appropriate correction is required.
Claim Objections
Claims 5-7, 10-12, 15, and 19-20 are objected to because of the following informalities:
In claims 5-12, terms used to identify specific food antigens are presented in parenthesis (for example: “ conarachin (Ara h 1)” ). The use of such parenthetical labels is a potential source of confusion regarding the actual antigens that are claimed. It appears from the specification that such terms are known in the art, and thus these are being interpreted as alternative names which do not introduce a level of indefiniteness per se. However, as these abbreviations/alternative names have already been presented in the specification, and are apparently known in the art, it is recommended, for the sake of improved clarity, that the parenthetical information is either removed from the claims or phrasing is added that clearly sets forth the alternative nature of these names.
In claim 7, the term “ -lactalbumin” appears to be a typo for “α-lactalbumin”
In claim 6, the term “kda” should instead say “kDa”.
In claims 15 and 20, the term “perplakin” should be “periplakin”.
In claim 19, the phrase “the food antigen is associated with celiac disease comprises” is incorrect grammar. It is suggested to amend the phrase to “the food antigen is associated with celiac disease and comprises”.
Similarly, in claim 20, the phrase “the self-antigen is associated with pemphigus vulgaris or myasthenia gravis comprises” should instead say “the self-antigen is associated with pemphigus vulgaris or myasthenia gravis and comprises”. This language is similar as the language applied in claims 15 and 16.
Appropriate correction is required.
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.
Claim 7 is 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.
Claim 7 recites the following:
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As presented, the phrase “;from kiwi: actinidin (Act c 1, Act d 1), phytocystatin, thaumatin-like protein (Act d 2), or kiwellin (Act d 5)” is indefinite as it is unclear if all of these alternatives must be from kiwi or if only the first item initially following the term in the series “actinidin (Act c 1, Act d 1)” is required to be “from kiwi”. The resulting claim is indefinite because one cannot determine the intended metes and bounds of the claim protection sought. For example, does the claimed subject matter include food antigens of actinidin, phytocystatin, and thaumatin-like protein only from kiwi fruit or those from other fruit sources? Further, in this case are the names in parenthesis only specific to kiwi fruit? Or are these general alternative names for these antigens, regardless of the source? This is not clear from the claim language nor the specification. Thus, claim 7 is rejected for indefiniteness. It is recommended to amend the claim to specifically indicate what of the alternatives come from kiwi fruit. This could be accomplished by starting a new line or further indenting these alternatives. The presence of the terms in parenthesis further complicates the claim language, as previously indicated above. Optionally, one could amend the claims such that the alternatives after “from kiwi” is in a dependent claim separate from the first two alternatives (α-lactalbumin (ALA); lactotransferrin).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 2-4, 13, and 17-19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6-8, 20 and 22 of U.S. Patent No. 9,518,087; claims 10-11 and 14 of U.S. Patent No. 9,901,645; and claims 1, 3, 8, and 9 of U.S. Patent No. 10,471,155. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the reference patents anticipate or make obvious the instantly claimed subject matter.
The instant claim 2 recites a method comprising: administering a composition to a subject in an amount effective to induce antigen-specific tolerance, the composition comprising: an erythrocyte-binding moiety, wherein the erythrocyte-binding moiety comprises an antibody fragment directed against glycophorin A, an antigen to which tolerance is desired, wherein the antigen is a food antigen to which a subject develops an unwanted immune response, and wherein the antigen to which tolerance is desired is recombinantly fused or chemically conjugated to the erythrocyte-binding moiety.
The instant claims 3 and 4 limit the method to those wherein the food antigen is associated with celiac disease and wherein the food antigen comprises high molecular weight glutenin, low molecular weight glutenin, alpha- and gamma-gliadin, hordein, secalin, or avenin. Claim 13 further recites the method of claim 3, wherein the food antigen is a portion of gliadin.
The instant claim 17 recites a method comprising the same as in claim 2, except for that the antigen may comprise a food antigen or a self-antigen; wherein the food antigen is associated with celiac disease, wherein the self-antigen is associated with pemphigus vulgaris or myasthenia gravis. These are considered two alternative embodiments, as the antigen against which tolerance is desired is different.
Instant claim 18 recites the method of Claim 17, wherein upon administration to a human in which tolerance to the antigen is desired, the composition binds to CD45 negative cells, but not to CD45 positive cells. Claim 19 recites that the food antigen is associated with celiac disease comprises a portion of tissue transglutaminase or gliadin.
Claim 21 recites the method of Claim 17, wherein the erythrocyte-binding moiety comprises an antibody fragment directed against glycophorin A.
Claim 1 of US 9,518,087 recites: a composition for use in inducing tolerance comprising: an antigen to which tolerance is desired; wherein the antigen is selected from the group consisting of gliadin and a portion thereof; an erythrocyte-binding moiety, wherein the erythrocyte-binding moiety has the ability to non-covalently, specifically bind an exterior erythrocyte surface in situ in blood, wherein the erythrocyte-binding moiety comprises an antibody fragment directed against glycophorin A, wherein the antigen to which tolerance is desired is recombinantly fused to the erythrocyte-binding moiety, wherein, upon administration to a human in which tolerance to the antigen is desired: the composition binds to CD45 negative cells, but not to CD45 positive cells, and the composition reduces, fails to induce, or prevents inflammatory responses in antigen-specific T cells as compared to when the human is exposed to the antigen alone.
Claim 6 of the ‘087 patent recites the composition of claim 1 wherein the antigen to which tolerance is desired is gliadin. Claims 7 and 8 further limit the composition to one wherein the erythrocyte-binding moiety is derived from 10F7 and wherein the administration of the composition ameliorates celiac disease.
Additionally, Claim 20 of the ‘087 patent discloses a composition comprising an antigen recombinantly fused or chemically conjugated with an erythrocyte-binding moiety; wherein the erythrocyte-binding moiety comprises an antibody, antibody fragment, or a single chain variable fragment (scFv) that binds to human glycophorin A; wherein the antigen is selected from the group consisting of gliadin, α-gliadin and γ-gliadin, and a portion thereof.
Claim 22 of the ‘087 patent discloses a method for treating Celiac disease in a subject, comprising administering to said subject a composition of claim 20.
The subject matter recited in the ‘087 patent, pertaining to compositions and methods for use in inducing tolerance is considered to anticipate the instantly recited methods of claims 2-4, 13, and 17-19, as the reference claim discloses subject matter involving compositions for inducing tolerance to food antigens involved in Celiac disease, including the antigens of gliadin, α-gliadin and γ-gliadin, or portions thereof, and having all of the features of the instant claims.
Claim 10 of US 9,901,645 recites a method for reducing an immune response of a subject to a foreign antigen, comprising: administering a fusion molecule for reducing an immune response to a subject, the fusion molecule comprising an immunogenic component coupled to a cell binding moiety, wherein the immunogenic component comprises an antigen foreign to a subject and to which the subject has developed or is likely to develop an unwanted immune response, wherein the foreign antigen is a food antigen selected from the group consisting of high molecular weight glutenin, low molecular weight glutenin, gliadin, hordein, secalin, and avenin, wherein the cell binding moiety comprises an antibody fragment that is capable of binding human glycophorin A; and wherein the fusion molecule is administered intravenously to the subject, wherein, upon administration the cell binding moiety non-covalently and specifically binds to the surface of erythrocytes in blood of the subject and does not specifically bind to other blood components, and wherein the binding of the fusion molecule results in the presentation of the foreign antigen to the immune system of the subject, which downregulates the degree to which the immune system responds to the foreign antigen, thereby reducing the immune response to the foreign antigen.
Further, claim 11 of the ‘645 patent recites that the cell binding moiety comprises an antibody fragment that is affinity matured and capable of binding human glycophorin A.
Claim 14 of the ‘645 recites a method for treating Celiac disease in a subject, comprising: administering a composition to a subject, the composition comprising an antigen recombinantly fused or chemically conjugated with an erythrocyte-binding moiety; wherein the antigen is an immunogenic gliadin fragment, wherein the immunogenic gliadin fragment elicits an immune response, and wherein the erythrocyte-binding moiety comprises an antibody fragment that binds to human glycophorin A.
Therefore, the subject matter recited in the claims of the ‘645 patent, pertaining to methods for reducing an immune response of a subject and for treating Celiac disease, is considered to anticipate or make obvious all of the limitations in the instant claims 2-4, 13, and 17-19, as the reference claim discloses subject matter involving compositions for inducing tolerance to food antigens involved in Celiac disease, including the antigens of gliadin or fragments (portions) thereof.
In regards to the instant claim 18, although the refence claims do not explicitly recite that upon administration to a human in which tolerance to the antigen is desired, the composition binds to CD45 negative cells, but not to CD45 positive cells, the reference claims do recite identical compositions administered for identical purposes (i.e. to the same subject population) and thus, the it would be prima facie obvious that the claimed compositions would achieve the same functional limitation of binding to CD45-neg cells. These intrinsic properties are demonstrated in the disclosure of the ‘645 patent (see the data in FIG 9). Therefore, the instant claim 18 would have been obvious over the subject matter of the ‘645 patent claims.
Claim 1 of US 10,471,155 recites: a composition for immunomodulation to achieve antigen-specific tolerance, the composition comprising: an antigen to which tolerance is desired; wherein the antigen is selected from the group consisting of high molecular weight glutenin, low molecular weight glutenin, gliadin, hordein, secalin, avenin, and immunogenic fragments thereof; an erythrocyte-binding moiety, wherein the erythrocyte-binding moiety comprises an antibody fragment that has the ability to non-covalently, specifically bind an exterior erythrocyte surface in situ in blood, wherein the antigen to which tolerance is desired is recombinantly fused or chemically conjugated to the erythrocyte-binding moiety, and wherein, upon administration to a human in which tolerance to the antigen is desired: the composition binds to CD45 negative cells, but not to CD45 positive cells, and the composition reduces, fails to induce, or prevents inflammatory responses in antigen-specific T cells as compared to when the human is exposed to the antigen alone.
Claim 3 of the ‘155 patent further recites the composition of claim 1, wherein the antibody fragment is directed against glycophorin A. Additionally, Claim 7 of the ‘155 patent recites that the administration of the composition ameliorates celiac disease, and wherein the antigen comprises an immunogenic fragment of gliadin.
Claim 8 of the ‘155 patent recites: a composition for immunomodulation to achieve antigen-specific tolerance, the composition comprising: an antigen recombinantly fused or chemically conjugated with an erythrocyte binding moiety; said antigen being recognizable by an immune system of a subject, the immune system of the subject being able to respond to the antigen with an unwanted immune response; wherein the antigen is selected from the group consisting of high molecular weight glutenin, low molecular weight glutenin, gliadin, hordein, secalin, avenin, and immunogenic fragments thereof; wherein said erythrocyte-binding moiety comprises an antibody fragment directed to glycophorin A; wherein upon administration of the composition, said erythrocyte-binding moiety non-covalently and specifically binds an erythrocyte in situ in blood and presents said antigen to the immune system of the subject; wherein the erythrocyte-binding moiety does not specifically bind to other blood components, wherein the other blood components comprises blood proteins, albumin, fibronectin, platelets, and white blood cells; and wherein said composition elicits a tolerogenic response upon administration to said subject.
Additionally, claim 9 of the ‘155 patent recites that the antigen is a food antigen to which a subject develops an unwanted immune response, wherein the food antigen is associated with celiac disease, and wherein the food antigen is selected from the group consisting gliadin or an immunogenic fragment thereof.
Therefore, the instantly claimed methods of claims 2-4, 13, and 17-19 are considered to be anticipated by the subject matter recited in the ‘155 patent, pertaining to compositions for immunomodulation to achieve antigen-specific tolerance, because the reference claim discloses subject matter involving compositions for inducing tolerance to food antigens involved in Celiac disease, including the antigens of high molecular weight glutenin, low molecular weight glutenin, gliadin, hordein, secalin, avenin, or fragments thereof, and disclose in combination all of the features of the instant claims.
Claims 2 and 5-12 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 8 and 9 of U.S. Patent No. 11,246,943. Although the claims at issue are not identical, they are not patentably distinct from each other because the subject matter of the instant claims is anticipated or made obvious in view of the reference patent claims.
The instant claims 5-12 recite specific food related antigens (allergens). These include:
Claim 5: conarachin (Ara h 1), allergen II (Ara h 2), arachis agglutinin, or conglutin (Ara h 6);
Claim 6: 31 kda major allergen/disease resistance protein homolog (Mal d 2), lipid transfer protein precursor (Mal d 3), or major allergen Mal d 1.03D (Mal d 1);
Claim 7: alpha-lactalbumin (ALA), lactotransferrin; from kiwi: actinidin (Act c 1, Act d 1), phytocystatin, thaumatin-like protein (Act d 2), or kiwellin (Act d 5);
Claim 8: 2S albumin (Sin a 1), 11S globulin (Sin a 2), lipid transfer protein (Sin a 3), or profilin (Sin a 4);
Claim 9: profilin (Api g 4), or high molecular weight glycoprotein (Api g 5);
Claim 10: Pen a 1 allergen (Pen a 1), allergen Pen m 2 (Pen m 2), or tropomyosin fast isoform;
Claim 11: major strawberry allergy Fra a 1-E (Fra a 1);
Claim 12: profilin (Mus xp 1).
Claim 8 of US 11,246,943 recites: a composition for immunomodulation to achieve antigen-specific tolerance, the composition comprising: an antigen recombinantly fused or chemically conjugated with an erythrocyte-binding moiety; said antigen being recognizable by an immune system of a subject, the immune system of the subject being able to respond to the antigen with an unwanted immune response, wherein the antigen is a food antigen; wherein said erythrocyte-binding moiety comprises a peptide; wherein upon administration of the composition, said erythrocyte-binding moiety non-covalently and specifically binds a human erythrocyte in situ in blood and presents said antigen to the immune system of the subject… wherein said composition elicits a tolerogenic response upon administration to said subject.
Claim 9 of the ‘943 patent recites that the erythrocyte-binding moiety comprises an antibody fragment, wherein the antibody fragment is derived from a 10F7 clone, and wherein the antibody fragment has undergone affinity maturation. It is evident from the instant disclosure (and that of the ‘943 patent- see Col 49, lines 16-18) that the 10F7 clone (i.e. a 10F7 monoclonal antibody) binds to glycophorin A, and thus fulfills the limitations of the instant claim 2.
Regarding the identity of the food antigens, one of ordinary skill would recognize that the scope of food antigens, as recited in claim 8 of the ‘943 patent, encompasses many food allergens against which immunotolerance would be desired.
MPEP §804.II.B.1. establishes that "The Patent and Trademark Office (‘PTO’) determines the scope of the 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.’ " Phillips v. AWH Corp., 415 F.3d 1303, 1316, 75 USPQ2d 1321, 1329 (Fed. Cir. 2005) (en banc) (quoting In re Am. Acad. of Sci. Tech. Ctr., 367 F.3d 1359, 1364, 70 USPQ2d 1827, 1830 (Fed. Cir. 2004);” and also describes that “the portion of the specification of the reference that describes subject matter that falls within the scope of a reference claim may be relied upon to properly construe the scope of that claim. In particular, when ascertaining the scope of the reference’s claim(s) to a compound, the examiner should consider the reference’s specification, including all of the compound’s uses that are disclosed. See Sun Pharm. Indus., 611 F.3d at 1386-88, 95 USPQ2d at 1801-02.” Further, MPEP §804.II.B.1. also states that “If the reference patent discloses several species within the scope of the reference genus claim, that portion of the disclosure should be analyzed to properly construe the reference patent claim and determine whether it anticipates or renders obvious the claim in the application being examined”.
In the instant case, the specification of the ‘943 patent describes a number of embodiments regarding food antigens in col 29, line 47 – Col 30, line 3. The disclosure states:
“…from peanut: conarachin (Ara h 1), allergen II (Ara h 2), arachis agglutinin, conglutin (Ara h 6); from apple: 31 kda major allergen/disease resistance protein homolog (Mal d 2), lipid transfer protein precursor (Mal d 3), major allergen Mal d 1.03D (Mal d 1); from milk: α-lactalbumin (ALA), lactotransferrin; from kiwi: actinidin (Act c 1, Act d 1), phytocystatin, thaumatin-like protein (Act d 2), kiwellin (Act d 5); from mustard: 2S albumin (Sin a 1), 11S globulin (Sin a 2), lipid transfer protein (Sin a 3), profilin (Sin a 4); from celery: profilin (Api g 4), high molecular weight glycoprotein (Api g 5); from shrimp: Pen a 1 allergen (Pen a 1), allergen Pen m 2 (Pen m 2), tropomyosin fast isoform; from wheat and/or other cereals: high molecular weight glutenin, low molecular weight glutenin, alpha- and gamma-gliadin, hordein, secalin, avenin; from strawberry: major strawberry allergy Fra a 1-E (Fra a 1), from banana: profilin (Mus xp 1)”.
Therefore, the scope of compositions encompassed by claims 8 and 9 of the ‘943 patent include all of those compositions intended for inducing immunotolerance to these specific food antigens defined in the specification. These include at least all of the specific food antigens recited in claims 5-12 of the instant application.
Claims 14-15, 17-18 and 20-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 2 of U.S. Patent No. 11,246,943; and claims 1-2 of U.S. Patent No. 12,060,414. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the reference patents anticipate or make obvious the instantly claimed subject matter.
The instant claim 14 recites a method comprising: administering a composition to a subject in an amount effective to induce antigen- specific tolerance, the composition comprising: an erythrocyte-binding moiety, wherein the erythrocyte-binding moiety is directed against glycophorin A, an antigen to which tolerance is desired, wherein the antigen is a self-antigen to which a subject develops an unwanted immune response, wherein the self-antigen is associated with pemphigus vulgaris or myasthenia gravis, and wherein the antigen to which tolerance is desired is recombinantly fused or chemically conjugated to the erythrocyte-binding moiety.
Claim 15 recites that the self-antigen is associated with pemphigus vulgaris and comprises one or more of desmoglein 3, desmoglein 1, desmoglein 4, pemphaxin, desmocollins, plakoglobin, perplakin, desmoplakins, and acetylcholine receptor, or a portion thereof.
The instant claim 17 recites a method comprising the same steps as claim 2, except for that the antigen may comprise a food antigen or a self-antigen; wherein the food antigen is associated with celiac disease, wherein the self-antigen is associated with pemphigus vulgaris or myasthenia gravis. These are considered two alternative embodiments, as the antigen against which tolerance is desired is different.
Instant claim 18 recites the method of Claim 17, wherein upon administration to a human in which tolerance to the antigen is desired, the composition binds to CD45 negative cells, but not to CD45 positive cells. Claim 20 recites that the self-antigen is associated with pemphigus vulgaris or myasthenia gravis comprises desmoglein 3, desmoglein 1, desmoglein 4, pemphaxin, desmocollins, plakoglobin, perplakin, desmoplakins, or acetylcholine receptor.
Claim 21 recites the method of Claim 17, wherein the erythrocyte-binding moiety comprises an antibody fragment directed against glycophorin A.
Claim 1 of US 11,246,943 recites a composition for immunomodulation to achieve antigen-specific tolerance, the composition comprising: an antigen to which tolerance is desired; wherein the antigen is selected from the group consisting of an immunogenic fragment of desmoglein 3, an immunogenic fragment of desmoglein 1, and an immunogenic fragment of desmoglein 4; an erythrocyte-binding moiety, wherein the erythrocyte-binding moiety has the ability to non-covalently, specifically bind an exterior erythrocyte surface in situ in blood, wherein the erythrocyte-binding moiety presents said antigen to the immune system of a human, wherein the erythrocyte-binding moiety comprises an antibody fragment, wherein the antigen to which tolerance is desired is recombinantly fused or chemically conjugated to the erythrocyte-binding moiety, and wherein, upon administration to a human in which tolerance to the antigen is desired: the composition binds to CD45 negative cells, but not to CD45 positive cells, and the composition reduces, fails to induce, or prevents inflammatory responses in antigen-specific T cells as compared to when the human is exposed to the antigen separately from the composition, and the composition reduces the number of resident lymph node and spleen cells expressing interferon-gamma (IFNγ), as compared to the number of resident lymph node and spleen cells expressing IFNγ when the human is exposed to the antigen separately from the composition.
Additionally, claim 2 of the ‘943 patent recites “The composition of claim 1, wherein the antibody fragment is directed against glycophorin A, wherein the erythrocyte-binding moiety is derived from a 10F7 clone, wherein the administration of the composition ameliorates pemphigus vulgaris.”.
Therefore, the subject matter disclosed in claims 1 and 2 of the reference patent (‘943) make obvious the methods of the instant claims 14-15, 17-18 and 20-21 as the reference claims disclose a composition having all of the limitations of the instant claims and having an intended use of for immunomodulation to achieve antigen-specific tolerance including targeting antigens for treating pemphigus vulgaris.
Claim 1 of US 12,060,414 recites: a method for inducing antigen-specific tolerance to an antigen in a subject, the method comprising: administering a composition to a subject in an amount effective to induce antigen-specific tolerance, the composition comprising: an antigen to which tolerance is desired; wherein the antigen is selected from a group consisting of an immunogenic fragment of desmoglein 3, an immunogenic fragment of desmoglein 1, and an immunogenic fragment of desmoglein 4; an erythrocyte-binding moiety, wherein the erythrocyte-binding moiety comprises an antibody fragment, wherein the antigen to which tolerance is desired is recombinantly fused or chemically conjugated to the erythrocyte-binding moiety at its antigen-binding site, wherein the erythrocyte-binding moiety has the ability to non-covalently, specifically bind an exterior erythrocyte surface in situ in blood, wherein the erythrocyte-binding moiety presents said antigen to an immune system of a human, wherein upon administration to a human in which tolerance to the antigen is desired: the composition reduces, fails to induce, or prevents inflammatory responses in antigen-specific T cells as compared to when the human is exposed to the antigen alone; and wherein the erythrocyte-binding moiety specifically binds to a biomolecule selected from the group consisting of Band 3 (CD233), glycophorin A, glycophorin B (CD235b), glycophorin C (CD235c), and glycophorin D (CD235d). Additionally, claim 2 of the ‘414 patent recites that the antibody fragment is directed against glycophorin A, wherein the administration of the composition ameliorates myasthenia gravis or pemphigus vulgaris.
Therefore, the subject matter disclosed in claims 1 and 2 of the reference patent (‘943) anticipate or make obvious the methods of the instant claims 14, 15, 20, and 21 as the reference claims disclose a composition having all of the limitations of the instant claims and having an intended use of for immunomodulation to achieve antigen-specific tolerance including targeting antigens for treating pemphigus vulgaris.
Further, regarding claim 18, although the ‘414 claims do not explicitly recite that the composition binds to CD45 negative cells, but not to CD45 positive cells, the reference claims do recite identical compositions administered for identical purposes (i.e. to the same subject population) and thus, the it would be prima facie obvious that the claimed compositions achieve the same functional limitation of binding to CD45-negative cells. These intrinsic properties are demonstrated in the disclosure of the ‘414 patent (Col 33, lines 36-46).
Claims 14 and 16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 2 of U.S. Patent No. 12,060,414 in view of Lindstrom et al. (“Antibody to acetylcholine receptor in myasthenia gravis. Prevalence, clinical correlates, and diagnostic value.” Neurology vol. 26,11; 1976) and Bindu et al. (“Myasthenia gravis and acetylcholine receptor antibodies: a clinical immunological correlative study on South Indian patients.” Annals of Indian Academy of Neurology vol. 11,4; 2008).
As discussed above, Claim 1 of US 12,060,414 recites a method comprising: administering a composition to a subject in an amount effective to induce antigen-specific tolerance, the composition comprising: an antigen to which tolerance is desired; an erythrocyte-binding moiety, wherein the erythrocyte-binding moiety comprises an antibody fragment, wherein the antigen to which tolerance is desired is recombinantly fused or chemically conjugated to the erythrocyte-binding moiety at its antigen-binding site, wherein the erythrocyte-binding moiety has the ability to non-covalently, specifically bind an exterior erythrocyte surface in situ in blood, wherein the erythrocyte-binding moiety presents said antigen to an immune system of a human, wherein upon administration to a human in which tolerance to the antigen is desired: the composition reduces, fails to induce, or prevents inflammatory responses in antigen-specific T cells as compared to when the human is exposed to the antigen alone; and wherein the erythrocyte-binding moiety specifically binds to a biomolecule selected from the group consisting of Band 3 (CD233), glycophorin A, glycophorin B (CD235b), glycophorin C (CD235c), glycophorin D (CD235d).
Additionally, claim 2 of the ‘414 patent recites that the antibody fragment is directed against glycophorin A, wherein the administration of the composition ameliorates myasthenia gravis or pemphigus vulgaris.
However, the reference patent claims do not explicitly recite a composition comprising an antigen against acetylcholine receptor for the treatment of myasthenia gravis, as in the instant claim 16.
Lindstrom is a landmark publication (dated 1976) that demonstrates the correlation of antibody titers with the clinical parameters of myasthenia gravis (Abstract, Introduction). Lindstrom teaches that high titers of antibodies against the acetylcholine receptor (AChR) is only observed in patients with myasthenia gravis (MG) whereas no significant titer of antireceptor antibody was found in subjects without myasthenia gravis (see Figure and Table 1, also Discussion on pages 1057-1058). The Discussion states that “The results thus far obtained indicate that antireceptor antibody is present in the serum of most myasthenia gravis patients and is specific to myasthenia gravis” (see page 1058, right col last two paragraphs). This study suggests that the presence of autoantibodies to AChRs in MG patients is a critical element of proof that MG is caused by an antibody-mediated autoimmune response.
In further support of the criticality of the AChR receptor and the level of knowledge in the field around the time of the invention, Bindu et al. teaches that myasthenia Gravis (MG) is a disorder of impaired neuromuscular transmission recognized as an autoimmune disorder, with a majority of the patients having antibodies against acetylcholine receptor (AChR antibodies) in the serum (Abstract). Bindu teaches that seropositive patients had higher age of onset and presentation, and more frequent occurrence of crises, both at presentation and at any time during the course (Abstract). Bindu also teaches that, in various studies in the art, the overall sero-prevalence of AchR antibody in different studies was varied, and has been noted in the 67-93% range while these antibodies are virtually absent in normal controls or in patients with other neurological or immunological diseases (see pg. 243, under Discussion, right col).
To one of ordinary skill in the art, it would have been obvious to modify the claimed method of the ‘414 patent by providing a composition comprising an antigen to which tolerance is desired; wherein the administration of the composition ameliorates myasthenia gravis, so that the antigen comprises an acetylcholine receptor because providing immunotolerance against antibodies for the acetylcholine receptor would predictably treat myasthenia gravis, as indicated by the teachings of Lindstrom and Bindu indicating the critical role of antibodies against the acetylcholine receptor in this disease.
When seeking to treat myasthenia gravis, one of ordinary skill in the art would have been aware of the critical role of unwanted autoantibodies against the acetylcholine receptor in the pathology of myasthenia gravis, as evidenced by the teachings of Lindstrom and Bindu. When choosing an antigen against which the antigen specific tolerance is sought in a subject having myasthenia gravis, the AChR antibody would clearly be the most promising candidate of the antigen to provide. Therefore, one would have been motivated to provide a composition wherein the antigen to gain tolerance against is an acetylcholine receptor with a reasonable expectation of success as the ‘414 patent claims involve treating myasthenia gravis and unwanted autoimmune action against the acetylcholine receptor is a very well know cause of this disease.
Claims 2-4, 13, 17, and 19 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 9 and 11-14 of copending Application No. 18/758,893 (published as US PGPub 20250059263). Although the claims at issue are not identical, they are not patentably distinct from each other because the reference application claims anticipate those of the instant application.
Claim 9 of the ‘893 application recites a method of treating an unwanted immune response comprising administering to a patient in need thereof a therapeutically effective amount of a pharmaceutically acceptable composition, the composition comprising an erythrocyte-binding moiety, a linker, and a tolerogenic antigen, which are recombinantly fused or chemically conjugated, wherein said erythrocyte-binding moiety is an antibody fragment having the ability to noncovalently specifically bind to glycophorin A on a human erythrocyte in situ in blood, said linker is a peptide, a covalent bond, a nucleic acid or a particle;said tolerogenic antigen is a food antigen to which patients develop an unwanted immune response, wherein the food antigen comprises glutein, low molecular weight glutein, a-gliadin, y-gliadin, hordein, secalin, avenin, or an antigenic fragment of any of the foregoing.
Further, claim 13 of the reference application recites that the unwanted immune response is celiac disease and claim 14 recites that the tolerogenic antigen is gliadin or an antigenic fragment thereof.
Therefore, the methods recited in claims 9 and 13-14 of the ‘893 application are identical to, or substantially identical to, the method of the instant claims such that the subject matter of the reference application is not patentable distinct from the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowable.
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ANDREW T MOEHLMANExaminer, Art Unit 1655
/AARON J KOSAR/Primary Examiner, Art Unit 1655