DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of Claims/Application
The preliminary amendment dated 08/26/2024 is acknowledged. Claims 1, 3, 6, 8, 11, 15, 18, 22, 24, 35, 37, 42, 45, 49, 52, and 53 are amended. Claims 2, 4-5, 7, 9-10, 13, 16-17, 19-20, 25-34, 36, 38, 43, 46-47, 50-51, and 54-60 have been cancelled.
Claims 1, 3, 6, 8, 11, 15, 18, 22, 24, 35, 37, 40-42, 44-45, 48-49, 52, and 53 are currently pending and are examined on the merits herein.
Priority
Applicant's claim for the benefit of a prior-filed application under 35 U.S.C. 119(e)
or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. The instant application is
a National Stage Application of PCT/IB2022/000515, filed on 09/14/2022, and claims
domestic benefit to U.S. provisional application no. 63/244,227, filed on 09/14/2021, U.S. provisional application no. 63/273,105, filed on 10/28/2021, U.S. provisional application no. 63/296,431, filed on 01/04/2022, and U.S. provisional application no. 63/308,011, filed on 02/08/2022.
Information Disclosure Statement
The information disclosure statement (IDS) submitted in the instant application on 03/13/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Specification
The attempt to incorporate subject matter into this application by reference to “See J. Clin. Invest. 2021” ([0320]) is ineffective because a hyperlink is provided. An incorporation by reference by hyperlink or other form of browser executable code is not permitted. See 37 CFR 1.57(e) and MPEP § 608.01.
Appropriate correction is required.
The use of the term Celite, Whatman, Dowex, Slide-A-Lyzer, and Matrigel which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claim 11 is objected to the usage “the composition comprises at least 30 glycopeptide-bound oligosaccharide having a general formulae”. As the claim was amended from “one” to recite 30, the oligosaccharide needs to be in plural.
Claim 52 is objected to the usage “A composition comprising at least 10 glycopeptide-bound oligosaccharide having a general formulae”. As the claim recites at least 10, the oligosaccharide needs to be in plural.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 11, 18, 44-45, and 48-49 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 11 recites several glycopeptide-bound oligosaccharides having a general formulae recited in the format Hex1HexNAc1 or Hex1HexNAc1Sul1, etc. In line 11 (pg. 7), the formula recited “Hex2HexNAc3deHex2 NeuGc1Hex2HexNAc3” is indefinite as it is not clear whether there are two oligosaccharides recited without a comma separation or a single oligosaccharide.
Claim 18 is indefinite as it depends on claim 11 and does not resolve the issue raised in claim 11.
Claim 44 is a method claim that recites steps (a) to (d). In step (d), the claim recites “subjecting the concentrate from (d) to diafiltration”. It is indefinite. For examining purposes, the claim limitation is being interpreted as “subjecting the concentration from (c) to diafiltration”.
Claim 45 is indefinite as it depends on claim 44 and does not resolve the issue raised in claim 44.
Claim 48 is a composition claim, wherein the composition is produced by a method that recites steps (a) to (d). In step (d), the claim recites “subjecting the concentrate from (d) to diafiltration”. It is indefinite. For examining purposes, the claim limitation is being interpreted as “subjecting the concentration from (c) to diafiltration”.
Claim 49 is indefinite as it depends on claim 48 and does not resolve the issue raised in claim 48.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 3, 6, 8, 11, 15, 18, 22, 24, 35, 40 – 42, 44 – 45, 48 – 49, and 52 – 53 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2019/162425 (IDS 03/13/2024) in view of WO 2020/157321 (IDS 03/13/2024) and WO 2020/104486 (IDS 03/13/2024).
WO’425 teaches glycan compositions and products derived therefrom, in particular glycan compositions useful as nutritional supplements, such as infant formula supplement, medical nutrition, domestic animal nutrition, adjuvant for on going treatments, cancer therapeutics and nutraceuticals products that enhance the growth of beneficial microorganisms in the mammalian microbiome, such as Akkermansia muciniphila (pg. 1, lines 4 – 8). There is a need to develop glycan compositions which would stimulate the immune system to recognize cancer cell-borne cell surface glycans and attack such cancer cells (pg. 3, lines 17 – 19). One aspect WO’425 is to provide a mixture of glycans and glycopeptides for use in the treatment of a cancer, in particular in combination with immunotherapy, radio therapy or chemotherapy (pg. 5, lines 20 – 22). The compositions are useful as a pharmaceutical composition to be used in combination with an immune-oncology treatment, e.g., treatment with an immune checkpoint inhibitor targeting the PD-1/PD-L1 axis. The compositions stimulate or prime the immune system to recognize cancer cell surface glycans and thus treat the cancer (pg. 18, lines 5 – 9). A composition or a pharmaceutical formulation thereof is to be administered in combination with another active agent. In one aspect, the pharmaceutical composition of the invention may be administered in combination with an anti-cancer agent, such as at least one immunotherapeutic agent, in particular at least one immune check point inhibitor, such as a PD-1 inhibitor (for example anti-PD-1 antibody selected from nivolumab and pembrolizumab), PD-L1 inhibitor (for example anti-PDL-1 antibody selected from atezolizumab and durvalumab), or CTLA4 inhibitor (for example anti-CTLA4 antibody such as ipilimumab); an anti-CD52 (cluster of differentiation 52) antibody such as alemtuzumab; an anti-CD20 (B-lymphocyte antigen CD20) antibody selected from ofatumumab and rituximab; or at least one agent used in anti-cancer cytokine therapy, such as interferon and interleukin; or at least one agent used in CAR-T therapy, such as anti-CD 19 CAR-T (B-lymphocyte antigen CD19-targeted chimeric antigen receptor T-cell therapy); or at least one agent used in dendritic cell therapy/oncolytic virus therapy. The mixture of glycans and glycopeptides is to be used in combination with an immune checkpoint inhibitor targeting the PD- 1/PD-L1 axis in the treatment of a cancer, particularly a cancer known to be responsive to such a checkpoint inhibitor. A mixture of glycans and glycopeptides for use in the treatment of a cancer as a cancer vaccine or as an immune system primer for subsequent treatment with an antibody that is directed against a cancer cell surface glycan. The term “in combination with” includes the administration of a pharmaceutical composition to an individual prior to, or simultaneously with, or following administration of the other active therapeutic agent. A pharmaceutical composition is to be administered in combination with an anti-cancer agent and additional therapeutic regimens or co-agents useful in the treatment of cancer (e.g. multiple drug regimens). These additional therapeutic regimens or co-agents are administered in a therapeutically effective amount, and include substances useful for treating, stabilizing, preventing, and/or delaying cancer such as substances used in conventional chemotherapy or radiotherapy directed against solid tumors and for control of establishment of metastases or any other molecule that act by triggering programmed cell death or with radio therapy (pg. 18 – 19). Subjects are suffering from a cancer, in particular subjects undergoing immunotherapy, radio therapy or chemotherapy. More particularly, subjects are suffering from a cancer and are undergoing a treatment with immunotherapy such as checkpoint inhibitors, such as PD-1 immunotherapy (for example anti-PD-1 antibody selected from nivolumab and pembrolizumab), PD-L1 inhibitor (for example anti-PDL-1 antibody selected from atezolizumab and durvalumab), or CTLA4 inhibitor (for example anti-CTLA4 antibody selected from ipilimumab) or other anti-cancer agents, for example selected from an anti-CD52 (cluster of differentiation 52) antibody such as alemtuzumab; anti-CD20 (B-lymphocyte antigen CD20) antibody selected from ofatumumab and rituximab; an agent used in anti-cancer cytokine therapy such as interferon and interleukin; an agent in development for anti-cancer therapy such as in anti-CD 19 CAR-T (B-lymphocyte antigen CD19-targeted chimeric antigen receptor T-cell therapy) cell therapy and dendritic cell therapy/oncolytic virus therapy (pg. 20 – 21). WO’425 exemplifies the production of liquid and solid glycan compositions in Example 1 (pg. 21 – 25).
Although WO’425 teaches a method of treating cancer with a glycan composition, WO’425 differs from the instant claims in that WO’425 does not teach the instantly recited glycopeptide composition obtained from gastrointestinal mucins.
WO’321 teaches compositions containing glycopeptides, additionally containing free glycans (i.e., free oligosaccharides), that enhance the growth of beneficial microorganisms in the mammalian microbiome, such as Akkermansia muciniphila, and methods of producing such compositions from gastrointestinal tract mucins (pg. 1, [0002]). WO’321 teaches the crucial role of Akkermansia muciniphila in immune stimulation and metabolic signaling (pg. 2, [0006]). The compositions are obtained from porcine gastric mucus (pg. 3, [0010]). The oligosaccharide-containing compositions obtained from gastrointestinal tract mucins, under conditions wherein the mucins or a partially purified fraction thereof are not subject to conditions or reagents that release, or fully release, oligosaccharides from glycoproteins or glycopeptides, promote beneficial bacteria growth in the gut including growth of Bifidobacterium bifidum, Bifidobacterium animalis subsp. lactis, Bifidobacterium breve, Lactobacillus acidophilus, Lactobacillus reuteri, Akkermansia muciniphila, Bifidobacterium infantis, and Bacteroides thetaiotaomicron (pg. 3, [0011]). A composition comprising glycopeptides obtained from gastrointestinal tract mucins, wherein the composition is obtained without subjecting the mucins or a partially purified fraction thereof to conditions or reagents that release oligosaccharides from glycopeptides; the total oligosaccharide content of the composition is >15% (w/w); the free glycan content of the composition is <1% (w/w); the total glycoprotein content of the composition is 6% or less (w/w); and the composition comprises at least one glycopeptide-bound oligosaccharide having each of the following general formulae: Hex1HexNAc1Fuc1; Hex1HexNAc2; Hex1HexNAc2Fuc1; Hex1HexNAc2Fuc1Sul1; Hex1HexNAc3; Hex2HexNAc2; Hex2HexNAc2Fuc1; Hex2HexNAc2Fuc2; Hex2HexNAc2Fuc2Sul1; Hex2HexNAc3; Hex2HexNAc3Fuc1; Hex2HexNAc4; Hex2HexNAc4Fuc1; and NeuAc1Hex1HexNAc2 (pg. 4, [0013]). The composition does not substantially contain particles having a diameter greater than about 4-8 µm, the composition has a total free amino acid content of 15% or less (w/w), and the composition has a protein content 6% or less (w/w) (pg. 5, [0014]). The composition comprising a mixture of free glycans and glycopeptides is obtained by a method comprising the steps of: suspending mucin powder in a volume of ethanol; mixing the suspension in a volume of 2% aqueous Ca(OH)2 that is at least 10X (e.g., 10-20X) the volume of ethanol and mixing the resulting suspension at a temperature of between 45-55° C for 16-24 hours; subjecting the suspension to centrifugation to separate any remaining insoluble material; neutralizing the supernatant from the centrifugation to a pH of between 7.0 and 7.5; contacting the neutralized supernatant with diatomaceous earth (Celite®) for at least 5 minutes; and filtering the mixture to remove particles larger than about 4-8 µm. In some embodiments, obtaining the composition further comprises contacting the filtrate, obtained from filtering the mixture to remove particles larger than 4-8 µm, with a cation exchange resin at a temperature of between 45-55° C for at least 15 minutes; removing the resin; and optionally drying the filtrate (pg. 7, [0021]). A composition comprising a mixture of glycoproteins obtained from mucins of the outer mucus layer of pig stomach, wherein: a) the composition is obtained without subjecting the mucins to conditions or reagents that release oligosaccharides from glycoproteins and glycopeptides; b) glycoprotein content of the composition is greater than about 70% (w/w); and c) the free glycan content of the composition is less than 1% (w/w), the oligosaccharide content of the composition is greater than or equal to about 35% (w/w), the composition has a salt content of less than about 2%, the composition is a powder and has a glycoprotein content of greater than 75% by weight, or the composition has a free glycan content of less than 0.1% by weight (pg. 9, [0027]). The term "glycoprotein" refers to proteins linked to oligosaccharides, e.g. proteins either N-linked or O-linked to oligosaccharides, and having a molecular weight of more than about 5 KDa. The term "glycopeptide" refers to peptides linked to oligosaccharides, e.g. peptides either N-linked or O-linked to oligosaccharides, and having a molecular weight of less than about 5 KDa (pg. 22, [0105]). The composition comprises glycopeptide-bound oligosaccharides having at least 20, 30, 35, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, or more different structures (pg. 26, [0119]). The protein (e.g., total protein and/or glycoprotein) content of the composition is less than about 12% (w/w) (pg. 31, [0136]). The composition comprises glycopeptide-bound oligosaccharides of several different structures including NeuAcα2-3Galβ1-3GalNAc (pg. 7, [0020]) and Galβ1-3(NeuAcα2-6)GalNAc (pg. 26, [0117]). WO’321 exemplifies a composition, GBX101 in Example 2 with glycan content of 12.06% (pg. 72, [0238]) and protein content of 11.7% (pg. 81, [0241]) that list several oligosaccharide species present on glycopeptides in Table 2 (pg. 72, [0239]). WO’321 exemplifies the production of GBX102, a composition derived from a sample of slime from pig stomachs in Example 8 (pg. 95 – 99, [0316 – 0329]).
WO’486 teaches compositions containing glycopeptides and products derived therefrom, in particular compositions useful as nutritional supplements, such as medical nutrition, domestic animal nutrition, and nutraceutical products that enhance the growth of beneficial microorganisms in the mammalian microbiome, such as Akkermansia muciniphila, and promote production of short-chain fatty acids (SCFA) in the gut (pg. 1, [0002]). WO’486 teaches the significance of Akkermansia muciniphila, and teaches that a correlation between clinical responses to immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis (Programmed cell death protein 1/ Programmed death-ligand 1) in cancer patients (non-small cell lung carcinoma, renal cell carcinoma) and the relative abundance of Akkermansia muciniphila was found. In particular, it was shown that fecal microbiota transplantation (FMT) from cancer patients who responded to ICIs into germ-free or antibiotic-treated mice ameliorated the antitumor effects of PD-1 blockade (pg. 3, [0009]). WO’486 teaches a composition comprising a mixture of glycopeptides obtained from gastrointestinal tract mucins (pg. [0004]). The composition comprises at least one glycoprotein- or glycopeptide-bound oligosaccharide of each of the following general formulae: Hex1HexNAc1, HexNAc2, NeuAc1HexNAc1, NeuGc1HexNAc1, Hex1HexNAc1Fuc1, Hex1HexNAc2, Hex1HexNAc2Sul1, NeuAc1Hex1HexNAc1, NeuGc1Hex1HexNAc1, NeuAc1HexNAc2, NeuGc1HexNAc2, Hex1HexNAc2Fuc1, Hex1HexNAc2Fuc1Sul1, NeuAc1Hex1HexNAc1Fuc1, Hex1HexNAc3Sul1,
Hex2HexNAc2Fuc1, Hex1HexNAc3Fuc1Sul1, and Hex2HexNAc2Fuc2Sul1 (pg. 5, [0005]). The composition does not substantially contain insoluble particles having a diameter greater than 7 µm (pg. 6, [0006]). The composition comprises at least one sialylated glycoprotein- or glycopeptide-bound oligosaccharide, or at least one sialylated glycopeptide-bound oligosaccharides. In some embodiments, the composition comprises at least three sialylated glycoprotein- or glycopeptide-bound oligosaccharides, or at least three sialylated glycopeptide-bound oligosaccharides. In some embodiments, the composition comprises at least six sialylated glycoprotein- or glycopeptide-bound oligosaccharides, or at least six sialylated glycopeptide-bound oligosaccharides. In some embodiments, the composition comprises ten sialylated glycoprotein- or glycopeptide-bound oligosaccharides, or at least ten sialylated glycopeptide-bound oligosaccharides. In some embodiments, the sialylated glycoprotein- or glycopeptide-bound oligosaccharides, or glycopeptide-bound oligosaccharides, are selected from the following: NeuAcα2-6GalNAc, NeuGcα2-6GalNAc, Galβ1-3(NeuAcα2-6)GalNAc, NeuAcα2-3Galβ1-3GalNAc, Galβ1-3(NeuGcα2-6)GalNAc, NeuGcα2-3Galβ1-3GalNAc, GlcNAc-(NeuAcα2-6)GalNAc, GalNAc-(NeuAcα2-6)GalNAc, HexNAc-(NeuGcα2-6)GalNAc, and Fucα1-2Galβ1-3(NeuAcβ2-6)GalNAc. The composition comprises at least 1, 2, 3, 4, 5, 6, 7, 8, 9, or all 10 sialylated glycoprotein- or glycopeptide-bound oligosaccharides, or glycopeptide-bound oligosaccharides (pg. 7, [0008]). The oligosaccharide content of the composition is >10% (w/w) and in some embodiments, the composition has substantially no free glycans (w/w) [pg. 7, [0009]). The gastrointestinal tract mucins are porcine gastrointestinal tract mucins [pg. 8, [0012]). The resulting composition comprising a mixture of glycopeptides comprises glycopeptide-bound oligosaccharides having at least 28, 29, or 30 different structures (pg. 11, [0021]). The protein content of the composition is less than 10% (w/w) (pg. 24, [0093]). The composition comprises glycoprotein- or glycopeptide-bound oligosaccharides having at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, at least 24, at least 25, at least 26, at least 27, or all of the following structures: Galβ1-3GalNAc, GlcNAcβ1 -6GalNAc, NeuAcα2-6GalNAc, NeuGcα2-6GalNAc, Fucα1-2Galβ1-3GalNAc, Gal+GlcNAcβ1 -6GalNAc, Galβ1-3(GlcNAcβ1-6)GalNAc, Galβ1-3GlcNAcβ1 -6GalNAc, Galβ1-3(GlcNAcβ1 -6)GalNAc, Galβ1-3(6SGlcNAcβ1-6)GalNAc, Galβ1-3(NeuAcα2-6)GalNAc, NeuAcα2-3 Galβ1-3GalNAc, Galβ1-3(NeuGcα2-6)GalNAc, NeuGcα2-3 Galβ1-3GalNAc, GlcNAc-(NeuAcα2-6)GalNAc, GalNAc-(NeuAcα2-6)GalNAc, HexNAc-(NeuGcα2-6)GalNAc, Fucα1 -2(GalNAcα1-3)Galβ1-3GalNAc, Fucα1-2Galβ1-4GlcNAcβ1 -6GalNAc, Fucα1-2Galβ1-3(GlcNAcβ1-6)GalNAc, Fucα1-2Galβ1-3(6S-GlcNAcβ1-6)GalNAc, Fucα1-2Galβl-3(NeuAcβ2-6)GalNAc, GlcNAcβ1 -3 [Galβ1-4(6S)GlcNAcβ1-6]GalNAc, Galβ1-4GlcNAcβ1-3[(6S)GlcNAcβ1-6]GalNAc, Galβ1-3(Fucα1 -2Galβ1-4GlcNAcβ1 -6)GalNAc, Fucα1-2Galβ1-4(6S)GlcNAcβ1-6[GlcNAcβ1-3]GalNAc, GlcNAcβ1-3[Fucα1-2Galβ1-3(6S-)GlcNAcβ1-6]GalNAc, Fucα1-2Galβ1-3[Fucα1-2Galβ1-4(6S)GlcNAcβ1-6]GalNAc (pg. 27, [0099]). The composition comprises glycoprotein- or glycopeptide-bound oligosaccharides having at least 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, or 40 different structures (pg. 29, [0105]). The composition is capable of inhibiting glycan-mediated binding of one or more pathogenic micro-organisms to mucosal cells when orally administered to a subject. Many pathogens like bacteria, viruses and protozoan parasites, express lectins to attach to the glycans of the epithelial cell surface of the host and colonize or invade the host and cause disease. Sialylated glycans in GNU 100 have structures similar to surface glycans of intestinal epithelial cells (i.e., epithelial cells of the gut). Thus, sialylated glycans in GNU 100 can serve as bacterial lectin ligand analogs blocking bacterial attachment and act as antiadhesive antimicrobials. GNU 100 structures can therefore serve as soluble decoy moieties to prevent pathogen binding and decrease the risk of infections as unbound pathogens are carried downstream and excreted with the feces. Alternatively, GNU 100 structures can bind receptors such as lectins on host cells which could block pathogen binding to host cells via a competition mechanism, reducing risk of infections (pg. 30, [0109]). Methods of manufacturing the compositions are described (pg. 41, [0150]). WO’486 exemplifies the preparation and analysis of GNU100 in Examples 1, 2, 3, 7, and 9. WO’486 teaches the oligosaccharides in GNU100 in Table 1 (pg. 57-58, [0205]). Sialylated glycans have been shown to play an important role in modulation of gut microbiome. GNU 100 antimicrobial proprieties are conferred by its unique formula that includes 30 different glycans, 10 of which have been identified as sialylated glycans (pg. 72, [0284]). Short-chain fatty acids (SCFA) production results from carbohydrate metabolism in the colon and is related with various health effects. The most abundantly produced SCFAs include acetate, propionate and butyrate. Whereas acetate can be used as an energy source for the host and as a potential substrate for lipid synthesis in the body, propionate reduces cholesterol and fatty acid synthesis in the liver (beneficial effect on metabolic homeostasis). Butyrate on the other hand, is a major energy source for colonocytes and induces differentiation in these cells (related to cancer prevention). Positive effects of the investigated substrates on SCFA production therefore include an increase of acetate, propionate and/or butyrate (pg. 74, [0304]).
It would have been obvious to combine WO’425 with WO’321 and WO’486 before the effective filing date of the instantly claimed invention by administering the specific composition comprising oligosaccharide-bound glycopeptides of WO’321 and WO’486 for the treatment of cancer in a subject as taught by WO’425 to arrive at the instantly claimed invention. It would have been prima facie obvious for one of ordinary skill in the art to administer the specific composition comprising oligosaccharide-bound glycopeptides taught by WO’321 and WO’486 to treat cancer and have a reasonable expectation of success because WO’425 teaches that the glycan compositions would stimulate the immune system to recognize cancer cell-borne cell surface glycans and attack such cancer cells, and WO’321 and WO’486 teach specific oligosaccharide-bound glycopeptide composition for stimulating the same bacteria, Akkermansia muciniphila. WO’486 teaches all the structures in instant claim 1 (c) in Table 1.
Regarding claim 3, as WO’425 teaches combination therapy, one of ordinary skill in the art would be motivated to administer the composition comprising glycopeptides taught by WO’321 and WO’486 to treat a tumor that is refractory to immune checkpoint inhibitor therapy.
Regarding claim 6, WO’486 teaches all the sialylated glycopeptide-bound oligosaccharides in Table 1.
Regarding claim 8, WO’425 teaches the administration of the oligosaccharide-bound glycopeptide composition prior to, or simultaneously with, or following administration of the other therapeutic agent. As the oligosaccharide-bound glycopeptide compositions are effective in increasing Akkermansia muciniphila, which has a role in the anti-tumor effects of immune checkpoint inhibitor treatment as taught by WO’486, the compositions would promote the growth of Akkermansia muciniphila which would in turn help reduce or prevent a rise in the level of Monocyte Chemoattract Protein-1 for the cancer treatment to be effective. As 0.5 % or 1.0% GNU 100 in dog and cat lumen samples causes more growth of commensal bacteria, causes increased production of SCFA (e.g., butyrate and/or propionate production), even though WO’486 is silent regarding MCP-1, the activation of the microbiome by the administration of the effective amount of the composition would reduce or prevent a rise in the level of MCP-1 .
Regarding claim 11, WO’486 teaches a composition comprising a mixture of glycopeptides comprises glycopeptide-bound oligosaccharides having at least 28, 29, or 30 different structures and WO’321 teaches a composition comprises glycopeptide-bound oligosaccharides having at least 20, 30, 35, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130 or more different structures (pg. 26, [0119]).
Regarding claim 15, WO’321 and WO’486 teach compositions comprising of Galβ1-3GalNAcol and NeuAcα2-3Galβ1-3GalNAcol in GBX101 and GNU100 respectively.
Regarding claim 18, WO’321 teaches the composition has a salt content of less than 2%, or the composition has a free glycan content of less than 0.1% by weight (pg. 9, [0027]), or the composition has a pH between 7.0 and 7.5 (pg. 8, [0024]).
Regarding claim 22, as the instant disclosure states that the composition is a composition comprising a mixture of glycopeptides or a composition obtained by a purification method provided in WO 2020/104486, published on May 28, 2020 and in some embodiments, the composition is a composition comprising a mixture of glycopeptides or a composition obtained by a purification method provided in WO 2020/157321, published on August 6, 2020 (pg. 52, [0133]), one would expect the compositions of WO’321 and WO’486 to have the oligosaccharides of general formulae recited in the instant claim. MPEP 2112 section I recites "[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). In In re Crish, 393 F.3d 1253, 1258, 73 USPQ2d 1364, 1368 (Fed. Cir. 2004), the court held that the claimed promoter sequence obtained by sequencing a prior art plasmid that was not previously sequenced was anticipated by the prior art plasmid which necessarily possessed the same DNA sequence as the claimed oligonucleotides. The court stated that "just as the discovery of properties of a known material does not make it novel, the identification and characterization of a prior art material also does not make it novel."
Regarding claim 24, WO’486 teaches that the composition GNU 100 includes 30 different glycans, 10 of which have been identified as sialylated glycans. As the instant disclosure states that the composition is a composition comprising a mixture of glycopeptides or a composition obtained by a purification method provided in WO 2020/104486, published on May 28, 2020 (pg. 52, [0133]), even though WO’486 is silent regarding the sialic acid content of the composition, one would necessarily expect the composition of WO’486 to have the recited sialic acid content.
Regarding claim 35, WO’321, WO’486 and WO’425 are silent regarding the administration of the composition for 28 days or more. However, all teach the increase in Akkermansia spp. Hence, one of ordinary skill in the art would be motivated to optimize the treatment regimen to increase the growth of certain beneficial bacteria in the microbiota, such as Akkermansia muciniphila.
Regarding claims 40 – 42 and 44 – 45, these are method claims that have product-by- process steps. Claim 48 is a product-by-process claim. WO’321 teaches the method of producing the compositions. MPEP states "[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985) (See MPEP 2113 (I)).
Regarding claims 52 and 53, the composition of WO’486 and WO’321 teach more than 10 oligosaccharide structures recited and the combination with WO’425 teaches the combined administration of the glycopeptide-bound oligosaccharide composition and a checkpoint inhibitor.
Claim 37 is rejected under 35 U.S.C. 103 as being unpatentable over WO 2019/162425 (IDS 03/13/2024), WO 2020/157321 (IDS 03/13/2024) and WO 2020/104486 (IDS 03/13/2024) as applied to claims 1, 3, 6, 8, 11, 15, 18, 22, 24, 35, 40 – 42, 44 – 45, 48 – 49, and 52 – 53 above, and further in view of WO 2021/022070 (IDS 03/13/2024).
The teachings of WO’425, WO’321, and WO’486 are as discussed above.
The combined teachings of WO’425, WO’321, and WO’486 differ from the instantly claimed invention in that they do not teach the method of treating cancer in a subject with stage 3 or 4 cancer selected from melanoma, colorectal cancer, breast cancer or lung cancer.
WO’070 teaches compositions and methods related generally to the fields of prebiotics, cancer, and anti-cancer immunity (pg. 1, [0003]). A method of enhancing anti-cancer immunity comprising: (a) administering to a subject a composition comprising mucin, wherein the subject has been identified as having a gut microbiome comprising one more microbial taxa that are members of a Clostridium cluster XlVa or an Actinobacteria phylum; and (b) altering the gut microbiome in the subject, wherein administration of the composition causes an enhanced anti-cancer immunity in the subject (pg. 1, [0006]). The gastrointestinal (GI) tract harbors a complex and dynamic population of bacteria referred to as the gut microbiota. The gut microbiota can affect key components of host physiology and homeostasis, and the composition of the gut microbiota is implicated in the maintenance of health in the onset and progression of disease, including cancer. Alterations in gut microbiota composition have been associated with, for example, the development and function of the immune system, cancer progression or control, and responsiveness to anti-cancer therapies. Strategies that alter the gut microbiota have the potential to reduce cancer growth or progression, for example, by promoting more effective anti-cancer immune responses. Prebiotics can alter the composition of the microbiota, for example, by providing nutrients that favor expansion of certain microbial taxa. WO’070 teaches methods for treating, reducing, or ameliorating cancer in a subject, by administering to the subject at least one prebiotic. For example, mucin and inulin are shown to promote expansion of microbial taxa that negatively correlate with tumor size, and promote anti -tumor immune responses in the subject (pg. 10, [0029 – 0030]). In some embodiments, a prebiotic is used to treat, reduce, ameliorate or prevent melanoma. In some embodiments, a prebiotic is used to treat, reduce, ameliorate or prevent colorectal cancer. In some embodiments, co-administration of a prebiotic with an additional agent results in an additive therapeutic effect. An additional agent can be, for example, a second prebiotic, a probiotic, or a drug (e.g., an anti-cancer agent, a kinase inhibitor, an immune checkpoint inhibitor, an antibiotic, a chemotherapeutic, a CAR-T cell, a transgenic T cell, etc.). An additive therapeutic effect can be, for example, increasing survival likelihood, preventing or delaying cancer progression, preventing or delaying tumor growth, inducing cancer remission, increasing the likelihood of progression-free survival, or a combination thereof (pg. 21-22, [0073 – 0074]).
It would have been obvious to combine WO’425, WO’321, WO’486 with WO’070 before the effective filing date of the instantly claimed invention in a method of treating cancer in a subject with stage 3 or 4 melanoma, colorectal cancer, breast cancer or lung cancer as WO’070 teaches methods and compositions comprising mucins to treat, reduce, ameliorate or prevent melanoma or colorectal cancer to arrive at the instantly claimed invention. Even though WO’070 is silent regarding the stage 3 or 4 cancers, one of ordinary skill in the art would be motivated to use the glycan compositions taught by the combined teachings of WO’425, WO’321, and WO’486 for the treatment of the recited cancers in a subject and have a reasonable expectation of success as WO’070 teaches that compositions comprising of mucins activate the gut microbiome which enhances the anti-cancer immunity in a subject and co-administration of a prebiotic with an additional agent results in an additive therapeutic effect, wherein an additional agent can be, for example, a second prebiotic, a probiotic, or a drug (e.g., an anti-cancer agent, a kinase inhibitor, an immune checkpoint inhibitor, an antibiotic, a chemotherapeutic, a CAR-T cell, a transgenic T cell, etc.) (pg. 21-22, [0073 – 0074]).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 3, 6, 8, 11, 15, 18, 22, 24, 35, 40 – 42, 44 – 45, 48 – 49, and 52 – 53 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4 – 8, 10, 12, and 14 – 15 of U.S. Patent No. 12550924 (PTO-892) in view of WO 2019/162425 (IDS 03/13/2024).
Although the claims at issue are not identical, they are not patentably distinct
from each other because claims 1, 4 – 8, and 14 – 15 of the ‘924 patent claim the glycoprotein-bound oligosaccharide composition similar to that of the instantly claimed invention. Claims 10 and 12 of the ‘924 patent claim the method of treating an unbalance of the microbiota causing the significant growth of Akkermansia muciniphila by the administration of the composition to a subject.
The claims of the ‘924 patent differ from the instantly claimed invention in that
the methods and composition are not used to treat cancer.
WO’425 teaches glycan compositions and products derived therefrom, in particular glycan compositions useful as nutritional supplements, such as infant formula supplement, medical nutrition, domestic animal nutrition, adjuvant for on going treatments, cancer therapeutics and nutraceuticals products that enhance the growth of beneficial microorganisms in the mammalian microbiome, such as Akkermansia muciniphila (pg. 1, lines 4 – 8).
It would have been obvious to combine ‘924 patent with WO’425 before the effective filing date of the instantly claimed invention by administering the composition comprising glycopeptides of ‘924 patent for the treatment of cancer in a subject as taught by WO’425 to arrive at the instantly claimed invention. It would have been prima facie obvious for one of ordinary skill in the art to administer the composition comprising glycopeptides claimed by ‘924 patent to treat cancer and have a reasonable expectation of success because WO’425 teaches that the glycan compositions would stimulate the immune system to recognize cancer cell-borne cell surface glycans and attack such cancer cells.
This is a nonstatutory double patenting rejection.
Claims 1, 3, 6, 8, and 37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 9 of Application No. 19/183,744.
Claims 1, 3, 6, 8, and 37 of this application are patentably indistinct from claims 1 – 9 of co-pending Application No. 19/183,744.
Claims 1 – 9 of the co-pending application recite a method of treating cancer in a mammal thereof wherein a standard therapy for the cancer is 5FU, the method comprising administering to the mammal an effective amount of a composition comprising a plurality of glycopeptides, wherein the cancer is selected from melanoma, breast cancer, lung cancer or colorectal cancer (CRC), wherein the composition is administered to the mammal for 28 days or more, wherein the plurality of glycopeptides is derived from porcine gastrointestinal mucins, and wherein the composition is obtained without subjecting the porcine gastrointestinal mucins to conditions or reagents that cause release of oligosaccharides from glycopeptides, wherein the cancer is stage 3 or 4 cancer, wherein the cancer is resistant to checkpoint inhibitor therapy, further comprising administering to the recipient mammal an immune checkpoint inhibitor before, after, or simultaneously with the composition and the immune checkpoint inhibitor is an anti-PD1 antibody or an anti-PDL1 antibody.
Claim 1 of the ‘744 application differ from the instantly claimed invention in that the ‘744 application includes 5FU along with the glycopeptide composition.
As both sets of claims recite a method of treatment of cancer by the administration of the glycopeptide composition, even though they are not exactly matching, they are overlapping in scope. Thus rendering one set of claims to be unpatentable.
This is a nonstatutory double patenting rejection.
Conclusion
Claims 1, 3, 6, 8, 11, 15, 18, 22, 24, 35, 37, 40-42, 44-45, 48-49, 52, and 53 are rejected.
No Claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JANAKI ANANTH MAHADEVAN whose telephone number is (571)272-0230. The examiner can normally be reached Monday-Friday 8-5PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Scarlett Goon can be reached at 5712705241. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/J.A.M./Examiner, Art Unit 1693
/SCARLETT Y GOON/Supervisory Patent Examiner, Art Unit 1693
Prosecution Insights