DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2 Applicant's amendment, filed on 10/14/2022, is acknowledged.
3. Claims 16-35 are pending.
4. Applicant’s election with traverse the species of (i) SEQ ID NO: 1 (sh28GST) as the specific polypeptide (ii) Betcet’s disease (BD) as a specific vasculitis condition, filed on 01/02/2026, is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.03(a)).
5. Claims 20, 22, 25, 27, 30 and 35 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions.
6. Claims 16-19, 21, 23-24, 26 and 28-34 are under examination as they read on an antibody that specifically binds the av subunit of integrin, an antibody that specifically binds the b3 subunit of integrin and antibodies that specifically bind to the av and b3 subunits of integrin.
7. Applicant’s IDS, filed 10/14/2022 and 01/18/2023, is acknowledged.
8. The following is a quotation of 35 U.S.C. 112(a) (Pre-AIA 35 U.S.C. 112, first paragraph):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
9. Claims 16-19, 21, 23-24, 26 and 28-34 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 16, 18, 21, 31 and dependent claims thereof encompass a broad genus of sh28GST polypeptides comprising/consisting of a fragment of a sequence of SEQ ID NO: 1 or a sequence having at least 80% of identity with SEQ ID NO: 1 which decreases the M1-type immune response and/or increases the M2-type immune response for the preventive or therapeutic treatment of vasculitis or a disease characterized by a M1/M2 macrophage ratio dysregulation.
However, there does not appear to be an adequate written description in the specification as-filed of the essential structural feature that provides the recited function of decrease the M1-type immune response and/or increase the M2-type immune response for the preventive or therapeutic treatment of vasculitis or a disease characterized by a M1/M2 macrophage ratio dysregulation. The Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, ¶ 1 "Written Description" Requirement make clear that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the genus.
The specification at [0223] discloses that the “variant”, “homologue” or “derivative” polypeptides are defined as comprising a sequence identical to at least 80%, preferably at least 85%, more preferably at least 90%, even at least 95%, 96%, 97%, 98% or 99% of the reference sequence.
The specification at [0226] discloses that by “amino acid sequence having (for instance) at least 80% of identity with a reference sequence” is meant herein a sequence identical to the reference sequence but this sequence may comprise up to twenty mutations (substitutions, deletions and/or insertions) per each part of one hundred amino acids of the reference sequence. Therefore, for a reference sequence of 100 amino acids, a fragment of 80 amino acids and a sequence of 100 amino acids comprising 20 substitutions compared with the reference sequence are two examples of sequences having 80% sequence identity with the reference sequence.
The specification at [0229] discloses a) a sequence having at least 80%, 85%, 90%, 95% or 100% of identity with the amino acid sequence SEQ ID NO: 1.
There is insufficient written description in the specification as-filed of the claimed method of decreasing the M1-type immune response and/or increasing the M2-type immune response by administering fragments and variants of SEQ ID NO: 1 (sh28GST).
The specification is not considered representative to fragments of SEQ ID NO: 1 or a sequence having at least 80% of identity with SEQ ID NO: 1.
The claims encompass antibodies in which modification (e.g., functionally active variants, % identity) of the amino acids of SEQ ID NO: 1 via addition, deletion, substitution or insertion of one or more amino acids. The specification discloses only one species within the instant claim scope. Besides SEQ ID NO: 1, the instant application encompasses (but does not exemplify) (deletion/addition/substitution) to the claimed SEQ ID NO: 1. There is no teaching identifying what amino acids can be varied within SEQ ID NO: 1 and still retain the function of decreasing the M1-type immune response and/or increasing the M2-type immune response and preventing and treating vasculitis or a disease characterized by a M1/M2 macrophage ratio dysregulation.
Further, with respect to the sh28GST variants, note that while it is not required that all potential embodiments be disclosed, the written description doctrine requires that sufficient representing species be disclosed in order to support the entire genus. Rather than simply listing various embodiments, the usual approach is to also describe common structural features of the species. See Regents of the University of California v. Eli Lilly & Co., 119 F.3d 1559 (Fed. Cir. 1997) and Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1355 (Fed. Cir. 2010).
The Federal Circuit has again recently discussed the inherent unpredictability of protein engineering in the Abbvie case, Abbvie Deutschland Gmbh & Co KG, Abbvie Bioresearch Center, Inc., and Abbvie Biotechnology, Ltd., v. Janssen Biotech In. And Centocor Biologics, LLC, Case No. 2013-1338 and 2013- 1346, C.A.Fed. ("Abbvie"). While Abbvie, similar to the previously discussed Novozymes case, is concerned with the written description requirement under §112, the Federal Circuit reiterates the inherent unpredictability of protein engineering in Abbvie: For example, functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description support, especially in technology fields that are highly unpredictable, where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus. Ariad, 598 F.3d at 1351 ("[T]he level of detail required to satisfy the written description requirement varies depending on the nature and scope of the claims and on the complexity and predictability of the relevant technology."); see also Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341, 1352 (Fed. Cir. 2011) (noting the technical challenges in developing fully human antibodies of a known human protein). It is true that functionally defined claims can meet the written description requirement if a reasonable structure-function correlation is established, whether by the inventor as described in the specification or known in the art at the time of the filing date. Enzo Biochem, Inc. v. Gen-Probe Inc., 323 F.3d 956, 964 (Fed. Cir. 2002). However, the record here does not indicate such an established correlation. Instead, AbbVie used a trial and error approach to modify individual amino acids in order to improve the IL-12 binding affinity. Moreover, the '128 and '485 patents do not describe any common structural features of the claimed antibodies. The asserted claims attempt to claim every fully human IL-12 antibody that would achieve a desired result, i.e., high binding affinity and neutralizing activity, and cover an antibody as different as Stelara, whereas the patents do not describe representative examples to support the full scope of the claims.
The facts of Abbvie parallel the claimed invention and provide significant guidance on the inherent unpredictability of protein engineering and the effect of amino acid substitutions on protein function. Abbvie is similar to the Federal Circuit's discussion in Novozymes A/S et al. v. Dupont Nutrition Biosciences APS et al., 2013 WL 3779376, Case No. 2012-1433, C.A.Fed; in both, the Federal Circuit emphasized the unpredictability in the art associated with changes in a parent enzyme or protein that can be effected at one or more positions in the sequence by amino acid addition, deletion, or substitution with at least nineteen other possibilities, e.g. counting natural amino acid residues. The basis of the unpredictability is rooted in the same principles that make improvements rare, namely that numerous subtle differences between amino acid residues determine protein binding and function. Because the subtle energetic contributions of each of these interactions is extraordinarily difficult to precisely quantify, and because the number of these interactions is so high even for a single protein-protein interface, innumerable small inaccuracies are amplified into unpredictability. This unpredictability is axiomatic in the field of protein engineering.
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the written description inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116.). Consequently, Applicant was not in possession of the instant claimed invention. See University of California v. Eli Lilly and Co. 43 USPQ2d 1398.
Applicant is invited to point to clear support or specific examples of the claimed invention in the specification as-filed.
10. The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
11. Claims 16-17 and 23-24 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US9593313 B2.
The `313 patent teaches methods of preventing and/or therapeutically treating a chronic inflammatory disease connected with an immune system disorder generating an immune response of type Th1/Th17, comprising administering to a subject in need thereof an effective amount of a product consisting of a protein, thereby leading to the induction of a Th2 response and/or the decrease of the Th1 response, wherein:
said protein comprises or is constituted by the 28 kDa glutathione S-transferase protein from a schistosome selected from the group consisting of Schistosoma haematobium, Schistosoma mansoni, and Schistosoma bovis represented by the sequences SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3, respectively, wherein said protein is represented by the sequence SEQ ID NO: 1, wherein, said disease is selected from the autoimmune inflammatory diseases consisting of Berger's disease, Basedow's disease, Hashimoto's thyroiditis, primary myxoedema, coeliac disease, ulcerative colitis, Crohn's disease, rheumatoid arthritis, primary biliary cirrhosis, primary sclerosing cholangitis, autoimmune haemolytic anaemias, Biermer's anaemia (pernicious anaemia), lupus erythematosus, CREST syndrome, type 1 diabetes, scleroderma, pemphigus vulgaris, bullous pemphigoid, acquired epidermolysis bullosa, dermatitis herpetiformis, myasthenia, Lambert-Eaton myasthenic syndrome, polymyositis, Goujerot-Sjögren syndrome, multiple sclerosis, rheumatoid arthritis, Graves' disease and psoriasis, wherein the pharmaceutical composition further comprises an adjuvant selected from the aluminium salts or aluminium hydroxide (see issued claims 1-10). The `313 patent teaches that the rats in group A received three injections (respectively on D0, D14 and D28) of 5ug/kg of rSh28GST in combination with aluminium hydroxide (alum) (see Figs 11, 14 and cols. 18-19, bridging ¶ and col., 10, lines 36-37). The `313 patent teaches fragments of SEQ ID NOs: 1-3 that induces a type-Th1 immune response wherein the fragments comprising at least the region comprised from positions 15 to 60, 20-50, 24 to 43, 170 to 220, 180 to 215, and 190 to 211 of the sequence SEQ ID NO: 1-3 (see col., 2, lines 10+). Further, the `313 patent teaches a polypeptide comprising an identity of at least 80% and 85% with one of SEQ ID NO: 1-3, provided that said homologous sequence induces a type-Th2 response; for use in the preventive and/or therapeutic treatment of a chronic inflammatory disease connected with an immune system disorder generating an immune response of type Th1/Th17 (col., 2, lines 45+ and col., 4, lines 40+).
Claim 17 is induced because the administration of the referenced S “vasculitis” or “a disease characterized by a M1/M2 macrophage ration dysregulation” would be “prevented” in the absent of evidenced to the contrary.
Alignment between claimed/patented SEQ ID NO: 1.
Qy 1 MTGDHIKVIYFNGRGRAESIRMTLVAAGVNYEDERISFQDWPKIKPTIPGGRLPAVKITD 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2 MTGDHIKVIYFNGRGRAESIRMTLVAAGVNYEDERISFQDWPKIKPTIPGGRLPAVKITD 61
Qy 61 NHGHVKWMVESLAIA RYMAKKHHMMGGTEEEYYNVEKLIGQAEDLEHEYYKTLMKPEEEK 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 62 NHGHVKWMVESLAIA RYMAKKHHMMGGTEEEYYNVEKLIGQAEDLEHEYYKTLMKPEEEK 121
Qy 121 QKIIKEILNGKVPVLLDIICESLKASTGKLAVGDKVTLADLVLIAVIDHVTDLDKEFLTG 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 122 QKIIKEILNGKVPVLLDIICESLKASTGKLAVGDKVTLADLVLIAVIDHVTDLDKEFLTG 181
Qy 181 KYPEIHKHRENLLASSPRLAKYLSDRAATPF 211
|||||||||||||||||||||||||||||||
Db 182 KYPEIHKHRENLLASSPRLAKYLSDRAATPF 212
Alignment between claimed/patented SEQ ID NO:1/ 2 Query Match 91.6%
Qy 1 MTGDHIKVIYFNGRGRAESIRMTLVAAGVNYEDERISFQDWPKIKPTIPGGRLPAVKITD 60
| |:|||||||:|||||||||||||||||:|||||||||||||||||||||||||||:||
Db 1 MAGEHIKVIYFDGRGRAESIRMTLVAAGVDYEDERISFQDWPKIKPTIPGGRLPAVKVTD 60
Qy 61 NHGHVKWMVESLAIA RYMAKKHHMMGGTEEEYYNVEKLIGQAEDLEHEYYKTLMKPEEEK 120
:|||||||:||||||||||||||||| |:||||:||||||||||:||||:||||||:|||
Db 61 DHGHVKWMLESLAIA RYMAKKHHMMGETDEEYYSVEKLIGQAEDVEHEYHKTLMKPQEEK 120
Qy 121 QKIIKEILNGKVPVLLDIICESLKASTGKLAVGDKVTLADLVLIAVIDHVTDLDKEFLTG 180
:|| ||||||||||||::|||||| |||||||||||||||||||||||||||||| ||||
Db 121 EKITKEILNGKVPVLLNMICESLKGSTGKLAVGDKVTLADLVLIAVIDHVTDLDKGFLTG 180
Qy 181 KYPEIHKHRENLLASSPRLAKYLSDRAATPF 211
||||||||||||||||||||||||:| ||||
Db 181 KYPEIHKHRENLLASSPRLAKYLSNRPATPF 211
Alignment between claimed/patented SEQ ID NO:1/ 3 Query Match 97.4%
Qy 1 MTGDHIKVIYFNGRGRAESIRMTLVAAGVNYEDERISFQDWPKIKPTIPGGRLPAVKITD 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MTGDHIKVIYFNGRGRAESIRMTLVAAGVNYEDERISFQDWPKIKPTIPGGRLPAVKITD 60
Qy 61 NHGHVKWMVESLAIA RYMAKKHHMMGGTEEEYYNVEKLIGQAEDLEHEYYKTLMKPEEEK 120
||||||||:||||||||||||||||| |:|||||||||||| |||||||:||||||||||
Db 61 NHGHVKWMLESLAIA RYMAKKHHMMGETDEEYYNVEKLIGQVEDLEHEYHKTLMKPEEEK 120
Qy 121 QKIIKEILNGKVPVLLDIICESLKASTGKLAVGDKVTLADLVLIAVIDHVTDLDKEFLTG 180
||| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 QKITKEILNGKVPVLLDIICESLKASTGKLAVGDKVTLADLVLIAVIDHVTDLDKEFLTG 180
Qy 181 KYPEIHKHRENLLASSPRLAKYLSDRAATPF 211
|||||||||||||||||||||||||||||||
Db 181 KYPEIHKHRENLLASSPRLAKYLSDRAATPF 211
The prior art reference meets the single step method of administering the sh28GST polypeptides to a patient. The mechanism of action "decreasing the M1-type immune response and/or increasing the M2-type immune response" is expressions of purposes and intended results, and as such are non-limiting, since language does not result in manipulative differences in steps of claims. It does not appear that the claim language or limitations result in a manipulative difference in the method steps when compared to the prior art disclosure. In re Hirao 190 USPQ 15, 15-16, (CCPA 179) held that the preamble was non-limiting because it merely recited the purpose of the process, which was fully set forth in the body of the claim.
The mechanism of action does not have a bearing on the patentability of the invention if the
invention was already known or obvious. Even though applicant has proposed or claimed the mechanism by decreasing the M1-type immune response and/or increasing the M2-type immune
response in the subject alleviates symptoms of a subject characterized by a M1/M2 macrophage immune response does not appear to distinguish the prior art teaching the same or nearly the same methods to achieve the same end-result. Mere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention. In re Wiseman, 201 USPQ 658 (CCPA 1979). Granting a patent on the discovery of an unknown but inherent function would remove from the public that which is in the public domain by virtue of its inclusion in, or obviousness from, the prior art. In re Baxter Travenol Labs, 21 USPQ2d 1281 (Fed. Cir. 1991). See M.P.E.P. 2145.
It is clear that both the `313 patent and applicant administer the same composition comprising the same sh28GST to the same subject to achieve the same results. The prior art and applicant have suggested different mechanisms. It is acknowledged that applicant now recites and believes in a different mechanism of action than the prior art. However, the instant methods do not negate or preclude the mechanism of action indicated by the prior art nor does applicant provide objective evidence to distinguish the prior art from the claimed invention.
The reference teachings anticipate the claimed invention.
11. Claims 16-17, 21, 23, 24, 28-29, 31-33 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Riveau et al (PLoS Negl Trop Dis. 2012 Jul 3;6(7):e1704).
Riveau et al teach therapeutic vaccines represent an attractive tool in the fight against schistosomiasis. Riveau et al assess the safety and immunogenicity of the recombinant 28GST of Schistosoma haematobium (rSh28GST) (i.e., claimed SEQ ID NO: 1) in healthy adult volunteers (i.e., subjects). After three administrations of 100 µg or two of 300 µg, no serious adverse events were reported in the days or weeks after each administration. Some mild adverse events were noted, including minor reactions at the injection site reported for four subjects receiving rSh28GST, but there was no hematological or biochemical evidence of toxicity. Immunological analysis showed that rSh28GST induced a consistent immune response characterized by antibodies endowed with the capacity to inhibit 28GST enzymatic activity. Present data provide evidence that clinical trials with rSh28GST could be continued in humans as a potential vaccine candidate against urinary schistosomiasis. Riveau et al concluded that rSh28GST in Alum (adjuvant) did not induce any significant toxicity in healthy adults and generated a Th2-type immune response. Together with previous preclinical results, the data of safety, tolerability and quality of the specific immune response provide evidence that clinical trials with rSh28GST could be continued in humans as a potential vaccine candidate against urinary schistosomiasis (see Abstract and Author Summary). Riveau et al teach that the cytokine production after in vitro stimulation with rSh28GST of cultured mononuclear cells from immunized patients. This showed a high level of the Th2- type cytokines IL-5 and IL-13 after the second vaccine administration.
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Claim 2 is included because the reference method of vaccination would prevent vasculitis or a disease characterized by a M1/M2 macrophage ration dysregulation recited in the claim.
The reference teachings anticipate the instant claims.
12. 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.
13. Claims 16-19, 21, 23-24, 26 and 28-34 are rejected under 35 U.S.C. 103 as being unpatentable over US9593313B2 in view of Nanke et al (J Clin Med . 2017 Jul 21;6(7):74. doi: 10.3390/jcm6070074)
The teachings of the `313 patent has been discussed, supra. The `313 patent further teaches and claims methods of preventing and/or therapeutically treating a chronic inflammatory disease connected with an immune system disorder generating an immune response of type Th1/Th17, comprising administering to a subject in need thereof an effective amount of a product consisting of a protein, thereby leading to the induction of a Th2 response and/or the decrease of the Th1 response, wherein:
said protein comprises or is constituted by the 28 kDa glutathione S-transferase protein from a schistosome selected from the group consisting of Schistosoma haematobium, Schistosoma mansoni, and Schistosoma bovis represented by the sequences SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3, respectively, wherein said protein is represented by the sequence SEQ ID NO: 1, wherein the concentration of adjuvant in the pharmaceutical composition is selected from the group consisting of from 0.5 mg/ml to 2 mg/ml, from 0.3 mg/ml to 1 mg/ml, from 220 μg/ml to 280 μg/ml, and approximately equal to 250 μg/ml (see issued claims 1-10, col., 6, lines 33+).
Surprisingly, the Sh28GST protein makes it possible, by generating an anti-inflammatory type-Th2 response, to reduce the Th1-type response. This decrease in the Th1-type response makes it possible to reduce the symptoms associated with the aforementioned disease, in particular the inflammation. Acting in particular on the interleukins that are present throughout the body, the protein can therefore be used for the preventive or therapeutic treatment of a disease such as mentioned above affecting any organ or even the whole body. The same effects may be envisaged for all the products of the invention (col 8, lines 27+).
a Th1-type response is defined as being characterized by the presence of lymphocytes producing cytokines such as IFN gamma but not producing IL-4 or IL-5. This response also leads to the production of TNF. A type-Th2 response is characterized by the presence of lymphocytes producing cytokines such as IL-4, IL-5 or IL-13 but without producing IFN gamma. The response of type Th17 is an inflammatory response where the lymphocytes produce IL-17 or IL-25, in addition to the TNF produced by many cellular types (see col., 4, lines 49+).
The `313 patent further teaches the composition may comprise an adjuvant, such as aluminium salts and more particularly aluminium hydroxide. The term "aluminium salts' denotes all the natural or non-natural aluminium salts. (see issued claim 9, and col., 6, lines 46+).
The `313 patent teaches that the rats in group A received three injections (respectively on D0, D14 and D28) of 5ug/kg of rSh28GST in combination with aluminium hydroxide (alum) (see Figs 11, 14 and cols. 18-19, bridging ¶ and col., 10, lines 36-37).
The reference teachings differ from the claimed invention only in the recitation that the chronic inflammatory disease is Behçet's disease in claims 26 and 34.
Nanke et al Behçet's disease (BD) is a polysymptomatic and recurrent systemic vasculitis with a chronic course and unknown cause. The pathogenesis of BD has not been fully elucidated; however, BD has been considered to be a typical Th1-mediated inflammatory disease, characterized by elevated levels of Th1 cytokines such as IFN-γ, IL-2, and TNF-α. Recently, some studies reported that Th17-associated cytokines were increased in BD; thus, Th17 cells and the IL17/IL23 pathway may play important roles in the pathogenesis of BD. In this chapter, we focus on the pathogenic role of Th17 cells in BD (abstract). Nanke et al teach that IL-17 and IFN-γ expressing CD4+memory T cells were significantly increased in patients with BD compared with healthy controls (HC). In addition, IL-17, IL-23, IL-12/23p40, and IFN-γ in serum and supernatants were significantly elevated in active BD patients compared with HC. IFN-γ-secreting Th17 cells have been found to be elevated in BD patients. Thus, BD is associated with a mixture of TH1/Th17 cytokines. Patients with BD in remission expressed low Th17 levels compared to active BD. Thus, the population of Th17 cells is correlated with BD activity (see section 3.2).
Those of skilled in the art would have had a reason to treat the Th1-mediated Behçet's disease characterized by elevated levels of Th1 cytokines taught by Nanke et al, with the sh25GST polypeptides in the prevention and/or therapeutically treatment taught by the `313 patent because like the inflammatory diseases taught by the `313 patent, Behçet's disease is a Th1-mediated inflammatory disease in view of the known utility of sh28GST in treating Th1/Th17-mediated diseases as taught by `313 patent would be an obvious, significant and promising direction in the development of therapies for the treatment of Behçet's disease.
From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
14. No claim is allowed.
15. The art made of record and not relied upon is considered pertinent to applicant's disclosure:
Capron et al. Safety of P28GST, a Protein Derived from a Schistosome Helminth Parasite, in Patients with Crohn’s Disease: A Pilot Study (ACROHNEM). J. Clin. Med. 2020, 9, 41; doi:10.3390/jcm9010041
Capron et al teach that among patients with mild CD, P28GST treatment was rather safe. The various scores and blood markers tested showed no increases with treatment. Because this investigation was a pilot study, these findings should not be over-interpreted; however, our preliminary data indicated that P28GST was safe and tolerable in patients with mild CD and shows therapeutic potential. Several questions remain to be investigated regarding the use of P28GST in intestinal diseases, such as: what are the appropriate dosing regimens? And, what is
the optimal timing for treatment? Moreover, we lack elucidation of the exact mechanisms that give rise to the protective e_ects of P28GST. Fully powered clinical studies with adequate sample sizes and randomization are required to validate these results. Moreover, future studies should extend the patient population to include patients with more severe CD and ulcerative colitis (see section 5).
16. Any inquiry concerning this communication or earlier communications from the examiner should be directed to MAHER M HADDAD whose telephone number is (571)272-0845. The examiner can normally be reached on Monday-Friday from7:00AM to 4:30PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu, can be reached at telephone number 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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January 13, 2026
/MAHER M HADDAD/ Primary Examiner, Art Unit 1644