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
Amendment filed on March 24, 2023 is acknowledged.
Claims 1-14 are amended.
Claims 15-18 are new.
Claims 1-18 are pending and under consideration.
Information Disclosure Statement
The information disclosure statement (IDS) filed on March 24, 2023 and November 1, 2024 are considered, initialed and are attached hereto.
Priority
Applicant’s claim for priority to Korean Patent Application No. 10-2020-0125197, filed on September 25, 2020, is acknowledged.
Election/Restriction
Applicant’s election of species of a peptide comprising the amino acid sequence of SEQ ID NO: 42 in the reply filed on April 27, 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 § 818.01(a)).
The requirement is still deemed proper and is therefore made FINAL.
Applicant’s comment on elected allowable claims is noted.
Applicant’s comment on the right to file a Divisional Application directed to non-elected species is noted.
Specification
The use of the term SIGMA-ALDRICH®, ChemPep®, GENZYME®, GE HEALTHCARE®, 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.
Correction is required.
Claim Interpretation
Claim 1 is drawn to a method for prevention or treatment of multiple sclerosis of a subject in need thereof, comprising administering to the subject a pharmaceutical composition comprising: a pharmaceutically acceptable vehicle; and a therapeutically effective amount of a peptide containing an amino acid sequence of SEQ ID NO: 42. The specification states the term “prevention” refers to any action that inhibit or delay the occurrence of multiple sclerosis by administration of the above peptide or a composition containing the peptide (page 38 line 8-11). Based on the definition, the peptide or the composition can be administered to anyone, even if the person or subject does not have multiple sclerosis, to inhibit or delay the first occurrence of multiple sclerosis. Therefore, the subject in claim 1 is not limited to a subject that has multiple sclerosis, but also include the subject that does not have multiple sclerosis. In other words, the subject is interpreted as any mammal.
In addition, “a peptide containing an amino acid sequence of SEQ ID NO: 42” is interpreted as a peptide of any length, as long as it contains the peptide or a fragment of the peptide with sequence set forth in SEQ ID NO: 42.
Claim Rejections - 35 USC § 112
Written Description
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-18 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed. The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include “level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention.”
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, disclosure of drawings, or by disclosure of relevant identifying characteristics, for example, 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 claimed genus.
The claims are drawn to a method for prevention or treatment of multiple sclerosis of a subject in need thereof, comprising administering to the subject a pharmaceutical composition comprising: a pharmaceutically acceptable vehicle; and a therapeutically effective amount of a peptide containing an amino acid sequence of SEQ ID NO: 42. The peptide could also be in the form of a long-acting conjugate and the long-acting conjugate is represented by Formula 1 below: [Formula 1] X - L - F wherein X represents a peptide containing an amino sequence of SEQ ID NO: 42; L represents a linker containing ethylene glycol repeat units; F represents an immunoglobulin Fc region; and "-" symbols represent covalent linkages between X and L and between L and F, respectively.
Regarding to a method for prevention multiple sclerosis, the specification states the term “prevention” refers to any action that inhibits or delays the occurrence of multiple sclerosis (instant specification page 38 line 8-13). Therefore, the claims encompasses administering the claimed composition to any subject, including the subject who does not have multiple sclerosis and who does not have clinical signs of multiple sclerosis, to inhibit or delay the occurrence of multiple sclerosis. Because the method could be used for prevention multiple sclerosis, The claims encompasses applying to method to any subject.
The specification has written description for following examples: SJL female mice were injected with proteolipid protein (PLP) and pertussis toxin (PTX) on day 0, and one specific long-acting conjugate of SEQ ID NO: 42 was administered subcutaneously starting day 1 once every two days until the experiment termination on day 37 (instant specification experimental example 2 on pages 59-62).
The results of the examples show the animals administered with the composition still developed mild symptoms of multiple sclerosis, which does not support that the claimed method can inhibit the occurrence of multiple sclerosis (see instant application figure 1). Furthermore, in the first symptom appearing section, the animals administered with the composition still developed symptoms at the same time as the vehicle treated negative control animals (Figure 1), which does not support the claimed method can delay the occurrent of all types of multiple sclerosis in all subjects. Therefore, the examples do not provide support that the claimed method can prevent multiple sclerosis.
Regarding multiple sclerosis, the specification teaches it is classified into four types according to the progression of the disease: relapsing/remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPMS), primary progressive multiple sclerosis (PPMS), and progressive relapsing multiple sclerosis (PRMS) (instant specification page 1 lines 19-24). The claims encompasses applying to claimed method to prevent or treat all four types of multiple sclerosis.
The specification has written description for following examples: SJL female mice were injected with proteolipid protein (PLP) and pertussis toxin (PTX) on day 0, and one specific long-acting conjugate of SEQ ID NO: 42 was administered subcutaneously starting day 1 or day 17 once every two days until the experiment termination on day 37 (instant specification experimental example 2 on pages 59-62).
The mouse model used in the example is a relapse-remitting autoimmune encephalomyelitis (EAE) model of multiple sclerosis, and thus the specification only has examples using relapse-remitting type of multiple sclerosis, but not the progressive types of multiple sclerosis. Therefore, the examples do not provide support that the claimed method can prevent or treat all four types of multiple sclerosis.
In the state of the art, treatment of different types of multiple sclerosis is dependent on the specific type of multiple sclerosis and the risk/benefit assessment as taught by Goldschmidt and McGinley (Neurol Clin. 2021 Feb; 39(1): 21-33). First, not all therapies for relapsing/remitting multiple sclerosis (RRMS) can treat progressive types, because progressive types of multiple sclerosis not only have inflammatory disease activity as shown in RRMS but also neurodegeneration to various degrees (see section Progressive Disease). Therefore, treatment targeting non-inflammatory portion of progressive disease is needed, especially for forms of progressive multiple sclerosis that have little inflammatory disease and more neurodegeneration (see section Progressive Disease). Second, different therapies for RRMS have different efficacy and safety profiles, and the treatment plan needs to be based on disease phenotype, patient demographic, and risk profile (see section Treatment Strategies for RRMS). For instance, Natalizumab, a monoclonal antibody against alpha-4 integrin, is an approved disease modifying therapy for RRMS and it is highly effective on relapses, but its use has been limited due to the serious risk of developing progressive multifocal leukoencephalopathy (section Infusions). Therefore, the state of the art support that the effect of a specific reagent to treat all types of multiple sclerosis is unpredictable.
Taken together, neither the specification or the state of the art provides support that a specific compound can be used to treat all types of multiple sclerosis.
The claims are drawn to a method of prevention or treatment of multiple sclerosis of a subject, comprising administering to the subject a pharmaceutical composition comprising: a pharmaceutically acceptable vehicle; and a therapeutically effective amount of a peptide containing an amino acid sequence of SEQ ID NO: 42.
Regarding a peptide containing an amino acid sequence of SEQ ID NO: 42, although the claims encompass the exact peptide with sequence set forth in SEQ ID NO 42, the claims also broadly encompass: 1) an amino acid sequence (a fragment) of the peptide with sequence set forth in SEQ ID NO 42, and 2) a peptide that comprises the peptide with sequence set forth in SEQ ID NO: 42 or its fragment, as long as they have an effect of treating and/or preventing multiple sclerosis (instant specification page 13 line 19-21). The specification does not provide limit on the length of the peptide, and also fails to teach the essential structures of the peptides. Therefore, the peptide can be the peptide with sequence set forth in SEQ ID NO: 42 which has 40 residues, can be any length shorter than 40 amino acid as long as it contains an amino acid sequence of SEQ ID NO: 42 and have the claimed function, and can be any length longer than 40 amino acid as long as it contains the peptide of SEQ ID NO 42 or its fragment and have the claimed function. Therefore, these structures (i.e., sequences) are claimed only by their functional characteristics and the specification fails to provide sufficient correlation between the claimed functional characteristics and the necessary structural components (i.e., critical domains or residues within the sequences).
Regarding to the peptide in the form of X-L-F, wherein X represents a peptide containing an amino sequence of SEQ ID NO: 42 and F represents an immunoglobulin Fc region, the peptide can have infinite structures. As stated above, the peptide X can be any length, as long as it contains the peptide with sequence set forth in SEQ ID NO 42 or its fragment and can be used to prevent or treat multiple sclerosis.
In addition, the immunoglobulin Fc region adds complexity to the peptide. The specification states the immunoglobulin Fc region could be derived from IgG, IgA, IgD, IgE or IgM, or be a hybrid of domains with different origins derived from an immunoglobulin selected from the group consisting of IgG, IgA, IgD, IgE or IgM (instant specification page 6 line 29 to page 7 line 5). Furthermore, the immunoglobulin Fc region may be an extended Fc region including a part or the entirety of the heavy chain constant region 1 (CH1) and/or the light chain constant region 1 (CL1), or with a considerably long part of the CH2 and/or CH3 is deleted, as long as the Fc region has substantially equivalent or improved effect compared with the native form (instant specification page 31 line 3-10). This would represent an unlimited number of immunoglobulin Fc region that could be used in the conjugate. Moreover, the specification provides limited guidance regarding which residues are essential and which residues can be modified while maintaining the claimed function. Therefore, these structures (i.e., sequence variants) are claimed only by their functional characteristics and the specification fails to provide sufficient correlation between the claimed functional characteristics and the necessary structural components (i.e., critical domains or residues within the sequences).
The specification has written description for following examples: one specific long-acting conjugate of SEQ ID NO: 42 was prepared and administered in mice for multiple sclerosis (instant specification example 2 on pages 52 to 54, experimental example 2 on pages 59-62). The long-acting conjugate of SEQ ID NO 42 is a 40 residue peptide with sequence set forth in SEQ ID NO: 42 amidated at the C-terminus and bound to the immunoglobulin Fc via PEG (instant specification page 54 line 3-7). The specification includes some sample sequences for parts of the conjugate peptide, such as the hinge sequences set forth in SEQ ID NO: 104-122 (instant specification page 29 line 27 – page 30 line 17), an immunoglobulin Fc region with sequence set forth in SEQ ID NO: 123-124 (instant specification page 35 line 13 – 18). However, the specification does not specify the sequence of the immunoglobulin Fc used in the long-acting conjugate peptide in the examples.
Applicant has not shown procession of a representative number of species that have the claimed function(s). The specification does not provide adequate written description to identify the broad and variable genus of the peptide because, inter alia, the specification does not disclose a correlation between the necessary structure of the peptide and the function(s) recited in the claims. A definition by function does not suffice to define the genus because it is only an indication of what the protein does, rather than what it is; therefore, it is only a definition of a useful result rather than a definition of what achieves that result. Further, given the highly diverse nature of proteins, even one of skill in the art cannot envision the structure of the fusion protein by knowing a partial structure and its functional characteristics. Thus, the specification does not provide substantive evidence for possession of this large and variable genus, encompassing infinite number of peptides claimed only by a functional characteristic and/or partial structure.
Therefore, the specification does not have written description for all the peptides encompasses in the claims.
Protein chemistry is probably one of the most unpredictable areas of biotechnology. Addition or removing of amino acids to a peptide could lead to change in 3D structure and thus change the protein function. For example, Ueki et al (Biopolymers. 2007;88(2):190-8) teach a lot of the peptidergic hormones, neurotransmitters, and neuromodulators are primarily translated as inactive precursor proteins, which are then cleaved by various protease to produce matured bioactive factors (see abstract). Such fragmented peptides may have distinct biological activities from their parent proteins, such as fragments of cytochrome c oxidase activate neutrophils (see abstract).
In addition, even adding a small peptide tag can affect the function of the peptide. Scarfe et al (The Plant Journal. 2025. 122, e70272) review the use of protein tags for recombinant proteins, and teach Strep-tag and His-tag can affect biofunctionality of the peptide (table 1, also see section Strep-tag and section His-tag).
Schmidt (Bioprocessing, Bioengineering and Process Chemistry in the Biopharmaceutical Industry. 2024. Springer, Cham) reviews the advantages and challenges of making fusion proteins. For examples, when a free N- or C- terminus is required for activity of a peptide, the orientation of fusion directions can affect the function of the fusion protein, and the orientation of bifunctional molecules not relying on the classical building blacks Fc domain or albumin is even more difficult to predict (section 11.3.4). In the case of IL28B and HSA (human serum albumin) fusion protein, only IL28B fused to HAS at its N-terminus is active but not when it is fused at its C-terminus (section 11.3.4).
In addition, a peptide can be conjugated to different types of peptides for different purposes. For example, a peptide can be fused with albumin or repetitive peptide to extend its half-life, fused to specific receptors to target the peptide to specific organs or certain cell types, fused to Fc domains to trigger cytotoxicity or cytolysis in oncology, and/or fused to a combination of these peptides (Schmidt section 11.5).
Furthermore, even the immunoglobulin Fc region in fusion peptide is unpredictable. First, not all immunoglobulin Fc region can extend the half-life of the fusion peptide compared with unconjugated peptide alone. For instance, Strohl (BioDrugs. 2015 Jul 16;29(4):215–239) teaches human IgA, IgM, IgD, and IgE do not possess an extended half-life compared with human IgG1, IgG2 and IgG4, and even IgG3 has a shorter half-life compared with other IgGs (page 219, left column). Second, some immunoglobulin Fc can induce strong effector mechanisms that is desirable in oncology but might not be desirable in other application. For instance, de Taeye et al (Antibodies 2019, 8, 30) teach IgG1 and IgG3 are strong inducers of Fc-mediated effector mechanisms, while IgG2 and IgG4 generally induce more subtle responses (Section 2).
Given the teachings of Ueki et al, Scarfe et al, Schmidt, Strohl, and de Taeye et al, the claimed peptide containing an amino acid with sequence set forth in SEQ ID NO 42, or a long-acting conjugate of the peptide in the form of X-L-F, having the required function(s) could not be predicted simply based on the 40 amino acid peptide as in SEQ ID NO 42 and/or a genus of immunoglobulin Fc regions (F). It could not be predicted that polypeptide that contains a given SEQ ID NO. will function in a given manner. Therefore, the state of the art supports that even the skilled artisan requires guidance on the critical structures of peptide per se and thereby the specification does not provide adequate written description support for which structural features of any given polypeptide would predictably retain their functional activities.
Given the lack of structure function correlation, the lack of a representative number of species and the unpredictability in the art, the specification provides insufficient written description to support the genus of peptides encompassed by the claim.
Taken together, neither the start of the art or the specification provide enough support to the method of administering a large genus of peptides to prevent or treat all four types of multiple sclerosis.
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.)
The skilled artisan cannot envision the detailed chemical structure of the encompassed molecules in the peptide as claimed. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. The nucleic acid and/or protein itself is required. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. In Fiddes v. Baird, 30 USPQ2d 1481, 1483, claims directed to mammalian FGF's were found unpatentable due to lack of written description for the broad class. The specification provided only the bovine sequence.
University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1404. 1405 held that:
...To fulfill the written description requirement, a patent specification must describe an invention and does so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines Inc. , 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (1997); In re Gosteli , 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (" [T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2datl966.
Applicant is reminded that generally, in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus (Enzo Biochem, Inc. v. Gen- Probe Inc., 323 F.3d 956 (Fed. Cir. 2002); Noelle v. Lederman, 355 F.3d 1343 (Fed. Cir. 2004); Regents of the University of California v. Eli Lilly Co., 119 F.3d 1559 (Fed. Cir. 1997)). A patentee must disclose “a representative number of species within the scope of the genus of structural features common to the members of the genus so that one of skill in the art can visualize or recognize the member of the genus” (see Amgen Inc. v. Sanofi, 124 USPQ2d 1354 (Fed. Cir. 2017) at page 1358). An adequate written description must contain enough information about the actual makeup of the claimed products — “a precise definition, such as structure, formula, chemic name, physical properties of other properties, of species falling with the genus sufficient to distinguish the gene from other materials”, which may be present in “functional terminology when the art has established a correlation between structure and function” (Amgen page 1361).
MPEP § 2163.02 states, “[a]n objective standard for determining compliance with the written description requirement is, ‘does the description clearly allow person of ordinary skill in the art to recognize that he or she invented what is claimed’”. The courts have decided: the purpose of the “written description" requirement is broader than to merely explain how to "make and use"; the 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 Vas-Cath, Inc v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Federal Circuit, 1991).
Furthermore, the written description provision of 35 USC §112 is severable from its enablement provision; and adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993). And Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. Moreover, an adequate written description of the claimed invention must include sufficient description of at least a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics sufficient to show that Applicant was in possession of the claimed genus. However, factual evidence of an actual reduction to practice has not been disclosed by Applicant in the specification; nor has Applicant shown the invention was “ready for patenting” by disclosure of drawings or structural chemical formulas that show that the invention was complete; nor has the Applicant described distinguishing identifying characteristics sufficient to show that Applicant were in possession of the claimed invention at the time the application was filed.
Therefore, for all these reasons the specification lacks adequate written description, and one of skill in the art cannot reasonably conclude that Applicant had possession of the claimed invention at the time the instant application was filed.
Claim Rejections - 35 USC § 102
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 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 3-7 and 14 are rejected under 35 U.S.C. 102 (a)(1) and (a)(2) as being anticipated by Oh et al (US 10370426 B2, filed June 29, 2018 and published as US2019/0002520 A1 on Jan 3, 2019, cited in office action mailed Feb 18, 2016).
Claim interpretation note: since the claimed method is used for prevention of multiple sclerosis, the subject is not limited to subject that has multiple sclerosis, (or specific types of multiple sclerosis such as relapsing/remitting multiple sclerosis). Instead, the examiner is reading the population as any subject, including the subject that does not have multiple sclerosis.
Claim 1 is drawn to a method for prevention or treatment of multiple sclerosis of a subject in need thereof, comprising administering to the subject a pharmaceutical composition comprising: a pharmaceutically acceptable vehicle; and a therapeutically effective amount of a peptide containing an amino acid sequence of SEQ ID NO: 42.
Claim 3 is drawn to the method according to claim 1, wherein the C-terminus of the peptide is amidated.
Claim 4 is drawn to the method according to claim 1, wherein the peptide contains an amino acid sequence selected from the group consisting of SEQ ID NO: 42.
Claim 5 is drawn to the method according to claim 4, wherein the peptide contains an amino acid sequence selected from the group consisting of SEQ ID NO: 42.
Claim 6 is drawn to the method according to claim 5, wherein the peptide contains an amino acid sequence selected from the group consisting of SEQ ID NO: 42.
Claim 7 is drawn to the method according to claim 1, wherein the amino acids at positions 16 and 20 from the N-terminus in the sequence of the peptide form a ring.
Claim 14 is drawn to the method according to claim 1, wherein the multiple sclerosis is relapsing/remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPMS), primary progressive multiple sclerosis (PPMS), or progressive relapsing multiple sclerosis (PRMS).
Oh et al teach a method for treating a target disease, comprising administering a composition containing the isolated peptide to a subject in need thereof, wherein the target disease may be a metabolic syndrome, including diabetes and obesity (column 20 line 63-67, column 32 line 37 – 42). The composition may contain a pharmaceutically acceptable carrier (vehicle) (column 19 line 28-30). The peptide may include a peptide which includes an amino acid sequence as set forth in SEQ ID NO: 42 (column 16 line 42-45), which is identical to the amino acid sequence of SEQ ID NO: 42 of instant application. This peptide has the function of triple agonists which can activate all of GLP-1 receptors, GIP receptors and glucagon receptors (column 32 line 37 – 42). This is relevant to claims 1, 4-6 and 14.
Oh et al also teach the C-terminus of the peptide is amidated (column 7 line 17-18). This is relevant to claim 3.
Oh et al further teach peptide with sequence set forth in SEQ ID NO:42 forms a ring at positions 16 and 20 (column 57, see SEQ ID NO: 42). This is relevant to claim 7.
Oh et al teach a method of treating a disease to a subject in need of, comprising administering a composition comprising a peptide that contains an amino acid that is identical to the instant application. Based on the definition of prevention as explained above and examiner is reading the population as any subject, Oh et al anticipate the claims.
Claims 1-8 and 11-18 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Kim et al (Diabetes. 2019. 1810-P. vol. 68, Supplement 1, cited in office action mailed Feb 18, 2016) as evidenced by Anonymous (EFOCIPEGTRUTIDE on PubChem, deposited on October 27, 2022, PubChem SID 472419645, referred to as EFOCIPEGTRUTIDE thereafter).
Claim 1 is drawn to a method for prevention or treatment of multiple sclerosis of a subject in need thereof, comprising administering to the subject a pharmaceutical composition comprising: a pharmaceutically acceptable vehicle; and a therapeutically effective amount of a peptide containing an amino acid sequence of SEQ ID NO: 42.
Claim 2 is drawn to the method according to claim 1, wherein the peptide is in the form of a long-acting conjugate and the long-acting conjugate is represented by Formula 1 below: [Formula 1] X – L – F wherein X represents a peptide containing an amino sequence of SEQ ID NO: 42; L represents a linker containing ethylene glycol repeat units; F represents an immunoglobulin Fc region; and "– " symbols represent covalent linkages between X and L and between L and F, respectively.
Claim 3 is drawn to the method according to claim 1, wherein the C-terminus of the peptide is amidated.
Claim 4 is drawn to the method according to claim 1, wherein the peptide contains an amino acid sequence selected from the group consisting of SEQ ID NO: 42.
Claim 5 is drawn to the method according to claim 4, wherein the peptide contains an amino acid sequence selected from the group consisting of SEQ ID NO: 42.
Claim 6 is drawn to the method according to claim 5, wherein the peptide contains an amino acid sequence selected from the group consisting of SEQ ID NO: 42.
Claim 7 is drawn to the method according to claim 1, wherein the amino acids at positions 16 and 20 from the N-terminus in the sequence of the peptide form a ring.
Claim 8 is drawn to the method according to claim 2, wherein L is polyethylene glycol.
Claim 11 is drawn to the method according to claim 2, wherein F is an IgG Fc region.
Claim 12 is drawn to the method according to claim 2, wherein the immunoglobulin Fc region is a dimer consisting of two polypeptide chains, and one end of L is linked only to one of the two polypeptide chains.
Claim 13 is drawn to the method according to claim 2, wherein in the conjugate, one end of L is linked to F via a covalent linkage formed by reaction with an amine or thiol group of F, and the other end of L is linked to X via a covalent linkage formed by reaction with an amine or thiol group of X.
Claim 14 is drawn to the method according to claim 1, wherein the multiple sclerosis is relapsing/remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPMS), primary progressive multiple sclerosis (PPMS), or progressive relapsing multiple sclerosis (PRMS).
Claim 15 is drawn to the method according to claim 2, wherein the C-terminus of the peptide is amidated.
Claim 16 is drawn to the method according to claim 2, wherein the peptide contains an amino acid sequence selected from the group consisting of SEQ ID NO: 42.
Claim 17 is drawn to the method according to claim 2, wherein the amino acids at positions 16 and 20 from the N- terminus in the sequence of the peptide form a ring.
Claim 18 is drawn to the method according to claim 2, wherein the multiple sclerosis is relapsing/remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPMS), primary progressive multiple sclerosis (PPMS), or progressive relapsing multiple sclerosis (PRMS).
Kim et al teach a long-acting triple agonist (HM15211) showing activities on GLP-1, GIP, and glucagon receptors, have anti-inflammatory and neuroprotective effects in a mouse model of relapsing-remitting multiple sclerosis (autoimmune encephalomyelitis, EAE), and reduces EAE clinical score and demyelination in the animals’ spinal cord (abstract and conclusion). Although Kim et al do not teach the structure of HM15211, its structure is disclosed in EFOCIPEGTRUTIDE. EFOCIPEGTRUTIDE teaches Efocipegtrutide, which is HM15211, contains the peptide with sequence set forth in SEQ ID NO: 42, linked to a dimer of human IgG4 Fc region (F) through a polyethylene glycol linker (L), which is composed of ethylene glycol repeat units (see section 1.4). Human IgG4 Fc region is a type of immunoglobulin Fc region. In addition, X and L, L and F are linked through covalent linkages respectively (see section 1.4). This is relevant to claims 1, 2, 4-6, 8, 11, 12, 14, 16 and 18.
EFOCIPEGTRUTIDE also teaches the C-terminus of the peptide (X) with sequence as set forth in SEQ ID NO:42 is amidated (L-CYSTEINAMIDE) (section 1.4). This is relevant to claims 3 and 15.
EFOCIPEGTRUTIDE also teaches the residues of 16 and 20 in the peptide (X) with sequence set forth in SEQ ID NO 42 forms a ring ((16->20)-LACTAM) (section 1.4). This is relevant to claims 7 and 17.
EFOCIPEGTRUTIDE further teaches L (the PEG linker) is linked to F (human IgG4 Fc dimer) via a covalent linkage formed by reaction with thiol group of F (3-mercapto-2,5-dioxo-1-pyrrolidinyl), and L is also linked to X (the peptide containing sequence set forth in SEQ ID NO: 42) via a covalent linkage formed by reaction with a thiol group of X (thioether with) (section 1.4). This is relevant to claim 13.
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 1-9 and 11-18 are rejected under 35 U.S.C. 103 as being unpatentable over Kim et al (Diabetes. 2019. 1810-P. vol. 68, Supplement 1, cited in office action mailed Feb 18, 2016) as evidenced by Anonymous (EFOCIPEGTRUTIDE on PubChem, deposited on October 27, 2022, PubChem SID 472419645, referred to as EFOCIPEGTRUTIDE thereafter) in view of Kar et al (Basic Fundamentals of Drug Delivery. 2019. Pages 29-83).
Claim 1 is drawn to a method for prevention or treatment of multiple sclerosis of a subject in need thereof, comprising administering to the subject a pharmaceutical composition comprising: a pharmaceutically acceptable vehicle; and a therapeutically effective amount of a peptide containing an amino acid sequence of SEQ ID NO: 42.
Claim 2 is drawn to the method according to claim 1, wherein the peptide is in the form of a long-acting conjugate and the long-acting conjugate is represented by Formula 1 below: [Formula 1] X – L – F wherein X represents a peptide containing an amino sequence of SEQ ID NO: 42; L represents a linker containing ethylene glycol repeat units; F represents an immunoglobulin Fc region; and "– " symbols represent covalent linkages between X and L and between L and F, respectively.
Claim 3 is drawn to the method according to claim 1, wherein the C-terminus of the peptide is amidated.
Claim 4 is drawn to the method according to claim 1, wherein the peptide contains an amino acid sequence selected from the group consisting of SEQ ID NO: 42.
Claim 5 is drawn to the method according to claim 4, wherein the peptide contains an amino acid sequence selected from the group consisting of SEQ ID NO: 42.
Claim 6 is drawn to the method according to claim 5, wherein the peptide contains an amino acid sequence selected from the group consisting of SEQ ID NO: 42.
Claim 7 is drawn to the method according to claim 1, wherein the amino acids at positions 16 and 20 from the N-terminus in the sequence of the peptide form a ring.
Claim 8 is drawn to the method according to claim 2, wherein L is polyethylene glycol.
Claim 9 is drawn to the method according to claim 2, wherein the formula weight of an ethylene glycol repeat unit moiety in L is in a range of 1 to 100 kDa.
Claim 11 is drawn to the method according to claim 2, wherein F is an IgG Fc region.
Claim 12 is drawn to the method according to claim 2, wherein the immunoglobulin Fc region is a dimer consisting of two polypeptide chains, and one end of L is linked only to one of the two polypeptide chains.
Claim 13 is drawn to the method according to claim 2, wherein in the conjugate, one end of L is linked to F via a covalent linkage formed by reaction with an amine or thiol group of F, and the other end of L is linked to X via a covalent linkage formed by reaction with an amine or thiol group of X.
Claim 14 is drawn to the method according to claim 1, wherein the multiple sclerosis is relapsing/remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPMS), primary progressive multiple sclerosis (PPMS), or progressive relapsing multiple sclerosis (PRMS).
Claim 15 is drawn to the method according to claim 2, wherein the C-terminus of the peptide is amidated.
Claim 16 is drawn to the method according to claim 2, wherein the peptide contains an amino acid sequence selected from the group consisting of SEQ ID NO: 42.
Claim 17 is drawn to the method according to claim 2, wherein the amino acids at positions 16 and 20 from the N- terminus in the sequence of the peptide form a ring.
Claim 18 is drawn to the method according to claim 2, wherein the multiple sclerosis is relapsing/remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPMS), primary progressive multiple sclerosis (PPMS), or progressive relapsing multiple sclerosis (PRMS).
Kim et al teach a long-acting triple agonist (HM15211) showing activities on GLP-1, GIP, and glucagon receptors, have anti-inflammatory and neuroprotective effects in a mouse model of relapsing-remitting multiple sclerosis (autoimmune encephalomyelitis, EAE), and reduces EAE clinical score and demyelination in the animals’ spinal cord (abstract and conclusion). Although Kim et al do not teach the structure of HM15211, its structure is disclosed in EFOCIPEGTRUTIDE. EFOCIPEGTRUTIDE teaches efocipegtrutide, which is HM15211, contains the peptide with sequence set forth in SEQ ID NO: 42, linked to a dimer of human IgG4 Fc region (F) through a polyethylene glycol linker (L), which is composed of ethylene glycol repeat units (see section 1.4). Human IgG4 Fc region is a type of immunoglobulin Fc region. In addition, X and L, L and F are linked through covalent linkages respectively (see section 1.4). This is relevant to claims 1, 2, 4-6, 8, 11, 12, 14, 16 and 18.
EFOCIPEGTRUTIDE also teaches the C-terminus of the peptide (X) with sequence as set forth in SEQ ID NO:42 is amidated (L-CYSTEINAMIDE) (section 1.4). This is relevant to claims 3 and 15.
EFOCIPEGTRUTIDE also teaches the residues of 16 and 20 in the peptide (X) with sequence set forth in SEQ ID NO 42 forms a ring ((16->20)-LACTAM) (section 1.4). This is relevant to claims 7 and 17.
EFOCIPEGTRUTIDE further teaches L (the PEG linker) is linked to F (human IgG4 Fc dimer) via a covalent linkage formed by reaction with thiol group of F (3-mercapto-2,5-dioxo-1-pyrrolidinyl), and L is also linked to X (the peptide containing sequence set forth in SEQ ID NO: 42) via a covalent linkage formed by reaction with a thiol group of X (thioether with) (section 1.4). This is relevant to claim 13.
Kim et al as evidenced by EFOCIPEGTRUTIDE fail to teach the formula weight of an ethylene glycol repeat unit moiety is in a range of 1 - 100 kDa as cited in claim 9.
However, Kar et al teach PEG is a widely used and stealth polymer and PEG of molar mass ranging from 400 Da to about 50 kDa is used in pharmaceutical and medical applications (see page 71 section 2.2.4.4). Kar et al also teaches for the conjugation of low-molar mass drugs such as oligonucleotides, PEG with molar mass of 20-50 kDa is used to slow renal clearance, and for conjugation of larger drug molecules such as nanoparticulate systems, PEG with lower molar mass (1-5 kDa) is used to reduce enzymatic degradation, opsonization and elimination by RES (section 2.2.4.4).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teaching of Kim et al evidenced by EFOSIPEGTRUTIDE and Kar et al, to optimize the molecular weight of the PEG. One of ordinary skill in the art would be motivated to optimize the formula weight of the ethylene glycol repeat unit moiety, since "it is the normal desire of scientists or artisans to improve upon what is already generally known". Kar et al teaches a range that overlaps with the claimed range, a prima facie case of obviousness exists. One of ordinary skill in the art would have a reasonable expectation of success for the entire range disclosed by Kar et al, absent evidence of criticality and/or unpredictability of the more specific formula weight claimed.
The MPEP states the following: Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In Peterson. 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."); In re Floeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc, v. Biocraft Laboratories Inc. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert, denied, 493 U.S. 975 (1989); In re Kulling. 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler. 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997). Although Kar et al. teach a dose range that overlaps with the claimed dose range, Applicant has not demonstrated criticality of the claimed formula weight, and determining the optimal formula weight of the ethylene glycol repeat unit moiety would be well within the knowledge of the skilled artisan.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that if a technique has been used to improve one method, and a person of ordinary skill would recognize that it would be used in similar methods in the same way, using the technique is obvious unless its application is beyond that person’s skill. It would be obvious to apply a known technique to a known product to be used in a known method that is ready for improvement to yield predictable results. Thus, the combination of prior art references as combined provided a prima facie case of obviousness, absent convincing evidence to the contrary.
Claims 1-8 and 10-18 are rejected under 35 U.S.C. 103 as being unpatentable over Kim et al (Diabetes. 2019. 1810-P. vol. 68, Supplement 1, cited in office action mailed Feb 18, 2016) as evidenced by Anonymous (EFOCIPEGTRUTIDE on PubChem, deposited on October 27, 2022, PubChem SID 472419645, referred to as EFOCIPEGTRUTIDE thereafter) in view Gunasekaran (US 9546203 B2, date of patent Jan 17, 2017).
Claim 1 is drawn to a method for prevention or treatment of multiple sclerosis of a subject in need thereof, comprising administering to the subject a pharmaceutical composition comprising: a pharmaceutically acceptable vehicle; and a therapeutically effective amount of a peptide containing an amino acid sequence of SEQ ID NO: 42.
Claim 2 is drawn to the method according to claim 1, wherein the peptide is in the form of a long-acting conjugate and the long-acting conjugate is represented by Formula 1 below: [Formula 1] X – L – F wherein X represents a peptide containing an amino sequence of SEQ ID NO: 42; L represents a linker containing ethylene glycol repeat units; F represents an immunoglobulin Fc region; and "– " symbols represent covalent linkages between X and L and between L and F, respectively.
Claim 3 is drawn to the method according to claim 1, wherein the C-terminus of the peptide is amidated.
Claim 4 is drawn to the method according to claim 1, wherein the peptide contains an amino acid sequence selected from the group consisting of SEQ ID NO: 42.
Claim 5 is drawn to the method according to claim 4, wherein the peptide contains an amino acid sequence selected from the group consisting of SEQ ID NO: 42.
Claim 6 is drawn to the method according to claim 5, wherein the peptide contains an amino acid sequence selected from the group consisting of SEQ ID NO: 42.
Claim 7 is drawn to the method according to claim 1, wherein the amino acids at positions 16 and 20 from the N-terminus in the sequence of the peptide form a ring.
Claim 8 is drawn to the method according to claim 2, wherein L is polyethylene glycol.
Claim 10 is drawn to the method according to claim 2, wherein the immunoglobulin Fc region is aglycosylated.
Claim 11 is drawn to the method according to claim 2, wherein F is an IgG Fc region.
Claim 12 is drawn to the method according to claim 2, wherein the immunoglobulin Fc region is a dimer consisting of two polypeptide chains, and one end of L is linked only to one of the two polypeptide chains.
Claim 13 is drawn to the method according to claim 2, wherein in the conjugate, one end of L is linked to F via a covalent linkage formed by reaction with an amine or thiol group of F, and the other end of L is linked to X via a covalent linkage formed by reaction with an amine or thiol group of X.
Claim 14 is drawn to the method according to claim 1, wherein the multiple sclerosis is relapsing/remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPMS), primary progressive multiple sclerosis (PPMS), or progressive relapsing multiple sclerosis (PRMS).
Claim 15 is drawn to the method according to claim 2, wherein the C-terminus of the peptide is amidated.
Claim 16 is drawn to the method according to claim 2, wherein the peptide contains an amino acid sequence selected from the group consisting of SEQ ID NO: 42.
Claim 17 is drawn to the method according to claim 2, wherein the amino acids at positions 16 and 20 from the N- terminus in the sequence of the peptide form a ring.
Claim 18 is drawn to the method according to claim 2, wherein the multiple sclerosis is relapsing/remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPMS), primary progressive multiple sclerosis (PPMS), or progressive relapsing multiple sclerosis (PRMS).
Kim et al teach a long-acting triple agonist (HM15211) showing activities on GLP-1, GIP, and glucagon receptors, have anti-inflammatory and neuroprotective effects in a mouse model of relapsing-remitting multiple sclerosis (autoimmune encephalomyelitis, EAE), and reduces EAE clinical score and demyelination in the animals’ spinal cord (abstract and conclusion). Although Kim et al do not teach the structure of HM15211, its structure is disclosed in EFOCIPEGTRUTIDE. EFOCIPEGTRUTIDE teaches efocipegtrutide, which is HM15211, contains the peptide with sequence set forth in SEQ ID NO: 42, linked to a dimer of human IgG4 Fc region (F) through a polyethylene glycol linker (L), which is composed of ethylene glycol repeat units (see section 1.4). Human IgG4 Fc region is a type of immunoglobulin Fc region. In addition, X and L, L and F are linked through covalent linkages respectively (see section 1.4). This is relevant to claims 1, 2, 4-6, 8, 11, 12, 14, 16 and 18.
EFOCIPEGTRUTIDE also teaches the C-terminus of the peptide (X) with sequence as set forth in SEQ ID NO:42 is amidated (L-CYSTEINAMIDE) (section 1.4). This is relevant to claims 3 and 15.
EFOCIPEGTRUTIDE also teaches the residues of 16 and 20 in the peptide (X) with sequence set forth in SEQ ID NO 42 forms a ring ((16->20)-LACTAM) (section 1.4). This is relevant to claims 7 and 17.
EFOCIPEGTRUTIDE further teaches L (the PEG linker) is linked to F (human IgG4 Fc dimer) via a covalent linkage formed by reaction with thiol group of F (3-mercapto-2,5-dioxo-1-pyrrolidinyl), and L is also linked to X (the peptide containing sequence set forth in SEQ ID NO: 42) via a covalent linkage formed by reaction with a thiol group of X (thioether with) (section 1.4). This is relevant to claim 13.
Kim et al as evidenced by EFOCIPEGTRUTIDE fail to teach the immunoglobulin Fc region is aglycosylated as cited in claim 10.
However, the aglycosylation of the IgG is well established in the art. For instance, Gunasekaran teaches aglycosylation of the IgG1 Fc provides greatly improved purification efficiency and abolish the effector functions, including using aglycosulated Fc in fusion protein (column 2 lines 13-27).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teaching of Kim et al evidenced by EFOSIPEGTRUTIDE and Gunasekaran, to aglycosylate the immunoglobulin Fc region, because doing so would improve purification efficiency and reduces the effector function. One is motivated to do so because aglycosylate the immunoglobulin Fc region in fusion protein has desirable features for the production and function of the fusion protein. One would have a reasonable expectation of success in making the combination because aglycosylating immunoglobulin Fc region in fusion protein is well established in the art.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that if a technique has been used to improve one method, and a person of ordinary skill would recognize that it would be used in similar methods in the same way, using the technique is obvious unless its application is beyond that person’s skill. It would be obvious to apply a known technique to a known product to be used in a known method that is ready for improvement to yield predictable results. Thus, the combination of prior art references as combined provided a prima facie case of obviousness, absent convincing evidence to the contrary.
Claims 1-18 are rejected under 35 U.S.C. 103 as being unpatentable over Oh et al (US 10370426 B2, filed June 29, 2018 and published as US2019/0002520 A1 on Jan 3, 2019, cited in office action mailed Feb 18, 2016) in view of Park et al (US 2020/0230250 A1, foreign application priority of 2017).
Claim interpretation note: As explained in Claim Interpretation, since the claimed method is used for prevention of multiple sclerosis, the subject is not limited to subject that has multiple sclerosis, (or specific types of multiple sclerosis such as relapsing/remitting multiple sclerosis). Instead, the examiner is reading the population as any subject, including the subject that does not have multiple sclerosis.
Claim 1 is drawn to a method for prevention or treatment of multiple sclerosis of a subject in need thereof, comprising administering to the subject a pharmaceutical composition comprising: a pharmaceutically acceptable vehicle; and a therapeutically effective amount of a peptide containing an amino acid sequence of SEQ ID NO: 42.
Claim 2 is drawn to the method according to claim 1, wherein the peptide is in the form of a long-acting conjugate and the long-acting conjugate is represented by Formula 1 below: [Formula 1] X – L – F wherein X represents a peptide containing an amino sequence of SEQ ID NO: 42; L represents a linker containing ethylene glycol repeat units; F represents an immunoglobulin Fc region; and "– " symbols represent covalent linkages between X and L and between L and F, respectively.
Claim 3 is drawn to the method according to claim 1, wherein the C-terminus of the peptide is amidated.
Claim 4 is drawn to the method according to claim 1, wherein the peptide contains an amino acid sequence selected from the group consisting of SEQ ID NO: 42.
Claim 5 is drawn to the method according to claim 4, wherein the peptide contains an amino acid sequence selected from the group consisting of SEQ ID NO: 42.
Claim 6 is drawn to the method according to claim 5, wherein the peptide contains an amino acid sequence selected from the group consisting of SEQ ID NO: 42.
Claim 7 is drawn to the method according to claim 1, wherein the amino acids at positions 16 and 20 from the N-terminus in the sequence of the peptide form a ring.
Claim 8 is drawn to the method according to claim 2, wherein L is polyethylene glycol.
Claim 9 is drawn to the method according to claim 2, wherein the formula weight of an ethylene glycol repeat unit moiety in L is in a range of 1 to 100 kDa.
Claim 10 is drawn to the method according to claim 2, wherein the immunoglobulin Fc region is aglycosylated.
Claim 11 is drawn to the method according to claim 2, wherein F is an IgG Fc region.
Claim 12 is drawn to the method according to claim 2, wherein the immunoglobulin Fc region is a dimer consisting of two polypeptide chains, and one end of L is linked only to one of the two polypeptide chains.
Claim 13 is drawn to the method according to claim 2, wherein in the conjugate, one end of L is linked to F via a covalent linkage formed by reaction with an amine or thiol group of F, and the other end of L is linked to X via a covalent linkage formed by reaction with an amine or thiol group of X.
Claim 14 is drawn to the method according to claim 1, wherein the multiple sclerosis is relapsing/remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPMS), primary progressive multiple sclerosis (PPMS), or progressive relapsing multiple sclerosis (PRMS).
Claim 15 is drawn to the method according to claim 2, wherein the C-terminus of the peptide is amidated.
Claim 16 is drawn to the method according to claim 2, wherein the peptide contains an amino acid sequence selected from the group consisting of SEQ ID NO: 42.
Claim 17 is drawn to the method according to claim 2, wherein the amino acids at positions 16 and 20 from the N- terminus in the sequence of the peptide form a ring.
Claim 18 is drawn to the method according to claim 2, wherein the multiple sclerosis is relapsing/remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPMS), primary progressive multiple sclerosis (PPMS), or progressive relapsing multiple sclerosis (PRMS).
Oh et al teach a method for treating a target disease, comprising administering a composition containing the isolated peptide to a subject in need thereof, where in the target disease may be a metabolic syndrome (column 20 line 63-67). The composition may contain a pharmaceutically acceptable carrier (vehicle) (column 19 line 28-30). The peptide may include a peptide which includes an amino acid sequence as set forth in SEQ ID NO: 42 (column 16 line 42-45), which is identical to the amino acid sequence of SEQ ID NO: 42 of instant application. It has the function of triple agonists which can activate all of GLP-1 receptors, GIP receptors and glucagon receptors, and thus is used to treat metabolic syndrome including diabetes and obesity (column 32 line 37 – 42). Because diabetic patients have higher risks of neurological damages, including multiple sclerosis, the triple agonist, when used to treat diabetes, is preventing the multiple sclerosis. This is relevant to claims 1, 4-6 and 14.
Oh et al also teach the C-terminus of the peptide is amidated (column 7 line 17-18). This is relevant to claims 3 and 15.
Oh et al further teach peptide with sequence set forth in SEQ ID NO:42 forms a ring at positions 16 and 20 (column 57, see SEQ ID NO: 42). This is relevant to claim 7.
It should be noted by Applicant that Oh et al teach a method of treating a disease to a subject in need of, comprising administering a composition comprising a peptide that contains an amino acid that is identical to the instant application. Based on the definition of prevention as explained above and examiner is reading the population as any subject, Oh et al anticipate the claims.
Oh et al fail to teach the peptide is in the form of a long-acting conjugate is represented by the formula X-L-F, wherein the X represents a peptide, L represents a linker containing ethylene glycol repeat units, and F represents an immunoglobulin Fc region and “-“ represents covalent linkage.
However, Park et al teach physiologically active polypeptides are easily denatured and degraded by in vivo proteases due to their relatively small size, which makes it necessary to administer these protein drugs more frequently to patients and this causes pain to the patients and incur high treatment cost (paragraph 0002). Therefore, maximizing the efficacy of protein drugs by increasing their stability while maintaining blood concentration at a high level for a long period of time is desired (paragraph 0002). Park et al also teach to achieve the objects, a conjugate of a physiologically active material and a material capable of increasing in vivo half-life of the physiologically active material are linked through polyethylene glycol that has a size of greater than 0 kDa to less than 3.4 kDa, in the form of X-L-F, in which X is a physiologically active material; L, polyethylene glycol; and F is a material capable increasing the in vivo half-life of the physiologically active material, which could be an IgG Fc region (paragraphs 0014-0021 and 0138). IgG Fc region is an immunoglobulin Fc region. Polyethylene glycol is a polymer comprising ethylene glycol repeat units. In addition, X and F are linked to teach other through L by a covalent bond (linkage) (paragraph 0133). Park et al further teach the immunoglobulin Fc region is aglycosylated (paragraph 0380). In addition, the Fc region may be in the form of a dimer, and in a form where one molecule of a physiologically active material may be linked to a single chain of an immunoglobulin Fc region in a dimeric form (paragraph 0367). Park et al also teach L is linked to F via a covalent bond formed by its amine or thiol functional group with L, and L is linked to X via a covalent bond formed by its amine or thiol group to L (paragraph 0144-1145).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teaching of Oh et al and Park et al, to increase the half-life of the short peptide with sequence set forth in SEQ ID NO: 42, by conjugating it to an IgG Fc region through a polyethylene glycol through covalent bonds as taught by Park et al, because doing so would increase the half-life of the peptide, make it long-acting and reducing the administration frequency for patients. One is motivated to do so because long-acting conjugate for protein drug has desirable features as taught by Park et al. One would have a reasonable expectation of success in making the combination because conjugate to extend half-life of a peptide is well established in the art.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that if a technique has been used to improve one method, and a person of ordinary skill would recognize that it would be used in similar methods in the same way, using the technique is obvious unless its application is beyond that person’s skill. It would be obvious to apply a known technique to a known product to be used in a known method that is ready for improvement to yield predictable results. Thus, the combination of prior art references as combined provided a prima facie case of obviousness, absent convincing evidence to the contrary.
Conclusion
No claims are allowed.
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/TIAN YANG/Examiner, Art Unit 1674
/VANESSA L. FORD/Supervisory Patent Examiner, Art Unit 1674
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