Recombinant Follicle-Stimulating Hormone Fusion Protein

Abstract

The present disclosure relates to a recombinant follicle-stimulating hormone fusion protein, which comprises two different peptide chains, which are folded into a stable heterodimer under the dual effects of non-covalent binding between Gnα subunit and Gnβ subunit and structure on Fc chain. The recombinant fusion protein provided by the present disclosure has a long half-life and high activity, and a small dose of one-time administration can promote animal induction and ripening, improve the efficiency of artificial reproduction, and can be applied to human assisted reproduction, treatment of polycystic ovary syndrome and anovulatory diseases, animal superovulation, animal synchronous estrus, conception and birth, treatment of animal infertility, promotion of animal reproduction, embryo transplantation, promotion of spermatogenesis and ovulation, stimulation of gonadal tissue secretion to produce estradiol and testosterone, treatment of animal infertility, treatment of female animal ovarian diseases, promotion of livestock reproduction, improvement of male animal semen quality, induction of female animal estrus, in vitro maturation and in vitro fertilization of oocytes.

Description

[0001] This application is a divisional application. The original application was filed on September 29, 2022, with application number 2022112016594 and invention title "Recombinant Follicle-Stimulating Hormone Fusion Protein". Technical Field

[0002] This disclosure belongs to the field of genetic engineering technology. Specifically, this disclosure relates to a novel long-acting gonadotropin, a method for preparing the same, and its use in promoting animal reproduction. Background Technology

[0003] Gonadotropins (Gn) are a class of glycoprotein hormones (GPHs) synthesized and secreted by the anterior pituitary cells of vertebrates. Their main physiological function is to stimulate the growth, development, maturation, ejaculation, and ovulation of germ cells.

[0004] Follicle-stimulating hormone (FSH), also known as follicle-stimulating hormone, is a glycoprotein hormone synthesized and secreted by the pituitary gland. The FSH molecule is a heterodimer composed of two non-covalently linked subunits: an α subunit and a β subunit. In the same species, FSH shares the same amino acid sequence as the α subunit of other glycoprotein hormones such as luteinizing hormone (LH) and thyroid-stimulating hormone (TSH), consisting of 92-96 amino acids (the specific sequence varies among different mammals). The FSH β subunit gene, composed of 109-115 amino acids, determines the biological specificity of FSH. Neither the α nor β subunits alone are biologically active; they only exert their biological effects when combined.

[0005] In women, FSH promotes follicle development and maturation, and works in conjunction with luteinizing hormone (LH) to stimulate mature follicles to secrete estrogen and ovulate, thus participating in the formation of normal menstruation. While FSH promotes follicle development and maturation, lower than normal FSH levels may indicate conditions such as polycystic ovary syndrome (PCOS). In animal husbandry, FSH is commonly used for superovulation and in vitro fertilization, and is closely related to animal reproduction.

[0006] FSH can be extracted from the pituitary gland or urine, or it can be produced through recombinant synthesis. Because natural FSH has a short half-life, daily injections are usually required to achieve good therapeutic effects, which is inconvenient and causes discomfort to patients and animals. Therefore, developing long-acting FSH, improving its bioactivity, reducing the number of injections, and increasing ease of use are imperative.

[0007] In 2010, Merck in Germany launched a long-acting FSH (Elonva), which adds CTP (the carboxyl-terminal peptide of hCG) to the C-terminus of the FSH β subunit (US5585345), and its half-life in the human body is about 70 hours.

[0008] CN108676096 discloses a method of directly or indirectly linking the porcine FSHβ subunit to the CTP of the β subunit of human, primate, or equine chorionic gonadotropin, and the porcine FSHα subunit binding to the porcine FSHβ subunit via van der Waals forces, with a half-life of approximately 30 hours in rats.

[0009] Several patents report linking FSH and Fc in different ways, which can prolong the half-life of FSH and improve its biological activity in vivo. CN103509121B discloses fusing the FSH β subunit directly or indirectly to the Fc fragment via a linker, with the α subunit binding to the FSH β subunit through the affinity of the α and β subunits or the linker, resulting in a half-life of 30-40 hours in rats. CN107540748A discloses fusing porcine FSH α / β subunits directly or indirectly to the Fc fragment via a linker element, with the β / α subunit binding to the α / β subunit through van der Waals forces or the linker element, resulting in a half-life of approximately 60 hours in rats. CN103554269B links the pFSH β subunit, CTP, and pFSH α subunit to a human IgG Fc variant, resulting in a half-life of approximately 40 hours in rats, which is more than 10 times that of porcine pituitary FSH. In CN106496331A, the FSH fusion protein folds into a stable heterodimeric form under the dual action of non-covalent binding between the FSHα and FSHβ subunits and the locking and locking Fc chain linkage (KiH, Knobs-into-Holes), with a half-life of approximately 248 hours. In contrast, the half-life of Gonal-F (recombinant FSH) measured at the same time was 17.3 hours, making the former's half-life 14 times that of the latter.

[0010] Fish exhibit two types of GtHs: GtHⅠ and GtHⅡ, corresponding to follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in mammals, respectively. GtH is a dimer molecule composed of a common α subunit containing antigenic determinants and a β subunit specific to hormone biology. The two subunits must bind together to exert their hormonal biological activity. Gonadotropin I is a heterodimer composed of GtHα and GtH Iβ, while gonadotropin II is a heterodimer composed of GtHα and GtH IIβ. It is generally believed that gonadotropin I, namely follicle-stimulating hormone (FSH), mainly plays a role in the early stages of gonadal development, namely the yolk sac formation and spermatogenesis periods. It is secreted in large quantities by the pituitary gland and plays a major role in stimulating gonadal tissue to secrete estradiol and testosterone. Studies have shown that FSH also plays an important role in inducing ovulation and sperm production (CN102080095A).

[0011] Practice has proven that fish pituitary glands, due to their natural GtH content, have excellent spawning-inducing effects and are widely applicable to various fish species. However, the high difficulty in collecting fish pituitary glands hinders large-scale production, resulting in high prices and scarcity. They are currently only used for fish where existing spawning induced agents are ineffective. Starting with the GtH genetic resources of carp, this paper proposes a recombinant gonadotropin (rGtH I) fish spawning induced agent developed using genetic engineering technology. This novel fish spawning induced agent has significant advantages: it not only has a highly efficient spawning-inducing effect but also enables large-scale industrial production, meeting current market demands and cost control requirements for fish spawning induced agents.

[0012] In CN201010572061.7, gonadotropin I from *Pichia pastoris* was expressed. Two molecular conformations were designed: GtH(β-α) co-expression with two subunits, GtHα and GtHβ, and GtH(β+α) co-expression in parallel. The physiological activity of the recombinant protein was verified through in vivo and in vitro experiments. The results showed that both conformations could promote the release of testosterone and estradiol.

[0013] It is generally believed that gonadotropin II, also known as luteinizing hormone (GtH II), mainly acts on the maturation and release of eggs and sperm.

[0014] In aquaculture, GtH plays a crucial role in reproduction and breeding. It can accelerate the secretion of steroid hormones such as ketones and estrogen, speed up the start of the reproductive cycle, promote the production of primitive reproductive cells such as spermatogonia and oogonia, accelerate the development and growth of gametes, promote the development and maturation of eggs and sperm, and ensure smooth release during the breeding season (Wang Wu. Cloning, prokaryotic expression and functional verification of gonadotropin gene in golden scorpion, China Excellent Master's Thesis Full-text Database Agricultural Science and Technology Series, 2018, Vol. 2018 (Issue 2)).

[0015] Practice has proven that fish pituitary glands, containing natural GtH, have excellent spawning-inducing effects and are widely applicable to various fish species. However, due to the high difficulty in collecting fish pituitary glands and the challenge of large-scale production, they are expensive and extremely scarce, limiting their use to fish where existing spawning induced agents are ineffective. Starting with the GtH genetic resources of carp, this study utilizes genetic engineering technology to develop a recombinant gonadotropin II (rGtH II) fish spawning induced agent for fish reproduction. This novel fish spawning induced agent has significant advantages: it not only has a highly efficient spawning-inducing effect but also enables large-scale industrial production, meeting current market demands and cost control requirements for fish spawning induced agents.

[0016] In patent CN106434684B, RNA was extracted from the gonads of the golden croaker (Gymnocypris spp.), and the full-length GtH II gene sequence was cloned using RT-PCR and RACE techniques. The GtH II gene was then expressed in prokaryotes, and purified using an affinity column to obtain pure recombinant GtH II protein. This protein was then used for in vitro injection in fish to promote gonadal development and thus induce synchronous gonadal development. In the experimental group, serum estradiol levels in female golden croakers significantly increased at day 7, while serum testosterone levels showed no significant change before and after treatment. In the experimental group, serum testosterone levels in male golden croakers significantly increased at day 14, while serum estradiol levels showed no significant change before and after treatment.

[0017] Patent JP5783522B2 describes the design of recombinant GtH I-CTP with the GtH configuration of GtH Iβ-CTP / GtHα-his and recombinant GtH II-CTP with the GtH configuration of GtH IIβ-CTP / GtHα-his, both containing CTP (the β-subunit carboxyl-terminal peptide of human chorionic gonadotropin). Both recombinant GtH I-CTP and GtH II-CTP are expressed in CHO cells. In vitro experiments showed that in immature testicular culture medium, the addition of GtH I, GtH II, GtH I-CTP, and GtH II-CTP, and the measurement of 11KT (11-ketotestosterone) concentrations, significantly promoted 11KT production at moderate concentrations above 200 ng / mL for GtH I and 500 ng / mL for GtH II. Notably, even a low concentration of 20 ng / mL of GtH II-CTP showed an effect. Meanwhile, in the high-dose group, the production of 11KT reached approximately 100 times that of the control group. In in vivo bioactivity tests, immature male eels were administered GtH I-CTP weekly at 200 μg / kg body weight for 8 weeks. Three days after the end of the administration experiment, the body weight of the experimental fish and the weight of the removed testes were measured, and the gonadal index (GSI: gonadal weight / body weight) was calculated. The results showed that the GSI of the control group was approximately 0.2, while the GSI of the GtH I-CTP-treated individuals was approximately 4.4, which is a very high value. In addition, histological observations showed that only pre-proliferating spermatogonia were present in the testes of the control group, while germ cells at different developmental stages, including sperm, were observed in the testes of individuals treated with GtH I-CTP, thus demonstrating that GtH I-CTP can promote the development of spermatogonia into germ cells at various stages. Recombinant eel GtH can artificially mature eels.

[0018] The methods for achieving heterodimers in bispecific antibodies include Knobs-into-Holes (US20030078385), ion interactions (WO2007147901), electrostatic reversal (WO2009089004), coiled helix, leucine zipper, helix-turn-helix motif, etc.

[0019] KiH technology, developed in 1996 by Paul Carter's team at Genentech, is the foundation for efficient heterodimerization of antibody heavy chains. Typically, when preparing heterodimers of antibody A and antibody B using recombinant expression systems, the correct assembly rate of the AB heterodimer in the expression product is less than 50%. By using a latching mechanism, the stability of the heterodimer can be increased, raising the correct assembly rate to over 80%.

[0020] Electrostatic reversal utilizes the favorable electrostatic interactions between oppositely charged amino acids, protein domains, and proteins within peptides to control the formation of higher-order protein molecules. US Patent Application Publication No. US2014 / 0024111 discloses a method for using electrostatic reversal effects to alter the interactions of antibody domains, thereby reducing homodimer formation in bispecific antibody production.

[0021] There are few studies on GtH recombinant expression, and no Fc modification for long-lasting effects has been observed. Generally, the half-life is short and the biological activity is not high. In JP5783522B2, GtH is linked to CTP, which improves the biological activity. However, purification is based on its his-tag, resulting in low purification efficiency. In addition, the high degree of CTP glycosylation leads to strong heterogeneity of the expressed protein.

[0022] Connecting GtHI and Fc in different ways can prolong the half-life of GtHI, improve its in vivo biological activity, and also enhance downstream purification efficiency. Using a locking mode (i.e., KiH mode) or an electrostatic orientation mode for the Fc portion can help the α and β subunits of GtHI to correctly assemble.

[0023] Connecting GtH II and Fc in different ways can prolong the half-life of GtH II, improve its in vivo biological activity, and also enhance downstream purification efficiency. Using a locking or electrostatic orientation mode for the Fc portion can help the α and β subunits of GtH II to assemble correctly.

[0024] Because the C-terminus of the FSH α subunit is involved in the interaction between FSH and the FSH receptor (FSHR) (Jiang et al., Molecular and Cellular Endocrinology, 2014, 382:424-451), the connection of the C-terminus of the α subunit to the Fc chain in CN107540748A, CN103554269B, and CN106496331A affects FSH activity. CN103509121B exhibits a problem where some α and β subunits cannot properly assemble. Summary of the Invention

[0025] To address the problems of existing technologies, this disclosure connects the Gnα and Gnβ subunits to the Fc chain using three connection modes:

[0026] (1) The C-terminus of the Gnα and Gnβ subunits is connected to the N-terminus of the Fc chain;

[0027] (2) Connect the N-terminus of the Gnα subunit to the C-terminus of the Fc chain, and connect the C-terminus of the Gnβ subunit to the N-terminus of the Fc chain.

[0028] (3) Connect the N-terminus of the Gnα and Gnβ subunits to the Fc chain.

[0029] Fc is modified using either a latching or electrostatic redirection mechanism to achieve a stable heterodimeric fusion protein that assembles correctly. Fc is linked to the α and β subunits via flexible peptides, minimizing impact on the structure of both subunits. Compared to wild-type IgG1, the coin-type Fck has mutations at EU sites S354C and T366W; the latching Fch has mutations at EU sites Y349C, T366S, L368A, and Y407V; the coin-type Fc4k has mutations at EU sites S354C and T366W; and the latching Fc4h has mutations at EU sites Y349C, T366S, L368A, and Y407V.

[0030] The two electrostatic deflection modes disclosed herein are named T-type and D-type, respectively:

[0031] In the electrostatically shifting T-type, the T positively charged chain (Fc(T+)) has mutations with EU numbers D221R, P228R, and K409R compared to wild-type IgG1; the T positively charged chain (Fc4(T+)) has mutations with EU numbers S228R and K409R compared to wild-type IgG4; the T negatively charged chain (Fc(T-)) has mutations with EU numbers D221E, P228E, and L368E compared to wild-type IgG1; and the T negatively charged chain (Fc4(T-)) has mutations with EU numbers S228E and L368E compared to wild-type IgG4.

[0032] In the electrostatic conversion D type, the D positive charge chain (Fc(D+)) has mutations with EU numbers L351K and T366K compared to wild-type IgG1; the D positive charge chain (Fc4(D+)) has mutations with EU numbers L351K and T366K compared to wild-type IgG4; the D negative charge chain (Fc(D-)) has mutations with EU numbers L351D and L368E compared to wild-type IgG1; and the D negative charge chain (Fc4(D-)) has mutations with EU numbers L351D and L368E compared to wild-type IgG4.

[0033] Meanwhile, some amino acids with large side chain steric hindrance were modified (EU sites numbered C220S, D356E, and L358M, and Kabat site numbered G230S) to change the distance between the two chains, making it easier for the connected α and β subunits to bind together.

[0034] This allows for the formation of a correctly assembled, stable heterodimeric form of the recombinant Fc-GtH fusion protein.

[0035] The recombinant Fc-GtH fusion protein disclosed herein has a long half-life and high activity. A single administration of a small dose can promote follicle development in mammals, induce ovulation and maturation in animals, and improve the efficiency of artificial reproduction. This fusion protein can be applied to human assisted reproduction, treatment of polycystic ovary syndrome and anovulatory diseases, superovulation in animals, estrus synchronization in animals, conception and farrowing, treatment of animal infertility, promotion of animal reproduction, embryo transfer, induction of sperm and ovulation, stimulation of gonadal tissue to secrete estradiol and testosterone, treatment of animal infertility, treatment of ovarian diseases in female animals, promotion of livestock reproduction, improvement of semen quality in male animals, induction of estrus in female animals, in vitro maturation of oocytes, and in vitro fertilization.

[0036] On one hand, this disclosure provides a recombinant Fc fusion protein comprising two different peptide chains, one of which is formed by the direct or indirect connection of a Gnα subunit and an Fc chain via a linker, and the other of which is formed by the direct or indirect connection of a Gnβ subunit and an Fc chain via a linker. These two peptide chains fold into a stable heterodimer under the dual action of non-covalent bonding between the Gnα and Gnβ subunits and the structure on the Fc chain. Preferably, the Fc chain comprises an Fc chain modified by a locking mode modification and an electrostatic orientation modification of a wild-type Fc chain.

[0037] According to the aforementioned recombinant fusion protein, the combination pattern of peptide chains in the recombinant fusion protein includes the following connections between Fc chains and Gnα or Gnβ subunits:

[0038] (1) The C-terminus of the Gnα subunit is connected to the N-terminus of the Fc chain to form the peptide chain Gnα-Fc; and the C-terminus of the Gnβ subunit is connected to the N-terminus of the Fc chain to form the peptide chain Gnβ-Fc; the peptide chains Gnα-Fc and Gnβ-Fc fold into a stable heterodimer in the form of Gnα-Fc:Gnβ-Fc under the dual effects of non-covalent bonding between the Gnα subunit and the Gnβ subunit, and the locking and snapping structures on the Fc chains or the electrostatic reversal on the positive and negative charge Fc chains;

[0039] (2) The N-terminus of the Gnα subunit is connected to the C-terminus of the Fc chain to form the peptide chain Fc-Gnα; and the C-terminus of the Gnβ subunit is connected to the N-terminus of the Fc chain to form the peptide chain Gnβ-Fc; the peptide chains Fc-Gnα and Gnβ-Fc fold into a stable heterodimer in the form of Fc-Gnα:Gnβ-Fc under the dual effects of non-covalent bonding between the Gnα and Gnβ subunits, and the locking and snapping structures on the Fc chains or the electrostatic reversal on the positive and negative charge Fc chains;

[0040] (3) The N-terminus of the Gnα subunit is connected to the C-terminus of the Fc chain to form the peptide chain Fc-Gnα; and the N-terminus of the Gnβ subunit is connected to the C-terminus of the Fc chain to form the peptide chain Fc-Gnβ; the peptide chains Fc-Gnα and Fc-Gnβ fold into a stable heterodimer in the form of Fc-Gnα:Fc-Gnβ under the dual effects of non-covalent bonding between the Gnα and Gnβ subunits, and the locking and snapping structures on the Fc chains or the electrostatic reversal on the positive and negative charge Fc chains.

[0041] According to the aforementioned recombinant Fc fusion protein, the Gn provided in this disclosure is selected from human FSH (hFSH), porcine FSH (pFSH), carp GtH I, and carp GtH II, wherein the Gnα subunit and Gnβ subunit are directly or indirectly linked to Fc through a linker; wherein the linker is a flexible polypeptide composed of 2-20 flexible amino acids, wherein the flexible amino acid is selected from at least one of Gly, Ser, Ala, and Thr, preferably (Gly-Gly-Gly-Gly-Ser)n, wherein n is an integer between 2 and 5, and more preferably n is 4;

[0042] On the other hand, this disclosure provides a nucleic acid encoding the aforementioned recombinant Fc fusion protein.

[0043] In another aspect, this disclosure provides a method for preparing the recombinant Fc and Gn fusion protein, the steps of which include:

[0044] (1) Construct an expression vector for expressing the recombinant Fc and Gn fusion protein:

[0045] (2) Introduce the expression vector constructed in step (1) into the host cell;

[0046] (3) The host cells are cultured under conditions suitable for the expression of the recombinant Fc and Gn fusion protein;

[0047] In some implementations, the method further includes step (4) separating the expressed recombinant Fc-Gn fusion protein.

[0048] In some embodiments, the isolated expression of the recombinant Fc-Gn fusion protein includes the following steps:

[0049] (i) Centrifuge the fermentation broth of the host cells, collect the supernatant, and obtain a clear fermentation broth;

[0050] (ii) The clarified fermentation broth was subjected to Protein A column chromatography and eluted to obtain the eluent;

[0051] (iii) The eluent is purified by cation exchange chromatography;

[0052] In another aspect, this disclosure provides a pharmaceutical composition comprising the aforementioned fusion protein or the aforementioned nucleic acid. The pharmaceutical composition further comprises a pharmaceutically acceptable carrier.

[0053] On the other hand, this disclosure provides the use of the recombinant Fc fusion protein, the nucleic acid, and the pharmaceutical composition in the preparation of a medicament for use in human assisted reproduction, treatment of polycystic ovary syndrome and anovulatory diseases, superovulation in animals, estrus synchronization in animals, conception and farrowing, treatment of animal infertility, promotion of animal reproduction, embryo transfer, induction of spermatogenesis and ovulation, stimulation of gonadal tissue to secrete estradiol and testosterone, and treatment of animal infertility, treatment of ovarian diseases in female animals, promotion of livestock reproduction, improvement of semen quality in male animals, induction of estrus in female animals, in vitro maturation of oocytes, and in vitro fertilization; wherein the animals include pigs, fish, cattle, sheep, horses, or dogs; preferably pigs or fish. Attached Figure Description

[0054] The accompanying drawings, which are incorporated in and form part of this specification, illustrate embodiments consistent with this specification and, together with the description, serve to explain the principles of this specification.

[0055] Figure 1 The sequence comparisons of the native human IgG Fc region sequences hIgG1 (SEQ ID NO.8), hIgG2, hIgG3, and hIgG4 (SEQ ID NO.10) are shown, with asterisks indicating the differences between these sequences.

[0056] Figure 2 The structure of the Fc fusion protein is shown, wherein the gonadotropin subunit can be linked to Fc1k, Fc4k, Fc1h, Fc4h, Fc1(T+), Fc4(T+), Fc1(T-), Fc4(T-), Fc1(D+), Fc4(D+), Fc1(D-), and Fc4(D-) via a flexible peptide.

[0057] Figure 3 The results of expression and purification of the Fc fusion protein are shown.

[0058] Figure 3 In A:

[0059] Band 1: 0811-1 (pK3), unpurified Fc-L-pFSH of this disclosure;

[0060] Band 2: 0811-1 (pK3), purified Fc-L-pFSH of this disclosure;

[0061] Band 3: 0811-2 (hK3), unpurified Fc-L-hFSH of this disclosure;

[0062] Band 4: 0811-2 (hK3), purified Fc-L-hFSH of this disclosure;

[0063] Band 5: 0811-3, unpurified Fc-L-pFSH(KiH) of this disclosure;

[0064] Band 6: 0811-3, purified Fc-L-pFSH(KiH) of this disclosure;

[0065] Band 7: 0811-4, unpurified Fc-L-hFSH(KiH) of this disclosure;

[0066] Band 8: 0811-4, purified Fc-L-hFSH(KiH) of this disclosure;

[0067] Band 9: 0811-5, unpurified CMPR1 (hFSH-IgG1-hFC, CN110041435A);

[0068] Band 10:0811-5, purified CMPR1 (hFSH-IgG1-hFC, CN110041435A);

[0069] Strip 11: Marker.

[0070] Figure 3 B:

[0071] Band 1: 0811-6, unpurified CMPR2 (hFSH-IgG2-hFC, CN103539862B);

[0072] Band 2: 0811-6, purified CMPR2 (hFSH-IgG2-hFC, CN103539862B);

[0073] Band 3: 0811-7, unpurified CMPR3 (pFSH-IgG1-hFC, CN103554269B);

[0074] Band 4: 0811-7, purified CMPR3 (pFSH-IgG1-hFC, CN103554269B);

[0075] Band 5: 0811-8, unpurified CMPR4 (pFSH-IgG2-hFC, CN103554269B);

[0076] Band 6: 0811-8, purified CMPR4 (pFSH-IgG2-hFC, CN103554269B);

[0077] Band 7: 0811-9, unpurified CMPR5 (pFSH-pFC, CN103554269B);

[0078] Band 8: 0811-9, purified CMPR5 (pFSH-pFC, CN103554269B);

[0079] Strip 9: Marker.

[0080] Figure 3 In C, band M represents the molecular weight standard, and band 1 represents purified Fc4-L-hFSH.

[0081] Figure 3 In D: Band M is the molecular weight standard, and bands 1-9 are hK1, hK2, hK3, hD1, hD2, hD3, hT1, hT2, and hT3, respectively.

[0082] Figure 3 In E: band M is the molecular weight standard, and bands 10-18 are pK1, pK2, pK3, pD1, pD2, pD3, pT1, pT2, and pT3, respectively.

[0083] Figure 3 In F: Band M is the molecular weight standard, and bands 19-27 are hK1-4, hK2-4, hK3-4, hD1-4, hD2-4, hD3-4, hT1-4, hT2-4, and hT3-4, respectively.

[0084] Figure 3 In G: Band 1 is the molecular weight standard, and bands 2-7 are the purified GtH I-K1, purified GtH I-K2, purified GtH I-K3, purified GtH I-T1, purified GtH I-T2, and purified GtH I-T3 of this disclosure, respectively.

[0085] Figure 3 In H: Band 1 is the molecular weight standard, and bands 2-4 are the purified GtH I-D1, purified GtH I-D2, and purified GtH I-D3 of this disclosure, respectively.

[0086] Figure 3 In section I: band M is the molecular weight standard, and bands 1-9 are GtH II fusion protein K1, GtH II fusion protein K2, GtH II fusion protein K3, GtH II fusion protein D1, GtH II fusion protein D2, GtH II fusion protein D3, GtH II fusion protein T1, GtH II fusion protein T2, and GtH II fusion protein T3, respectively.

[0087] Figure 4 The in vivo activity results of the recombinant Fc fusion protein are shown. Figure 4 A shows the in vivo activity results of the Fc-pFSH fusion protein, where the Fc-L-pFSH(Kih+Mut) protein corresponds to the pK3 protein, the Fc-L-hFSH(Kih+Mut) protein corresponds to the hK3 protein, and the Fc-L-hFSH(Kih+Mut) protein corresponds to the hK3-4 protein. Figure 4 B shows the in vivo activity results of the Fc-FSH fusion protein; Figure 4 C shows the in vivo activity results of the Fc / GtHI fusion protein; Figure 4 D shows the in vivo activity results of the Fc-GtH II fusion protein, where K1-K3, D1-D3, and T1-T3 are GtH II fusion protein K1, GtH II fusion protein K2, GtH II fusion protein K3, GtH II fusion protein D1, GtH II fusion protein D2, GtH II fusion protein D3, GtH II fusion protein T1, GtH II fusion protein T2, and GtH II fusion protein T3, respectively.

[0088] Figure 5 A typical image is shown showing how recombinant Fc-FSH fusion protein promotes superovulation in mice. Figure 5-1 5 is a typical image of an oocyte from the Fc-L-pFSH group; Figure 5 -6 is a typical image of an oocyte from the Fc-L-hFSH group; Figure 5-1 This is a typical image of an oocyte from the Fc-L-pFSH(KiH) group; Figure 5-2 This is a typical image of an oocyte from the Fc-L-hFSH(KiH) group; Figure 5-2 5 is a typical image of PMSG group oocytes; Figure 5 The other images in the table are typical pictures of oocytes from other recombinant Fc-FSH fusion protein groups in Table 9. Detailed Implementation

[0089] I. Definition

[0090] In this disclosure, unless otherwise stated, scientific and technical terms used herein have the meanings commonly understood by those skilled in the art. Furthermore, the terms and laboratory procedures related to protein and nucleic acid chemistry, molecular biology, cell and tissue culture, microbiology, and immunology used herein are all widely used terms and routine procedures in their respective fields. To better understand this disclosure, definitions and explanations of relevant terms are provided below.

[0091] As used herein and unless otherwise stated, the terms “about” or “approximately” mean within 10% of a given value or range. Where an integer is required, the term means within 10% of a given value or range, rounded up or down to the nearest integer.

[0092] It is well known that minute changes in the amino acid sequence, such as the deletion, addition, or substitution of one or more amino acids, can result in an allelic form of the original protein, which has substantially the same properties.

[0093] The term "Fc region" is used to define the C-terminus of an immunoglobulin heavy chain. The "Fc region" can be a native Fc region sequence or an Fc region variant. While the boundaries of the Fc region in an immunoglobulin heavy chain can vary, the human IgG heavy chain Fc region is generally defined as a sequence from amino acid residue Cys226 or Pro230 to its C-terminus. The Fc region of an immunoglobulin typically includes two constant regions, CH2 and CH3.

[0094] The "CH2 domain" (also known as the "Cγ2" domain) of the human IgG Fc region typically extends from about amino acid 231 to about amino acid 340. The unique feature of the CH2 domain is that it is not tightly paired with other domains. Instead, two N-linked branched sugar chains are located between the two CH2 domains of the intact native IgG molecule. It is speculated that these sugars can provide substitutions for domain-domain pairing and help stabilize the CH2 domain. (Burton, Molecular Immunology 22:161-206 (1985)).

[0095] The term "CH3 domain" includes a segment of residues in the Fc region from the C-terminus to the CH2 domain (i.e., from approximately amino acid residue 341 to approximately amino acid residue 447 in IgG).

[0096] "Natural Fc region sequences" include amino acid sequences identical to those found in naturally occurring Fc regions. Human natural Fc region sequences include the natural sequences of the human IgG1 Fc region (hIgG1), the human IgG2 Fc region (hIgG2), the human IgG3 Fc region (hIgG3), and the human IgG4 Fc region (hIgG4), as well as their naturally occurring variants. Figure 1 Sequence comparisons of the native human IgG Fc region sequences hIgG1 (SEQ ID NO. 8), hIgG2, hIgG3, and hIgG4 (SEQ ID NO. 10) are described, with asterisks indicating differences between these sequences.

[0097] "Fc variants" include amino acid sequences that differ from the native Fc region sequence by at least one "amino acid modification" as defined herein. Preferably, the Fc variant has at least one amino acid substitution compared to the native Fc region sequence or the Fc region of the parent polypeptide, such as about 1-10 amino acid substitutions, more preferably about 1-5 amino acid substitutions, in the native Fc region sequence or the Fc region of the parent polypeptide. The Fc variant preferably shares at least about 80% homology with the native Fc region sequence and / or the Fc region of the parent polypeptide, most preferably at least about 90% homology, and more preferably at least about 95% homology.

[0098] As used herein, the terms identity and homology, or optionally identical and homologous, are interchangeable and refer to the similarity of two polypeptide sequences. Each molecule is homologous to a position occupied by the same amino acid monomeric subunit when a position in two compared sequences is occupied by the same amino acid monomeric subunit. The percentage of homology between two sequences is a function of the number of corresponding or homologous positions shared by the two sequences divided by the total number of positions x 100. For example, if 10 positions are identical or 6 are identical in two sequences, then the two sequences are 60% homologous. For example, the amino acid sequences ASVIDT and AGVFPT have 50% homology (3 out of 6 positions correspond). Typically, sequence comparisons are performed to obtain the maximum homology. Such comparisons can be performed, for example, using the method of Needleman et al., J. Mol Biol. 48:443453 (1970), which can be easily performed using procedures such as Align (DNASTAR, Inc.). Similar sequences are those sequences that share the same and similar amino acid residues when compared, where similar residues represent conserved substitutions of the corresponding amino acid residues with permissible point mutations compared to a reference sequence. In this sense, a conserved substitution of residues in a reference sequence is a substitution of residues that are physically or functionally similar to the corresponding reference residue, such as having similar size, shape, charge, chemical properties, including the ability to form covalent or hydrogen bonds. Therefore, a sequence variant with conserved substitutions is one that differs from a reference or wild-type sequence in that it contains one or more conserved substitutions or permissible gene mutations.

[0099] The term "amino acid modification" refers to an alteration in a predetermined amino acid sequence. Examples of modifications include amino acid substitution, insertion, and / or deletion. Substitution is the preferred amino acid modification described herein.

[0100] "Amino acid modification" at a specific site, such as the Fc region, refers to the substitution or deletion of a specific residue, or the insertion of at least one amino acid residue near a specific residue. Insertion "near" a specific residue means insertion one or two residues away. This insertion can occur at the N-terminus or C-terminus of the specific residue.

[0101] The term "amino acid substitution" refers to replacing at least one amino acid already present in a predetermined amino acid sequence with another different "substitute" amino acid residue. The substituted residue can be a "natural amino acid residue" (i.e., encoded by the genetic code) and is selected from: alanine (Ala), arginine (Arg), asparagine (Asn), aspartic acid (Asp), cysteine ​​(Cys), glutamine (Gln), glutamic acid (Glu), glycine (Gly), histidine (His), isoleucine (Ile), leucine (Leu), lysine (Lys), methionine (Met), phenylalanine (Phe), proline (Pro), serine (Ser), threonine (Thr), tryptophan (Trp), tyrosine (Tyr), and valine (Val). Preferably, the substituted residue is not cysteine. Substitution with one or more non-natural amino acid residues is also included in the definition of amino acid substitution herein. "Non-natural amino acid residues" refers to those, other than the natural amino acid residues listed above, that can covalently bind to adjacent amino acid residues in the peptide chain. Non-natural amino acid residues include ornithine, ornithine, valine, homoserine, and other amino acid residue analogs, such as those described in Ellman et al., Enzymatic Methods 202:301-336 (1991). To prepare these non-natural amino acids, methods can be used as described in Noren et al., Science 244:182 (1989) and Ellman et al., ibid. In short, these methods involve the chemical activation of repressive tRNA from non-natural amino acid residues, followed by in vitro transcription and translation of that RNA.

[0102] The term "amino acid insertion" refers to the incorporation of at least one amino acid into a predetermined amino acid sequence. While such insertion typically involves the insertion of one or two amino acid residues, this disclosure contemplates larger "peptide inserts," such as insertions of about 3-5 or up to about 10 amino acid residues. The inserted residues can be either natural or non-natural residues as described above.

[0103] The term "amino acid deletion" refers to the removal of at least one amino acid residue from a predetermined amino acid sequence.

[0104] The term "hinge region" is generally defined as a sequence from Glu216 to Pro230 of human IgG1 (Burton, Molecular Immunology 22:161-206 (1985)). Hinge regions of other IgG isotypes can be compared with the IgG1 sequence by placing the first and last cysteine ​​residues that form the SS bond in the heavy chain at the same position.

[0105] The term "linker" refers to a peptide containing one or more amino acids, typically about 2-20 amino acids. Linkers are known in the art or described herein. In some embodiments, the linker is a flexible polypeptide. The flexible polypeptide is composed of flexible amino acids selected from at least one of Gly, Ser, Ala, and Thr. Suitable non-immunogenic linker peptides are, for example, (G4S)n, (SG4)n, or G4(SG4)n peptide linkers, where "n" is generally between 1 and 10, typically between 1 and 4, especially 3 or 4, i.e., peptides selected from GGGGS (SEQ ID NO. 136), GGGGSGGGGS (SEQ ID NO. 137), SGGGGSGGGG (SEQ ID NO. 138), GGGGGSGGGGSSGGGGS (SEQ ID NO. 139), GGGGSGGGGSGGGGS (SEQ ID NO. 140), GGGGSGGGGSGGG (SEQ ID NO. 141), GGGGSGGGGSGGGGSGGGGS (SEQ ID NO. 142), GGGGSGGGGSGGGSGGGS (SEQ ID NO. 143), GSPGSSSSGS (SEQ ID NO. 144), GSGSGSGS (SEQ ID NO. 145), GSPGSSSSGS (SEQ ID NO. 146), GSGSGSGS (SEQ ID NO. 147), GGGGSGGGSGGGS (SEQ ID NO. 148), GGGGSGGGSGGGSGGGS (SEQ ID NO. 149), GGGGSGGGSGGGSGGGS (SEQ ID NO. 140), GGGGSGGGGSGGGGSGGGS (SEQ ID NO. 141), GGGGSGGGGSGGGSGGGSGGGS (SEQ ID NO. 142), GGGGSGGGGSGGGSGGGS (SEQ ID NO. 143), GSPGSSSSGS (SEQ ID NO. 144), GSGSGSGS (SEQ ID NO. 145), GSGSGSGSGS (SEQ ID NO. 146), GGGGSGGGSGGGSGGGS (SEQ ID NO.145), GSGSGNGS (SEQ ID NO.146), GGSGSGSG (SEQ ID NO.147), GGSGSG (SEQ ID NO.148), GGSG (SEQ ID NO.149), GGSGNGSG (SEQ ID NO.150), GGNGSGSG (SEQ ID NO.151) and GGNGSG (SEQ ID NO.152); the peptide linkers of particular interest are (G4S)2 or GGGGSGGGGGS (SEQ ID NO.137), GGGGSGGGGGSGGGGSGGGGS (SEQ ID NO.142) and GGGGSGGGGSGGGSGGGGS (SEQ ID NO.143).

[0106] The term "GtH" stands for Gonadotropin Hormone, which is a class of glycoprotein hormones (GPHs) synthesized and secreted by the anterior pituitary cells of vertebrates. Its main physiological function is to stimulate the growth, development, maturation, ejaculation, and ovulation of germ cells.

[0107] The term "FSH" stands for follicle-stimulating hormone. It mainly plays a role in the early stages of gonadal development, namely the yolk sac formation and spermatogenesis periods. It is secreted in large quantities by the pituitary gland and plays a major role in stimulating gonadal tissue to secrete estradiol and testosterone.

[0108] The term "lock-in mode" refers to the modification of the Fc chain using the KiH technology developed by Paul Carter's team at Genentech in 1996. This technology is fundamental to the efficient heterodimerization of antibody heavy chains. Typically, when preparing heterodimers of antibody A and antibody B using recombinant expression systems, the correct assembly rate of the AB heterodimer in the expression product is less than 50%. The lock-in mode can increase the stability of the heterodimer, raising the correct assembly rate to over 80%.

[0109] The term "electrostatic reversal mode" refers to the use of oppositely charged amino acids, protein domains, and favorable electrostatic interactions between proteins to control the formation of higher-order protein molecules. U.S. Patent Application Publication No. 2014 / 0024111 discloses a method for using the electrostatic reversal effect to alter the interactions of antibody domains to reduce the formation of homodimers, which is conducive to the formation of heterodimers in bispecific antibody production. When two pairs of positive and negative charges are introduced, the electrostatic reversal D-type is named after the first letter "D" of "Double." In the electrostatic reversal D-type, the D positively charged chain has mutations with EU designations L351K and T366K compared to wild-type IgG1; the D negatively charged chain has mutations with EU designations L351D and L368E compared to wild-type IgG1. When three pairs of positive and negative charges are introduced, the electrostatic shifting T-type is named after the first letter T of "Triple". Compared with wild-type IgG1, the T positive charge chain has mutations with EU numbers D221R, P228R, and K409R; the T negative charge chain has mutations with EU numbers D221E, P228E, and L368E compared with wild-type IgG1.

[0110] The term "pharmaceutical composition" refers to a formulation which is present in a form that allows the biological activity of the active ingredient contained therein to be effective, and which does not contain any additional ingredients that would have unacceptable toxicity to a subject administering the formulation.

[0111] The term “pharmaceutical carrier” or “pharmaceuticalally acceptable carrier” refers to a diluent, adjuvant (e.g., Freund’s adjuvant (complete and incomplete)), excipient, or medium that is administered with a therapeutic agent.

[0112] As used herein and unless otherwise stated, the terms “comprising,” “including,” “having,” “containing,” and their grammatical equivalents, including their grammatical equivalents, should generally be understood as open-ended and non-restrictive, e.g., not excluding other unlisted elements or steps.

[0113] II. Detailed Implementation Plan

[0114] In a first aspect, this disclosure provides a recombinant Fc fusion protein comprising two different peptide chains. One chain is formed by directly or indirectly connecting a gonadotropin α subunit (Gnα subunit) to an Fc chain according to a certain linkage mode, or through a linker. The other chain is formed by directly or indirectly connecting a gonadotropin β subunit (Gnβ subunit) to an Fc chain according to a certain linkage mode. The peptide chains fold into stable heterodimers under the dual effects of non-covalent binding between the Gnα and Gnβ subunits, and the locking and latching structures on the Fc chains (lock and snap-lock) or the electrostatic reversal on the positively and negatively charged Fc chains.

[0115] In some specific embodiments, the connection mode includes a connection between an Fc chain and a Gnα or Gnβ subunit selected from the following:

[0116] (1) The C-terminus of the Gnα subunit is connected to the N-terminus of the Fc chain to form the peptide chain Gnα-Fc; and the C-terminus of the Gnβ subunit is connected to the N-terminus of the Fc chain to form the peptide chain Gnβ-Fc; the peptide chains Gnα-Fc and Gnβ-Fc fold into a stable heterodimer in the form of Gnα-Fc:Gnβ-Fc under the dual effects of non-covalent bonding between the Gnα subunit and the Gnβ subunit, and the locking and snapping structures on the Fc chains or the electrostatic reversal on the positive and negative charge Fc chains;

[0117] (2) The N-terminus of the Gnα subunit is connected to the C-terminus of the Fc chain to form the peptide chain Fc-Gnα; and the C-terminus of the Gnβ subunit is connected to the N-terminus of the Fc chain to form the peptide chain Gnβ-Fc; the peptide chains Fc-Gnα and Gnβ-Fc fold into a stable heterodimer in the form of Fc-Gnα:Gnβ-Fc under the dual effects of non-covalent bonding between the Gnα and Gnβ subunits, and the locking and snapping structures on the Fc chains or the electrostatic reversal on the positive and negative charge Fc chains;

[0118] (3) The N-terminus of the Gnα subunit is connected to the C-terminus of the Fc chain to form the peptide chain Fc-Gnα; and the N-terminus of the Gnβ subunit is connected to the C-terminus of the Fc chain to form the peptide chain Fc-Gnβ; the peptide chains Fc-Gnα and Fc-Gnβ fold into a stable heterodimer in the form of Fc-Gnα:Fc-Gnβ under the dual effects of non-covalent bonding between the Gnα and Gnβ subunits, and the locking and snapping structures on the Fc chains or the electrostatic reversal on the positive and negative charge Fc chains.

[0119] In some specific embodiments, the locking structure or electrostatic deflection mode is characterized as follows:

[0120] (1) The locking structure includes two different Fc chains, one of which is a buckle Fc chain (Fck) and the other is a lock Fc chain (Fch).

[0121] In some preferred embodiments, the heterodimer in the form of Gnα-Fc:Gnβ-Fc obtained by folding under the locking structure comprises a peptide chain Gnα-Fck formed by connecting the C-terminus of the Gnα subunit to the N-terminus of the clasp-type Fc chain (Fck); and a peptide chain Gnβ-Fch formed by connecting the C-terminus of the Gnβ subunit to the N-terminus of the clasp-type Fc chain (Fch). The peptide chains Gnα-Fck and Gnβ-Fch fold into a stable heterodimer in the form of Gnα-Fck:Gnβ-Fch under the action of the locking structure.

[0122] In some preferred embodiments, the heterodimer in the form of Gnα-Fc:Gnβ-Fc obtained by folding under the locking structure comprises a peptide chain Gnα-Fch formed by connecting the C-terminus of the Gnα subunit to the N-terminus of the locked Fc chain (Fch); and a peptide chain Gnβ-Fck formed by connecting the C-terminus of the Gnβ subunit to the N-terminus of the button Fc chain (Fck). The peptide chains Gnα-Fch and Gnβ-Fck fold into a stable heterodimer in the form of Gnα-Fch:Gnβ-Fck under the action of the locking structure.

[0123] In some preferred embodiments, the heterodimer in the form of Fc-Gnα:Gnβ-Fc obtained by folding under the locking structure comprises one peptide chain, Fck-Gnα, formed by connecting the N-terminus of the Gnα subunit to the C-terminus of the clasp-type Fc chain (Fck); and another peptide chain, Gnβ-Fch, formed by connecting the C-terminus of the Gnβ subunit to the N-terminus of the clasp-type Fc chain (Fch). The peptide chains Fck-Gnα and Gnβ-Fch fold into a stable heterodimer in the form of Fck-Gnα:Gnβ-Fch under the action of the locking structure.

[0124] In some preferred embodiments, the heterodimer in the form of Fc-Gnα:Gnβ-Fc obtained by folding under the locking structure comprises one peptide chain, Fch-Gnα, formed by connecting the N-terminus of the Gnα subunit to the C-terminus of the locked Fc chain (Fch); and another peptide chain, Gnβ-Fck, formed by connecting the C-terminus of the Gnβ subunit to the N-terminus of the button Fc chain (Fck). The peptide chains Fch-Gnα and Gnβ-Fck fold into a stable heterodimer in the form of Fch-Gnα:Gnβ-Fck under the action of the locking structure.

[0125] In some preferred embodiments, the heterodimer in the form of Fc-Gnα:Fc-Gnβ obtained by folding under the locking structure comprises one peptide chain, Fck-Gnα, formed by connecting the N-terminus of the Gnα subunit to the C-terminus of the clasp-type Fc chain (Fck); and another peptide chain, Fch-Gnβ, formed by connecting the N-terminus of the Gnβ subunit to the C-terminus of the clasp-type Fc chain (Fch). The peptide chains Fck-Gnα and Fch-Gnβ fold into a stable heterodimer in the form of Fck-Gnα:Fch-Gnβ under the action of the locking structure.

[0126] In some preferred embodiments, the heterodimer in the form of Fc-Gnα:Fc-Gnβ obtained by folding under the locking structure comprises one peptide chain, Fch-Gnα, formed by connecting the N-terminus of the Gnα subunit to the C-terminus of the locked Fc chain (Fch); and another peptide chain, Fck-Gnβ, formed by connecting the N-terminus of the Gnβ subunit to the C-terminus of the button Fc chain (Fck). The peptide chains Fch-Gnα and Fck-Gnβ fold into a stable heterodimer in the form of Fch-Gnα:Fck-Gnβ under the action of the locking structure.

[0127] (2) The electrostatic reversal mode contains two different Fc chains, one of which is a positive charge chain (Fc(+)) and the other is a negative charge chain (Fc(-)).

[0128] In some preferred embodiments, the heterodimer in the form of Gnα-Fc:Gnβ-Fc obtained by electrostatic reversal folding comprises one peptide chain, Gnα-Fc(+), formed by connecting the C-terminus of the Gnα subunit to the N-terminus of the positively charged chain (Fc(+)); and the other peptide chain, Gnβ-Fc(-), formed by connecting the C-terminus of the Gnβ subunit to the N-terminus of the negatively charged chain (Fc(-)). The peptide chains Gnα-Fc(+) and Gnβ-Fc(-) fold into a stable heterodimer in the form of Gnα-Fc(+):Gnβ-Fc(-) under electrostatic reversal.

[0129] In some preferred embodiments, the electrostatic steering modes include electrostatic steering T-type and electrostatic steering D-type:

[0130] (i) The electrostatically redirecting T-type contains two Fc chains, one of which is a T-type positive charge chain (Fc(T+)) and the other is a T-type negative charge chain (Fc(T-)). Under the action of electrostatic redirection, it folds into a stable heterodimer in the form of Gnα-Fc(T+):Gnβ-Fc(T-).

[0131] (ii) The electrostatically redirected D-type contains two Fc chains, one of which is a D-type positive charge chain (Fc(D+)) and the other is a D-type negative charge chain (Fc(D-)). Under the action of electrostatic redirection, it folds into a stable heterodimer in the form of Gnα-Fc(D+):Gnβ-Fc(D-).

[0132] In some preferred embodiments, the heterodimer in the form of Gnα-Fc:Gnβ-Fc obtained by electrostatic reversal folding comprises one peptide chain, Gnα-Fc(-), formed by connecting the C-terminus of the Gnα subunit to the N-terminus of the negatively charged chain (Fc(-)); and the other peptide chain, Gnβ-Fc(+), formed by connecting the C-terminus of the Gnβ subunit to the N-terminus of the positively charged chain (Fc(+)). The peptide chains Gnα-Fc(-) and Gnβ-Fc(+) fold into a stable heterodimer in the form of Gnα-Fc(-):Gnβ-Fc(+) under electrostatic reversal.

[0133] In some preferred embodiments, the electrostatic steering modes include electrostatic steering T-type and electrostatic steering D-type:

[0134] (i) The electrostatically redirecting T-type contains two Fc chains, one of which is a T-type positive charge chain (Fc(T+)) and the other is a T-type negative charge chain (Fc(T-)). Under the action of electrostatic redirection, it folds into a stable heterodimer in the form of Gnα-Fc(T-):Gnβ-Fc(T+);

[0135] (ii) The electrostatically redirected D-type contains two Fc chains, one of which is a D-type positive charge chain (Fc(D+)) and the other is a D-type negative charge chain (Fc(D-)). Under the action of electrostatic redirection, it folds into a stable heterodimer in the form of Gnα-Fc(D-):Gnβ-Fc(D+).

[0136] In some preferred embodiments, the heterodimer in the form of Fc-Gnα:Gnβ-Fc obtained by electrostatic reversal folding comprises one peptide chain, Fc(+)-Gnα, formed by connecting the N-terminus of the Gnα subunit to the C-terminus of the positively charged chain (Fc(+)); and the other peptide chain, Gnβ-Fc(-), formed by connecting the C-terminus of the Gnβ subunit to the N-terminus of the negatively charged chain (Fc(-)). The peptide chains Fc(+)-Gnα and Gnβ-Fc(-) fold into a stable heterodimer in the form of Fc(+)-Gnα:Gnβ-Fc(-) under electrostatic reversal.

[0137] In some preferred embodiments, the electrostatic steering modes include electrostatic steering T-type and electrostatic steering D-type:

[0138] (i) The electrostatically redirecting T-type contains two Fc chains, one of which is a T-type positive charge chain (Fc(T+)) and the other is a T-type negative charge chain (Fc(T-)). Under the action of electrostatic redirection, it folds into a stable heterodimer in the form of Fc(T+)-Gnα:Gnβ-Fc(T-).

[0139] (ii) The electrostatically redirected D-type contains two Fc chains, one of which is a D-type positive charge chain (Fc(D+)) and the other is a D-type negative charge chain (Fc(D-)). Under the action of electrostatic redirection, it folds into a stable heterodimer in the form of Fc(D+)-Gnα:Gnβ-Fc(D-).

[0140] In some preferred embodiments, the heterodimer in the form of Fc-Gnα:Gnβ-Fc obtained by electrostatic reversal folding comprises one peptide chain, Fc(-)-Gnα, formed by connecting the N-terminus of the Gnα subunit to the C-terminus of the negatively charged chain (Fc(-)); and the other peptide chain, Gnβ-Fc(+), formed by connecting the C-terminus of the Gnβ subunit to the N-terminus of the positively charged chain (Fc(+)). The peptide chains Fc(-)-Gnα and Gnβ-Fc(+) fold into a stable heterodimer in the form of Fc(-)-Gnα:Gnβ-Fc(+) under electrostatic reversal.

[0141] In some preferred embodiments, the electrostatic steering modes include electrostatic steering T-type and electrostatic steering D-type:

[0142] (i) The electrostatically redirecting T-type contains two Fc chains, one of which is a T-type positive charge chain (Fc(T+)) and the other is a T-type negative charge chain (Fc(T-)). Under the action of electrostatic redirection, it folds into a stable heterodimer in the form of Fc(T-)-Gnα:Gnβ-Fc(T+).

[0143] (ii) The electrostatically redirected D-type contains two Fc chains, one of which is a D-type positive charge chain (Fc(D+)) and the other is a D-type negative charge chain (Fc(D-)). Under the action of electrostatic redirection, it folds into a stable heterodimer in the form of Fc(D-)-Gnα:Gnβ-Fc(D+).

[0144] In some preferred embodiments, the heterodimer in the form of Fc-Gnα:Fc-Gnβ obtained by electrostatic reversal folding comprises one peptide chain, Fc(+)-Gnα, formed by connecting the N-terminus of the Gnα subunit to the C-terminus of the positively charged chain (Fc(+)); and the other peptide chain, Fc(-)-Gnβ, formed by connecting the N-terminus of the Gnβ subunit to the C-terminus of the negatively charged chain (Fc(-)). The peptide chains Fc(+)-Gnα and Fc(-)-Gnβ fold into a stable heterodimer in the form of Fc(+)-Gnα:Fc(-)-Gnβ under electrostatic reversal.

[0145] In some preferred embodiments, the electrostatic steering modes include electrostatic steering T-type and electrostatic steering D-type:

[0146] (i) The electrostatically redirecting T-type contains two Fc chains, one of which is a T-type positive charge chain (Fc(T+)) and the other is a T-type negative charge chain (Fc(T-)). Under the action of electrostatic redirection, it folds into a stable heterodimer in the form of Fc(T+)-Gnα:Fc(T-)-Gnβ.

[0147] (ii) The electrostatically redirected D-type contains two Fc chains, one of which is a D-type positive charge chain (Fc(D+)) and the other is a D-type negative charge chain (Fc(D-)). Under the action of electrostatic redirection, it folds into a stable heterodimer in the form of Fc(D+)-Gnα:Fc(D-)-Gnβ.

[0148] In some preferred embodiments, the heterodimer in the form of Fc-Gnα:Fc-Gnβ obtained by electrostatic reversal folding comprises one peptide chain, Fc(-)-Gnα, formed by connecting the N-terminus of the Gnα subunit to the C-terminus of the negatively charged chain (Fc(-)); and the other peptide chain, Fc(+)-Gnβ, formed by connecting the N-terminus of the Gnβ subunit to the C-terminus of the positively charged chain (Fc(+)). The peptide chains Fc(-)-Gnα and Fc(+)-Gnβ fold into a stable heterodimer in the form of Fc(-)-Gnα:Fc(+)-Gnβ under electrostatic reversal.

[0149] In some preferred embodiments, the electrostatic steering modes include electrostatic steering T-type and electrostatic steering D-type:

[0150] (i) The electrostatically redirecting T-type contains two Fc chains, one of which is a T-type positive charge chain (Fc(T+)) and the other is a T-type negative charge chain (Fc(T-)). Under the action of electrostatic redirection, it folds into a stable heterodimer in the form of Fc(T-)-Gnα:Fc(T+)-Gnβ.

[0151] (ii) The electrostatically redirected D-type contains two Fc chains, one of which is a D-type positive charge chain (Fc(D+)) and the other is a D-type negative charge chain (Fc(D-)). Under the action of electrostatic redirection, it folds into a stable heterodimer in the form of Fc(D-)-Gnα:Fc(D+)-Gnβ.

[0152] In some specific embodiments, the gonadotropin is a vertebrate gonadotropin.

[0153] In some preferred embodiments, the vertebrate is selected from humans, pigs, cattle, sheep, horses, dogs, or fish.

[0154] In some preferred embodiments, the gonadotropin (Gn) is selected from human FSH (hFSH), porcine FSH (pFSH), carp GtH I, and carp GtH II.

[0155] In some preferred embodiments, the pFSHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO.1, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, and more preferably having 98% or 99% or more identity; preferably, the pFSHα subunit has the amino acid sequence shown in SEQ ID NO.1 or has an amino acid sequence obtained by deleting, adding, or substituting 1, 2, or 3 residues in SEQ ID NO.1.

[0156] In some preferred embodiments, the pFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO.2, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, and more preferably having 98% or 99% or more identity; preferably, the pFSHβ subunit has the amino acid sequence shown in SEQ ID NO.2 or has an amino acid sequence obtained by deleting, adding, or substituting 1, 2, or 3 residues in SEQ ID NO.2.

[0157] In some preferred embodiments, the hFSHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO.3, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, and more preferably having 98% or 99% or more identity; preferably, the hFSHα subunit has the amino acid sequence shown in SEQ ID NO.3 or has an amino acid sequence obtained by deleting, adding, or substituting 1, 2, or 3 residues in SEQ ID NO.3.

[0158] In some preferred embodiments, the hFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO.4, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, and more preferably having 98% or 99% or more identity; preferably, the hFSHβ subunit has the amino acid sequence shown in SEQ ID NO.4 or has an amino acid sequence obtained by deleting, adding, or substituting 1, 2, or 3 residues in SEQ ID NO.4.

[0159] More preferably, the carp GtHα subunit contains an amino acid sequence that has 80% or more identity with the amino acid sequence shown in SEQ ID NO. 5, preferably with 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, and more preferably with 98% or 99% or more identity; preferably, the carp GtHα subunit has the amino acid sequence shown in SEQ ID NO. 5 or has an amino acid sequence obtained by deleting, adding, or substituting 1, 2, or 3 residues in SEQ ID NO. 5.

[0160] In some preferred embodiments, the carp GtH Iβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 6, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, and more preferably having 98% or 99% or more identity; preferably, the carp GtH Iβ subunit has the amino acid sequence shown in SEQ ID NO. 6 or has an amino acid sequence obtained by deleting, adding, or substituting 1, 2, or 3 residues in SEQ ID NO. 6.

[0161] Preferably, the carp GtH IIβ subunit contains an amino acid sequence that has 80% or more identity with the amino acid sequence shown in SEQ ID NO.7, more preferably with 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, and more preferably with 98% or 99% or more identity; preferably, the carp GtH IIβ subunit has the amino acid sequence shown in SEQ ID NO.7 or has an amino acid sequence obtained by deleting, adding, or substituting 1, 2, or 3 residues in SEQ ID NO.7.

[0162] In some specific embodiments, the Fc chain includes the hinge region of IgG as well as the CH2 and CH3 regions.

[0163] In some preferred embodiments, the IgG is derived from human, pig, cow, sheep, horse, or dog. In some preferred embodiments, the IgG is human IgG.

[0164] In some preferred embodiments, the Fc chain is an Fc chain of IgG1 or IgG4. In some preferred embodiments, the Fc chain is an Fc chain of human IgG1 or IgG4.

[0165] In some preferred embodiments, the hinge region of the Fc chain and the CH2 and CH3 regions contain an amino acid sequence that has 80% or more identity with the wild-type IgG Fc region shown in SEQ ID NO. 8 or 10, preferably having an amino acid sequence with 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, and more preferably having an amino acid sequence with 98% or 99% or more identity.

[0166] In some preferred embodiments, the Fc chain has an amino acid mutation selected from any one or more of the following according to EU numbers:

[0167] C220S;

[0168] D221E;

[0169] D221R;

[0170] P228E;

[0171] S228E;

[0172] P228R;

[0173] S228R;

[0174] Y349C;

[0175] L351D;

[0176] L351K;

[0177] S354C;

[0178] D356E;

[0179] L358M;

[0180] T366K;

[0181] T366S;

[0182] T366W;

[0183] L368A;

[0184] L368E;

[0185] Y407V;

[0186] K409R.

[0187] In some preferred embodiments, the Fc chain has an amino acid mutation selected from those numbered according to Kabat: G230S.

[0188] In some preferred embodiments, the Fc chain further comprises amino acid mutations selected from any one or more of the following according to EU numbers:

[0189] E233 is missing;

[0190] L234P or L234F;

[0191] L235V;

[0192] G236A;

[0193] H268Q;

[0194] K274Q;

[0195] N276K;

[0196] Y296F;

[0197] Y300F;

[0198] L309V;

[0199] A327G;

[0200] A330S;

[0201] P331S;

[0202] A339T;

[0203] R355Q;

[0204] N384S;

[0205] K392N;

[0206] V397M;

[0207] K409R;

[0208] Q419E;

[0209] V422I;

[0210] H435R;

[0211] Y436F;

[0212] P445L.

[0213] In some preferred embodiments, the coin-type Fc chain (Fc1k) has S354C and T366W mutations; more preferably, the coin-type Fc chain (Fc1k) also has C220S, D356E and L358M mutations.

[0214] In some preferred embodiments, the coin-type Fc chain (Fc4k) has S354C and T366W mutations; more preferably, the coin-type Fc chain (Fc4k) also has a G230S mutation.

[0215] In some preferred embodiments, the locked Fc chain (Fc1h) has Y349C, T366S, L368A and Y407V mutations; more preferably, the locked Fc chain (Fc1h) also has C220S, D356E and L358M mutations.

[0216] In some preferred embodiments, the locked Fc chain (Fc4h) has Y349C, T366S, L368A and Y407V mutations; more preferably, the locked Fc chain (Fc4h) also has G230S mutations.

[0217] In some preferred embodiments, the electrostatically redirecting T-type positive charge chain (Fc1(T+)) has D221R, P228R, and K409R mutations; more preferably, the electrostatically redirecting T-type positive charge chain (Fc1(T+)) also has C220S, D356E, and L358M mutations.

[0218] In some preferred embodiments, the electrostatically redirecting T-type positive charge chain (Fc4(T+)) has S228R and K409R mutations; more preferably, the electrostatically redirecting T-type positive charge chain (Fc4(T+)) also has G230S mutation.

[0219] In some preferred embodiments, the electrostatically redirecting T-type negative charge chain (Fc1(T-)) has D221E, P228E and L368E mutations; more preferably, the electrostatically redirecting T-type negative charge chain (Fc1(T-)) also has C220S, D356E and L358M mutations.

[0220] In some preferred embodiments, the electrostatically redirecting T-type negative charge chain (Fc4(T-)) has S228E and L368E mutations; more preferably, the electrostatically redirecting T-type negative charge chain (Fc4(T-)) also has G230S mutation.

[0221] In some preferred embodiments, the electrostatically redirected D-type positive charge chain (Fc1(D+)) has L351K and T366K mutations; more preferably, the electrostatically redirected D-type positive charge chain (Fc1(D+)) also has C220S, D356E and L358M mutations.

[0222] In some preferred embodiments, the electrostatically redirected D-type positive charge chain (Fc4(D+)) has L351K and T366K mutations; more preferably, the electrostatically redirected D-type positive charge chain (Fc4(D+)) also has G230S mutation.

[0223] In some preferred embodiments, the electrostatically redirected D-type negative charge chain (Fc1(D-)) has L351D and L368E mutations; more preferably, the electrostatically redirected D-type negative charge chain (Fc1(D-)) also has C220S, D356E and L358M mutations.

[0224] In some preferred embodiments, the electrostatically redirected D-type negative charge chain (Fc4(D-)) has L351D and L368E mutations; more preferably, the electrostatically redirected D-type negative charge chain (Fc4(D-)) also has G230S mutation.

[0225] In some preferred embodiments, the coin-type Fc chain (Fc1k) comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO.9, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, and more preferably having 98% or 99% or more identity; preferably, the coin-type Fc chain (Fc1k) has the amino acid sequence shown in SEQ ID NO.9 or has an amino acid sequence obtained by deleting, adding, or substituting 1, 2, or 3 residues in SEQ ID NO.9.

[0226] In some preferred embodiments, the coin-type Fc chain (Fc4k) comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 11, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, and more preferably having 98% or 99% or more identity; preferably, the coin-type Fc chain (Fc4k) has the amino acid sequence shown in SEQ ID NO. 11 or has an amino acid sequence obtained by deleting, adding, or substituting 1, 2, or 3 residues in SEQ ID NO. 11.

[0227] In some preferred embodiments, the coin-type Fc chain (Fc1k(KiH)) comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 130, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, and more preferably having 98% or 99% or more identity; preferably, the coin-type Fc chain (Fc1k(KiH)) has the amino acid sequence shown in SEQ ID NO. 130 or has an amino acid sequence obtained by deleting, adding, or substituting 1, 2, or 3 residues in SEQ ID NO. 130.

[0228] In some preferred embodiments, the locked Fc chain (Fc1h) comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 12, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, and more preferably having 98% or 99% or more identity; preferably, the locked Fc chain (Fc1h) has the amino acid sequence shown in SEQ ID NO. 12 or has an amino acid sequence obtained by deleting, adding, or substituting 1, 2, or 3 residues in SEQ ID NO. 12.

[0229] In some preferred embodiments, the locked Fc chain (Fc4h) comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 13, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, and more preferably having 98% or 99% or more identity; preferably, the locked Fc chain (Fc1h) has the amino acid sequence shown in SEQ ID NO. 13 or has an amino acid sequence obtained by deleting, adding, or substituting 1, 2, or 3 residues in SEQ ID NO. 13.

[0230] In some preferred embodiments, the locked Fc chain (Fc1h(KiH)) comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 131, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, and more preferably having 98% or 99% or more identity; preferably, the locked Fc chain (Fc1h(KiH)) has the amino acid sequence shown in SEQ ID NO. 131 or has an amino acid sequence obtained by deleting, adding, or substituting 1, 2, or 3 residues in SEQ ID NO. 131.

[0231] In some preferred embodiments, the electrostatically redirected T-type positive charge chain (Fc1(T+)) comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 14, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, and more preferably having 98% or 99% or more identity; preferably, the electrostatically redirected T-type positive charge chain (Fc1(T+)) has the amino acid sequence shown in SEQ ID NO. 14 or has an amino acid sequence obtained by deleting, adding, or substituting 1, 2, or 3 residues in SEQ ID NO. 14.

[0232] In some preferred embodiments, the electrostatically redirected T-type positive charge chain (Fc4(T+)) comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 15, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, and more preferably having 98% or 99% or more identity; preferably, the electrostatically redirected T-type positive charge chain (Fc4(T+)) has the amino acid sequence shown in SEQ ID NO. 15 or has an amino acid sequence obtained by deleting, adding, or substituting 1, 2, or 3 residues in SEQ ID NO. 15.

[0233] In some preferred embodiments, the electrostatically redirected T-type negative charge chain (Fc1(T-)) comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 16, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, and more preferably having 98% or 99% or more identity; preferably, the electrostatically redirected T-type negative charge chain (Fc1(T-)) has the amino acid sequence shown in SEQ ID NO. 16 or has an amino acid sequence obtained by deleting, adding, or substituting 1, 2, or 3 residues in SEQ ID NO. 16.

[0234] In some preferred embodiments, the electrostatically redirected T-type negative charge chain (Fc4(T-)) comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 17, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, and more preferably having 98% or 99% or more identity; preferably, the electrostatically redirected T-type negative charge chain (Fc4(T-)) has the amino acid sequence shown in SEQ ID NO. 17 or has an amino acid sequence obtained by deleting, adding, or substituting 1, 2, or 3 residues in SEQ ID NO. 17.

[0235] In some preferred embodiments, the electrostatically redirected D-type positively charged chain (Fc1(D+)) comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 18, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, and more preferably having 98% or 99% or more identity; preferably, the electrostatically redirected D-type positively charged chain (Fc1(D+)) has the amino acid sequence shown in SEQ ID NO. 18 or has an amino acid sequence obtained by deleting, adding, or substituting 1, 2, or 3 residues in SEQ ID NO. 18.

[0236] In some preferred embodiments, the electrostatically redirected D-type positively charged chain (Fc4(D+)) comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 19, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, and more preferably having 98% or 99% or more identity; preferably, the electrostatically redirected D-type positively charged chain (Fc4(D+)) has the amino acid sequence shown in SEQ ID NO. 19 or has an amino acid sequence obtained by deleting, adding, or substituting 1, 2, or 3 residues in SEQ ID NO. 19.

[0237] In some preferred embodiments, the electrostatically redirected D-type negative charge chain (Fc1(D-)) comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 20, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, and more preferably having 98% or 99% or more identity; preferably, the electrostatically redirected D-type negative charge chain (Fc1(D-)) has the amino acid sequence shown in SEQ ID NO. 20 or has an amino acid sequence obtained by deleting, adding, or substituting 1, 2, or 3 residues in SEQ ID NO. 20.

[0238] In some preferred embodiments, the electrostatically redirected D-type negative charge chain (Fc4(D-)) comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 21, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, and more preferably having 98% or 99% or more identity; preferably, the electrostatically redirected D-type negative charge chain (Fc4(D-)) has the amino acid sequence shown in SEQ ID NO. 21 or has an amino acid sequence obtained by deleting, adding, or substituting 1, 2, or 3 residues in SEQ ID NO. 21.

[0239] In some specific embodiments, the Gnα subunit and Gnβ subunit are indirectly connected to the Fc chain via a connector.

[0240] In some preferred embodiments, the linker is a flexible polypeptide; preferably, the flexible polypeptide is composed of flexible amino acids, and more preferably, the flexible polypeptide is composed of 2-20 flexible amino acids, wherein the flexible amino acids are selected from at least one of Gly, Ser, Ala and Thr.

[0241] In some preferred embodiments, the flexible polypeptide is (G4S)n, (SG4)n, or G4(SG4)n, where n is an integer between 1 and 10, preferably an integer between 1 and 4, particularly 3 or 4.

[0242] In some preferred embodiments, the linker is selected from GGGGS (SEQ ID NO. 136), GGGGSGGGGS (SEQ ID NO. 137), SGGGGSGGGG (SEQ ID NO. 138), GGGGGSGGGGSSGGGGS (SEQ ID NO. 139), GGGGSGGGGSGGGGS (SEQ ID NO. 140), GGGGSGGGGSGGGG (SEQ ID NO. 139), NO.141), GGGGSGGGGSGGGGSGGGGS (SEQ ID NO.142), GGGGSGGGGSGGGSGGGGS (SEQ ID NO.143), GSPGSSSSGS (SEQ ID NO.144), GSGSGSGS (SEQ ID NO.145), GSGSGNGS (SEQ ID NO.146), GGSGSGSG (SEQ ID NO.147), GGSGSG (SEQ ID NO.141) NO.148), GGSG (SEQ ID NO.149), GGSGNGSG (SEQ ID NO.150), GGNGSGSG (SEQ ID NO.151) and GGNGSG (SEQ ID NO.152).

[0243] In some preferred embodiments, the flexible polypeptide is selected from GGGGSGGGGS (SEQ ID NO.137), GGGGSGGGGSGGGGSGGGGS (SEQ ID NO.142), and GGGGSGGGGSGGGSGGGS (SEQ ID NO.143).

[0244] In some specific embodiments, the recombinant Fc fusion protein comprises a combination of peptide chains selected from the following, which include an Fc chain and a Gn subunit:

[0245] (a) The C-terminus of the Gnα and Gnβ subunits is connected to the N-terminus of the Fc chain;

[0246] (1) The peptide chain comprising a clasp-type Fc chain (Fc1k) and a pFSHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 22, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably having 98% or 99% or more identity, and more preferably, the amino acid sequence of the peptide chain comprising a clasp-type Fc chain (Fc1k) and a pFSHα subunit is as shown in SEQ ID NO. 22; and the peptide chain comprising a lock-type Fc chain (Fc1h) and a pFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 22; and the peptide chain comprising a lock-type Fc chain (Fc1h) and a pFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 22; The amino acid sequence shown in NO.23 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain containing the locked Fc chain (Fc1h) and the pFSHβ subunit is as shown in SEQ ID NO.23.

[0247] In some preferred embodiments, the peptide chain comprising the coin-type Fc chain (Fc1k) and the pFSHα subunit has the amino acid sequence shown in SEQ ID NO. 22 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 22.

[0248] In some preferred embodiments, the peptide chain comprising the locked Fc chain (Fc1h) and the pFSHβ subunit has the amino acid sequence shown in SEQ ID NO.23 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO.23.

[0249] (2) The peptide chain comprising the locked Fc chain (Fc1h) and the pFSHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 24, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably having 98% or 99% or more identity, and more preferably, the amino acid sequence of the peptide chain comprising the locked Fc chain (Fc1h) and the pFSHα subunit is as shown in SEQ ID NO. 24; and the peptide chain comprising the button Fc chain (Fc1k) and the pFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 24. The amino acid sequence shown in NO.25 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain containing the coin-type Fc chain (Fc1k) and the pFSHβ subunit is as shown in SEQ ID NO.25.

[0250] In some preferred embodiments, the peptide chain comprising the locked Fc chain (Fc1h) and the pFSHα subunit has the amino acid sequence shown in SEQ ID NO.24 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO.24.

[0251] In some preferred embodiments, the peptide chain comprising the coin-type Fc chain (Fc1k) and the pFSHβ subunit has the amino acid sequence shown in SEQ ID NO. 25 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 25.

[0252] (3) The peptide chain comprising an electrostatically redirected T-type positively charged chain (Fc1(T+)) and a pFSHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 26, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably having 98% or 99% or more identity, more preferably, the amino acid sequence of the peptide chain comprising an electrostatically redirected T-type positively charged chain (Fc1(T+)) and a pFSHα subunit is as shown in SEQ ID NO. 26; and the peptide chain comprising an electrostatically redirected T-type negatively charged chain (Fc1(T-)) and a pFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 26. The amino acid sequence shown in NO.27 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain comprising the electrostatically directed T-type negatively charged chain (Fc1(T-)) and the pFSHβ subunit is as shown in SEQ ID NO.27.

[0253] In some preferred embodiments, the peptide chain comprising the electrostatically directed T-type positively charged chain (Fc1(T+)) and the pFSHα subunit has the amino acid sequence shown in SEQ ID NO.26 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO.26.

[0254] In some preferred embodiments, the peptide chain comprising the electrostatically directed T-type negative charge chain (Fc1(T-)) and the pFSHβ subunit has the amino acid sequence shown in SEQ ID NO.27 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO.27.

[0255] (4) The peptide chain comprising an electrostatically redirected T-type negatively charged chain (Fc1(T-)) and a pFSHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 28, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably having 98% or 99% or more identity, more preferably, the amino acid sequence of the peptide chain comprising an electrostatically redirected T-type negatively charged chain (Fc1(T-)) and a pFSHα subunit is as shown in SEQ ID NO. 28; and the peptide chain comprising an electrostatically redirected T-type positively charged chain (Fc1(T+)) and a pFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 28. The amino acid sequence shown in NO.29 has 80% or more identity, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably 98% or 99% or more identity, and more preferably, the amino acid sequence of the peptide chain comprising the electrostatically directed T-type positively charged chain (Fc1(T+)) and the pFSHβ subunit is as shown in SEQ ID NO.29.

[0256] In some preferred embodiments, the peptide chain comprising the electrostatically directed T-type negatively charged chain (Fc1(T-)) and the pFSHα subunit has the amino acid sequence shown in SEQ ID NO.28 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO.28.

[0257] In some preferred embodiments, the peptide chain comprising the electrostatically directed T-type positively charged chain (Fc1(T+)) and the pFSHβ subunit has the amino acid sequence shown in SEQ ID NO.29 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO.29.

[0258] (5) The peptide chain comprising the electrostatically redirected D-type positively charged chain (Fc1(D+)) and the pFSHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 30, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably having 98% or 99% or more identity, more preferably, the amino acid sequence comprising the electrostatically redirected D-type positively charged chain (Fc1(D+)) and the pFSHα subunit is as shown in SEQ ID NO. 30; and the peptide chain comprising the electrostatically redirected D-type negatively charged chain (Fc1(D-)) and the pFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 30. The amino acid sequence shown in NO.31 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain comprising the electrostatically directed D-type negatively charged chain (Fc1(D-)) and the pFSHβ subunit is as shown in SEQ ID NO.31.

[0259] In some preferred embodiments, the peptide chain comprising the electrostatically directed D-type positively charged chain (Fc1(D+)) and the pFSHα subunit has the amino acid sequence shown in SEQ ID NO.30 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO.30.

[0260] In some preferred embodiments, the peptide chain comprising the electrostatically directed D-type negatively charged chain (Fc1(D-)) and the pFSHβ subunit has the amino acid sequence shown in SEQ ID NO.31 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO.31.

[0261] (6) The peptide chain comprising the electrostatically redirected D-type negatively charged chain (Fc1(D-)) and the pFSHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 32, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably having 98% or 99% or more identity, more preferably, the amino acid sequence of the peptide chain comprising the electrostatically redirected D-type negatively charged chain (Fc1(D-)) and the pFSHα subunit is as shown in SEQ ID NO. 32; and the peptide chain comprising the electrostatically redirected D-type positively charged chain (Fc1(D+)) and the pFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 32. The amino acid sequence shown in NO.33 has 80% or more identity, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably 98% or 99% or more identity, and more preferably, the amino acid sequence of the peptide chain comprising the electrostatically directed D-type positively charged chain (Fc1(D+)) and the pFSHβ subunit is as shown in SEQ ID NO.33.

[0262] In some preferred embodiments, the peptide chain comprising the electrostatically directed D-type negatively charged chain (Fc1(D-)) and the pFSHα subunit has the amino acid sequence shown in SEQ ID NO.32 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO.32.

[0263] In some preferred embodiments, the peptide chain comprising the electrostatically directed D-type positively charged chain (Fc1(D+)) and the pFSHβ subunit has the amino acid sequence shown in SEQ ID NO.33 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO.33.

[0264] (7) The peptide chain comprising the clasp-type Fc chain (Fc1k) and the hFSHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 46, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably having 98% or 99% or more identity, and more preferably, the amino acid sequence of the peptide chain comprising the clasp-type Fc chain (Fc1k) and the hFSHα subunit is as shown in SEQ ID NO. 46; and the peptide chain comprising the lock-type Fc chain (Fc1h) and the hFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 46. The amino acid sequence shown in NO.47 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain containing the locked Fc chain (Fc1h) and the hFSHβ subunit is as shown in SEQ ID NO.47.

[0265] In some preferred embodiments, the peptide chain comprising the coin-type Fc chain (Fc1k) and the hFSHα subunit has the amino acid sequence shown in SEQ ID NO.46 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO.46.

[0266] In some preferred embodiments, the peptide chain comprising the locked Fc chain (Fc1h) and the hFSHβ subunit has the amino acid sequence shown in SEQ ID NO.47 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO.47.

[0267] (8) The peptide chain comprising the locked Fc chain (Fc1h) and the hFSHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 48, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably having 98% or 99% or more identity, and more preferably, the amino acid sequence of the peptide chain comprising the locked Fc chain (Fc1h) and the hFSHα subunit is as shown in SEQ ID NO. 48; and the peptide chain comprising the button Fc chain (Fc1k) and the hFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 48. The amino acid sequence shown in NO.49 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain containing the coin-type Fc chain (Fc1k) and the hFSHβ subunit is as shown in SEQ ID NO.49.

[0268] In some preferred embodiments, the peptide chain comprising the locked Fc chain (Fc1h) and the hFSHα subunit has the amino acid sequence shown in SEQ ID NO.48 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO.48.

[0269] In some preferred embodiments, the peptide chain comprising the coin-type Fc chain (Fc1k) and the hFSHβ subunit has the amino acid sequence shown in SEQ ID NO.49 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO.49.

[0270] (9) The peptide chain comprising an electrostatically redirected T-type positively charged chain (Fc1(T+)) and an hFSHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 50, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, preferably having 98% or 99% or more identity, more preferably, the amino acid sequence comprising the electrostatically redirected T-type positively charged chain (Fc1(T+)) and an hFSHα subunit is as shown in SEQ ID NO. 50; and the peptide chain comprising an electrostatically redirected T-type negatively charged chain (Fc1(T-)) and an hFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 50. The amino acid sequence shown in NO.51 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain comprising the electrostatically directed T-type negatively charged chain (Fc1(T-)) and the hFSHβ subunit is as shown in SEQ ID NO.51.

[0271] In some preferred embodiments, the peptide chain comprising the electrostatically directed T-type positively charged chain (Fc1(T+)) and the hFSHα subunit has the amino acid sequence shown in SEQ ID NO. 50 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 50.

[0272] In some preferred embodiments, the peptide chain comprising the electrostatically directed T-type negative charge chain (Fc1(T-)) and the hFSHβ subunit has the amino acid sequence shown in SEQ ID NO. 51 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 51.

[0273] (10) The peptide chain comprising an electrostatically redirected T-type negatively charged chain (Fc1(T-)) and an hFSHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 52, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, preferably having 98% or 99% or more identity, more preferably, the amino acid sequence of the peptide chain comprising an electrostatically redirected T-type negatively charged chain (Fc1(T-)) and an hFSHα subunit is as shown in SEQ ID NO. 52; and the peptide chain comprising an electrostatically redirected T-type positively charged chain (Fc1(T+)) and an hFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 52. The amino acid sequence shown in NO.53 has 80% or more identity, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably 98% or 99% or more identity, and more preferably, the amino acid sequence of the peptide chain comprising the electrostatically directed T-type positively charged chain (Fc1(T+)) and the hFSHβ subunit is as shown in SEQ ID NO.53.

[0274] In some preferred embodiments, the peptide chain comprising the electrostatically directed T-type negatively charged chain (Fc1(T-)) and the hFSHα subunit has the amino acid sequence shown in SEQ ID NO. 52 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 52.

[0275] In some preferred embodiments, the peptide chain comprising the electrostatically directed T-type positively charged chain (Fc1(T+)) and the hFSHβ subunit has the amino acid sequence shown in SEQ ID NO. 53 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 53.

[0276] (11) The peptide chain comprising an electrostatically redirected D-type positively charged chain (Fc1(D+)) and an hFSHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 54, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, preferably having 98% or 99% or more identity, more preferably, the amino acid sequence comprising the electrostatically redirected D-type positively charged chain (Fc1(D+)) and an hFSHα subunit is as shown in SEQ ID NO. 54; and the peptide chain comprising an electrostatically redirected D-type negatively charged chain (Fc1(D-)) and an hFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 54. The amino acid sequence shown in NO.55 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain comprising the electrostatically directed D-type negatively charged chain (Fc1(D-)) and the hFSHβ subunit is as shown in SEQ ID NO.55.

[0277] In some preferred embodiments, the peptide chain comprising the electrostatically directed D-type positively charged chain (Fc1(D+)) and the hFSHα subunit has the amino acid sequence shown in SEQ ID NO. 54 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 54.

[0278] In some preferred embodiments, the peptide chain comprising the electrostatically directed D-type negatively charged chain (Fc1(D-)) and the hFSHβ subunit has the amino acid sequence shown in SEQ ID NO. 55 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 55.

[0279] (12) The peptide chain comprising an electrostatically redirected D-type negatively charged chain (Fc1(D-)) and an hFSHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 56, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably having 98% or 99% or more identity, more preferably, the amino acid sequence of the peptide chain comprising an electrostatically redirected D-type negatively charged chain (Fc1(D-)) and an hFSHα subunit is as shown in SEQ ID NO. 56; and the peptide chain comprising an electrostatically redirected D-type positively charged chain (Fc1(D+)) and an hFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 56. The amino acid sequence shown in NO.57 has 80% or more identity, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably 98% or 99% or more identity, and more preferably, the amino acid sequence of the peptide chain comprising the electrostatically directed D-type positively charged chain (Fc1(D+)) and the hFSHβ subunit is as shown in SEQ ID NO.57.

[0280] In some preferred embodiments, the peptide chain comprising the electrostatically directed D-type negatively charged chain (Fc1(D-)) and the hFSHα subunit has the amino acid sequence shown in SEQ ID NO. 56 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 56.

[0281] In some preferred embodiments, the peptide chain comprising the electrostatically directed D-type positively charged chain (Fc1(D+)) and the hFSHβ subunit has the amino acid sequence shown in SEQ ID NO. 57 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 57.

[0282] (13) The peptide chain comprising the clasp-type Fc chain (Fc4k) and the hFSHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 70, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably having 98% or 99% or more identity, and more preferably, the amino acid sequence of the peptide chain comprising the clasp-type Fc chain (Fc4k) and the hFSHα subunit is as shown in SEQ ID NO. 70; and the peptide chain comprising the lock-type Fc chain (Fc4h) and the hFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 70. The amino acid sequence shown in NO.71 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain containing the locked Fc chain (Fc4h) and the hFSHβ subunit is as shown in SEQ ID NO.71.

[0283] In some preferred embodiments, the peptide chain comprising the coin-type Fc chain (Fc4k) and the hFSHα subunit has the amino acid sequence shown in SEQ ID NO. 70 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 70.

[0284] In some preferred embodiments, the peptide chain comprising the locked Fc chain (Fc4h) and the hFSHβ subunit has the amino acid sequence shown in SEQ ID NO. 71 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 71.

[0285] (14) The peptide chain comprising the locked Fc chain (Fc4h) and the hFSHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 72, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably having 98% or 99% or more identity, and more preferably, the amino acid sequence of the peptide chain comprising the locked Fc chain (Fc4h) and the hFSHα subunit is as shown in SEQ ID NO. 72; and the peptide chain comprising the button Fc chain (Fc4k) and the hFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 72; and the peptide chain comprising the button Fc chain (Fc4k) and the hFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 72. The amino acid sequence shown in NO.73 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain containing the coin-type Fc chain (Fc4k) and the hFSHβ subunit is as shown in SEQ ID NO.73.

[0286] In some preferred embodiments, the peptide chain comprising the locked Fc chain (Fc4h) and the hFSHα subunit has the amino acid sequence shown in SEQ ID NO. 72 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 72.

[0287] In some preferred embodiments, the peptide chain comprising the coin-type Fc chain (Fc4k) and the hFSHβ subunit has the amino acid sequence shown in SEQ ID NO. 73 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 73.

[0288] (15) The peptide chain comprising an electrostatically redirected T-type positively charged chain (Fc4(T+)) and an hFSHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 74, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably having 98% or 99% or more identity, more preferably, the amino acid sequence of the peptide chain comprising an electrostatically redirected T-type positively charged chain (Fc4(T+)) and an hFSHα subunit is as shown in SEQ ID NO. 74; and the peptide chain comprising an electrostatically redirected T-type negatively charged chain (Fc4(T-)) and an hFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 74. The amino acid sequence shown in NO.75 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain comprising the electrostatically directed T-type negatively charged chain (Fc4(T-)) and the hFSHβ subunit is as shown in SEQ ID NO.75.

[0289] In some preferred embodiments, the peptide chain comprising the electrostatically directed T-type positively charged chain (Fc4(T+)) and the hFSHα subunit has the amino acid sequence shown in SEQ ID NO.74 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO.74.

[0290] In some preferred embodiments, the peptide chain comprising the electrostatically directed T-type negatively charged chain (Fc4(T-)) and the hFSHβ subunit has the amino acid sequence shown in SEQ ID NO. 75 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 75.

[0291] (16) The peptide chain comprising an electrostatically redirected T-type negatively charged chain (Fc4(T-)) and an hFSHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 76, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably having 98% or 99% or more identity, more preferably, the amino acid sequence of the peptide chain comprising an electrostatically redirected T-type negatively charged chain (Fc4(T-)) and an hFSHα subunit is as shown in SEQ ID NO. 76; and the peptide chain comprising an electrostatically redirected T-type positively charged chain (Fc4(T+)) and an hFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 76. The amino acid sequence shown in NO.77 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain comprising the electrostatically directed T-type positively charged chain (Fc4(T+)) and the hFSHβ subunit is as shown in SEQ ID NO.77.

[0292] In some preferred embodiments, the peptide chain comprising the electrostatically directed T-type negatively charged chain (Fc4(T-)) and the hFSHα subunit has the amino acid sequence shown in SEQ ID NO. 76 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 76.

[0293] In some preferred embodiments, the peptide chain comprising the electrostatically directed T-type positively charged chain (Fc4(T+)) and the hFSHβ subunit has the amino acid sequence shown in SEQ ID NO.77 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO.77.

[0294] (17) The peptide chain comprising an electrostatically redirected D-type positively charged chain (Fc4(D+)) and an hFSHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 78, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably having 98% or 99% or more identity, more preferably, the amino acid sequence comprising the electrostatically redirected D-type positively charged chain (Fc4(D+)) and an hFSHα subunit is as shown in SEQ ID NO. 78; and the peptide chain comprising an electrostatically redirected D-type negatively charged chain (Fc4(D-)) and an hFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 78. The amino acid sequence shown in NO. 79 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain comprising the electrostatically directed D-type negatively charged chain (Fc4(D-)) and the hFSHβ subunit is as shown in SEQ ID NO. 79.

[0295] In some preferred embodiments, the peptide chain comprising the electrostatically directed D-type positively charged chain (Fc4(D+)) and the hFSHα subunit has the amino acid sequence shown in SEQ ID NO. 78 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 78.

[0296] In some preferred embodiments, the peptide chain comprising the electrostatically directed D-type negatively charged chain (Fc4(D-)) and the hFSHβ subunit has the amino acid sequence shown in SEQ ID NO. 79 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 79.

[0297] (18) The peptide chain comprising an electrostatically redirected D-type negatively charged chain (Fc4(D-)) and an hFSHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 80, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably having 98% or 99% or more identity, more preferably, the amino acid sequence of the peptide chain comprising an electrostatically redirected D-type negatively charged chain (Fc4(D-)) and an hFSHα subunit is as shown in SEQ ID NO. 80; and the peptide chain comprising an electrostatically redirected D-type positively charged chain (Fc4(D+)) and an hFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 80. The amino acid sequence shown in NO.81 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain comprising the electrostatically directed D-type positively charged chain (Fc4(D+)) and the hFSHβ subunit is as shown in SEQ ID NO.81.

[0298] In some preferred embodiments, the peptide chain comprising the electrostatically directed D-type negatively charged chain (Fc4(D-)) and the hFSHα subunit has the amino acid sequence shown in SEQ ID NO. 80 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 80.

[0299] In some preferred embodiments, the peptide chain comprising the electrostatically directed D-type positively charged chain (Fc4(D+)) and the hFSHβ subunit has the amino acid sequence shown in SEQ ID NO. 81 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 81.

[0300] (19) The peptide chain comprising the clasp-type Fc chain (Fc1k) and the GtHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 94, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably having 98% or 99% or more identity, more preferably, the amino acid sequence of the peptide chain comprising the clasp-type Fc chain (Fc1k) and the GtHα subunit is as shown in SEQ ID NO. 94; and the peptide chain comprising the lock-type Fc chain (Fc1h) and the GtH Iβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 94; and the peptide chain comprising the lock-type Fc chain (Fc1h) and the GtH Iβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 94; The amino acid sequence shown in NO. 95 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain containing the locked Fc chain (Fc1h) and the GtH Iβ subunit is as shown in SEQ ID NO. 95.

[0301] In some preferred embodiments, the peptide chain comprising the coin-type Fc chain (Fc1k) and the GtHα subunit has the amino acid sequence shown in SEQ ID NO. 94 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 94.

[0302] In some preferred embodiments, the peptide chain comprising the locked Fc chain (Fc1h) and the GtH Iβ subunit has the amino acid sequence shown in SEQ ID NO.95 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO.95.

[0303] (20) The peptide chain comprising the locked Fc chain (Fc1h) and the GtHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 96, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably having 98% or 99% or more identity, more preferably, the amino acid sequence of the peptide chain comprising the locked Fc chain (Fc1h) and the GtHα subunit is as shown in SEQ ID NO. 96; and the peptide chain comprising the button Fc chain (Fc1k) and the GtH Iβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 96. The amino acid sequence shown in NO.97 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain containing the coin-type Fc chain (Fc1k) and the GtH Iβ subunit is as shown in SEQ ID NO.97.

[0304] In some preferred embodiments, the peptide chain comprising the locked Fc chain (Fc1h) and the GtHα subunit has the amino acid sequence shown in SEQ ID NO.96 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO.96.

[0305] In some preferred embodiments, the peptide chain comprising the coin-type Fc chain (Fc1k) and the GtH Iβ subunit has the amino acid sequence shown in SEQ ID NO.97 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO.97.

[0306] (21) The peptide chain comprising an electrostatically redirected T-type positively charged chain (Fc1(T+)) and a GtHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 98, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably having 98% or 99% or more identity, more preferably, the amino acid sequence of the peptide chain comprising an electrostatically redirected T-type positively charged chain (Fc1(T+)) and a GtHα subunit is as shown in SEQ ID NO. 98; and the peptide chain comprising an electrostatically redirected T-type negatively charged chain (Fc1(T-)) and a GtH Iβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 98. The amino acid sequence shown in NO.99 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain comprising the electrostatically directed T-type negatively charged chain (Fc1(T-)) and the GtH Iβ subunit is as shown in SEQ ID NO.99.

[0307] In some preferred embodiments, the peptide chain comprising the electrostatically directed T-type positively charged chain (Fc1(T+)) and the GtHα subunit has the amino acid sequence shown in SEQ ID NO.98 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO.98.

[0308] In some preferred embodiments, the peptide chain comprising the electrostatically directed T-type negatively charged chain (Fc1(T-)) and the GtH Iβ subunit has the amino acid sequence shown in SEQ ID NO.99 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO.99.

[0309] (22) The peptide chain comprising an electrostatically redirected T-type negatively charged chain (Fc1(T-)) and a GtHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 100, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, preferably having 98% or 99% or more identity, more preferably, the amino acid sequence comprising the electrostatically redirected T-type negatively charged chain (Fc1(T-)) and a GtHα subunit is as shown in SEQ ID NO. 100; and the peptide chain comprising an electrostatically redirected T-type positively charged chain (Fc1(T+)) and a GtH Iβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 100. The amino acid sequence shown in NO.101 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain comprising the electrostatically directed T-type positively charged chain (Fc1(T+)) and the GtH Iβ subunit is as shown in SEQ ID NO.101.

[0310] In some preferred embodiments, the peptide chain comprising the electrostatically directed T-type negatively charged chain (Fc1(T-)) and the GtHα subunit has the amino acid sequence shown in SEQ ID NO. 100 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 100.

[0311] In some preferred embodiments, the peptide chain comprising the electrostatically directed T-type positively charged chain (Fc1(T+)) and the GtH Iβ subunit has the amino acid sequence shown in SEQ ID NO. 101 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 101.

[0312] (23) The peptide chain comprising an electrostatically redirected D-type positively charged chain (Fc1(D+)) and a GtHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 102, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, preferably having 98% or 99% or more identity, more preferably, the amino acid sequence of the peptide chain comprising an electrostatically redirected D-type positively charged chain (Fc1(D+)) and a GtHα subunit is as shown in SEQ ID NO. 102; and the peptide chain comprising an electrostatically redirected D-type negatively charged chain (Fc1(D-)) and a GtH Iβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 102. The amino acid sequence shown in NO.103 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain comprising the electrostatically directed D-type negatively charged chain (Fc1(D-)) and the GtH Iβ subunit is as shown in SEQ ID NO.103.

[0313] In some preferred embodiments, the peptide chain comprising the electrostatically directed D-type positively charged chain (Fc1(D+)) and the GtHα subunit has the amino acid sequence shown in SEQ ID NO. 102 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 102.

[0314] In some preferred embodiments, the peptide chain comprising the electrostatically directed D-type negatively charged chain (Fc1(D-)) and the GtH Iβ subunit has the amino acid sequence shown in SEQ ID NO. 103 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 103.

[0315] (24) The peptide chain comprising an electrostatically redirected D-type negatively charged chain (Fc1(D-)) and a GtHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 104, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, preferably having 98% or 99% or more identity, more preferably, the amino acid sequence comprising the electrostatically redirected D-type negatively charged chain (Fc1(D-)) and a GtHα subunit is as shown in SEQ ID NO. 104; and the peptide chain comprising an electrostatically redirected D-type positively charged chain (Fc1(D+)) and a GtH Iβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 104, preferably having 98% or 99% or more identity, more preferably, the amino acid sequence comprising the electrostatically redirected D-type negatively charged chain (Fc1(D-)) and a GtH Iβ subunit is as shown in SEQ ID NO. 104; and the peptide chain comprising the electrostatically redirected D-type positively charged chain (Fc1(D+)) and a GtH Iβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 104, preferably having 98 ... The amino acid sequence shown in NO. 105 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain comprising the electrostatically directed D-type positively charged chain (Fc1(D+)) and the GtH Iβ subunit is as shown in SEQ ID NO. 105.

[0316] In some preferred embodiments, the peptide chain comprising the electrostatically directed D-type negatively charged chain (Fc1(D-)) and the GtHα subunit has the amino acid sequence shown in SEQ ID NO. 104 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 104.

[0317] In some preferred embodiments, the peptide chain comprising the electrostatically directed D-type positively charged chain (Fc1(D+)) and the GtH Iβ subunit has the amino acid sequence shown in SEQ ID NO. 105 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 105.

[0318] (25) The peptide chain comprising a clasp-type Fc chain (Fc1k) and a GtHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 94, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably having 98% or 99% or more identity, more preferably, the amino acid sequence of the peptide chain comprising a clasp-type Fc chain (Fc1k) and a GtHα subunit is as shown in SEQ ID NO. 94; and the peptide chain comprising a lock-type Fc chain (Fc1h) and a GtH IIβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 94; and the peptide chain comprising a lock-type Fc chain (Fc1h) and a GtH IIβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 94; The amino acid sequence shown in NO. 118 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain containing the locked Fc chain (Fc1h) and the GtH IIβ subunit is as shown in SEQ ID NO. 118.

[0319] In some preferred embodiments, the peptide chain comprising the coin-type Fc chain (Fc1k) and the GtHα subunit has the amino acid sequence shown in SEQ ID NO. 94 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 94.

[0320] In some preferred embodiments, the peptide chain comprising the locked Fc chain (Fc1h) and the GtH IIβ subunit has the amino acid sequence shown in SEQ ID NO. 118 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 118.

[0321] (26) The peptide chain comprising the locked Fc chain (Fc1h) and the GtHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 96, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably having 98% or 99% or more identity, more preferably, the amino acid sequence of the peptide chain comprising the locked Fc chain (Fc1h) and the GtHα subunit is as shown in SEQ ID NO. 96; and the peptide chain comprising the button Fc chain (Fc1k) and the GtH IIβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 96. The amino acid sequence shown in NO.119 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain containing the coin-type Fc chain (Fc1k) and the GtH IIβ subunit is as shown in SEQ ID NO.119.

[0322] In some preferred embodiments, the peptide chain comprising the locked Fc chain (Fc1h) and the GtHα subunit has the amino acid sequence shown in SEQ ID NO.96 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO.96.

[0323] In some preferred embodiments, the peptide chain comprising the coin-type Fc chain (Fc1k) and the GtH IIβ subunit has the amino acid sequence shown in SEQ ID NO. 119 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 119.

[0324] (27) The peptide chain comprising an electrostatically redirected T-type positively charged chain (Fc1(T+)) and a GtHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 98, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably having 98% or 99% or more identity, more preferably, the amino acid sequence of the peptide chain comprising an electrostatically redirected T-type positively charged chain (Fc1(T+)) and a GtHα subunit is as shown in SEQ ID NO. 98; and the peptide chain comprising an electrostatically redirected T-type negatively charged chain (Fc1(T-)) and a GtH IIβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 98. The amino acid sequence shown in NO. 120 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain comprising the electrostatically directed T-type negatively charged chain (Fc1(T-)) and the GtH IIβ subunit is as shown in SEQ ID NO. 120.

[0325] In some preferred embodiments, the peptide chain comprising the electrostatically directed T-type positively charged chain (Fc1(T+)) and the GtHα subunit has the amino acid sequence shown in SEQ ID NO.98 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO.98.

[0326] In some preferred embodiments, the peptide chain comprising the electrostatically directed T-type negatively charged chain (Fc1(T-)) and the GtH IIβ subunit has the amino acid sequence shown in SEQ ID NO. 120 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 120.

[0327] (28) The peptide chain comprising an electrostatically redirected T-type negatively charged chain (Fc1(T-)) and a GtHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 100, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, preferably having 98% or 99% or more identity, more preferably, the amino acid sequence comprising the electrostatically redirected T-type negatively charged chain (Fc1(T-)) and a GtHα subunit is as shown in SEQ ID NO. 100; and the peptide chain comprising an electrostatically redirected T-type positively charged chain (Fc1(T+)) and a GtH IIβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 100. The amino acid sequence shown in NO.121 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain comprising the electrostatically directed T-type positively charged chain (Fc1(T+)) and the GtH IIβ subunit is as shown in SEQ ID NO.121.

[0328] In some preferred embodiments, the peptide chain comprising the electrostatically directed T-type negatively charged chain (Fc1(T-)) and the GtHα subunit has the amino acid sequence shown in SEQ ID NO. 100 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 100.

[0329] In some preferred embodiments, the peptide chain comprising the electrostatically directed T-type positively charged chain (Fc1(T+)) and the GtH IIβ subunit has the amino acid sequence shown in SEQ ID NO. 121 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 121.

[0330] (29) The peptide chain comprising an electrostatically redirected D-type positively charged chain (Fc1(D+)) and a GtHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 102, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, preferably having 98% or 99% or more identity, more preferably, the amino acid sequence comprising the electrostatically redirected D-type positively charged chain (Fc1(D+)) and a GtHα subunit is as shown in SEQ ID NO. 102; and the peptide chain comprising an electrostatically redirected D-type negatively charged chain (Fc1(D-)) and a GtH IIβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 102, preferably having 98% or 99% or more identity, more preferably, the amino acid sequence comprising the electrostatically redirected D-type positively charged chain (Fc1(D+)) and a GtH IIβ subunit is as shown in SEQ ID NO. 102; and the peptide chain comprising the electrostatically redirected D-type negatively charged chain (Fc1(D-)) and a GtH IIβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 102, preferably having 98% or more identity, more preferably, the amino acid sequence comprising the electrostatically redirected D-type positively charged chain (Fc1(D+)) and a GtH IIβ subunit is as shown in SEQ ID NO. 102; The amino acid sequence shown in NO.122 has 80% or more identity, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably 98% or 99% or more identity, and more preferably, the amino acid sequence of the peptide chain comprising the electrostatically directed D-type negatively charged chain (Fc1(D-)) and the GtH IIβ subunit is as shown in SEQ ID NO.122.

[0331] In some preferred embodiments, the peptide chain comprising the electrostatically directed D-type positively charged chain (Fc1(D+)) and the GtHα subunit has the amino acid sequence shown in SEQ ID NO. 102 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 102.

[0332] In some preferred embodiments, the peptide chain comprising the electrostatically directed D-type negatively charged chain (Fc1(D-)) and the GtH IIβ subunit has the amino acid sequence shown in SEQ ID NO. 122 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 122.

[0333] (30) The peptide chain comprising an electrostatically redirected D-type negatively charged chain (Fc1(D-)) and a GtHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 104, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, preferably having 98% or 99% or more identity, more preferably, the amino acid sequence comprising the electrostatically redirected D-type negatively charged chain (Fc1(D-)) and a GtHα subunit is as shown in SEQ ID NO. 104; and the peptide chain comprising an electrostatically redirected D-type positively charged chain (Fc1(D+)) and a GtH IIβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 104. The amino acid sequence shown in NO.123 has 80% or more identity, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably 98% or 99% or more identity, and more preferably, the amino acid sequence of the peptide chain comprising the electrostatically directed D-type positively charged chain (Fc1(D+)) and the GtH IIβ subunit is as shown in SEQ ID NO.123.

[0334] In some preferred embodiments, the peptide chain comprising the electrostatically directed D-type negatively charged chain (Fc1(D-)) and the GtHα subunit has the amino acid sequence shown in SEQ ID NO. 104 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 104.

[0335] In some preferred embodiments, the peptide chain comprising the electrostatically directed D-type positively charged chain (Fc1(D+)) and the GtH IIβ subunit has the amino acid sequence shown in SEQ ID NO. 123 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 123.

[0336] (b) The N-terminus of the Gnα subunit is connected to the C-terminus of the Fc chain; and the C-terminus of the Gnβ subunit is connected to the N-terminus of the Fc chain.

[0337] (1) The peptide chain comprising a clasp-type Fc chain (Fc1k) and a pFSHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 34, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably having 98% or 99% or more identity, and more preferably, the amino acid sequence of the peptide chain comprising a clasp-type Fc chain (Fc1k) and a pFSHα subunit is as shown in SEQ ID NO. 34; and the peptide chain comprising a lock-type Fc chain (Fc1h) and a pFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 34; and the peptide chain comprising a lock-type Fc chain (Fc1h) and a pFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 34; The amino acid sequence shown in NO.23 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain containing the locked Fc chain (Fc1h) and the pFSHβ subunit is as shown in SEQ ID NO.23.

[0338] In some preferred embodiments, the peptide chain comprising the coin-type Fc chain (Fc1k) and the pFSHα subunit has the amino acid sequence shown in SEQ ID NO. 34 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 34.

[0339] In some preferred embodiments, the peptide chain comprising the locked Fc chain (Fc1h) and the pFSHβ subunit has the amino acid sequence shown in SEQ ID NO.23 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO.23.

[0340] (2) The peptide chain comprising the locked Fc chain (Fc1h) and the pFSHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 35, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably having 98% or 99% or more identity, and more preferably, the amino acid sequence of the peptide chain comprising the locked Fc chain (Fc1h) and the pFSHα subunit is as shown in SEQ ID NO. 35; and the peptide chain comprising the button Fc chain (Fc1k) and the pFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 35. The amino acid sequence shown in NO.25 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain containing the coin-type Fc chain (Fc1k) and the pFSHβ subunit is as shown in SEQ ID NO.25.

[0341] In some preferred embodiments, the peptide chain comprising the locked Fc chain (Fc1h) and the pFSHα subunit has the amino acid sequence shown in SEQ ID NO. 35 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 35.

[0342] In some preferred embodiments, the peptide chain comprising the coin-type Fc chain (Fc1k) and the pFSHβ subunit has the amino acid sequence shown in SEQ ID NO. 25 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 25.

[0343] (3) The peptide chain comprising an electrostatically redirected T-type positively charged chain (Fc1(T+)) and a pFSHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 36, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably having 98% or 99% or more identity, more preferably, the amino acid sequence of the peptide chain comprising an electrostatically redirected T-type positively charged chain (Fc1(T+)) and a pFSHα subunit is as shown in SEQ ID NO. 36; and the peptide chain comprising an electrostatically redirected T-type negatively charged chain (Fc1(T-)) and a pFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 36. The amino acid sequence shown in NO.27 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain comprising the electrostatically directed T-type negatively charged chain (Fc1(T-)) and the pFSHβ subunit is as shown in SEQ ID NO.27.

[0344] In some preferred embodiments, the peptide chain comprising the electrostatically directed T-type positively charged chain (Fc1(T+)) and the pFSHα subunit has the amino acid sequence shown in SEQ ID NO.36 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO.36.

[0345] In some preferred embodiments, the peptide chain comprising the electrostatically directed T-type negative charge chain (Fc1(T-)) and the pFSHβ subunit has the amino acid sequence shown in SEQ ID NO.27 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO.27.

[0346] (4) The peptide chain comprising an electrostatically redirected T-type negatively charged chain (Fc1(T-)) and a pFSHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 37, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably having 98% or 99% or more identity, more preferably, the amino acid sequence of the peptide chain comprising an electrostatically redirected T-type negatively charged chain (Fc1(T-)) and a pFSHα subunit is as shown in SEQ ID NO. 37; and the peptide chain comprising an electrostatically redirected T-type positively charged chain (Fc1(T+)) and a pFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 37. The amino acid sequence shown in NO.29 has 80% or more identity, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably 98% or 99% or more identity, and more preferably, the amino acid sequence of the peptide chain comprising the electrostatically directed T-type positively charged chain (Fc1(T+)) and the pFSHβ subunit is as shown in SEQ ID NO.29.

[0347] In some preferred embodiments, the peptide chain comprising the electrostatically directed T-type negatively charged chain (Fc1(T-)) and the pFSHα subunit has the amino acid sequence shown in SEQ ID NO.37 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO.37.

[0348] In some preferred embodiments, the peptide chain comprising the electrostatically directed T-type positively charged chain (Fc1(T+)) and the pFSHβ subunit has the amino acid sequence shown in SEQ ID NO.29 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO.29.

[0349] (5) The peptide chain comprising the electrostatically redirected D-type positively charged chain (Fc1(D+)) and the pFSHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 38, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably having 98% or 99% or more identity, more preferably, the amino acid sequence comprising the electrostatically redirected D-type positively charged chain (Fc1(D+)) and the pFSHα subunit is as shown in SEQ ID NO. 38; and the peptide chain comprising the electrostatically redirected D-type negatively charged chain (Fc1(D-)) and the pFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 38. The amino acid sequence shown in NO.31 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain comprising the electrostatically directed D-type negatively charged chain (Fc1(D-)) and the pFSHβ subunit is as shown in SEQ ID NO.31.

[0350] In some preferred embodiments, the peptide chain comprising the electrostatically directed D-type positively charged chain (Fc1(D+)) and the pFSHα subunit has the amino acid sequence shown in SEQ ID NO.38 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO.38.

[0351] In some preferred embodiments, the peptide chain comprising the electrostatically directed D-type negatively charged chain (Fc1(D-)) and the pFSHβ subunit has the amino acid sequence shown in SEQ ID NO.31 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO.31.

[0352] (6) The peptide chain comprising the electrostatically redirected D-type negatively charged chain (Fc1(D-)) and the pFSHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 39, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably having 98% or 99% or more identity, more preferably, the amino acid sequence of the peptide chain comprising the electrostatically redirected D-type negatively charged chain (Fc1(D-)) and the pFSHα subunit is as shown in SEQ ID NO. 39; and the peptide chain comprising the electrostatically redirected D-type positively charged chain (Fc1(D+)) and the pFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 39. The amino acid sequence shown in NO.33 has 80% or more identity, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably 98% or 99% or more identity, and more preferably, the amino acid sequence of the peptide chain comprising the electrostatically directed D-type positively charged chain (Fc1(D+)) and the pFSHβ subunit is as shown in SEQ ID NO.33.

[0353] In some preferred embodiments, the peptide chain comprising the electrostatically directed D-type negatively charged chain (Fc1(D-)) and the pFSHα subunit has the amino acid sequence shown in SEQ ID NO.39 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO.39.

[0354] In some preferred embodiments, the peptide chain comprising the electrostatically directed D-type positively charged chain (Fc1(D+)) and the pFSHβ subunit has the amino acid sequence shown in SEQ ID NO.33 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO.33.

[0355] (7) The peptide chain comprising the clasp-type Fc chain (Fc1k) and the hFSHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 58, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably having 98% or 99% or more identity, and more preferably, the amino acid sequence of the peptide chain comprising the clasp-type Fc chain (Fc1k) and the hFSHα subunit is as shown in SEQ ID NO. 58; and the peptide chain comprising the lock-type Fc chain (Fc1h) and the hFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 58. The amino acid sequence shown in NO.47 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain containing the locked Fc chain (Fc1h) and the hFSHβ subunit is as shown in SEQ ID NO.47.

[0356] In some preferred embodiments, the peptide chain comprising the coin-type Fc chain (Fc1k) and the hFSHα subunit has the amino acid sequence shown in SEQ ID NO. 58 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 58.

[0357] In some preferred embodiments, the peptide chain comprising the locked Fc chain (Fc1h) and the hFSHβ subunit has the amino acid sequence shown in SEQ ID NO.47 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO.47.

[0358] (8) The peptide chain comprising the locked Fc chain (Fc1h) and the hFSHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 59, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably having 98% or 99% or more identity, and more preferably, the amino acid sequence of the peptide chain comprising the locked Fc chain (Fc1h) and the hFSHα subunit is as shown in SEQ ID NO. 59; and the peptide chain comprising the button Fc chain (Fc1k) and the hFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 59. The amino acid sequence shown in NO.49 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain containing the coin-type Fc chain (Fc1k) and the hFSHβ subunit is as shown in SEQ ID NO.49.

[0359] In some preferred embodiments, the peptide chain comprising the locked Fc chain (Fc1h) and the hFSHα subunit has the amino acid sequence shown in SEQ ID NO. 59 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 59.

[0360] In some preferred embodiments, the peptide chain comprising the coin-type Fc chain (Fc1k) and the hFSHβ subunit has the amino acid sequence shown in SEQ ID NO.49 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO.49.

[0361] (9) The peptide chain comprising an electrostatically redirected T-type positively charged chain (Fc1(T+)) and an hFSHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 60, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, preferably having 98% or 99% or more identity, more preferably, the amino acid sequence comprising the electrostatically redirected T-type positively charged chain (Fc1(T+)) and an hFSHα subunit is as shown in SEQ ID NO. 60; and the peptide chain comprising an electrostatically redirected T-type negatively charged chain (Fc1(T-)) and an hFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 60. The amino acid sequence shown in NO.51 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain comprising the electrostatically directed T-type negatively charged chain (Fc1(T-)) and the hFSHβ subunit is as shown in SEQ ID NO.51.

[0362] In some preferred embodiments, the peptide chain comprising the electrostatically directed T-type positively charged chain (Fc1(T+)) and the hFSHα subunit has the amino acid sequence shown in SEQ ID NO. 60 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 60.

[0363] In some preferred embodiments, the peptide chain comprising the electrostatically directed T-type negative charge chain (Fc1(T-)) and the hFSHβ subunit has the amino acid sequence shown in SEQ ID NO. 51 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 51.

[0364] (10) The peptide chain comprising an electrostatically redirected T-type negatively charged chain (Fc1(T-)) and an hFSHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 61, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, preferably having 98% or 99% or more identity, more preferably, the amino acid sequence of the peptide chain comprising an electrostatically redirected T-type negatively charged chain (Fc1(T-)) and an hFSHα subunit is as shown in SEQ ID NO. 61; and the peptide chain comprising an electrostatically redirected T-type positively charged chain (Fc1(T+)) and an hFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 61. The amino acid sequence shown in NO.53 has 80% or more identity, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably 98% or 99% or more identity, and more preferably, the amino acid sequence of the peptide chain comprising the electrostatically directed T-type positively charged chain (Fc1(T+)) and the hFSHβ subunit is as shown in SEQ ID NO.53.

[0365] In some preferred embodiments, the peptide chain comprising the electrostatically directed T-type negatively charged chain (Fc1(T-)) and the hFSHα subunit has the amino acid sequence shown in SEQ ID NO. 61 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 61.

[0366] In some preferred embodiments, the peptide chain comprising the electrostatically directed T-type positively charged chain (Fc1(T+)) and the hFSHβ subunit has the amino acid sequence shown in SEQ ID NO. 53 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 53.

[0367] (11) The peptide chain comprising an electrostatically redirected D-type positively charged chain (Fc1(D+)) and an hFSHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 62, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably having 98% or 99% or more identity, more preferably, the amino acid sequence of the peptide chain comprising an electrostatically redirected D-type positively charged chain (Fc1(D+)) and an hFSHα subunit is as shown in SEQ ID NO. 62; and the peptide chain comprising an electrostatically redirected D-type negatively charged chain (Fc1(D-)) and an hFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 62. The amino acid sequence shown in NO.55 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain comprising the electrostatically directed D-type negatively charged chain (Fc1(D-)) and the hFSHβ subunit is as shown in SEQ ID NO.55.

[0368] In some preferred embodiments, the peptide chain comprising the electrostatically directed D-type positively charged chain (Fc1(D+)) and the hFSHα subunit has the amino acid sequence shown in SEQ ID NO. 62 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 62.

[0369] In some preferred embodiments, the peptide chain comprising the electrostatically directed D-type negatively charged chain (Fc1(D-)) and the hFSHβ subunit has the amino acid sequence shown in SEQ ID NO. 55 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 55.

[0370] (12) The peptide chain comprising an electrostatically redirected D-type negatively charged chain (Fc1(D-)) and an hFSHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 63, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, preferably having 98% or 99% or more identity, more preferably, the amino acid sequence of the peptide chain comprising an electrostatically redirected D-type negatively charged chain (Fc1(D-)) and an hFSHα subunit is as shown in SEQ ID NO. 63; and the peptide chain comprising an electrostatically redirected D-type positively charged chain (Fc1(D+)) and an hFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 63 ... more identity with the amino acid sequence shown in SEQ ID NO. 63, more preferably, the amino acid sequence of the peptide chain comprising an electrostatically redirected D-type negatively charged chain (Fc1(D-)) and an hFSHβ subunit is as shown in SEQ ID NO. 63; The amino acid sequence shown in NO.57 has 80% or more identity, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably 98% or 99% or more identity, and more preferably, the amino acid sequence of the peptide chain comprising the electrostatically directed D-type positively charged chain (Fc1(D+)) and the hFSHβ subunit is as shown in SEQ ID NO.57.

[0371] In some preferred embodiments, the peptide chain comprising the electrostatically directed D-type negatively charged chain (Fc1(D-)) and the hFSHα subunit has the amino acid sequence shown in SEQ ID NO. 63 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 63.

[0372] In some preferred embodiments, the peptide chain comprising the electrostatically directed D-type positively charged chain (Fc1(D+)) and the hFSHβ subunit has the amino acid sequence shown in SEQ ID NO. 57 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 57.

[0373] (13) The peptide chain comprising the clasp-type Fc chain (Fc4k) and the hFSHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 82, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably having 98% or 99% or more identity, and more preferably, the amino acid sequence of the peptide chain comprising the clasp-type Fc chain (Fc4k) and the hFSHα subunit is as shown in SEQ ID NO. 82; and the peptide chain comprising the lock-type Fc chain (Fc4h) and the hFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence ...k) and the hFSHβ subunit is as shown in SEQ ID NO. 82; The amino acid sequence shown in NO.71 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain containing the locked Fc chain (Fc4h) and the hFSHβ subunit is as shown in SEQ ID NO.71.

[0374] In some preferred embodiments, the peptide chain comprising the coin-type Fc chain (Fc4k) and the hFSHα subunit has the amino acid sequence shown in SEQ ID NO. 82 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 82.

[0375] In some preferred embodiments, the peptide chain comprising the locked Fc chain (Fc4h) and the hFSHβ subunit has the amino acid sequence shown in SEQ ID NO. 71 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 71.

[0376] (14) The peptide chain comprising the locked Fc chain (Fc4h) and the hFSHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 83, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably having 98% or 99% or more identity, more preferably, the amino acid sequence of the peptide chain comprising the locked Fc chain (Fc4h) and the hFSHα subunit is as shown in SEQ ID NO. 83; and the peptide chain comprising the button Fc chain (Fc4k) and the hFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 83; and the peptide chain comprising the button Fc chain (Fc4k) and the hFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 83; The amino acid sequence shown in NO.73 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain containing the coin-type Fc chain (Fc4k) and the hFSHβ subunit is as shown in SEQ ID NO.73.

[0377] In some preferred embodiments, the peptide chain comprising the locked Fc chain (Fc4h) and the hFSHα subunit has the amino acid sequence shown in SEQ ID NO. 83 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 83.

[0378] In some preferred embodiments, the peptide chain comprising the coin-type Fc chain (Fc4k) and the hFSHβ subunit has the amino acid sequence shown in SEQ ID NO. 73 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 73.

[0379] (15) The peptide chain comprising an electrostatically redirected T-type positively charged chain (Fc4(T+)) and an hFSHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 84, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably having 98% or 99% or more identity, more preferably, the amino acid sequence of the peptide chain comprising an electrostatically redirected T-type positively charged chain (Fc4(T+)) and an hFSHα subunit is as shown in SEQ ID NO. 84; and the peptide chain comprising an electrostatically redirected T-type negatively charged chain (Fc4(T-)) and an hFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 84. The amino acid sequence shown in NO.75 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain comprising the electrostatically directed T-type negatively charged chain (Fc4(T-)) and the hFSHβ subunit is as shown in SEQ ID NO.75.

[0380] In some preferred embodiments, the peptide chain comprising the electrostatically directed T-type positively charged chain (Fc4(T+)) and the hFSHα subunit has the amino acid sequence shown in SEQ ID NO. 84 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 84.

[0381] In some preferred embodiments, the peptide chain comprising the electrostatically directed T-type negatively charged chain (Fc4(T-)) and the hFSHβ subunit has the amino acid sequence shown in SEQ ID NO. 75 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 75.

[0382] (16) The peptide chain comprising an electrostatically redirected T-type negatively charged chain (Fc4(T-)) and an hFSHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 85, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably having 98% or 99% or more identity, more preferably, the amino acid sequence of the peptide chain comprising an electrostatically redirected T-type negatively charged chain (Fc4(T-)) and an hFSHα subunit is as shown in SEQ ID NO. 85; and the peptide chain comprising an electrostatically redirected T-type positively charged chain (Fc4(T+)) and an hFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 85. The amino acid sequence shown in NO.77 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain comprising the electrostatically directed T-type positively charged chain (Fc4(T+)) and the hFSHβ subunit is as shown in SEQ ID NO.77.

[0383] In some preferred embodiments, the peptide chain comprising the electrostatically directed T-type negatively charged chain (Fc4(T-)) and the hFSHα subunit has the amino acid sequence shown in SEQ ID NO. 85 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 85.

[0384] In some preferred embodiments, the peptide chain comprising the electrostatically directed T-type positively charged chain (Fc4(T+)) and the hFSHβ subunit has the amino acid sequence shown in SEQ ID NO.77 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO.77.

[0385] (17) The peptide chain comprising an electrostatically redirected D-type positively charged chain (Fc4(D+)) and an hFSHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 86, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, preferably having 98% or 99% or more identity, more preferably, the amino acid sequence comprising the electrostatically redirected D-type positively charged chain (Fc4(D+)) and an hFSHα subunit is as shown in SEQ ID NO. 86; and the peptide chain comprising an electrostatically redirected D-type negatively charged chain (Fc4(D-)) and an hFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 86. The amino acid sequence shown in NO. 79 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain comprising the electrostatically directed D-type negatively charged chain (Fc4(D-)) and the hFSHβ subunit is as shown in SEQ ID NO. 79.

[0386] In some preferred embodiments, the peptide chain comprising the electrostatically directed D-type positively charged chain (Fc4(D+)) and the hFSHα subunit has the amino acid sequence shown in SEQ ID NO. 86 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 86.

[0387] In some preferred embodiments, the peptide chain comprising the electrostatically directed D-type negatively charged chain (Fc4(D-)) and the hFSHβ subunit has the amino acid sequence shown in SEQ ID NO. 79 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 79.

[0388] (18) The peptide chain comprising an electrostatically redirected D-type negatively charged chain (Fc4(D-)) and an hFSHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 87, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably having 98% or 99% or more identity, more preferably, the amino acid sequence of the peptide chain comprising an electrostatically redirected D-type negatively charged chain (Fc4(D-)) and an hFSHα subunit is as shown in SEQ ID NO. 87; and the peptide chain comprising an electrostatically redirected D-type positively charged chain (Fc4(D+)) and an hFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 87. The amino acid sequence shown in NO.81 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain comprising the electrostatically directed D-type positively charged chain (Fc4(D+)) and the hFSHβ subunit is as shown in SEQ ID NO.81.

[0389] In some preferred embodiments, the peptide chain comprising the electrostatically directed D-type negatively charged chain (Fc4(D-)) and the hFSHα subunit has the amino acid sequence shown in SEQ ID NO. 87 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 87.

[0390] In some preferred embodiments, the peptide chain comprising the electrostatically directed D-type positively charged chain (Fc4(D+)) and the hFSHβ subunit has the amino acid sequence shown in SEQ ID NO. 81 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 81.

[0391] (19) The peptide chain comprising a clasp-type Fc chain (Fc1k) and a GtHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 106, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably having 98% or 99% or more identity, more preferably, the amino acid sequence of the peptide chain comprising a clasp-type Fc chain (Fc1k) and a GtHα subunit is as shown in SEQ ID NO. 106; and the peptide chain comprising a lock-type Fc chain (Fc1h) and a GtH Iβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 106. The amino acid sequence shown in NO. 95 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain containing the locked Fc chain (Fc1h) and the GtH Iβ subunit is as shown in SEQ ID NO. 95.

[0392] In some preferred embodiments, the peptide chain comprising the coin-type Fc chain (Fc1k) and the GtHα subunit has the amino acid sequence shown in SEQ ID NO. 106 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 106.

[0393] In some preferred embodiments, the peptide chain comprising the locked Fc chain (Fc1h) and the GtH Iβ subunit has the amino acid sequence shown in SEQ ID NO.95 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO.95.

[0394] (20) The peptide chain comprising the locked Fc chain (Fc1h) and the GtHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 107, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably having 98% or 99% or more identity, more preferably, the amino acid sequence of the peptide chain comprising the locked Fc chain (Fc1h) and the GtHα subunit is as shown in SEQ ID NO. 107; and the peptide chain comprising the button Fc chain (Fc1k) and the GtH Iβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 107. The amino acid sequence shown in NO.97 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain containing the coin-type Fc chain (Fc1k) and the GtH Iβ subunit is as shown in SEQ ID NO.97.

[0395] In some preferred embodiments, the peptide chain comprising the locked Fc chain (Fc1h) and the GtHα subunit has the amino acid sequence shown in SEQ ID NO. 107 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 107.

[0396] In some preferred embodiments, the peptide chain comprising the coin-type Fc chain (Fc1k) and the GtH Iβ subunit has the amino acid sequence shown in SEQ ID NO.97 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO.97.

[0397] (21) The peptide chain comprising an electrostatically redirected T-type positively charged chain (Fc1(T+)) and a GtHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 108, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, preferably having 98% or 99% or more identity, more preferably, the amino acid sequence comprising the electrostatically redirected T-type positively charged chain (Fc1(T+)) and a GtHα subunit is as shown in SEQ ID NO. 108; and the peptide chain comprising an electrostatically redirected T-type negatively charged chain (Fc1(T-)) and a GtH Iβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 108. The amino acid sequence shown in NO.99 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain comprising the electrostatically directed T-type negatively charged chain (Fc1(T-)) and the GtH Iβ subunit is as shown in SEQ ID NO.99.

[0398] In some preferred embodiments, the peptide chain comprising the electrostatically directed T-type positively charged chain (Fc1(T+)) and the GtHα subunit has the amino acid sequence shown in SEQ ID NO. 108 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 108.

[0399] In some preferred embodiments, the peptide chain comprising the electrostatically directed T-type negatively charged chain (Fc1(T-)) and the GtH Iβ subunit has the amino acid sequence shown in SEQ ID NO.99 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO.99.

[0400] (22) The peptide chain comprising an electrostatically redirected T-type negatively charged chain (Fc1(T-)) and a GtHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 109, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, preferably having 98% or 99% or more identity, more preferably, the amino acid sequence of the peptide chain comprising an electrostatically redirected T-type negatively charged chain (Fc1(T-)) and a GtHα subunit is as shown in SEQ ID NO. 109; and the peptide chain comprising an electrostatically redirected T-type positively charged chain (Fc1(T+)) and a GtH Iβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 109. The amino acid sequence shown in NO.101 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain comprising the electrostatically directed T-type positively charged chain (Fc1(T+)) and the GtH Iβ subunit is as shown in SEQ ID NO.101.

[0401] In some preferred embodiments, the peptide chain comprising the electrostatically directed T-type negatively charged chain (Fc1(T-)) and the GtHα subunit has the amino acid sequence shown in SEQ ID NO. 109 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 109.

[0402] In some preferred embodiments, the peptide chain comprising the electrostatically directed T-type positively charged chain (Fc1(T+)) and the GtH Iβ subunit has the amino acid sequence shown in SEQ ID NO. 101 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 101.

[0403] (23) The peptide chain comprising an electrostatically redirected D-type positively charged chain (Fc1(D+)) and a GtHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 110, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, preferably having 98% or 99% or more identity, more preferably, the amino acid sequence comprising the electrostatically redirected D-type positively charged chain (Fc1(D+)) and a GtHα subunit is as shown in SEQ ID NO. 110; and the peptide chain comprising an electrostatically redirected D-type negatively charged chain (Fc1(D-)) and a GtH Iβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 110. The amino acid sequence shown in NO.103 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain comprising the electrostatically directed D-type negatively charged chain (Fc1(D-)) and the GtH Iβ subunit is as shown in SEQ ID NO.103.

[0404] In some preferred embodiments, the peptide chain comprising the electrostatically directed D-type positively charged chain (Fc1(D+)) and the GtHα subunit has the amino acid sequence shown in SEQ ID NO. 110 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 110.

[0405] In some preferred embodiments, the peptide chain comprising the electrostatically directed D-type negatively charged chain (Fc1(D-)) and the GtH Iβ subunit has the amino acid sequence shown in SEQ ID NO. 103 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 103.

[0406] (24) The peptide chain comprising an electrostatically redirected D-type negatively charged chain (Fc1(D-)) and a GtHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 111, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, preferably having 98% or 99% or more identity, more preferably, the amino acid sequence of the peptide chain comprising an electrostatically redirected D-type negatively charged chain (Fc1(D-)) and a GtHα subunit is as shown in SEQ ID NO. 111; and the peptide chain comprising an electrostatically redirected D-type positively charged chain (Fc1(D+)) and a GtH Iβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 111. The amino acid sequence shown in NO. 105 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain comprising the electrostatically directed D-type positively charged chain (Fc1(D+)) and the GtH Iβ subunit is as shown in SEQ ID NO. 105.

[0407] In some preferred embodiments, the peptide chain comprising the electrostatically directed D-type negatively charged chain (Fc1(D-)) and the GtHα subunit has the amino acid sequence shown in SEQ ID NO. 111 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 111.

[0408] In some preferred embodiments, the peptide chain comprising the electrostatically directed D-type positively charged chain (Fc1(D+)) and the GtH Iβ subunit has the amino acid sequence shown in SEQ ID NO. 105 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 105.

[0409] (25) The peptide chain comprising a clasp-type Fc chain (Fc1k) and a GtHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 106, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably having 98% or 99% or more identity, and more preferably, the amino acid sequence of the peptide chain comprising a clasp-type Fc chain (Fc1k) and a GtHα subunit is as shown in SEQ ID NO. 106; and the peptide chain comprising a lock-type Fc chain (Fc1h) and a GtH IIβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 106. The amino acid sequence shown in NO. 118 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain containing the locked Fc chain (Fc1h) and the GtH IIβ subunit is as shown in SEQ ID NO. 118.

[0410] In some preferred embodiments, the peptide chain comprising the coin-type Fc chain (Fc1k) and the GtHα subunit has the amino acid sequence shown in SEQ ID NO. 106 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 106.

[0411] In some preferred embodiments, the peptide chain comprising the locked Fc chain (Fc1h) and the GtH IIβ subunit has the amino acid sequence shown in SEQ ID NO. 118 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 118.

[0412] (26) The peptide chain comprising the locked Fc chain (Fc1h) and the GtHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 107, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably having 98% or 99% or more identity, more preferably, the amino acid sequence of the peptide chain comprising the locked Fc chain (Fc1h) and the GtHα subunit is as shown in SEQ ID NO. 107; and the peptide chain comprising the button Fc chain (Fc1k) and the GtH IIβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 107. The amino acid sequence shown in NO.119 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain containing the coin-type Fc chain (Fc1k) and the GtH IIβ subunit is as shown in SEQ ID NO.119.

[0413] In some preferred embodiments, the peptide chain comprising the locked Fc chain (Fc1h) and the GtHα subunit has the amino acid sequence shown in SEQ ID NO. 107 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 107.

[0414] In some preferred embodiments, the peptide chain comprising the coin-type Fc chain (Fc1k) and the GtH IIβ subunit has the amino acid sequence shown in SEQ ID NO. 119 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 119.

[0415] (27) The peptide chain comprising an electrostatically redirected T-type positively charged chain (Fc1(T+)) and a GtHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 108, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, preferably having 98% or 99% or more identity, more preferably, the amino acid sequence comprising the electrostatically redirected T-type positively charged chain (Fc1(T+)) and a GtHα subunit is as shown in SEQ ID NO. 108; and the peptide chain comprising an electrostatically redirected T-type negatively charged chain (Fc1(T-)) and a GtH IIβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 108. The amino acid sequence shown in NO. 120 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain comprising the electrostatically directed T-type negatively charged chain (Fc1(T-)) and the GtH IIβ subunit is as shown in SEQ ID NO. 120.

[0416] In some preferred embodiments, the peptide chain comprising the electrostatically directed T-type positively charged chain (Fc1(T+)) and the GtHα subunit has the amino acid sequence shown in SEQ ID NO. 108 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 108.

[0417] In some preferred embodiments, the peptide chain comprising the electrostatically directed T-type negatively charged chain (Fc1(T-)) and the GtH IIβ subunit has the amino acid sequence shown in SEQ ID NO. 120 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 120.

[0418] (28) The peptide chain comprising an electrostatically redirected T-type negatively charged chain (Fc1(T-)) and a GtHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 109, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, preferably having 98% or 99% or more identity, more preferably, the amino acid sequence comprising the electrostatically redirected T-type negatively charged chain (Fc1(T-)) and a GtHα subunit is as shown in SEQ ID NO. 109; and the peptide chain comprising an electrostatically redirected T-type positively charged chain (Fc1(T+)) and a GtH IIβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 109. The amino acid sequence shown in NO.121 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain comprising the electrostatically directed T-type positively charged chain (Fc1(T+)) and the GtH IIβ subunit is as shown in SEQ ID NO.121.

[0419] In some preferred embodiments, the peptide chain comprising the electrostatically directed T-type negatively charged chain (Fc1(T-)) and the GtHα subunit has the amino acid sequence shown in SEQ ID NO. 109 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 109.

[0420] In some preferred embodiments, the peptide chain comprising the electrostatically directed T-type positively charged chain (Fc1(T+)) and the GtH IIβ subunit has the amino acid sequence shown in SEQ ID NO. 121 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 121.

[0421] (29) The peptide chain comprising an electrostatically redirected D-type positively charged chain (Fc1(D+)) and a GtHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 110, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, preferably having 98% or 99% or more identity, more preferably, the amino acid sequence comprising the electrostatically redirected D-type positively charged chain (Fc1(D+)) and a GtHα subunit is as shown in SEQ ID NO. 110; and the peptide chain comprising an electrostatically redirected D-type negatively charged chain (Fc1(D-)) and a GtH IIβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 110. The amino acid sequence shown in NO.122 has 80% or more identity, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably 98% or 99% or more identity, and more preferably, the amino acid sequence of the peptide chain comprising the electrostatically directed D-type negatively charged chain (Fc1(D-)) and the GtH IIβ subunit is as shown in SEQ ID NO.122.

[0422] In some preferred embodiments, the peptide chain comprising the electrostatically directed D-type positively charged chain (Fc1(D+)) and the GtHα subunit has the amino acid sequence shown in SEQ ID NO. 110 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 110.

[0423] In some preferred embodiments, the peptide chain comprising the electrostatically directed D-type negatively charged chain (Fc1(D-)) and the GtH IIβ subunit has the amino acid sequence shown in SEQ ID NO. 122 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 122.

[0424] (30) The peptide chain comprising an electrostatically redirected D-type negatively charged chain (Fc1(D-)) and a GtHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 111, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, preferably having 98% or 99% or more identity, more preferably, the amino acid sequence of the peptide chain comprising an electrostatically redirected D-type negatively charged chain (Fc1(D-)) and a GtHα subunit is as shown in SEQ ID NO. 111; and the peptide chain comprising an electrostatically redirected D-type positively charged chain (Fc1(D+)) and a GtH IIβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 111. The amino acid sequence shown in NO.123 has 80% or more identity, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably 98% or 99% or more identity, and more preferably, the amino acid sequence of the peptide chain comprising the electrostatically directed D-type positively charged chain (Fc1(D+)) and the GtH IIβ subunit is as shown in SEQ ID NO.123.

[0425] In some preferred embodiments, the peptide chain comprising the electrostatically directed D-type negatively charged chain (Fc1(D-)) and the GtHα subunit has the amino acid sequence shown in SEQ ID NO. 111 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 111.

[0426] In some preferred embodiments, the peptide chain comprising the electrostatically directed D-type positively charged chain (Fc1(D+)) and the GtH IIβ subunit has the amino acid sequence shown in SEQ ID NO. 123 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 123.

[0427] (c) The N-terminus of the Gnα and Gnβ subunits is connected to the C-terminus of the Fc chain;

[0428] (1) The peptide chain comprising a clasp-type Fc chain (Fc1k) and a pFSHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 34, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably having 98% or 99% or more identity, and more preferably, the amino acid sequence of the peptide chain comprising a clasp-type Fc chain (Fc1k) and a pFSHα subunit is as shown in SEQ ID NO. 34; and the peptide chain comprising a lock-type Fc chain (Fc1h) and a pFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 34; and the peptide chain comprising a lock-type Fc chain (Fc1h) and a pFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 34; The amino acid sequence shown in NO.40 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain containing the locked Fc chain (Fc1h) and the pFSHβ subunit is as shown in SEQ ID NO.40.

[0429] In some preferred embodiments, the peptide chain comprising the coin-type Fc chain (Fc1k) and the pFSHα subunit has the amino acid sequence shown in SEQ ID NO. 34 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 34.

[0430] In some preferred embodiments, the peptide chain comprising the locked Fc chain (Fc1h) and the pFSHβ subunit has the amino acid sequence shown in SEQ ID NO.40 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO.40.

[0431] (2) The peptide chain comprising the locked Fc chain (Fc1h) and the pFSHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 35, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably having 98% or 99% or more identity, and more preferably, the amino acid sequence of the peptide chain comprising the locked Fc chain (Fc1h) and the pFSHα subunit is as shown in SEQ ID NO. 35; and the peptide chain comprising the button Fc chain (Fc1k) and the pFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 35. The amino acid sequence shown in NO.41 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain containing the coin-type Fc chain (Fc1k) and the pFSHβ subunit is as shown in SEQ ID NO.41.

[0432] In some preferred embodiments, the peptide chain comprising the locked Fc chain (Fc1h) and the pFSHα subunit has the amino acid sequence shown in SEQ ID NO. 35 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 35.

[0433] In some preferred embodiments, the peptide chain comprising the coin-type Fc chain (Fc1k) and the pFSHβ subunit has the amino acid sequence shown in SEQ ID NO.41 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO.41.

[0434] (3) The peptide chain comprising an electrostatically redirected T-type positively charged chain (Fc1(T+)) and a pFSHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 36, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably having 98% or 99% or more identity, more preferably, the amino acid sequence of the peptide chain comprising an electrostatically redirected T-type positively charged chain (Fc1(T+)) and a pFSHα subunit is as shown in SEQ ID NO. 36; and the peptide chain comprising an electrostatically redirected T-type negatively charged chain (Fc1(T-)) and a pFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 36. The amino acid sequence shown in NO.42 has 80% or more identity, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably 98% or 99% or more identity, and more preferably, the amino acid sequence of the peptide chain comprising the electrostatically directed T-type negatively charged chain (Fc1(T-)) and the pFSHβ subunit is as shown in SEQ ID NO.42.

[0435] In some preferred embodiments, the peptide chain comprising the electrostatically directed T-type positively charged chain (Fc1(T+)) and the pFSHα subunit has the amino acid sequence shown in SEQ ID NO.36 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO.36.

[0436] In some preferred embodiments, the peptide chain comprising the electrostatically directed T-type negatively charged chain (Fc1(T-)) and the pFSHβ subunit has the amino acid sequence shown in SEQ ID NO.42 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO.42.

[0437] (4) The peptide chain comprising an electrostatically redirected T-type negatively charged chain (Fc1(T-)) and a pFSHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 37, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably having 98% or 99% or more identity, more preferably, the amino acid sequence of the peptide chain comprising an electrostatically redirected T-type negatively charged chain (Fc1(T-)) and a pFSHα subunit is as shown in SEQ ID NO. 37; and the peptide chain comprising an electrostatically redirected T-type positively charged chain (Fc1(T+)) and a pFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 37. The amino acid sequence shown in NO.43 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain comprising the electrostatically directed T-type positively charged chain (Fc1(T+)) and the pFSHβ subunit is as shown in SEQ ID NO.43.

[0438] In some preferred embodiments, the peptide chain comprising the electrostatically directed T-type negatively charged chain (Fc1(T-)) and the pFSHα subunit has the amino acid sequence shown in SEQ ID NO.37 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO.37.

[0439] In some preferred embodiments, the peptide chain comprising the electrostatically directed T-type positively charged chain (Fc1(T+)) and the pFSHβ subunit has the amino acid sequence shown in SEQ ID NO.43 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO.43.

[0440] (5) The peptide chain comprising the electrostatically redirected D-type positively charged chain (Fc1(D+)) and the pFSHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 38, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably having 98% or 99% or more identity, more preferably, the amino acid sequence comprising the electrostatically redirected D-type positively charged chain (Fc1(D+)) and the pFSHα subunit is as shown in SEQ ID NO. 38; and the peptide chain comprising the electrostatically redirected D-type negatively charged chain (Fc1(D-)) and the pFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 38. The amino acid sequence shown in NO.44 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain comprising the electrostatically directed D-type negatively charged chain (Fc1(D-)) and the pFSHβ subunit is as shown in SEQ ID NO.44.

[0441] In some preferred embodiments, the peptide chain comprising the electrostatically directed D-type positively charged chain (Fc1(D+)) and the pFSHα subunit has the amino acid sequence shown in SEQ ID NO.38 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO.38.

[0442] In some preferred embodiments, the peptide chain comprising the electrostatically directed D-type negatively charged chain (Fc1(D-)) and the pFSHβ subunit has the amino acid sequence shown in SEQ ID NO.44 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO.44.

[0443] (6) The peptide chain comprising the electrostatically redirected D-type negatively charged chain (Fc1(D-)) and the pFSHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 39, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably having 98% or 99% or more identity, more preferably, the amino acid sequence of the peptide chain comprising the electrostatically redirected D-type negatively charged chain (Fc1(D-)) and the pFSHα subunit is as shown in SEQ ID NO. 39; and the peptide chain comprising the electrostatically redirected D-type positively charged chain (Fc1(D+)) and the pFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 39. The amino acid sequence shown in NO.45 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain comprising the electrostatically directed D-type positively charged chain (Fc1(D+)) and the pFSHβ subunit is as shown in SEQ ID NO.45.

[0444] In some preferred embodiments, the peptide chain comprising the electrostatically directed D-type negatively charged chain (Fc1(D-)) and the pFSHα subunit has the amino acid sequence shown in SEQ ID NO.39 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO.39.

[0445] In some preferred embodiments, the peptide chain comprising the electrostatically directed D-type positively charged chain (Fc1(D+)) and the pFSHβ subunit has the amino acid sequence shown in SEQ ID NO.45 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO.45.

[0446] (7) The peptide chain comprising the clasp-type Fc chain (Fc1k) and the hFSHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 58, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably having 98% or 99% or more identity, and more preferably, the amino acid sequence of the peptide chain comprising the clasp-type Fc chain (Fc1k) and the hFSHα subunit is as shown in SEQ ID NO. 58; and the peptide chain comprising the lock-type Fc chain (Fc1h) and the hFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 58. The amino acid sequence shown in NO. 64 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain containing the locked Fc chain (Fc1h) and the hFSHβ subunit is as shown in SEQ ID NO. 64.

[0447] In some preferred embodiments, the peptide chain comprising the coin-type Fc chain (Fc1k) and the hFSHα subunit has the amino acid sequence shown in SEQ ID NO. 58 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 58.

[0448] In some preferred embodiments, the peptide chain comprising the locked Fc chain (Fc1h) and the hFSHβ subunit has the amino acid sequence shown in SEQ ID NO. 64 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 64.

[0449] (8) The peptide chain comprising the locked Fc chain (Fc1h) and the hFSHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 59, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably having 98% or 99% or more identity, and more preferably, the amino acid sequence of the peptide chain comprising the locked Fc chain (Fc1h) and the hFSHα subunit is as shown in SEQ ID NO. 59; and the peptide chain comprising the button Fc chain (Fc1k) and the hFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 59. The amino acid sequence shown in NO. 65 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain containing the coin-type Fc chain (Fc1k) and the hFSHβ subunit is as shown in SEQ ID NO. 65.

[0450] In some preferred embodiments, the peptide chain comprising the locked Fc chain (Fc1h) and the hFSHα subunit has the amino acid sequence shown in SEQ ID NO. 59 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 59.

[0451] In some preferred embodiments, the peptide chain comprising the coin-type Fc chain (Fc1k) and the hFSHβ subunit has the amino acid sequence shown in SEQ ID NO. 65 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 65.

[0452] (9) The peptide chain comprising an electrostatically redirected T-type positively charged chain (Fc1(T+)) and an hFSHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 60, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, preferably having 98% or 99% or more identity, more preferably, the amino acid sequence comprising the electrostatically redirected T-type positively charged chain (Fc1(T+)) and an hFSHα subunit is as shown in SEQ ID NO. 60; and the peptide chain comprising an electrostatically redirected T-type negatively charged chain (Fc1(T-)) and an hFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 60. The amino acid sequence shown in NO. 66 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain comprising the electrostatically directed T-type negatively charged chain (Fc1(T-)) and the hFSHβ subunit is as shown in SEQ ID NO. 66.

[0453] In some preferred embodiments, the peptide chain comprising the electrostatically directed T-type positively charged chain (Fc1(T+)) and the hFSHα subunit has the amino acid sequence shown in SEQ ID NO. 60 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 60.

[0454] In some preferred embodiments, the peptide chain comprising the electrostatically directed T-type negative charge chain (Fc1(T-)) and the hFSHβ subunit has the amino acid sequence shown in SEQ ID NO. 66 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 66.

[0455] (10) The peptide chain comprising an electrostatically redirected T-type negatively charged chain (Fc1(T-)) and an hFSHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 61, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, preferably having 98% or 99% or more identity, more preferably, the amino acid sequence of the peptide chain comprising an electrostatically redirected T-type negatively charged chain (Fc1(T-)) and an hFSHα subunit is as shown in SEQ ID NO. 61; and the peptide chain comprising an electrostatically redirected T-type positively charged chain (Fc1(T+)) and an hFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 61. The amino acid sequence shown in NO. 67 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain comprising the electrostatically directed T-type positively charged chain (Fc1(T+)) and the hFSHβ subunit is as shown in SEQ ID NO. 67.

[0456] In some preferred embodiments, the peptide chain comprising the electrostatically directed T-type negatively charged chain (Fc1(T-)) and the hFSHα subunit has the amino acid sequence shown in SEQ ID NO. 61 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 61.

[0457] In some preferred embodiments, the peptide chain comprising the electrostatically directed T-type positively charged chain (Fc1(T+)) and the hFSHβ subunit has the amino acid sequence shown in SEQ ID NO. 67 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 67.

[0458] (11) The peptide chain comprising an electrostatically redirected D-type positively charged chain (Fc1(D+)) and an hFSHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 62, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably having 98% or 99% or more identity, more preferably, the amino acid sequence of the peptide chain comprising an electrostatically redirected D-type positively charged chain (Fc1(D+)) and an hFSHα subunit is as shown in SEQ ID NO. 62; and the peptide chain comprising an electrostatically redirected D-type negatively charged chain (Fc1(D-)) and an hFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 62. The amino acid sequence shown in NO. 68 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain comprising the electrostatically directed D-type negatively charged chain (Fc1(D-)) and the hFSHβ subunit is as shown in SEQ ID NO. 68.

[0459] In some preferred embodiments, the peptide chain comprising the electrostatically directed D-type positively charged chain (Fc1(D+)) and the hFSHα subunit has the amino acid sequence shown in SEQ ID NO. 62 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 62.

[0460] In some preferred embodiments, the peptide chain comprising the electrostatically directed D-type negatively charged chain (Fc1(D-)) and the hFSHβ subunit has the amino acid sequence shown in SEQ ID NO. 68 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 68.

[0461] (12) The peptide chain comprising an electrostatically redirected D-type negatively charged chain (Fc1(D-)) and an hFSHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 63, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, preferably having 98% or 99% or more identity, more preferably, the amino acid sequence of the peptide chain comprising an electrostatically redirected D-type negatively charged chain (Fc1(D-)) and an hFSHα subunit is as shown in SEQ ID NO. 63; and the peptide chain comprising an electrostatically redirected D-type positively charged chain (Fc1(D+)) and an hFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 63 ... more identity with the amino acid sequence shown in SEQ ID NO. 63, more preferably, the amino acid sequence of the peptide chain comprising an electrostatically redirected D-type negatively charged chain (Fc1(D-)) and an hFSHβ subunit is as shown in SEQ ID NO. 63; The amino acid sequence shown in NO. 69 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain comprising the electrostatically directed D-type positively charged chain (Fc1(D+)) and the hFSHβ subunit is as shown in SEQ ID NO. 69.

[0462] In some preferred embodiments, the peptide chain comprising the electrostatically directed D-type negatively charged chain (Fc1(D-)) and the hFSHα subunit has the amino acid sequence shown in SEQ ID NO. 63 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 63.

[0463] In some preferred embodiments, the peptide chain comprising the electrostatically directed D-type positively charged chain (Fc1(D+)) and the hFSHβ subunit has the amino acid sequence shown in SEQ ID NO. 69 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 69.

[0464] (13) The peptide chain comprising the clasp-type Fc chain (Fc4k) and the hFSHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 82, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably having 98% or 99% or more identity, and more preferably, the amino acid sequence of the peptide chain comprising the clasp-type Fc chain (Fc4k) and the hFSHα subunit is as shown in SEQ ID NO. 82; and the peptide chain comprising the lock-type Fc chain (Fc4h) and the hFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence ...k) and the hFSHβ subunit is as shown in SEQ ID NO. 82; The amino acid sequence shown in NO.88 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain containing the locked Fc chain (Fc4h) and the hFSHβ subunit is as shown in SEQ ID NO.88.

[0465] In some preferred embodiments, the peptide chain comprising the coin-type Fc chain (Fc4k) and the hFSHα subunit has the amino acid sequence shown in SEQ ID NO. 82 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 82.

[0466] In some preferred embodiments, the peptide chain comprising the locked Fc chain (Fc4h) and the hFSHβ subunit has the amino acid sequence shown in SEQ ID NO. 88 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 88.

[0467] (14) The peptide chain comprising the locked Fc chain (Fc4h) and the hFSHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 83, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably having 98% or 99% or more identity, more preferably, the amino acid sequence of the peptide chain comprising the locked Fc chain (Fc4h) and the hFSHα subunit is as shown in SEQ ID NO. 83; and the peptide chain comprising the button Fc chain (Fc4k) and the hFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 83; and the peptide chain comprising the button Fc chain (Fc4k) and the hFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 83; The amino acid sequence shown in NO.89 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain containing the coin-type Fc chain (Fc4k) and the hFSHβ subunit is as shown in SEQ ID NO.89.

[0468] In some preferred embodiments, the peptide chain comprising the locked Fc chain (Fc4h) and the hFSHα subunit has the amino acid sequence shown in SEQ ID NO. 83 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 83.

[0469] In some preferred embodiments, the peptide chain comprising the coin-type Fc chain (Fc4k) and the hFSHβ subunit has the amino acid sequence shown in SEQ ID NO. 89 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 89.

[0470] (15) The peptide chain comprising an electrostatically redirected T-type positively charged chain (Fc4(T+)) and an hFSHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 84, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably having 98% or 99% or more identity, more preferably, the amino acid sequence of the peptide chain comprising an electrostatically redirected T-type positively charged chain (Fc4(T+)) and an hFSHα subunit is as shown in SEQ ID NO. 84; and the peptide chain comprising an electrostatically redirected T-type negatively charged chain (Fc4(T-)) and an hFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 84. The amino acid sequence shown in NO. 90 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain comprising the electrostatically directed T-type negatively charged chain (Fc4(T-)) and the hFSHβ subunit is as shown in SEQ ID NO. 90.

[0471] In some preferred embodiments, the peptide chain comprising the electrostatically directed T-type positively charged chain (Fc4(T+)) and the hFSHα subunit has the amino acid sequence shown in SEQ ID NO. 84 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 84.

[0472] In some preferred embodiments, the peptide chain comprising the electrostatically directed T-type negative charge chain (Fc4(T-)) and the hFSHβ subunit has the amino acid sequence shown in SEQ ID NO. 90 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 90.

[0473] (16) The peptide chain comprising an electrostatically redirected T-type negatively charged chain (Fc4(T-)) and an hFSHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 85, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably having 98% or 99% or more identity, more preferably, the amino acid sequence of the peptide chain comprising an electrostatically redirected T-type negatively charged chain (Fc4(T-)) and an hFSHα subunit is as shown in SEQ ID NO. 85; and the peptide chain comprising an electrostatically redirected T-type positively charged chain (Fc4(T+)) and an hFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 85. The amino acid sequence shown in NO.91 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain comprising the electrostatically directed T-type positively charged chain (Fc4(T+)) and the hFSHβ subunit is as shown in SEQ ID NO.91.

[0474] In some preferred embodiments, the peptide chain comprising the electrostatically directed T-type negatively charged chain (Fc4(T-)) and the hFSHα subunit has the amino acid sequence shown in SEQ ID NO. 85 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 85.

[0475] In some preferred embodiments, the peptide chain comprising the electrostatically directed T-type positively charged chain (Fc4(T+)) and the hFSHβ subunit has the amino acid sequence shown in SEQ ID NO.91 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO.91.

[0476] (17) The peptide chain comprising an electrostatically redirected D-type positively charged chain (Fc4(D+)) and an hFSHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 86, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, preferably having 98% or 99% or more identity, more preferably, the amino acid sequence comprising the electrostatically redirected D-type positively charged chain (Fc4(D+)) and an hFSHα subunit is as shown in SEQ ID NO. 86; and the peptide chain comprising an electrostatically redirected D-type negatively charged chain (Fc4(D-)) and an hFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 86. The amino acid sequence shown in NO.92 has 80% or more identity, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably 98% or 99% or more identity, and more preferably, the amino acid sequence of the peptide chain comprising the electrostatically directed D-type negatively charged chain (Fc4(D-)) and the hFSHβ subunit is as shown in SEQ ID NO.92.

[0477] In some preferred embodiments, the peptide chain comprising the electrostatically directed D-type positively charged chain (Fc4(D+)) and the hFSHα subunit has the amino acid sequence shown in SEQ ID NO. 86 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 86.

[0478] In some preferred embodiments, the peptide chain comprising the electrostatically directed D-type negatively charged chain (Fc4(D-)) and the hFSHβ subunit has the amino acid sequence shown in SEQ ID NO.92 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO.92.

[0479] (18) The peptide chain comprising an electrostatically redirected D-type negatively charged chain (Fc4(D-)) and an hFSHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 87, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably having 98% or 99% or more identity, more preferably, the amino acid sequence of the peptide chain comprising an electrostatically redirected D-type negatively charged chain (Fc4(D-)) and an hFSHα subunit is as shown in SEQ ID NO. 87; and the peptide chain comprising an electrostatically redirected D-type positively charged chain (Fc4(D+)) and an hFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 87. The amino acid sequence shown in NO. 93 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain comprising the electrostatically directed D-type positively charged chain (Fc4(D+)) and the hFSHβ subunit is as shown in SEQ ID NO. 93.

[0480] In some preferred embodiments, the peptide chain comprising the electrostatically directed D-type negatively charged chain (Fc4(D-)) and the hFSHα subunit has the amino acid sequence shown in SEQ ID NO. 87 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 87.

[0481] In some preferred embodiments, the peptide chain comprising the electrostatically directed D-type positively charged chain (Fc4(D+)) and the hFSHβ subunit has the amino acid sequence shown in SEQ ID NO.93 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO.93.

[0482] (19) The peptide chain comprising a clasp-type Fc chain (Fc1k) and a GtHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 106, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably having 98% or 99% or more identity, more preferably, the amino acid sequence of the peptide chain comprising a clasp-type Fc chain (Fc1k) and a GtHα subunit is as shown in SEQ ID NO. 106; and the peptide chain comprising a lock-type Fc chain (Fc1h) and a GtH Iβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 106. The amino acid sequence shown in NO.112 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain containing the locked Fc chain (Fc1h) and the GtH Iβ subunit is as shown in SEQ ID NO.112.

[0483] In some preferred embodiments, the peptide chain comprising the coin-type Fc chain (Fc1k) and the GtHα subunit has the amino acid sequence shown in SEQ ID NO. 106 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 106.

[0484] In some preferred embodiments, the peptide chain comprising the locked Fc chain (Fc1h) and the GtH Iβ subunit has the amino acid sequence shown in SEQ ID NO. 112 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 112.

[0485] (20) The peptide chain comprising the locked Fc chain (Fc1h) and the GtHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 107, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably having 98% or 99% or more identity, more preferably, the amino acid sequence of the peptide chain comprising the locked Fc chain (Fc1h) and the GtHα subunit is as shown in SEQ ID NO. 107; and the peptide chain comprising the button Fc chain (Fc1k) and the GtH Iβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 107. The amino acid sequence shown in NO. 113 has an amino acid sequence with 80% or more identity, preferably with 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably with 98% or 99% or more identity, and more preferably, the amino acid sequence of the peptide chain containing the coin-type Fc chain (Fc1k) and the GtH Iβ subunit is as shown in SEQ ID NO. 113.

[0486] In some preferred embodiments, the peptide chain comprising the locked Fc chain (Fc1h) and the GtHα subunit has the amino acid sequence shown in SEQ ID NO. 107 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 107.

[0487] In some preferred embodiments, the peptide chain comprising the coin-type Fc chain (Fc1k) and the GtH Iβ subunit has the amino acid sequence shown in SEQ ID NO. 113 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 113.

[0488] (21) The peptide chain comprising an electrostatically redirected T-type positively charged chain (Fc1(T+)) and a GtHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 108, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, preferably having 98% or 99% or more identity, more preferably, the amino acid sequence comprising the electrostatically redirected T-type positively charged chain (Fc1(T+)) and a GtHα subunit is as shown in SEQ ID NO. 108; and the peptide chain comprising an electrostatically redirected T-type negatively charged chain (Fc1(T-)) and a GtH Iβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 108. The amino acid sequence shown in NO. 114 has an amino acid sequence with 80% or more identity, preferably with 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably with 98% or 99% or more identity, and more preferably, the amino acid sequence of the peptide chain comprising the electrostatically directed T-type negatively charged chain (Fc1(T-)) and the GtH Iβ subunit is as shown in SEQ ID NO. 114.

[0489] In some preferred embodiments, the peptide chain comprising the electrostatically directed T-type positively charged chain (Fc1(T+)) and the GtHα subunit has the amino acid sequence shown in SEQ ID NO. 108 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 108.

[0490] In some preferred embodiments, the peptide chain comprising the electrostatically directed T-type negatively charged chain (Fc1(T-)) and the GtH Iβ subunit has the amino acid sequence shown in SEQ ID NO. 114 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 114.

[0491] (22) The peptide chain comprising an electrostatically redirected T-type negatively charged chain (Fc1(T-)) and a GtHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 109, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, preferably having 98% or 99% or more identity, more preferably, the amino acid sequence of the peptide chain comprising an electrostatically redirected T-type negatively charged chain (Fc1(T-)) and a GtHα subunit is as shown in SEQ ID NO. 109; and the peptide chain comprising an electrostatically redirected T-type positively charged chain (Fc1(T+)) and a GtH Iβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 109. The amino acid sequence shown in NO. 115 has an amino acid sequence with 80% or more identity, preferably with 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably with 98% or 99% or more identity, and more preferably, the amino acid sequence of the peptide chain comprising the electrostatically directed T-type positively charged chain (Fc1(T+)) and the GtH Iβ subunit is as shown in SEQ ID NO. 115.

[0492] In some preferred embodiments, the peptide chain comprising the electrostatically directed T-type negatively charged chain (Fc1(T-)) and the GtHα subunit has the amino acid sequence shown in SEQ ID NO. 109 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 109.

[0493] In some preferred embodiments, the peptide chain comprising the electrostatically directed T-type positively charged chain (Fc1(T+)) and the GtH Iβ subunit has the amino acid sequence shown in SEQ ID NO. 115 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 115.

[0494] (23) The peptide chain comprising an electrostatically redirected D-type positively charged chain (Fc1(D+)) and a GtHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 110, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, preferably having 98% or 99% or more identity, more preferably, the amino acid sequence comprising the electrostatically redirected D-type positively charged chain (Fc1(D+)) and a GtHα subunit is as shown in SEQ ID NO. 110; and the peptide chain comprising an electrostatically redirected D-type negatively charged chain (Fc1(D-)) and a GtH Iβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 110. The amino acid sequence shown in NO. 116 has an amino acid sequence with 80% or more identity, preferably with 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably with 98% or 99% or more identity, and more preferably, the amino acid sequence of the peptide chain comprising the electrostatically directed D-type negatively charged chain (Fc1(D-)) and the GtH Iβ subunit is as shown in SEQ ID NO. 116.

[0495] In some preferred embodiments, the peptide chain comprising the electrostatically directed D-type positively charged chain (Fc1(D+)) and the GtHα subunit has the amino acid sequence shown in SEQ ID NO. 110 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 110.

[0496] In some preferred embodiments, the peptide chain comprising the electrostatically directed D-type negatively charged chain (Fc1(D-)) and the GtH Iβ subunit has the amino acid sequence shown in SEQ ID NO. 116 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 116.

[0497] (24) The peptide chain comprising an electrostatically redirected D-type negatively charged chain (Fc1(D-)) and a GtHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 111, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, preferably having 98% or 99% or more identity, more preferably, the amino acid sequence of the peptide chain comprising an electrostatically redirected D-type negatively charged chain (Fc1(D-)) and a GtHα subunit is as shown in SEQ ID NO. 111; and the peptide chain comprising an electrostatically redirected D-type positively charged chain (Fc1(D+)) and a GtH Iβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 111. The amino acid sequence shown in NO.117 has 80% or more identity, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably 98% or 99% or more identity, and more preferably, the amino acid sequence of the peptide chain comprising the electrostatically directed D-type positively charged chain (Fc1(D+)) and the GtH Iβ subunit is as shown in SEQ ID NO.117.

[0498] In some preferred embodiments, the peptide chain comprising the electrostatically directed D-type negatively charged chain (Fc1(D-)) and the GtHα subunit has the amino acid sequence shown in SEQ ID NO. 111 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 111.

[0499] In some preferred embodiments, the peptide chain comprising the electrostatically directed D-type positively charged chain (Fc1(D+)) and the GtH Iβ subunit has the amino acid sequence shown in SEQ ID NO. 117 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 117.

[0500] (25) The peptide chain comprising a clasp-type Fc chain (Fc1k) and a GtHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 106, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably having 98% or 99% or more identity, and more preferably, the amino acid sequence of the peptide chain comprising a clasp-type Fc chain (Fc1k) and a GtHα subunit is as shown in SEQ ID NO. 106; and the peptide chain comprising a lock-type Fc chain (Fc1h) and a GtH IIβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 106. The amino acid sequence shown in NO. 124 has an amino acid sequence with 80% or more identity, preferably with 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably with 98% or 99% or more identity, and more preferably, the amino acid sequence of the peptide chain containing the locked Fc chain (Fc1h) and the GtH IIβ subunit is as shown in SEQ ID NO. 124.

[0501] In some preferred embodiments, the peptide chain comprising the coin-type Fc chain (Fc1k) and the GtHα subunit has the amino acid sequence shown in SEQ ID NO. 106 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 106.

[0502] In some preferred embodiments, the peptide chain comprising the locked Fc chain (Fc1h) and the GtH IIβ subunit has the amino acid sequence shown in SEQ ID NO. 124 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 124.

[0503] (26) The peptide chain comprising the locked Fc chain (Fc1h) and the GtHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 107, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably having 98% or 99% or more identity, more preferably, the amino acid sequence of the peptide chain comprising the locked Fc chain (Fc1h) and the GtHα subunit is as shown in SEQ ID NO. 107; and the peptide chain comprising the button Fc chain (Fc1k) and the GtH IIβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 107. The amino acid sequence shown in NO. 125 has an amino acid sequence with 80% or more identity, preferably with 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably with 98% or 99% or more identity, and more preferably, the amino acid sequence of the peptide chain containing the coin-type Fc chain (Fc1k) and the GtH IIβ subunit is as shown in SEQ ID NO. 125.

[0504] In some preferred embodiments, the peptide chain comprising the locked Fc chain (Fc1h) and the GtHα subunit has the amino acid sequence shown in SEQ ID NO. 107 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 107.

[0505] In some preferred embodiments, the peptide chain comprising the coin-type Fc chain (Fc1k) and the GtH IIβ subunit has the amino acid sequence shown in SEQ ID NO. 125 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 125.

[0506] (27) The peptide chain comprising an electrostatically redirected T-type positively charged chain (Fc1(T+)) and a GtHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 108, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, preferably having 98% or 99% or more identity, more preferably, the amino acid sequence comprising the electrostatically redirected T-type positively charged chain (Fc1(T+)) and a GtHα subunit is as shown in SEQ ID NO. 108; and the peptide chain comprising an electrostatically redirected T-type negatively charged chain (Fc1(T-)) and a GtH IIβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 108. The amino acid sequence shown in NO.126 has 80% or more identity, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably 98% or 99% or more identity, and more preferably, the amino acid sequence of the peptide chain comprising the electrostatically directed T-type negatively charged chain (Fc1(T-)) and the GtH IIβ subunit is as shown in SEQ ID NO.126.

[0507] In some preferred embodiments, the peptide chain comprising the electrostatically directed T-type positively charged chain (Fc1(T+)) and the GtHα subunit has the amino acid sequence shown in SEQ ID NO. 108 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 108.

[0508] In some preferred embodiments, the peptide chain comprising the electrostatically directed T-type negatively charged chain (Fc1(T-)) and the GtH IIβ subunit has the amino acid sequence shown in SEQ ID NO. 126 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 126.

[0509] (28) The peptide chain comprising an electrostatically redirected T-type negatively charged chain (Fc1(T-)) and a GtHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 109, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, preferably having 98% or 99% or more identity, more preferably, the amino acid sequence comprising the electrostatically redirected T-type negatively charged chain (Fc1(T-)) and a GtHα subunit is as shown in SEQ ID NO. 109; and the peptide chain comprising an electrostatically redirected T-type positively charged chain (Fc1(T+)) and a GtH IIβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 109. The amino acid sequence shown in NO.127 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain comprising the electrostatically directed T-type positively charged chain (Fc1(T+)) and the GtH IIβ subunit is as shown in SEQ ID NO.127.

[0510] In some preferred embodiments, the peptide chain comprising the electrostatically directed T-type negatively charged chain (Fc1(T-)) and the GtHα subunit has the amino acid sequence shown in SEQ ID NO. 109 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 109.

[0511] In some preferred embodiments, the peptide chain comprising the electrostatically directed T-type positively charged chain (Fc1(T+)) and the GtH IIβ subunit has the amino acid sequence shown in SEQ ID NO. 127 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 127.

[0512] (29) The peptide chain comprising an electrostatically redirected D-type positively charged chain (Fc1(D+)) and a GtHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 110, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, preferably having 98% or 99% or more identity, more preferably, the amino acid sequence comprising the electrostatically redirected D-type positively charged chain (Fc1(D+)) and a GtHα subunit is as shown in SEQ ID NO. 110; and the peptide chain comprising an electrostatically redirected D-type negatively charged chain (Fc1(D-)) and a GtH IIβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 110. The amino acid sequence shown in NO.128 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain comprising the electrostatically directed D-type negatively charged chain (Fc1(D-)) and the GtH IIβ subunit is as shown in SEQ ID NO.128.

[0513] In some preferred embodiments, the peptide chain comprising the electrostatically directed D-type positively charged chain (Fc1(D+)) and the GtHα subunit has the amino acid sequence shown in SEQ ID NO. 110 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 110.

[0514] In some preferred embodiments, the peptide chain comprising the electrostatically directed D-type negatively charged chain (Fc1(D-)) and the GtH IIβ subunit has the amino acid sequence shown in SEQ ID NO. 128 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 128.

[0515] (30) The peptide chain comprising an electrostatically redirected D-type negatively charged chain (Fc1(D-)) and a GtHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 111, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, preferably having 98% or 99% or more identity, more preferably, the amino acid sequence of the peptide chain comprising an electrostatically redirected D-type negatively charged chain (Fc1(D-)) and a GtHα subunit is as shown in SEQ ID NO. 111; and the peptide chain comprising an electrostatically redirected D-type positively charged chain (Fc1(D+)) and a GtH IIβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 111. The amino acid sequence shown in NO.129 has 80% or more identity, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, more preferably 98% or 99% or more identity, and more preferably, the amino acid sequence of the peptide chain comprising the electrostatically directed D-type positively charged chain (Fc1(D+)) and the GtH IIβ subunit is as shown in SEQ ID NO.129.

[0516] In some preferred embodiments, the peptide chain comprising the electrostatically directed D-type negatively charged chain (Fc1(D-)) and the GtHα subunit has the amino acid sequence shown in SEQ ID NO. 111 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 111.

[0517] In some preferred embodiments, the peptide chain comprising the electrostatically directed D-type positively charged chain (Fc1(D+)) and the GtH IIβ subunit has the amino acid sequence shown in SEQ ID NO. 129 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 129.

[0518] (31) The peptide chain comprising a clasp-type Fc chain (Fc1k(KiH)) and a pFSHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 132, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, preferably having 98% or 99% or more identity, more preferably, the amino acid sequence comprising the clasp-type Fc chain (Fc1k(KiH)) and the pFSHα subunit is as shown in SEQ ID NO. 132; and the peptide chain comprising a lock-type Fc chain (Fc1h(KiH)) and a pFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 132. The amino acid sequence shown in NO. 133 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain containing the locked Fc chain (Fc1h(KiH)) and the pFSHβ subunit is as shown in SEQ ID NO. 133.

[0519] In some preferred embodiments, the peptide chain comprising the coin-type Fc chain (Fc1k(KiH)) and the pFSHα subunit has the amino acid sequence shown in SEQ ID NO. 132 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 132.

[0520] In some preferred embodiments, the peptide chain comprising the locked Fc chain (Fc1h(KiH)) and the pFSHβ subunit has the amino acid sequence shown in SEQ ID NO. 133 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 133.

[0521] (32) The peptide chain comprising the locked Fc chain (Fc1h(KiH)) and the hFSHα subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 134, preferably having 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more identity, preferably having 98% or 99% or more identity, more preferably, the amino acid sequence comprising the locked Fc chain (Fc1h(KiH)) and the hFSHα subunit is as shown in SEQ ID NO. 134; and the peptide chain comprising the button Fc chain (Fc1k(KiH)) and the hFSHβ subunit comprises an amino acid sequence having 80% or more identity with the amino acid sequence shown in SEQ ID NO. 134. The amino acid sequence shown in NO. 135 has 80% or more of the same amino acid sequence, preferably 85%, 90%, 95%, 96%, 97%, 98%, or 99% or more of the same amino acid sequence, more preferably 98% or 99% or more of the same amino acid sequence, and more preferably, the amino acid sequence of the peptide chain containing the coin-type Fc chain (Fc1k(KiH)) and the hFSHβ subunit is as shown in SEQ ID NO. 135.

[0522] In some preferred embodiments, the peptide chain comprising the locked Fc chain (Fc1h(KiH)) and the hFSHα subunit has the amino acid sequence shown in SEQ ID NO. 134 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 134.

[0523] In some preferred embodiments, the peptide chain comprising the coin-type Fc chain (Fc1k(KiH)) and the hFSHβ subunit has the amino acid sequence shown in SEQ ID NO. 135 or has an amino acid sequence obtained by deleting, adding or substituting 1, 2 or 3 residues in SEQ ID NO. 135.

[0524] On the other hand, this disclosure provides nucleic acids encoding the aforementioned recombinant Fc fusion protein.

[0525] On the other hand, this disclosure provides a method for preparing the aforementioned recombinant Fc fusion protein, the steps of which include:

[0526] (1) Constructing an expression vector for recombinant Fc fusion protein:

[0527] In some preferred embodiments, the expression vector is a prokaryotic expression vector or an expression vector.

[0528] In some preferred embodiments, the prokaryotic expression vector is selected from pcDNA II, pSL301, pSE280, pSE380, pSE420, pTrcHisA, B and C, pRSET A, B and C, pGEMEX-1 and pGEMEX-2, pET vector, pTrc99A, pKK223-3, pGEX vector, pEZZ18, pRIT2T and pMC1871, pKK233-2 and pKK388-1, and pProEx-HT and its variants and derivatives.

[0529] In some preferred embodiments, the eukaryotic expression vector is selected from pFastBac, pFastBacHT, pFastBacDUAL, pSFV, pTet-Splice, pEUK-C1, pPUR, pMAM, pMAMneo, pBI101, pBI121, pDR2, pCMVEBNA, pYACneo, pSVK3, pSVL, pMSG, pCH110, pKK232-8, p3′SS, pXT1, pSG5, pPbac, pMbac, pMC1neo, pOG44, pYES2, pAC360, pBlueBacHis A, B and C, pVL1392, pBsueBacIII, pCDM8, pcDNA1, pZeoSV, pcDNA3, pREP4, pCEP4, and pEBVHi, and their variants or derivatives; preferably, said pcDNA3 is pcDNA3.1.

[0530] (2) The expression vector constructed in step (1) is introduced into the host cell.

[0531] In some preferred embodiments, the expression vector is introduced into host cells using a method selected from the following: electroporation transfection, calcium phosphate transfection, liposome transfection, protoplasmic fusion transfection, microinjection, electroporation, gene gun method, cationic polymer and viral vector infection method.

[0532] (3) The host cells are cultured under conditions suitable for the expression of the recombinant Fc fusion protein.

[0533] The host cell is a prokaryotic host cell or a eukaryotic host cell.

[0534] In some preferred embodiments, the prokaryotic host cell is any one of bacterial cells, Bacillus subtilis, and mycobacteria; preferably, the bacterial cell is Escherichia coli.

[0535] In some preferred embodiments, the eukaryotic host cell is selected from any one of animal cells, plant cells, or fungi.

[0536] In some preferred embodiments, the eukaryotic host cell is selected from any one of yeast, insect, bird, plant, Caenorhabditis elegans, and mammalian host cells.

[0537] In some preferred embodiments, the insect cells are selected from any one of the following: grassland noctuid moth cells (e.g., Sf9, Sf21), white noctuid moth cells (e.g., High Five cells), and fruit fly S2 cells.

[0538] In some preferred embodiments, the fungus is selected from any one of Saccharomyces cerevisiae, Kluyveromyces lactis, Candida species (e.g., Candida albicans or Candida glabrata), Aspergillus nidulans, Schizosaccharomyces cerevisiae, Pichia pastoris, and Jeromea lipophila.

[0539] In some preferred embodiments, the mammalian cells are selected from any one of COS cells, mouse L cells, LNCaP cells, Chinese hamster ovary (CHO) cells, human embryonic kidney (HEK) cells (e.g., HEK293 cells), 633 cells, Vero, BHK cells, African green monkey cells, CV1 cells, HeLa cells, MDCK cells, Hep-2, NSO, and Sp2 / O cells.

[0540] In some preferred embodiments, the method further includes step (4) of isolating the expressed recombinant Fc fusion protein.

[0541] In some preferred embodiments, the isolated and expressed recombinant Fc fusion protein includes the following steps:

[0542] (i) Centrifuge the fermentation broth of the host cells, collect the supernatant, and obtain a clear fermentation broth;

[0543] (ii) The clarified fermentation broth was subjected to Protein A column chromatography and eluted to obtain the eluent;

[0544] (iii) Purify the eluent using a cation exchange column.

[0545] In some preferred embodiments, the cation exchange column is selected from cation exchange columns packed with SP Sepharose C25, SPFF, SP Sepharose C50, SE52, SE92, Souece 15S, CaptoMMC, Souece 30S, SynChropak S300 or Ultrasil CX, preferably CaptoMMC.

[0546] On the other hand, this disclosure also provides a pharmaceutical composition comprising the recombinant Fc fusion protein of any one of claims 1-6 or the nucleic acid of claim 7, and optionally a pharmaceutically acceptable carrier.

[0547] On the other hand, this disclosure provides the use of the aforementioned recombinant Fc fusion protein, the aforementioned nucleic acid, and the aforementioned pharmaceutical composition in the preparation of a medicine for human assisted reproduction, treatment of polycystic ovary syndrome and anovulatory diseases, superovulation in animals, estrus synchronization in animals, conception and farrowing, treatment of animal infertility, promotion of animal reproduction, embryo transfer, induction of sperm and ovulation, stimulation of gonadal tissue to secrete estradiol and testosterone, and treatment of animal infertility, treatment of ovarian diseases in female animals, promotion of livestock reproduction, improvement of semen quality in male animals, induction of estrus in female animals, in vitro maturation of oocytes, and in vitro fertilization; wherein the animals include pigs, fish, cattle, sheep, horses, or dogs.

[0548] In some preferred embodiments, the aforementioned animal is a pig or a fish.

[0549] For the purpose of clarity and concise description, the features are described herein as part of some identical or separate embodiments; however, it will be understood that the scope of this disclosure may include some embodiments having a combination of all or some of the features described.

[0550] Example

[0551] Example 1: Construction of a heterodimer expression vector

[0552] 1.1 Obtaining Gn fragments

[0553] 1.1.1 pFSHα subunit mature peptide

[0554] Based on the amino acid sequence of the porcine FSH (pFSH) α subunit with accession number P01219 in the UniProt database, the following amino acid sequence of the mature peptide of the pFSH α subunit was obtained (SEQ ID NO.1).

[0555] FPDGEFTMQGCPECKLKENKYFSKLGAPIYQCMGCCFSRAYPTPARSKKTMLVPKNITSEATCCV

[0556] AKAFTKATVMGNARVENHTECHCSTCYYHKS

[0557] 1.1.2 pFSHβ subunit mature peptide

[0558] Based on the amino acid sequence of the porcine FSH (pFSH) β subunit with accession number P01228 in the UniProt database, the following amino acid sequence of the mature peptide of the pFSH β subunit was obtained (SEQ ID NO.2).

[0559] CELTNITITVEKEECNFCISINTTWCAGYCYTRDLVYKDPARPNIQKTCTFKELVYETVKVPGCAH

[0560] HADSLYTYPVATECHCGKCDSDSTDCTVRGLGPSYCSFSEMKE

[0561] 1.1.3hFSHα subunit mature peptide

[0562] Based on the amino acid sequence of the human FSH (hFSH) α subunit with accession number P01215 in the UniProt database, the following mature peptide amino acid sequence of the hFSH α subunit was obtained (SEQ ID NO.3).

[0563] APDVQDCPECTLQENPFFSQPGAPILQCMGCCFSRAYPTPLRSKKTMLVQKNVTSESTCCVAKSY

[0564] NRVTVMGGFKVENHTACHCSTCYYHKS

[0565] 1.1.4hFSHβ subunit mature peptide

[0566] Based on the amino acid sequence of the human FSH (hFSH) β subunit with accession number P01225 in the UniProt database, the following amino acid sequence of the mature peptide of the hFSH β subunit was obtained (SEQ ID NO.4).

[0567] NSCELTNITIAIEKEECRFCISINTTWCAGYCYTRDLVYKDPARPKIQKTCTFKELVYETVRVPGCA

[0568] HHADSLYTYPVATQCHCGKCDSDSTDCTVRGLGPSYCSFGEMKE

[0569] 1.1.5 Matured GtHα subunit peptide from carp

[0570] Based on the amino acid sequence of the carp GtHα subunit with accession number P18857 in the UniProt database, the following mature peptide amino acid sequence of the carp GtHα subunit (SEQ ID NO.5) was obtained.

[0571] YPRNDMNNFGCRECRLRRNNITSRPGAPVYQCMGCCFSRAYPTPLRSKKTMLVPKNITSEATCCV

[0572] AKEVKRVLVNDVKLVNHTDCHCSTCYHKS

[0573] 1.1.6 Matured peptide of carp GtH Iβ subunit

[0574] Based on the amino acid sequence of the carp GtH Iβ subunit with accession number O13050 in the UniProt database, the following mature peptide amino acid sequence of the carp GtH Iβ subunit (SEQ ID NO. 6) was obtained.

[0575] GSECRSSCRLTNISITVESEECGSCITIDTTACAGLCKTQESVYRSPLMLSYQNTCNFREWTYETYEF

[0576] KGCPARADSVFTYPVALSCECSKCNSDITDCGALSQQTLSCNAH

[0577] 1.1.7 Matured peptide of carp GtH IIβ subunit

[0578] Based on the amino acid sequence of the carp GtH IIβ subunit with accession number P01235 in the UniProt database, the following mature peptide amino acid sequence of the carp GtH IIβ subunit (SEQ ID NO.7) was obtained.

[0579] SYLPPCEPVNETVAVEKEGCPKCLVLQTTICSGHCLTKEPVYKSPFSTVYQHVCTYRDVRYETVRL

[0580] PDCPPGVDPHITYPVALSCDCSLCTMDTSDCTIESLQPDFCMSQREDFL

[0581] 1.2 Modification of Fc area

[0582] 1.2.1 Fastener Fck

[0583] Based on the amino acid sequence of human IgG1 (hIgG1) with accession number P01857 in the UniProt database, the following amino acid sequence of the Fc region of wild-type IgG1 was obtained (SEQ ID NO.8).

[0584] EPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDG

[0585] VEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE

[0586] PQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT

[0587] VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0588] The wild-type IgG1 Fc region (SEQ ID NO.8) was modified to obtain the coin-type Fc1k (SEQ ID NO.9).

[0589] EPKS S DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDG

[0590] VEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE

[0591] PQVYTLPP C R E E M TKNQVSL W CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL

[0592] TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0593] Among them, the coin-type Fc1k has S354C and T366W mutations according to EU codes compared to the wild-type IgG1 Fc region. Additionally, it has modified some amino acids with significant side chain steric hindrance, exhibiting C220S, D356E, and L358M mutations according to EU codes.

[0594] Some amino acids with large steric hindrance in the side chains of wild-type IgG1 Fc chain were modified to change the distance between the two chains, making it easier for the connected GtHα and Gnβ subunits to bind together.

[0595] Based on the amino acid sequence of human IgG4 (hIgG4) with accession number P01861 in the UniProt database, the following amino acid sequence of the Fc region of wild-type IgG4 was obtained (SEQ ID NO.10).

[0596] ESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEV

[0597] HNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVY

[0598] TLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKS

[0599] RWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK

[0600] The wild-type IgG4 Fc region (SEQ ID NO.10) was modified to obtain the coin-type Fc4k (SEQ ID NO.11).

[0601] ESKY S PPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEV

[0602] HNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVY

[0603] TLPP C QEEMTKNQVSL W CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDK

[0604] SRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK

[0605] Among them, the coin-type Fc4k has S354C and T366W mutations according to EU code, compared with the wild-type IgG4 Fc region. Simultaneously, some side-chain amino acids have been modified, possessing G230S according to Kabat code, increasing the interaction force of amino acid side-chain groups and making it easier for the linked Gnα and Gnβ subunits to bind together.

[0606] 1.2.2 Locking Fch

[0607] The wild-type IgG1 Fc region (SEQ ID NO.8) was modified to obtain the locked Fc1h (SEQ ID NO.12).

[0608] EPKS S DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDG

[0609] VEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE

[0610] PQV C TLPPSR E E M TKNQVSL S C A VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL V SKLT

[0611] VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0612] Among them, the locked Fc1h has mutations Y349C, T366S, L368A, and Y407V according to EU codes compared to the wild-type IgG1Fc region. Additionally, it has modified some amino acids with significant side chain steric hindrance, exhibiting mutations C220S, D356E, and L358M according to EU codes.

[0613] Some amino acids with large steric hindrance in the side chains of wild-type IgG1 Fc chain were modified to change the distance between the two chains, making it easier for the connected Gnα and Gnβ subunits to bind together.

[0614] The wild-type IgG4 Fc region (SEQ ID NO.10) was modified to obtain lock-type Fc4h (SEQ ID NO.13).

[0615] ESKY SPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEV

[0616] HNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQV C

[0617] TLPPSQEEMTKNQVSL S C A VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL V SRLTVDKS

[0618] RWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK

[0619] Among them, the locked-type Fc4h has mutations Y349C, T366S, L368A, and Y407V according to EU codes compared to the wild-type IgG4 Fc region. Furthermore, some side-chain amino acids have been modified, possessing G230S according to Kabat codes, increasing the interaction forces of the amino acid side-chain groups and making it easier for the linked Gnα and Gnβ subunits to bind together.

[0620] 1.2.3 Electrostatic redirection T-shaped positive charge chain (Fc(T+))

[0621] The wild-type IgG1 Fc region (SEQ ID NO.8) was modified to obtain an electrostatically directed T-type positive charge chain (Fc1(T+)) (SEQ ID NO.14).

[0622] EPKS SR KTHTCP R CPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDG

[0623] VEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE

[0624] PQVYTLPPSR E E M TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS R LT

[0625] VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0626] Among them, the electrostatically redirected T-type positively charged chain (Fc1(T+)) has mutations D221R, P228R, and K409R according to EU codes compared to the wild-type IgG1 Fc region. Additionally, it has modified some amino acids with significant side chain steric hindrance, exhibiting mutations C220S, D356E, and L358M according to EU codes.

[0627] Some amino acids with large steric hindrance in the side chains of wild-type IgG1 Fc chain were modified to change the distance between the two chains, making it easier for the connected Gnα and Gnβ subunits to bind together.

[0628] The Fc region of wild-type IgG4 (SEQ ID NO.10) was modified to obtain an electrostatically directed T-type positive charge chain (Fc4(T+)) (SEQ ID NO.15).

[0629] ESKY S PPCP R CPAPEFLGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEV

[0630] HNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVY

[0631] TLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS R LTVDKS

[0632] RWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK

[0633] Among them, the electrostatically redirected T-type positively charged chain (Fc4(T+)) has S228R and K409R mutations according to EU designation compared to the wild-type IgG4 Fc region. Additionally, it has modified some amino acids with significant side chain steric hindrance, exhibiting G230S according to Kabat designation.

[0634] Some amino acids with large steric hindrance in the side chains of wild-type IgG4 Fc chain were modified to change the distance between the two chains, making it easier for the connected Gnα and Gnβ subunits to bind together.

[0635] 1.2.4 Electrostatic redirection T-shaped negative charge chain (Fc(T-))

[0636] The Fc region of wild-type IgG1 (SEQ ID NO.8) was modified to obtain an electrostatically directed T-type negative charge chain (Fc1(T-)) (SEQ ID NO.16).

[0637] EPKS SE KTHTCP E CPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDG

[0638] VEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE

[0639] PQVYTLPPSR E E M TKNQVSLTC E VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT

[0640] VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0641] Among them, the electrostatically redirected T-type negatively charged chain (Fc1(T-)) has mutations D221E, P228E, and L368E according to EU codes compared to the wild-type IgG1 Fc region. Additionally, it has modified some amino acids with significant side chain steric hindrance, exhibiting mutations C220S, D356E, and L358M according to EU codes.

[0642] Some amino acids with large steric hindrance in the side chains of wild-type IgG1 Fc chain were modified to change the distance between the two chains, making it easier for the connected Gnα and Gnβ subunits to bind together.

[0643] The Fc region of wild-type IgG4 (SEQ ID NO.10) was modified to obtain an electrostatically directed T-type positive charge chain (Fc4(T-)) (SEQ ID NO.17).

[0644] ESKY S PPCP E CPAPEFLGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEV

[0645] HNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVY

[0646] TLPPSQEEMTKNQVSLTC E VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS

[0647] RWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK

[0648] Among them, the electrostatically redirected T-type negatively charged chain (Fc4(T-)) has S228E and L368E mutations according to EU designation compared to the wild-type IgG4 Fc region. Additionally, it has modified some amino acids with significant side chain steric hindrance, exhibiting G230S according to Kabat designation.

[0649] Some amino acids with large steric hindrance in the side chains of wild-type IgG4 Fc chain were modified to change the distance between the two chains, making it easier for the connected Gnα and Gnβ subunits to bind together.

[0650] 1.2.5 Electrostatic redirection of the D-type positive charge chain (Fc(D+))

[0651] The Fc region of wild-type IgG1 (SEQ ID NO.8) was modified to obtain an electrostatically directed D-type positive charge chain (Fc1(D+)) (SEQ ID NO.18).

[0652] EPKS S DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDG

[0653] VEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE

[0654] PQVYT K PPSR E E M TKNQVSL K CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL

[0655] TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0656] Among them, the electrostatically redirected D-type positively charged chain (Fc1(D+)) has L351K and T366K mutations according to EU codes compared to the wild-type IgG1 Fc region. Additionally, it has modified some amino acids with significant side chain steric hindrance, exhibiting C220S, D356E, and L358M mutations according to EU codes.

[0657] Some amino acids with large steric hindrance in the side chains of wild-type IgG1 Fc chain were modified to change the distance between the two chains, making it easier for the connected Gnα and Gnβ subunits to bind together.

[0658] The Fc region of wild-type IgG4 (SEQ ID NO.10) was modified to obtain an electrostatically directed D-type positive charge chain (Fc4(D+)) (SEQ ID NO.19).

[0659] ESKY S PPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEV

[0660] HNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVY

[0661] T K PPSQEEMTKNQVSL K CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDK

[0662] SRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK

[0663] Among them, the electrostatically redirected T-type positively charged chain (Fc4(D+)) has L351K and T366K mutations according to EU code compared to the wild-type IgG4 Fc region. Additionally, it has modified some amino acids with significant side chain steric hindrance, exhibiting G230S according to Kabat code.

[0664] Some amino acids with large steric hindrance in the side chains of wild-type IgG4 Fc chain were modified to change the distance between the two chains, making it easier for the connected Gnα and Gnβ subunits to bind together.

[0665] 1.2.6 Electrostatic redirection of the D-type negative charge chain (Fc(D-))

[0666] The Fc region of wild-type IgG1 (SEQ ID NO.8) was modified to obtain an electrostatically directed D-type negatively charged chain (Fc1(D-)) (SEQ ID NO.20).

[0667] EPKS S DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDG

[0668] VEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE

[0669] PQVYT D PPSR E E M TKNQVSLTC E VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL

[0670] TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0671] Among them, the electrostatically redirected D-type negatively charged chain (Fc1(D-)) has L351D and L368E mutations according to EU codes compared with the wild-type IgG1 Fc region. At the same time, some amino acids with large side chain steric hindrance have also been modified, with C220S, D356E, and L358M according to EU codes.

[0672] Some amino acids with large steric hindrance in the side chains of wild-type IgG1 Fc chain were modified to change the distance between the two chains, making it easier for the connected Gnα and Gnβ subunits to bind together.

[0673] The Fc region of wild-type IgG4 (SEQ ID NO.10) was modified to obtain an electrostatically directed D-type negatively charged chain (Fc4(D-)) (SEQ ID NO.21).

[0674] ESKY S PPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEV

[0675] HNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVY

[0676] TD PPSQEEMTKNQVSLTC E VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKS

[0677] RWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK

[0678] Among them, the electrostatically redirected D-type negatively charged chain (Fc4(D-)) has L351D and L368E mutations according to EU designation compared to the wild-type IgG4 Fc region. Additionally, it has modified some amino acids with significant steric hindrance in the side chains, exhibiting G230S according to Kabat designation.

[0679] Some amino acids with large steric hindrance in the side chains of wild-type IgG4Fc were modified to change the distance between the two chains, making it easier for the connected Gnα and Gnβ subunits to bind together.

[0680] 1.2.7 Fastener Fc1k(KiH)

[0681] The wild-type IgG1 Fc region (SEQ ID NO.8) was modified to obtain the coin-type Fc1k(KiH) (SEQ ID NO.130).

[0682] EPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDG

[0683] VEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE

[0684] PQVYTLPP C RDELTKNQVSL W CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL

[0685] TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0686] Among them, the coin-type Fc1k(KiH) has S354C and T366W mutations according to EU numbering compared with the wild-type IgG1 Fc region.

[0687] 1.2.8 Locking Fc1h(KiH)

[0688] The wild-type IgG1 Fc region (SEQ ID NO.8) was modified to obtain the locked Fc1h (KiH) (SEQ ID NO.131).

[0689] EPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDG

[0690] VEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE

[0691] PQV C TLPPSRDELTKNQVSL S C A VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL V SKLT

[0692] VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0693] Among them, locked-type Fc1h (KiH) has the Y349C, T366S, L368A and Y407 mutations according to EU numbers compared with the wild-type IgG1 Fc region.

[0694] 1.3 Preparation of peptide chains

[0695] 1.3.1 Peptide chain pFSHα-L-Fc1k

[0696] The pFSHα subunit, linker (L), and coin-type Fc chain (Fc1k) were sequentially linked to synthesize the peptide chain pFSHα-L-Fc1k (SEQ ID NO.22).

[0697] FPDGEFTMQGCPECKLKENKYFSKLGAPIYQCMGCCFSRAYPTPARSKKTMLVPKNITSEATCCV

[0698] AKAFTKATVMGNARVENHTECHCSTCYYHKSGGGGSGGGGSGGGGSGGGGSEPKS S DKTHTCP

[0699] PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPR

[0700] EEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP C R E E

[0701] M TKNQVSL W CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN

[0702] VFSCSVMHEALHNHYTQKSLSLSPGK

[0703] Peptide chain pFSHβ-L-Fc1h of 1.3.2

[0704] The pFSHβ subunit, linker (L), and locked Fc chain (Fc1h) were sequentially linked to artificially synthesize the peptide chain pFSHβ-L-Fc1h (SEQ ID NO.23). CELTNITITVEKEECNFC1ISINTTWCAGYCYTRDLVYKDPARPNIQKTCTFKELVYETVKVPGCAH

[0705] HADSLYTYPVATECHCGKCDSDSTDCTVRGLGPSYCSFSEMKEGGGGSGGGGSGGGGSGGGGSE

[0706] PKS S DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGV

[0707] EVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREP

[0708] QV C TLPPSR E E M TKNQVSL S C A VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL V SKLT

[0709] VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0710] 1.3.3 Peptide chain pFSHα-L-Fc1h

[0711] The pFSHα subunit, linker (L), and locked Fc chain (Fc1h) were sequentially linked to synthesize the peptide chain pFSHα-L-Fc1h (SEQ ID NO.24).

[0712] FPDGEFTMQGCPECKLKENKYFSKLGAPIYQCMGCCFSRAYPTPARSKKTMLVPKNITSEATCCV

[0713] AKAFTKATVMGNARVENHTECHCSTCYYHKSGGGGSGGGGSGGGGSGGGGSEPKS S DKTHTCP

[0714] PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPR

[0715] EEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQV C TLPPSR E E

[0716] M TKNQVSL S C A VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL V SKLTVDKSRWQQGN

[0717] VFSCSVMHEALHNHYTQKSLSLSPGK

[0718] 1.3.4 Peptide chain pFSHβ-L-Fc1k

[0719] The pFSHβ subunit, linker (L), and coin-type Fc chain (Fc1k) were sequentially linked to synthesize the peptide chain pFSHβ-L-Fc1k (SEQ ID NO. 25).

[0720] HADSLYTYPVATECHCGKCDSDSTDCTVRGLGPSYCSFSEMKEGGGGGSGGGGSGGGGSGGGGSE

[0721] PKS S DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGV

[0722] EVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREP

[0723] QVYTLPP C R E E M TKNQVSL W CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT

[0724] VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0725] 1.3.5 Peptide chain pFSHα-L-(Fc1(T+))

[0726] The pFSHα subunit, the linker (L), and the electrostatically directed T-shaped modified Fc1 positive charge chain (Fc1(T+)) were sequentially connected to synthesize the peptide chain pFSHα-L-(Fc1(T+))(SEQ ID NO.26).

[0727] FPDGEFTMQGCPECKLKENKYFSKLGAPIYQCMGCCFSRAYPTPARSKKTMLVPKNITSEATCCV

[0728] AKAFTKATVMGNARVENHTECHCSTCYYHKSGGGGSGGGGSGGGGSGGGGSEPKS SR KTHTCP

[0729] R CPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPR

[0730] EEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR E E

[0731] MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS R LTVDKSRWQQGN

[0732] VFSCSVMHEALHNHYTQKSLSLSPGK

[0733] 1.3.6 Peptide chain pFSHβ-L-(Fc1(T-))

[0734] The pFSHβ subunit, the linker (L), and the electrostatically directed T-shaped modified Fc1 negative charge chain (Fc1(T-)) were sequentially connected to artificially synthesize the peptide chain pFSHβ-L-(Fc1(T-)) (SEQ ID NO.27).

[0735] CELTNITITVEKEECNFC1ISINTTWCAGYCYTRDLVYKDPARPNIQKTCTFKELVYETVKVPGCAH

[0736] HADSLYTYPVATECHCGKCDSDSTDCTVRGLGPSYCSFSEMKEGGGGGSGGGGSGGGGSGGGGSE

[0737] PKS SE KTHTCP E CPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGV

[0738] EVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREP

[0739] QVYTLPPSR E E M TKNQVSLTC E VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT

[0740] VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0741] 1.3.7 Peptide chain pFSHα-L-(Fc1(T-))

[0742] The pFSHα subunit, the linker (L), and the electrostatically directed T-shaped modified Fc1 negative charge chain (Fc1(T-)) were sequentially connected to synthesize the peptide chain pFSHα-L-(Fc1(T-)) (SEQ ID NO.28).

[0743] FPDGEFTMQGCPECKLKENKYFSKLGAPIYQCMGCCFSRAYPTPARSKKTMLVPKNITSEATCCV

[0744] AKAFTKATVMGNARVENHTECHCSTCYYHKSGGGGSGGGGSGGGGSGGGGSEPKS SE KTHTCP

[0745] E CPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPR

[0746] EEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR E E

[0747] M TKNQVSLTC E VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN

[0748] VFSCSVMHEALHNHYTQKSLSLSPGK

[0749] 1.3.8 Peptide chain pFSHβ-L-(Fc1(T+))

[0750] The pFSHβ subunit, the linker (L), and the electrostatically directed T-shaped modified Fc1 positive charge chain (Fc1(T+)) were sequentially connected to artificially synthesize the peptide chain pFSHβ-L-(Fc1(T+)) (SEQ ID NO.29).

[0751] CELTNITITVEKEECNFC1ISINTTWCAGYCYTRDLVYKDPARPNIQKTCTFKELVYETVKVPGCAH

[0752] HADSLYTYPVATECHCGKCDSDSTDCTVRGLGPSYCSFSEMKEGGGGGSGGGGSGGGGSGGGGSE

[0753] PKS SR KTHTCP R CPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGV

[0754] EVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREP

[0755] QVYTLPPSR E E M TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS R LT

[0756] VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0757] 1.3.9 Peptide chain pFSHα-L-(Fc1(D+))

[0758] The pFSHα subunit, the linker (L), and the electrostatically directed D-type modified Fc1 positive charge chain (Fc1(D+)) were sequentially connected to artificially synthesize the peptide chain pFSHα-L-(Fc1(D+)) (SEQ ID NO.30).

[0759] FPDGEFTMQGCPECKLKENKYFSKLGAPIYQCMGCCFSRAYPTPARSKKTMLVPKNITSEATCCV

[0760] AKAFTKATVMGNARVENHTECHCSTCYYHKSGGGGSGGGGSGGGGSGGGGSEPKS S DKTHTCP

[0761] PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPR

[0762] EEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT K PPSR E E

[0763] M TKNQVSL KCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN

[0764] VFSCSVMHEALHNHYTQKSLSLSPGK

[0765] 1.3.10 Peptide chain pFSHβ-L-(Fc1(D-))

[0766] The pFSHβ subunit, the linker (L), and the electrostatically directed D-type modified Fc1 negative charge chain (Fc1(D-)) were sequentially linked to artificially synthesize the peptide chain pFSHβ-L-(Fc1(D-)) (SEQ ID NO.31).

[0767] CELTNITITVEKEECNFC1ISINTTWCAGYCYTRDLVYKDPARPNIQKTCTFKELVYETVKVPGCAH

[0768] HADSLYTYPVATECHCGKCDSDSTDCTVRGLGPSYCSFSEMKEGGGGGSGGGGSGGGGSGGGGSE

[0769] PKS S DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGV

[0770] EVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREP

[0771] QVYT D PPSR E E M TKNQVSLTC E VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT

[0772] VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0773] 1.3.11 Peptide chain pFSHα-L-(Fc1(D-))

[0774] The pFSHα subunit, the linker (L), and the electrostatically directed D-type modified Fc1 negative charge chain (Fc1(D-)) were sequentially connected to synthesize the peptide chain pFSHα-L-(Fc1(D-)) (SEQ ID NO.32).

[0775] FPDGEFTMQGCPECKLKENKYFSKLGAPIYQCMGCCFSRAYPTPARSKKTMLVPKNITSEATCCV

[0776] AKAFTKATVMGNARVENHTECHCSTCYYHKSGGGGSGGGGSGGGGSGGGGSEPKS S DKTHTCP

[0777] PCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPR

[0778] EEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT D PPSR E E

[0779] M TKNQVSLTC E VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN

[0780] VFSCSVMHEALHNHYTQKSLSLSPGK

[0781] 1.3.12 Peptide chain pFSHβ-L-(Fc1(D+))

[0782] The pFSHβ subunit, the linker (L), and the electrostatically directed D-type modified Fc1 positive charge chain (Fc1(D+)) were sequentially connected to artificially synthesize the peptide chain pFSHβ-L-(Fc1(D+)) (SEQ ID NO.33).

[0783] CELTNITITVEKEECNFC1ISINTTWCAGYCYTRDLVYKDPARPNIQKTCTFKELVYETVKVPGCAH

[0784] HADSLYTYPVATECHCGKCDSDSTDCTVRGLGPSYCSFSEMKEGGGGGSGGGGSGGGGSGGGGSE

[0785] PKS S DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGV

[0786] EVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREP

[0787] QVYT K PPSR E E M TKNQVSL K CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT

[0788] VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0789] 1.3.13 Peptide Chain Fc1k-L-pFSHα

[0790] The button-type Fc chain (Fc1k), linker (L), and pFSHα subunit were sequentially linked to artificially synthesize the peptide chain Fc1k-L-pFSHα (SEQ ID NO.34).

[0791] EPKS S DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDG

[0792] VEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE

[0793] PQVYTLPP C R E E M TKNQVSL W CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL

[0794] TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSFPDGEF

[0795] TMQGCPECKLKENKYFSKLGAPIYQCMGCCFSRAYPTPARSKKTMLVPKNITSEATCCVAKAFTK

[0796] ATVMGNARVENHTECHCSTCYYHKS

[0797] 1.3.14 Peptide chain Fc1h-L-pFSHα

[0798] The locked Fc chain (Fc1h), the linker (L), and the pFSHα subunit were sequentially linked to artificially synthesize the peptide chain Fc1h-L-pFSHα (SEQ ID NO.35).

[0799] EPKS S DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDG

[0800] VEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE

[0801] PQV C TLPPSR E E M TKNQVSL S C A VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL V SKLT

[0802] VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSFPDGEFT

[0803] MQGCPECKLKENKYFSKLGAPIYQCMGCCFSRAYPTPARSKKTMLVPKNITSEATCCVAKAFTKA

[0804] TVMGNARVENHTECHCSTCYYHKS

[0805] 1.3.15 Peptide chain (Fc1(T+))-L-pFSHα

[0806] The electrostatically directed T-shaped modified Fc1 positive charge chain (Fc1(T+)), the connector (L) and the pFSHα subunit were sequentially connected to form an artificially synthesized peptide chain (Fc1(T+))-L-pFSHα (SEQ ID NO.36).

[0807] EPKS SR KTHTCP R CPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDG

[0808] VEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE

[0809] PQVYTLPPSR E E M TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS R LT

[0810] VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSFPDGEFT

[0811] MQGCPECKLKENKYFSKLGAPIYQCMGCCFSRAYPTPARSKKTMLVPKNITSEATCCVAKAFTKA

[0812] TVMGNARVENHTECHCSTCYYHKS

[0813] 1.3.16 Peptide chain (Fc1(T-))-L-pFSHα

[0814] The electrostatically directed T-shaped modified Fc1 negative charge chain (Fc1(T-)), the linker (L) and the pFSHα subunit were sequentially connected to synthesize the peptide chain (Fc1(T-))-L-pFSHα (SEQ ID NO.37).

[0815] EPKS SE KTHTCP E CPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDG

[0816] VEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE

[0817] PQVYTLPPSR E E M TKNQVSLTCE VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT

[0818] VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSFPDGEFT

[0819] MQGCPECKLKENKYFSKLGAPIYQCMGCCFSRAYPTPARSKKTMLVPKNITSEATCCVAKAFTKA

[0820] TVMGNARVENHTECHCSTCYYHKS

[0821] 1.3.17 Peptide chain (Fc1(D+))-L-pFSHα

[0822] The electrostatically directed D-type modified Fc1 positive charge chain (Fc1(D+)), the linker (L) and the pFSHα subunit were sequentially connected to form an artificially synthesized peptide chain (Fc1(D+))-L-pFSHα (SEQ ID NO.38).

[0823] EPKS S DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDG

[0824] VEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE

[0825] PQVYT K PPSR E E M TKNQVSL K CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL

[0826] TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSFPDGEF

[0827] TMQGCPECKLKENKYFSKLGAPIYQCMGCCFSRAYPTPARSKKTMLVPKNITSEATCCVAKAFTK

[0828] ATVMGNARVENHTECHCSTCYYHKS

[0829] 1.3.18 Peptide chain (Fc1(D-))-L-pFSHα

[0830] The electrostatically directed D-type modified Fc1 negative charge chain (Fc1(D-)), the linker (L) and the pFSHα subunit were sequentially connected to form an artificially synthesized peptide chain (Fc1(D-))-L-pFSHα (SEQ ID NO.39).

[0831] EPKS S DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDG

[0832] VEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE

[0833] PQVYT D PPSR E E M TKNQVSLTC E VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL

[0834] TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSFPDGEF

[0835] TMQGCPECKLKENKYFSKLGAPIYQCMGCCFSRAYPTPARSKKTMLVPKNITSEATCCVAKAFTK

[0836] ATVMGNARVENHTECHCSTCYYHKS

[0837] 1.3.19 Peptide chain Fc1h-L-pFSHβ

[0838] The locked Fc chain (Fc1h), the linker (L), and the pFSHβ subunit were sequentially linked to artificially synthesize the peptide chain Fc1h-L-pFSHβ (SEQ ID NO.40).

[0839] EPKS S DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDG

[0840] VEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE

[0841] PQV C TLPPSR E E M TKNQVSL S C A VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL V SKLT

[0842] VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSCELTNITI

[0843] TVEKEECNFC1ISINTTWCAGYCYTRDLVYKDPARPNIQKTCTFKELVYETVKVPGCAHHADSLY

[0844] TYPVATECHCGKCDSDSTDCTVRGLGPSYCSFSEMKE

[0845] 1.3.20 Peptide chain Fc1k-L-pFSHβ

[0846] The button-type Fc chain (Fc1k), linker (L) and pFSHβ subunit were sequentially connected to artificially synthesize the peptide chain Fc1k-L-pFSHβ (SEQ ID NO. 41).

[0847] EPKS S DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDG

[0848] VEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE

[0849] PQVYTLPP C R E E M TKNQVSL W CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL

[0850] TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSCELTNIT

[0851] ITVEKEECNFC1ISINTTWCAGYCYTRDLVYKDPARPNIQKTCTFKELVYETVKVPGCAHHADSLY

[0852] TYPVATECHCGKCDSDSTDCTVRGLGPSYCSFSEMKE

[0853] 1.3.21 Peptide chain (Fc1(T-))-L-pFSHβ

[0854] The electrostatically directed T-shaped modified Fc1 negative charge chain (Fc1(T-)), the linker (L) and the pFSHβ subunit were sequentially connected to form an artificially synthesized peptide chain (Fc1(T-))-L-pFSHβ (SEQ ID NO.42).

[0855] EPKS SE KTHTCP E CPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDG

[0856] VEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE

[0857] PQVYTLPPSR E E M TKNQVSLTC E VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT

[0858] VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSCELTNITI

[0859] TVEKEECNFC1ISINTTWCAGYCYTRDLVYKDPARPNIQKTCTFKELVYETVKVPGCAHHADSLY

[0860] TYPVATECHCGKCDSDSTDCTVRGLGPSYCSFSEMKE

[0861] 1.3.22 Peptide chain (Fc1(T+))-L-pFSHβ

[0862] The electrostatically directed T-shaped modified Fc1 positive charge chain (Fc1(T+)), the linker (L) and the pFSHβ subunit were sequentially connected to synthesize the peptide chain (Fc1(T+))-L-pFSHβ (SEQ ID NO.43).

[0863] EPKS SR KTHTCP R CPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDG

[0864] VEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE

[0865] PQVYTLPPSR E E M TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS R LT

[0866] VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSCELTNITI

[0867] TVEKEECNFC1ISINTTWCAGYCYTRDLVYKDPARPNIQKTCTFKELVYETVKVPGCAHHADSLY

[0868] TYPVATECHCGKCDSDSTDCTVRGLGPSYCSFSEMKE

[0869] 1.3.23 Peptide chain (Fc1(D-))-L-pFSHβ

[0870] The electrostatically directed D-type modified Fc1 negative charge chain (Fc1(D-)), the linker (L) and the pFSHβ subunit were sequentially connected to form an artificially synthesized peptide chain (Fc1(D-))-L-pFSHβ (SEQ ID NO.44).

[0871] EPKS S DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDG

[0872] VEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE

[0873] PQVYT D PPSR E E M TKNQVSLTC E VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL

[0874] TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSCELTNIT

[0875] ITVEKEECNFC1ISINTTWCAGYCYTRDLVYKDPARPNIQKTCTFKELVYETVKVPGCAHHADSLY

[0876] TYPVATECHCGKCDSDSTDCTVRGLGPSYCSFSEMKE

[0877] 1.3.24 Peptide chain (Fc1(D+))-L-pFSHβ

[0878] The electrostatically directed D-type modified Fc1 positive charge chain (Fc1(D+)), the linker (L) and the pFSHβ subunit were sequentially connected to form an artificially synthesized peptide chain (Fc1(D+))-L-pFSHβ (SEQ ID NO.45).

[0879] EPKS S DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDG

[0880] VEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE

[0881] PQVYT K PPSR E E M TKNQVSL K CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL

[0882] TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSCELTNIT

[0883] ITVEKEECNFC1ISINTTWCAGYCYTRDLVYKDPARPNIQKTCTFKELVYETVKVPGCAHHADSLY

[0884] TYPVATECHCGKCDSDSTDCTVRGLGPSYCSFSEMKE

[0885] 1.3.25 Peptide chain hFSHα-L-Fc1k

[0886] The hFSHα subunit, linker (L), and button-type Fc chain (Fc1k) were sequentially linked to artificially synthesize the peptide chain hFSHα-L-Fc1k (SEQ ID NO.46).

[0887] APDVQDCPECTLQENPFFSQPGAPILQCMGCCFSRAYPTPLRSKKTMLVQKNVTSESTCCVAKSY

[0888] NRVTVMGGFKVENHTACHCSTCYYHKSGGGGSGGGGSGGGGSGGGGSEPKS S DKTHTCPPCPAP

[0889] ELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN

[0890] STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP C R E E M TKN

[0891] QVSL W CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSC

[0892] SVMHEALHNHYTQKSLSLSPGK

[0893] 1.3.26 Peptide chain hFSHβ-L-Fc1h

[0894] The hFSHβ subunit, linker (L), and locked Fc chain (Fc1h) were sequentially linked to synthesize the peptide chain hFSHβ-L-Fc1h (SEQ ID NO.47).

[0895] NSCELTNITIAIEKEECRFC1ISINTTWCAGYCYTRDLVYKDPARPKIQKTCTFKELVYETVRVPGC

[0896] AHHADSLYTYPVATQCHCGKCDSDSTDCTVRGLGPSYCSFGEMKEGGGGSGGGGSGGGGSGGG

[0897] GSEPKS S DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV

[0898] DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQP

[0899] REPQV C TLPPSR E E M TKNQVSL S C A VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL V S

[0900] KLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0901] 1.3.27 peptide chain hFSHα-L-Fc1h

[0902] The hFSHα subunit, linker (L), and locked Fc chain (Fc1h) were sequentially linked to synthesize the peptide chain hFSHα-L-Fc1h (SEQ ID NO.48).

[0903] APDVQDCPECTLQENPFFSQPGAPILQCMGCCFSRAYPTPLRSKKTMLVQKNVTSESTCCVAKSY

[0904] NRVTVMGGFKVENHTACHCSTCYYHKSGGGGSGGGGSGGGGSGGGGSEPKS S DKTHTCPPCPAP

[0905] ELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN

[0906] STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQV C TLPPSR E E M TKNQ

[0907] VSL S C A VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL V SKLTVDKSRWQQGNVFSCSV

[0908] MHEALHNHYTQKSLSLSPGK

[0909] 1.3.28 Peptide chain hFSHβ-L-Fc1k

[0910] The hFSHβ subunit, linker (L), and button-type Fc chain (Fc1k) were sequentially linked to artificially synthesize the peptide chain hFSHβ-L-Fc1k (SEQ ID NO. 49).

[0911] NSCELTNITIAIEKEECRFC1ISINTTWCAGYCYTRDLVYKDPARPKIQKTCTFKELVYETVRVPGC

[0912] AHHADSLYTYPVATQCHCGKCDSDSTDCTVRGLGPSYCSFGEMKEGGGGSGGGGSGGGGSGGG

[0913] GSEPKS S DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV

[0914] DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQP <00​​​​​​​​CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS

[0916] KLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0917] 1.3.29 Peptide chain hFSHα-L-(Fc1(T+))

[0918] The hFSHα subunit, the linker (L), and the electrostatically directed T-shaped modified Fc1 positive charge chain (Fc1(T+)) were sequentially connected to synthesize the peptide chain hFSHα-L-(Fc1(T+))(SEQ ID NO.50).

[0919] APDVQDCPECTLQENPFFSQPGAPILQCMGCCFSRAYPTPLRSKKTMLVQKNVTSESTCCVAKSY

[0920] NRVTVMGGFKVENHTACHCSTCYYHKSGGGGSGGGGSGGGGSGGGGSEPKS SR KTHTCP R CPA

[0921] PELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY

[0922] NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR E E M TKN

[0923] QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS R LTVDKSRWQQGNVFSCS

[0924] VMHEALHNHYTQKSLSLSPGK

[0925] 1.3.30 peptide chain hFSHβ-L-(Fc1(T-))

[0926] The peptide chain hFSHβ-L-(Fc1(T-)) (SEQ ID NO.51) was artificially synthesized by sequentially connecting the hFSHβ subunit, the linker (L) and the electrostatically directed T-shaped modified Fc1 negative charge chain (Fc1(T-)).

[0927] NSCELTNITIAIEKEECRFC1ISINTTWCAGYCYTRDLVYKDPARPKIQKTCTFKELVYETVRVPGC

[0928] AHHADSLYTYPVATQCHCGKCDSDSTDCTVRGLGPSYCSFGEMKEGGGGSGGGGSGGGGSGGG

[0929] GSEPKS SE KTHTCP E CPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV

[0930] DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQP

[0931] REPQVYTLPPSR E E M TKNQVSLTC E VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS

[0932] KLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0933] 1.3.31 Peptide chain hFSHα-L-(Fc1(T-))

[0934] The hFSHα subunit, the linker (L), and the electrostatically directed T-shaped modified Fc1 negative charge chain (Fc1(T-)) were sequentially connected to synthesize the peptide chain hFSHα-L-(Fc1(T-))(SEQ ID NO.52).

[0935] APDVQDCPECTLQENPFFSQPGAPILQCMGCCFSRAYPTPLRSKKTMLVQKNVTSESTCCVAKSY

[0936] NRVTVMGGFKVENHTACHCSTCYYHKSGGGGSGGGGSGGGGSGGGGSEPKS SE KTHTCP E CPAP

[0937] ELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN

[0938] STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR E E M TKNQ

[0939] VSLTC E VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSV

[0940] MHEALHNHYTQKSLSLSPGK

[0941] 1.3.32 peptide chain hFSHβ-L-(Fc1(T+))

[0942] The hFSHβ subunit, the linker (L), and the electrostatically directed T-shaped modified Fc1 positive charge chain (Fc1(T+)) were sequentially connected to synthesize the peptide chain hFSHβ-L-(Fc1(T+))(SEQ ID NO.53).

[0943] NSCELTNITIAIEKEECRFC1ISINTTWCAGYCYTRDLVYKDPARPKIQKTCTFKELVYETVRVPGC

[0944] AHHADSLYTYPVATQCHCGKCDSDSTDCTVRGLGPSYCSFGEMKEGGGGSGGGGSGGGGSGGG

[0945] GSEPKS SR KTHTCP R CPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV

[0946] DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQP

[0947] REPQVYTLPPSR E E M TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSR

[0948] LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0949] 1.3.33 peptide chain hFSHα-L-(Fc1(D+))

[0950] The hFSHα subunit, the linker (L), and the electrostatically directed D-type modified Fc1 positive charge chain (Fc1(D+)) were sequentially connected to artificially synthesize the peptide chain hFSHα-L-(Fc1(D+)) (SEQ ID NO.54).

[0951] APDVQDCPECTLQENPFFSQPGAPILQCMGCCFSRAYPTPLRSKKTMLVQKNVTSESTCCVAKSY

[0952] NRVTVMGGFKVENHTACHCSTCYYHKSGGGGSGGGGSGGGGSGGGGSEPKS S DKTHTCPPCPAP

[0953] ELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN

[0954] STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT K PPSR E E M TKN

[0955] QVSL K CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCS

[0956] VMHEALHNHYTQKSLSLSPGK

[0957] 1.3.34 Peptide chain hFSHβ-L-(Fc1(D-))

[0958] The peptide chain hFSHβ-L-(Fc1(D-)) (SEQ ID NO.55) was artificially synthesized by sequentially connecting the hFSHβ subunit, the linker (L) and the electrostatically directed D-type modified Fc1 negative charge chain (Fc1(D-)).

[0959] NSCELTNITIAIEKEECRFC1ISINTTWCAGYCYTRDLVYKDPARPKIQKTCTFKELVYETVRVPGC

[0960] AHHADSLYTYPVATQCHCGKCDSDSTDCTVRGLGPSYCSFGEMKEGGGGSGGGGSGGGGSGGG

[0961] GSEPKS S DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV

[0962] DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQP

[0963] REPQVYT D PPSR E E M TKNQVSLTC E VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS

[0964] KLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0965] 1.3.35 peptide chain hFSHα-L-(Fc1(D-))

[0966] The peptide chain hFSHα-L-(Fc1(D-)) (SEQ ID NO.56) was artificially synthesized by sequentially connecting the hFSHα subunit, the linker (L) and the electrostatically directed D-type modified Fc1 negative charge chain (Fc1(D-)).

[0967] APDVQDCPECTLQENPFFSQPGAPILQCMGCCFSRAYPTPLRSKKTMLVQKNVTSESTCCVAKSY

[0968] NRVTVMGGFKVENHTACHCSTCYYHKSGGGGSGGGGSGGGGSGGGGSEPKS S DKTHTCPPCPAP

[0969] ELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN

[0970] STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT D PPSR E E M TKN

[0971] QVSLTC E VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCS

[0972] VMHEALHNHYTQKSLSLSPGK

[0973] 1.3.36 peptide chain hFSHβ-L-(Fc1(D+))

[0974] The hFSHβ subunit, the linker (L), and the electrostatically directed D-type modified Fc1 positive charge chain (Fc1(D+)) were sequentially connected to synthesize the peptide chain hFSHβ-L-(Fc1(D+)) (SEQ ID NO.57).

[0975] NSCELTNITIAIEKEECRFC1ISINTTWCAGYCYTRDLVYKDPARPKIQKTCTFKELVYETVRVPGC

[0976] AHHADSLYTYPVATQCHCGKCDSDSTDCTVRGLGPSYCSFGEMKEGGGGSGGGGSGGGGSGGG

[0977] GSEPKS S DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV

[0978] DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQP

[0979] REPQVYT K PPSR E E M TKNQVSL K CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS

[0980] KLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0981] 1.3.37 Peptide chain Fc1k-L-hFSHα

[0982] The coin-type Fc chain (Fc1k), the linker (L), and the hFSHα subunit were sequentially linked to artificially synthesize the peptide chain Fc1k-L-hFSHα (SEQ ID NO.58).

[0983] EPKS S DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDG

[0984] VEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE

[0985] PQVYTLPP C R E E M TKNQVSL W CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL

[0986] TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSAPDVQD

[0987] CPECTLQENPFFSQPGAPILQCMGCCFSRAYPTPLRSKKTMLVQKNVTSESTCCVAKSYNRVTVM

[0988] GGFKVENHTACHCSTCYYHKS

[0989] 1.3.38 peptide chain Fc1h-L-hFSHα

[0990] The locked Fc chain (Fc1h), the linker (L), and the hFSHα subunit were sequentially linked to artificially synthesize the peptide chain Fc1h-L-hFSHα (SEQ ID NO.59).

[0991] EPKS S DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDG

[0992] VEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE

[0993] PQV C TLPPSR E E M TKNQVSL S C A VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL V SKLT

[0994] VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSAPDVQDC

[0995] PECTLQENPFFSQPGAPILQCMGCCFSRAYPTPLRSKKTMLVQKNVTSESTCCVAKSYNRVTVMG

[0996] GFKVENHTACHCSTCYYHKS

[0997] 1.3.39 peptide chain (Fc1(T+))-L-hFSHα

[0998] The electrostatically directed T-shaped modified Fc1 positive charge chain (Fc1(T+)), the connector (L) and the hFSHα subunit were sequentially connected to form an artificially synthesized peptide chain (Fc1(T+))-L-hFSHα (SEQ ID NO.60).

[0999] EPKS SR KTHTCP R CPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDG

[1000] VEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE

[1001] PQVYTLPPSR E E M TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS R LT

[1002] VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSAPDVQDC

[1003] PECTLQENPFFSQPGAPILQCMGCCFSRAYPTPLRSKKTMLVQKNVTSESTCCVAKSYNRVTVMG

[1004] GFKVENHTACHCSTCYYHKS

[1005] 1.3.40 Peptide chain (Fc1(T-))-L-hFSHα

[1006] The electrostatically directed T-shaped modified Fc1 negative charge chain (Fc1(T-)), the connector (L) and the hFSHα subunit were sequentially connected to form an artificially synthesized peptide chain (Fc1(T-))-L-hFSHα (SEQ ID NO.61).

[1007] EPKS SE KTHTCP E CPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDG

[1008] VEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE

[1009] PQVYTLPPSR E E M TKNQVSLTC E VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT

[1010] VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSAPDVQDC

[1011] PECTLQENPFFSQPGAPILQCMGCCFSRAYPTPLRSKKTMLVQKNVTSESTCCVAKSYNRVTVMG

[1012] GFKVENHTACHCSTCYYHKS

[1013] 1.3.41 Peptide chain (Fc1(D+))-L-hFSHα

[1014] The electrostatically converted D-type modified Fc1 positive charge chain (Fc1(D+)), the linker (L) and the hFSHα subunit were sequentially connected to form an artificially synthesized peptide chain (Fc1(D+))-L-hFSHα (SEQ ID NO.62).

[1015] EPKS S DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDG

[1016] VEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE

[1017] PQVYT K PPSR E E M TKNQVSL K CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL

[1018] TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSAPDVQD

[1019] CPECTLQENPFFSQPGAPILQCMGCCFSRAYPTPLRSKKTMLVQKNVTSESTCCVAKSYNRVTVM

[1020] GGFKVENHTACHCSTCYYHKS

[1021] 1.3.42 Peptide chain (Fc1(D-))-L-hFSHα

[1022] The electrostatically directed D-type modified Fc1 negative charge chain (Fc1(D-)), the linker (L) and the hFSHα subunit were sequentially connected to form an artificially synthesized peptide chain (Fc1(D-))-L-hFSHα (SEQ ID NO.63).

[1023] EPKS S DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDG

[1024] VEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE

[1025] PQVYT D PPSR E E M TKNQVSLTC E VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL

[1026] TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSAPDVQD

[1027] CPECTLQENPFFSQPGAPILQCMGCCFSRAYPTPLRSKKTMLVQKNVTSESTCCVAKSYNRVTVM

[1028] GGFKVENHTACHCSTCYYHKS

[1029] 1.3.4 34 - peptide chain Fc1h - L - hFSHβ

[1030] The locked Fc chain (Fc1h), linker (L) and hFSHβ subunit are sequentially linked to artificially synthesize the peptide chain Fc1h - L - hFSHβ (SEQ ID NO.64).

[1031] EPKS S DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDG

[1032] VEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE

[1033] PQV C TLPPSR E E M TKNQVSL[[ID=4!]] S C A VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL V SKLT

[1034] VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSNSCELTNI

[1035] It should be noted that in the provided text, there seems to be a mislabeling in line 41 where it says "ID=4!" instead of "ID=41". I've translated it as it is while pointing out this potential error.TIAIEKEECRFC1ISINTTWCAGYCYTRDLVYKDPARPKIQKTCTFKELVYETVRVPGCAHHADSL

[1036] YTYPVATQCHCGKCDSDSTDCTVRGLGPSYCSFGEMKE

[1037] 1.3.44 Peptide chain Fc1k-L-hFSHβ

[1038] The coin-type Fc chain (Fc1k), the linker (L), and the hFSHβ subunit were sequentially linked to synthesize the peptide chain Fc1k-L-hFSHβ (SEQ ID NO.65).

[1039] EPKS S DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDG

[1040] VEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE

[1041] PQVYTLPP C R E E M TKNQVSL W CLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL

[1042] TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSNSCELT

[1043] NITIAIEKEECRFC1ISINTTWCAGYCYTRDLVYKDPARPKIQKTCTFKELVYETVRVPGCAHHADS

[1044] LYTYPVATQCHCGKCDSDSTDCTVRGLGPSYCSFGEMKE

[1045] 1.3.45 peptide chain (Fc1(T-))-L-hFSHβ

[1046] The electrostatically directed T-shaped modified Fc1 negative charge chain (Fc1(T-)), the linker (L) and the hFSHβ subunit were sequentially connected to form an artificially synthesized peptide chain (Fc1(T-))-L-hFSHβ (SEQ ID NO.66).

[1047] EPKS SE KTHTCP E CPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDG

[1048] VEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE

[1049] PQVYTLPPSR E E M TKNQVSLTC E VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT

[1050] VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSNSCELTNI

[1051] TIAIEKEECRFC1ISINTTWCAGYCYTRDLVYKDPARPKIQKTCTFKELVYETVRVPGCAHHADSL

[1052] YTYPVATQCHCGKCDSDSTDCTVRGLGPSYCSFGEMKE

[1053] 1.3.46 Peptide chain (Fc1(T+))-L-hFSHβ

[1054] The electrostatically directed T-shaped modified Fc1 positive charge chain (Fc1(T+)), the connector (L) and the hFSHβ subunit were sequentially connected to form an artificially synthesized peptide chain (Fc1(T+))-L-hFSHβ (SEQ ID NO.67).

[1055] EPKS SR KTHTCP R CPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDG

[1056] VEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPRE

[1057] PQVYTLPPSR E E M TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS R LT

[1058] VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGSGGGGSGGGGSGGGGSNSCELTNI

[1059] TIAIEKEECRFC1ISINTTWCAGYCYTRDLVYKDPARPKIQKTCTFKELVYETVRVPGCAHHADSL

[1060] YTYPVATQCHCGKCDSDSTDCTVRGLGPSYCSFGEMKE

[1061] 1.3.47 Peptide chain (Fc1(D-))-L-hFSHβ

[1062] The electrostatically directed D-type modified Fc1 negative charge chain (Fc1(D-)), the linker (L) and the hFSHβ subunit were sequentially connected to form an artificially synthesized peptide chain (Fc1(D-))-L-hFSHβ (SEQ ID NO.68).

[1063] EPKS S DKTH...

Claims

1. A recombinant Fc fusion protein, comprising a combination of peptide chains comprising an Fc chain and a Gn subunit selected from the following: (1) The amino acid sequence of the peptide chain comprising the buttoned Fc chain (Fc1k) and the pFSHα subunit is shown in SEQ ID NO. 34; and the amino acid sequence of the peptide chain comprising the locked Fc chain (Fc1h) and the pFSHβ subunit is shown in SEQ ID NO. 40; (2) The amino acid sequence of the peptide chain comprising the electrostatically-directed T-shaped positively-charged chain (Fc1(T+)) and the pFSHα subunit is shown in SEQ ID NO. 36; and the amino acid sequence of the peptide chain comprising the electrostatically-directed T-shaped negatively-charged chain (Fc1(T-)) and the pFSHβ subunit is shown in SEQ ID NO. 42; (3) The amino acid sequence of the peptide chain comprising the electrostatically diverted D-type positively charged chain (Fc1(D+)) and the pFSHα subunit is shown in SEQ ID NO. 38; and the amino acid sequence of the peptide chain comprising the electrostatically diverted D-type negatively charged chain (Fc1(D-)) and the pFSHβ subunit is shown in SEQ ID NO. 44; (4) The amino acid sequence of the peptide chain comprising the buttoned Fc chain (Fc1k) and the hFSH α subunit is shown in SEQ ID NO. 58; and the amino acid sequence of the peptide chain comprising the locked Fc chain (Fc1h) and the hFSH β subunit is shown in SEQ ID NO. 64; (5) The amino acid sequence of the peptide chain comprising the electrostatically-directed T-shaped positively-charged chain (Fc1(T+)) and the hFSHα subunit is shown in SEQ ID NO. 60; and the amino acid sequence of the peptide chain comprising the electrostatically-directed T-shaped negatively-charged chain (Fc1(T-)) and the hFSHβ subunit is shown in SEQ ID NO. 66; (6) The amino acid sequence of the peptide chain comprising the electrostatically diverted D-type positively charged chain (Fc1(D+)) and the hFSHα subunit is shown in SEQ ID NO. 62; and the amino acid sequence of the peptide chain comprising the electrostatically diverted D-type negatively charged chain (Fc1(D-)) and the hFSHβ subunit is shown in SEQ ID NO. 68; (7) The amino acid sequence of the peptide chain comprising the buttoned Fc chain (Fc4k) and the hFSH α subunit is shown in SEQ ID NO. 82; and the amino acid sequence of the peptide chain comprising the locked Fc chain (Fc4h) and the hFSH β subunit is shown in SEQ ID NO. 88; (8) The amino acid sequence of the peptide chain comprising the electrostatically-directed T-shaped positively-charged chain (Fc4(T+)) and the hFSHα subunit is shown in SEQ ID NO. 84; and the amino acid sequence of the peptide chain comprising the electrostatically-directed T-shaped negatively-charged chain (Fc4(T-)) and the hFSHβ subunit is shown in SEQ ID NO. 90; (9) The amino acid sequence of the peptide chain comprising the electrostatically diverted D-type positively charged chain (Fc4 (D+)) and the hFSHα subunit is shown in SEQ ID NO. 86; and the amino acid sequence of the peptide chain comprising the electrostatically diverted D-type negatively charged chain (Fc4 (D-)) and the hFSHβ subunit is shown in SEQ ID NO. 92; (10) The amino acid sequence of the peptide chain comprising the buttoned Fc chain (Fc1k) and the GtHα subunit is shown in SEQ ID NO. 106; and the amino acid sequence of the peptide chain comprising the locked Fc chain (Fc1h) and the GtH Iβ subunit is shown in SEQ ID NO. 112; (11) The amino acid sequence of the peptide chain comprising the electrostatically-directed T-shaped positively-charged chain (Fc1(T+)) and the GtHα subunit is shown in SEQ ID NO. 108; and the amino acid sequence of the peptide chain comprising the electrostatically-directed T-shaped negatively-charged chain (Fc1(T-)) and the GtH Iβ subunit is shown in SEQ ID NO. 114; (12) The amino acid sequence of the peptide chain comprising the electrostatically diverted D-type positively charged chain (Fc1(D+)) and the GtHα subunit is shown in SEQ ID NO. 110; and the amino acid sequence of the peptide chain comprising the electrostatically diverted D-type negatively charged chain (Fc1(D-)) and the GtH Iβ subunit is shown in SEQ ID NO. 116; (13) The amino acid sequence of the peptide chain comprising the buttoned Fc chain (Fc1k) and the GtHα subunit is shown in SEQ ID NO. 106; and the amino acid sequence of the peptide chain comprising the locked Fc chain (Fc1h) and the GtH IIβ subunit is shown in SEQ ID NO. 124; (14) The amino acid sequence of the peptide chain comprising the electrostatically-directed T-shaped positively-charged chain (Fc1(T+)) and the GtHα subunit is shown in SEQ ID NO. 108; and the amino acid sequence of the peptide chain comprising the electrostatically-directed T-shaped negatively-charged chain (Fc1(T-)) and the GtH IIβ subunit is shown in SEQ ID NO. 126; (15) The amino acid sequence of the peptide chain comprising the electrostatically diverted D-type positively charged chain (Fc1(D+)) and the GtHα subunit is shown in SEQ ID NO. 110; and the amino acid sequence of the peptide chain comprising the electrostatically diverted D-type negatively charged chain (Fc1(D-)) and the GtH IIβ subunit is shown in SEQ ID NO. 128; (16) The amino acid sequence of the peptide chain comprising the buttoned Fc chain (Fc1k (KiH)) and the pFSHα subunit is shown in SEQ ID NO. 132; and the amino acid sequence of the peptide chain comprising the locked Fc chain (Fc1h (KiH)) and the pFSHβ subunit is shown in SEQ ID NO. 133; (17) The amino acid sequence of the peptide chain comprising the locked Fc chain (Fc1h (KiH)) and the hFSH α subunit is shown in SEQ ID NO. 134; and the amino acid sequence of the peptide chain comprising the buckled Fc chain (Fc1k (KiH)) and the hFSH β subunit is shown in SEQ ID NO.

135.

2. A nucleic acid encoding the recombinant Fc fusion protein according to claim 1.

3. A pharmaceutical composition comprising the recombinant Fc fusion protein of claim 1 or the nucleic acid of claim 2, and optionally a pharmaceutically acceptable carrier.

4. Use of the recombinant Fc fusion protein according to claim 1, the nucleic acid according to claim 2, and the pharmaceutical composition according to claim 3 in the preparation of a drug for promoting superovulation, estrus synchronization, and conception and farrowing in animals; wherein the animal is a pig or a fish.

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