Gerotherapeutic mitochondrial-targeting cell penetrating peptide compositions and uses

Abstract

The technology relates in part to compositions containing a gerotherapeutic cell penetrating peptide that can be used to selectively reduce a senescent cell population, selective reduce a cancer cell population, and / or improve mitochondrial efficiency in a non-senescent cell population. The technology also relates to methods of treatment of ageing and ageing-associated diseases using a gerotherapeutic cell penetrating peptide to selectively reduce a senescent cell population, selectively reduce a cancer cell population, and / or improve mitochondrial efficiency in a non-senescent cell population.

Description

[0001] ATTORNEY DOCKET: 05336.0008W001

[0002] GEROTHERAPEUTIC MITOCHONDRIAL-TARGETING CELL PENETRATING PEPTIDE COMPOSITIONS AND USES

[0003] Cross-Reference to Related Applications

[0004] This application claims priority to, and is a non-provisional of, U. S. Patent Applications 63 / 749,409 (filed January 24, 2025), 63 / 763,214 (filed February 25, 2025), and 63 / 882,029 (filed September 15, 2025), the entirety of which are incorporated herein by reference. Related compositions and uses are described in PCT Application PCT / US25 / 55407 filed on November 13, 2025, U. S. Patent Applications 63 / 719,899 (filed November 13, 2024), 63 / 749,376 (filed January 24, 2025), 63 / 763,206 (filed February 25, 2025), 63 / 889,340 (filed September 27, 2025) and 63 / 895,071 (filed October 7, 2025), the entirety of which are incorporated herein by reference.

[0005] Reference to a Sequence Listing

[0006] This application contains a Sequence Listing in computer readable form. The computer readable form is incorporated herein by reference. The computer readable file is named Sequence.xml and was created on January 23, 2026 (1,275,360 bytes, 1,246 kB). The content of this file is hereby incorporated by reference.

[0007] Field

[0008] The technology relates in part to compositions containing a cell penetrating peptide that can be used to target age-related conditions and age-related decline by selectively reducing a senescent cell population, by selectively eliminating cancer cells, and / or improving mitochondrial efficiency in a non-senescent cell population. The technology also relates to methods of treatment of ageing, ageing-associated diseases, and cancer using a cell penetrating peptide.

[0009] Background

[0010] All living species undergo aging and associated decline. As subjects age, cells including mitochondria enter senescence. Further, one specific, universal finding in aging subject is a decline in mitochondrial function / efficiency and corresponding decline in ATP production. This mitochondrial decline in function and efficiency is also seen broadly in cancer cells. Senescence is a process of cellular aging, in which cells lose their ability to divide but do not die. During senescence, these cells transform into an inflammatory phenotype,ATTORNEY DOCKET: 05336.0008W001

[0011] secreting pro-inflammatory molecules, including certain cytokines and chemokines, altogether termed the Senescence-Associated Secretory Phenotype (“SASP”). During a subject’s youthful years, specific cells in our immune system continuously remove unwanted senescent cells (“SCs”). The immune system’s rate of SC clearance mostly keeps up with the rate of SC formation, leaving few SCs persistently present. As subjects continue to age, SCs begin to accumulate as the immune system becomes less efficient at removing SCs. Chronic inflammation from SCs further impairs the immune system and cellular stresses increase the rate of formation of SCs, leading to progressive accumulation of SCs. Organ function begins to deteriorate due to this adverse cellular and tissue microenvironment. As subjects continue to age, SCs continue to accumulate even further. Widespread “inflammaging”, the chronic, low-grade inflammation that occurs as people age that is not caused by infections but is a result of the aging process itself, reaches critical levels, leading to organ dysfunction and causing widespread aging-related diseases e.g. cognitive decline, sarcopenia and frailty, cataracts, and glucose metabolic disorders like obesity and diabetes.

[0012] Thus, over the lifetime of a subject, a growing population of senescent cells can build up in tissues throughout the body contributing to the process of aging. These cells remain active and release harmful SASP factors that cause inflammation and damage to nearby nonsenescent cells, which may lead to organ dysfunction. The accumulation of senescent cells may contribute to the development of many diseases that commonly occur during aging, including cancer. Furthermore, the elimination of senescent cells has been shown in pre-clinical animal models to be a safe and effective method of preventing or even reversing many of these aging-related diseases. A safe, effective, and selective method to reduce the proportion of senescent cells, relative to non-senescent cells, in an organ, tissue or whole organism, is therefore desirable.

[0013] Further, as discussed above, aging subjects also show a decline in mitochondrial function / efficiency and corresponding decline in ATP production even in non-senescent cells. A safe, effective, and selective method to improve mitochondrial function / efficiency and ATP production in an organ, tissue or whole organism, is therefore desirable.

[0014] Still further, as discussed above, cancer cells also demonstrate decline in mitochondrial function / efficiency. A safe, effective, and selective method to target cancer cells is therefore desirable.ATTORNEY DOCKET: 05336.0008W001

[0015] Geroscience is the study of mechanisms that make aging a major risk factor for common chronic conditions and diseases of aging. Geroscience research seeks to understand how aging affects the disease process and to use that knowledge to slow the rate of aging, reverse its effects, and delay or even cure age-related diseases.

[0016] The primary goal of geroscience is to extend the healthy years of life by targeting the underlying biological processes of aging. Research areas encompass genetics, molecular biology, cellular biology, and physiology to study how aging contributes to diseases like cancer, diabetes, Alzheimer’s, and cardiovascular diseases. By understanding common pathways that drive both aging and age-related diseases, interventions can be developed to delay and / or prevent these conditions. Geroscience therapeutics ("gerotherapeutics”) have the potential to improve healthspan (the period of life spent in good health) and reduce the burden of chronic diseases on individuals and healthcare systems.

[0017] The decline in mitochondrial function and ATP production is a primary driver of aging and age-related diseases; accordingly, a therapeutic that reduces, prevents, or even reverses this decline would be an effective gerotherapeutic and would be well received in the art. Relatedly, accumulation of senescent cells is a primary driver of aging and age-related diseases and a therapeutic that reduces or eliminates these senescent cells would be an effective gerotherapeutic and would be well received in the art. Still further, a therapeutic that eliminated cancer cells would be an effective gerotherapeutic and would be well received in the art.

[0018] Summary

[0019] In an embodiment, a method comprises administering a cell penetrating peptide to a patient in an amount sufficient to selectively eliminate senescent cells, selectively eliminate cancer cells, and / or improve mitochondrial efficiency.

[0020] In an embodiment, a method for selectively reducing a senescent cell population, selectively eliminating cancer cells, and / or improving mitochondrial efficiency in a non¬ senescent cell population comprises administering a composition comprising an active ingredient to cells in an amount sufficient to selectively reduce the senescent cell population, selectively eliminate cancer cells, and / or improve mitochondrial efficiency in the non-senescent cell population, wherein the active ingredient comprises a gerotherapeutic cell penetrating peptide.ATTORNEY DOCKET: 05336.0008W001

[0021] In an embodiment, a gerotherapeutic CPP composition comprises an active ingredient consisting essentially of a gerotherapeutic cell penetrating peptide.

[0022] In an embodiment, a method comprises administering a cell penetrating peptide to a patient in an amount sufficient to reduce effects of aging and improve overall health and functioning of the patient by elimination of senescent cells and improvement of mitochondrial efficiency.

[0023] In an embodiment, a method comprises administering a gerotherapeutic cell penetrating peptide to a patient in an amount sufficient to selectively eliminate cancer cells.

[0024] Brief Description of the Drawings

[0025] The drawings illustrate certain implementations of the technology and are not limiting. For clarity and ease of illustration, the drawings are not made to scale, and, in some instances, various aspects may be shown exaggerated or enlarged to facilitate an understanding of particular implementations.

[0026] FIG. 1 shows age-related reduction in ATP in relation to oxygen consumption.

[0027] FIG. 2 shows quantification of senescence-associated beta-galactosidase (“SA-β-Gal”) percent levels, a marker of senescent cells, in various tissues of naturally aged untreated mice at specified, Increasing ages e.g. 6 weeks old, 30 weeks old, 60 weeks old, 75 weeks old and 90 weeks old.

[0028] FIG. 3A shows cytochrome C binding in aging-impaired mitochondria.

[0029] FIG. 3B shows cytochrome C binding in senescent mitochondria.

[0030] FIG. 4 shows cardiolipin binding affinity for negative control, elamipretide, and exemplary gerotherapeutic peptide P5.

[0031] FIG. 5 shows TOM20 / cytochrome C lo-localization in proliferating and senescent cells treated with gerotherapeutic peptide and control (saline).

[0032] FIG. 6A shows ROS generation in cells treated with gerotherapeutic peptide and control (saline).

[0033] FIG. 6B shows change in ATP production in cells treated with gerotherapeutic peptide treated relative to control.ATTORNEY DOCKET: 05336.0008W001

[0034] FIG. 7 illustrates a mitochondrial-mediated apoptosis pathway.

[0035] FIG. 8A shows change in mitochondrial calcein levels in proliferating and senescent cells treated with gerotherapeutic peptide relative to control.

[0036] FIG. 8B shows change in TOM20 / TFAM co-localization in proliferating and senescent cells treated with gerotherapeutic peptide relative to control.

[0037] FIG. 8C shows change in caspase-3 induction in proliferating and senescent cells treated with gerotherapeutic peptide relative to control.

[0038] FIG. 9 shows relative apoptotic thresholds for senescent cells compared with proliferating cells.

[0039] FIG. 10 shows mitochondrial membrane potential (TMRM staining) in proliferating and senescent cells treated with gerotherapeutic peptide.

[0040] FIG. 11 shows C. elegans activity in control, uncoupler treated, and uncoupler + gerotherapeutic peptide treated groups.

[0041] FIG. 12 shows selective senolytic effect at various dosage of gerotherapeutic peptide treatment.

[0042] FIG. 13 shows quantification of senescent cells as measured by percent SA-β-gal+ area in the spleen for mice treated with gerotherapeutic peptide and control (saline).

[0043] FIG. 14 shows quantification of senescent cells as measured by percent uPAR area for mice treated with gerotherapeutic peptide and control (saline).

[0044] FIG. 15 shows quantification of senescent cells as measured by percent p16 area for mice treated with gerotherapeutic peptide and control (saline).

[0045] FIG. 16 shows post-treatment senescent cell elimination measured by percent SA-β-gal+ area in mice treated with gerotherapeutic peptide relative to control (saline).

[0046] FIG. 17 shows post-treatment reduction in intermyocyte space in gastrocnemius in mice treated with gerotherapeutic peptide and control (saline).

[0047] FIG. 18 shows post-treatment reduction in adipocyte area in inguinal adipose tissue in mice treated with gerotherapeutic peptide and control (saline).ATTORNEY DOCKET: 05336.0008W001

[0048] FIG. 19 shows normalized body weights over time for naturally aged diet induced obesity mice treated with gerotherapeutic peptide, semaglutide, gerotherapeutic peptide + semaglutide, and control (saline).

[0049] FIG. 20 shows rotarod latency over time for naturally aged mice treated with gerotherapeutic peptide and control (saline).

[0050] FIG. 21 shows rotarod latency over time for naturally aged mice treated with gerotherapeutic peptide, semaglutide, gerotherapeutic peptide + semaglutide, and control (saline).

[0051] FIG. 22A shows normalized body weights over time for 20 week old mice treated with gerotherapeutic peptide and control (saline).

[0052] FIG. 22B shows normalized body weights over time for 75 week old mice treated with gerotherapeutic peptide and control (saline).

[0053] FIG. 23A shows post-treatment fat mass for 20 week old mice treated with gerotherapeutic peptide and control (saline) and for 75 week old mice treated with gerotherapeutic peptide and control (saline).

[0054] FIG. 23B shows post-treatment lean mass for 20 week old mice treated with gerotherapeutic peptide and control (saline) and for 75 week old mice treated with gerotherapeutic peptide and control (saline).

[0055] FIG. 24 shows post-treatment rotarod latency for 20 week old mice treated with gerotherapeutic peptide and control (saline) and for 75 week old mice treated with gerotherapeutic peptide and control (saline).

[0056] FIG. 25 shows an overview of a smart cage or smart lid system for monitoring animal activity.

[0057] FIG. 26 shows baseline change in average speed in peptide-treated naturally aged mice monitored by a smart cage.

[0058] FIG. 27A shows baseline change in average acceleration in peptide-treated naturally aged mice monitored by a smart cage.

[0059] FIG. 27B shows baseline change in total distance traveled in peptide-treated naturally aged mice monitored by a smart cage.ATTORNEY DOCKET: 05336.0008W001

[0060] FIG. 28A shows normalized body weights over time for naturally aged mice treated with gerotherapeutic peptide and control (saline).

[0061] FIG. 28B shows food consumption over time for naturally aged mice treated with gerotherapeutic peptide and control (saline).

[0062] FIG. 28C shows post-treatment fat mass for naturally aged mice treated with gerotherapeutic peptide and control (saline).

[0063] FIG. 28D shows post-treatment lean mass for naturally aged mice treated with gerotherapeutic peptide and control (saline).

[0064] FIG. 29 shows data associated with the phenotypic change of PHB2.

[0065] FIG. 30 depicts data associated with the phenotypic changes of PTGS2, HSPA8, IRS2, EGR1, JAG1.

[0066] FIG. 31 shows a study schema for a co-precipitation study of gerotherapeutic peptides. FIG. 32 shows fold-change analysis for select genes / proteins from the co-precipitation study.

[0067] FIG. 33A shows a schematic representation of portions of an electron transport chain including the role of COX4I1 and COX7A2.

[0068] FIG. 33B shows a schematic representation of how membrane stabilization due to gerotherapeutic peptide binding to cardiolipin triggers improved efficiency of nuclear-encoded subunits, supports metabolic integration for Complex IV, and reduces ROS by improving electron flow between Complex III and IV.

[0069] FIG. 34A shows probability of survival over time for naturally aged male mice treated with gerotherapeutic peptide and control (saline).

[0070] FIG. 34B shows cancer-specific probability of survival over time for naturally aged male mice treated with gerotherapeutic peptide and control (saline).

[0071] FIG. 34C shows percent survival over time for untreated male and female mice.

[0072] FIG. 35A shows an experimental schema for colorectal cancer (SW620) tumor evaluation in mice treated with gerotherapeutic peptide and control (saline).

[0073] FIG. 35B shows normalized SW620 tumor volumes (mean) for treatment and control groups.ATTORNEY DOCKET: 05336.0008W001

[0074] FIG. 35C shows normalized SW620 tumor volumes (individual) for control-treated mice. FIG. 35D shows normalized SW620 tumor volumes (individual) for P9-treated mice.

[0075] FIG. 35E shows normalized SW620 tumor volumes (individual) for P14-treated mice. FIG. 36A shows normalized tumor volumes for control-treated mice with data tracked by individual subject.

[0076] FIG. 36B shows normalized tumor volumes for P9-treated mice with data tracked by individual subject.

[0077] FIG. 36C shows normalized tumor volumes for P14-treated mice with data tracked by individual subject.

[0078] FIG. 36D shows tumor cells per subject across treatment and control groups.

[0079] FIG. 36E shows neutrophils per subject across treatment and control groups.

[0080] FIG. 36F shows ratio of tumor cells to tumor infiltrating neutrophils per subject across treatment and control groups.

[0081] FIG. 36G shows ratio of tumor cells to normalized tumor volume per subject across treatment and control groups.

[0082] FIG. 36H shows ratio of neutrophils to normalized tumor volume per subject across treatment and control groups.

[0083] Detailed Description

[0084] Compositions containing certain components can reduce the quantity and proportion of senescent cells in an organ, tissue or whole organism, reduce or eliminate cancer cells, and / or provide improved mitochondrial function. A component that selectively eliminates senescent cells may be referred to as having a senolytic effect. A component that selectively eliminates cancer cells may be referred to as having an oncolytic effect. In embodiments, both the senolytic effect and the oncolytic effect may occur through, or may involve, apoptotic processes, and may be referred to, separately or jointly, as an apoptotic effect. A component that provides improved mitochondrial function may be referred to as having a protective effect. These effects may be referred to, either together or separately, as a gerotherapeutic effect.ATTORNEY DOCKET: 05336.0008W001

[0085] Compounds providing one or both of these effects may be referred to as a gerotherapeutic. It will be understood that a gerotherapeutic may provide both improved mitochondrial function and selective elimination of cells, i.e., may be a dual-action therapeutic and / or may provide a dual-action therapeutic effect (also referred to as a dual-action gerotherapeutic effect). In embodiments, compounds providing these benefits may be or may comprise peptides and may be referred to as gerotherapeutic peptides. In embodiments, a gerotherapeutic peptide may be or may comprise a cell penetrating peptide (CPP). Thus, a peptide may be referred to herein as a gerotherapeutic peptide, a gerotherapeutic cell penetrating peptide, and / or a gerotherapeutic CPP.

[0086] Provided in certain aspects is a composition containing a gerotherapeutic cell penetrating peptide and which may be referred to as a gerotherapeutic composition, a gerotherapeutic cell penetrating peptide compositions, and / or a gerotherapeutic CPP composition. In the conventional art, CPPs have been used to provide a carrier or transporter function, for example, to deliver an additional active component into a cell, across a cell membrane, etc. However, CPPs have not been known to provide direct apoptotic, senolytic, and / or oncolytic effect on their own, irrespective of this carrier function. Likewise, CPPs providing apoptotic, senolytic, and / or oncolytic effect have not been known to provide improved mitochondrial efficiency in aging cells.

[0087] In certain aspects, a gerotherapeutic CPP composition contains an active ingredient containing, consisting essentially of, consisting of, or comprising the gerotherapeutic peptide itself, i.e., comprising the gerotherapeutic CPP itself. In certain aspects, a gerotherapeutic CPP composition is used to reduce a senescent cell population, eliminate a cancer cell population, and / or to provide improved mitochondrial efficiency in a non¬ senescent cell population. Certain implementations are described further in the following description, examples and claims, and in the drawings.

[0088] Described herein are gerotherapeutic CPP compositions, comprising the gerotherapeutic CPPs themselves and uses of such gerotherapeutic CPP compositions that demonstrate safe, effective, and selective gerotherapeutic activity.

[0089] In certain aspects, provided is a composition comprising, consisting essentially of, or consisting of a gerotherapeutic CPP in an amount sufficient to provide a gerotherapeutic effect.ATTORNEY DOCKET: 05336.0008W001

[0090] Overview of Aging: Mitochondrial Decline and Senescent Cell Accumulation Mitochondrial Decline

[0091] As discussed above, mitochondrial function and ATP production efficiency declines with age. This is a universal finding across all living species. For example, significant decreases in mitochondrial coupling (coupling ATP synthesis to oxygen uptake) in vivo is observed in aged mouse skeletal muscle leading to reduced ATP production as shown FIG.

[0092] 1.

[0093] This reduced ATP production may be attributable to mitochondrial membrane damage from aging (e.g., lipid peroxidation via cytochrome C release) which increases inner mitochondrial membrane (IMM) proton permeability, causing “proton leak”. Proton leak in turn dissipates the Mitochondrial Membrane Potential (MMP or Δψm), which steadily declines with age, and reduces ATP production.

[0094] Senescent Cell Accumulation in Naturally Aged Mice

[0095] In addition to general mitochondrial decline discussed above, senescent cells also accumulate as animals age. FIG. 2 shows a representative increase in senescent cells throughout various tissues over the lifespan of naturally aged untreated mice.

[0096] Naturally aged C57BL / 6J mice were surveyed at 6, 30, 60, 75, and 90 weeks old. As a note, 75 week old mice are considered analogous to middle aged humans, approximately 50-55 years of age. Tissues from organs were stained and analyzed (using SA-β-gal+ staining methods as will be discussed in more detail below) to quantify senescent cells. As shown in FIG. 2, a general increase in senescent cells occurs throughout the body correlated with increasing age.

[0097] FIG. 2 depicts representative organs and analysis showing accumulation of senescent cell populations in a survey of naturally aged mice. As shown therein, the survey demonstrated a general increase in senescent cells throughout the body correlated with age.

[0098] Aging / Senescent Mitochondria and Normal Mitochondria

[0099] Aging and / or senescent mitochondria display distinct differences compared to normal, healthy mitochondria. Differences are displayed with respect to membrane potential (MMPATTORNEY DOCKET: 05336.0008W001

[0100] or Δψm), mitochondrial outer membrane permeabilization, BAX / BAK protein state, cardiolipin status, apoptotic priming, bioenergetics, and others.

[0101] For example, with respect to mitochondrial membrane potential (MMP or Δψm), normal healthy mitochondria display stable, high (-150 to -180 mV) levels and efficient electron transport. Aging and / or senescent mitochondria display depolarized subsets and compromised bioenergetics.

[0102] Similarly, normal healthy mitochondria display intact outer membranes and no oligomerization of BAX proteins and BAK proteins. However, aging and / or senescent mitochondria begin to display constitutive mitochondrial outer membrane permeabilization (for example, 10-20%), pre-formed BAX / BAK pores; and / or sub-lethal leakage of cytochrome C and / or mitochondrial DNA.

[0103] Cardiolipin status also differs between healthy normal mitochondria and aging and / or senescent mitochondria. For example, healthy normal mitochondria are characterized by native cardiolipin, stable protective cytochrome C binding, and optimal electron transfer. Contrarily, aging and / or senescent mitochondria often display increased oxidized cardiolipin (for example, increases of 2-3 times), pro-apoptotic cytochrome C binding, and / or peroxidase activity.

[0104] Normal healthy mitochondria also display low BH3-priming as well as undetectable or minimal caspase -3 levels. Aging and / or senescent mitochondria begin to display elevated priming, activated BAX proteins, and subthreshold caspase-3 levels. Aging and / or senescent mitochondria may be approximately 80% to apoptotic thresholds.

[0105] Finally, normal healthy mitochondria display high ATP production, low reactive oxygen species (ROS) levels, and stable calcium homeostasis while aging and / or senescent mitochondria are characterized by reduced ATP production, high ROS levels, compromised calcium handling, and / or changes to mitochondrial permeability transition pore flickering. In summary, aging / senescent mitochondria display a number of negative differences compared with normal, healthy mitochondria. As discussed in more detail below, gerotherapeutic peptides and / or gerotherapeutic compositions may reduce, reverse, or otherwise alleviate these differences.ATTORNEY DOCKET: 05336.0008W001

[0106] Overview of Dual-Action Therapeutic Effect of Gerotherapeutic Peptides

[0107] As discussed above, gerotherapeutic compositions described herein may provide a gerotherapeutic effect, for example, a protective effect that improves mitochondrial function / efficiency and / or an apoptotic effect, for example, a senolytic effect that eliminates senescent cells. In embodiments, gerotherapeutic compositions may provide a dual-action therapeutic effect, for example, may provide both an apoptotic effect and a protective effect. In embodiments, the dual-action effect may provide the apoptotic effect with respect to senescent cells (for example, as a senolytic effect) while providing the protective effect to aging cells that have not yet become senescent. Additionally or alternatively, in embodiments, dual-action effect may provide the apoptotic effect with respect to cancer cells (for example, as an oncolytic effect).

[0108] For example, both aging and senescent cells display reduced mitochondrial membrane potential (MMP or Δψm) as discussed above. A gerotherapeutic CPP administered to a patient may provide a protective effect for aging cells by improving the mitochondrial membrane potential (MMP or Δψm), improving ATP production, and / or decreasing ROS levels. Other characteristics such as those discussed above may also be improved.

[0109] Additionally or alternatively, a gerotherapeutic CPP administered to the patient may provide a senolytic effect by eliminating senescent cells. Elimination of senescent cells is discussed in more detail below as well as in PCT Application PCT / US25 / 55407 filed on November 13, 2025, U. S. Patent Applications 63 / 719,899 (filed November 13, 2024), 63 / 749,376 (filed January 24, 2025), 63 / 763,206 (filed February 25, 2025), 63 / 889,340 (filed September 27, 2025) and 63 / 895,071 (filed October 7, 2025), the entirety of which are incorporated herein by reference.

[0110] Referring again to the protective effect for aging cells, in embodiments, a gerotherapeutic peptide and / or gerotherapeutic composition may bind to cardiolipin (native form cardiolipin) and may stabilize the cytochrome C cardiolipin complex (CytC-CL). A stabilized CytC-CL complex sequesters cytochrome C inside the inner mitochondrial membrane(IMM) thereby reducing / preventing ROS generation, which prevents degradation of the mitochondrial membrane potential (MMP or Δψm). Maintenance / increase of the MMP results in increased ATP production and reduced ROS. ROS oxidizes cardiolipin leading to a release of cytochrome C from the Cyt-CL complex, which results in a forward feedback loop of cytochrome C release, ROS generation, MMP reduction, and senescence generation. ThisATTORNEY DOCKET: 05336.0008W001

[0111] stabilization is depicted schematically in FIG. 3A. This general protective effect of increasing the mitochondrial membrane potential (MMP or Δψm) may also be referred to as Mechanism #1.

[0112] Additionally or alternatively, in senescent cells and / or cancer cells a gerotherapeutic peptide and / or gerotherapeutic composition may bind to oxidized cardiolipin, which has a lower affinity for cytochrome C, and may displace cytochrome C. The displaced cytochrome C may transit to the cytosol, resulting in increased ROS levels, mitochondrial DNA export, increased caspase-3 levels, and apoptosis. Cytochrome C displacement is depicted schematically in FIG. 3B. This pathway may ultimately lead to elimination of senescent cells, providing a senolytic effect. This senolytic effect may also be referred to as Mechanism #2. This pathway may also ultimately lead to elimination of cancer cells, providing an oncolytic effect. This oncolytic effect may also be referred to as Mechanism #2. Thus, Mechanism #2 may be referred to more broadly as an apoptotic effect such as that discussed above.

[0113] As a result of Mechanism #1 and / or Mechanism #2, including combinations thereof, gerotherapeutic peptides and compositions described herein may provide benefits including increased muscle strength, increased exercise endurance, improved cognitive function, improvement in obesity-related metabolic dysfunction, improved body composition (including loss of fat and increase in muscle), reduction in cancer, and others. Overview of Exemplary Gerotherapeutic Peptides

[0114] Exemplary gerotherapeutic peptides are listed in the following table:

[0115] Peptide Sequence

[0116] P1 WEARLARALARALARHLARALARALRACEA (SEQ ID NO: 5)

[0117] P3 CRRLRHLRHHYRRRWHRFRC (SEQ ID NO: 15)

[0118] P4 RQIKIWFQNRRMKWKK (SEQ ID NO: 16)

[0119] LLIILRRRIRKQAHAHSK (SEQ ID NO: 13) (derived from murine VE- P5

[0120] Cadherin and referred to as murine pVEC (“m-pVEC”)

[0121] P6 WEARLARALARALARHLARALAHALHACEA (SEQ ID NO: 18)

[0122] P8 WEAHLAHALAHALARHLARALARALRAGEA (SEQ ID NO: 19)

[0123] P9 WEARLARALARALARHLAHALAHALHACEA (SEQ ID NO: 20)

[0124] P10 LLIFLRRRLRKQARAHGK (SEQ ID NO: 14)

[0125]

[0126] P11 kshahaqkrirrrliill (SEQ ID NO: 1009)ATTORNEY DOCKET: 05336.0008W001

[0127] P12 kgharaqkrlrrrlfill (SEQ ID NO: 1010)

[0128] P13 aecahlahalahalhralaralaralraew (SEQ ID NO: 1077)

[0129] P14 wearlaralaralarhlahalahalhacea (SEQ ID NO: 1078)

[0130] aecahlahalaralhralaralaralraew (SEQ ID NO: 1079)

[0131] P15

[0132] lliilrrrirkqahahsk (SEQ ID NO: 1080)

[0133] P16

[0134] wearlaralaralarhlaralahalhacea (SEQ ID NO: 1081)

[0135] P17

[0136]

[0137] P18 lliflrrrlrkqarahgk (SEQ ID NO: 1084)

[0138] A more comprehensive list is provided in Table 1 below.

[0139] As discussed in more detail below, in certain embodiments, a gerotherapeutic peptide or gerotherapeutic CPP may have a iogP measure lower than 0.1 (with log P measurements extending into the negative range), may have a net positive charge, one or more positively charged amino acids, an Arg (R) or Lys(K) residue, and combinations thereof. These criteria are evaluated for the frequently used peptides P1-P17 in the table below.

[0140] Peptide Length Number Percent Number LogP LogD Origin Category Number of + of + of - Charged Charged Charged

[0141] AA’s AA’s AA’s

[0142] (K, R, H) (D, E)

[0143] P1 30 8 26.7% 2 -3.99 -10.15 Synthetic Amphipathic

[0144] P5 18 8 44.4% -0.27 -10.73 Protein Amphipathic Derived

[0145] P6 30 8 26.7% 2 -3.03 -7.73 Synthetic Amphipathic P8 30 8 26.7% -2.55 -6.52 Synthetic Amphipathic P9 30 8 26.7% -2.55 -6.52 Synthetic Amphipathic P10 18 8 44.4% 0.04 -11.13 Protein Amphipathic Derived

[0146] P11 18 8 44.4% -0.27 -10.73 Protein Amphipathic Derived

[0147] P12 18 8 44.4% 0.04 -11.13 Protein Amphipathic

[0148] Derived

[0149]

[0150] ATTORNEY DOCKET: 05336.0008W001

[0151] P13 30 8 26.7% -2.55 -6.52 Synthetic Amphipathic P14 30 8 26.7% -2.55 -6.52 Synthetic Amphipathic P15 30 8 26.7% 2 -3.03 -7.73 Synthetic Amphipathic P16 18 8 44.4% -0.27 -10.73 Protein Amphipathic Derived

[0152] P17 30 8 26.7% 2 -3.03 -7.73 Synthetic Amphipathic P18 18 8 44.4% 0.04 -11.13 Protein Amphipathic

[0153] Derived

[0154]

[0155] in embodiments, a gerotherapeutic peptide or gerotherapeutic CPP may have a logP lower than 0.1, a charge of at least positive 1, one or more positively charged amino acids, and / or one or more of Arg(R) and / or Lys(K) residues. In some embodiments, a gerotherapeutic CPP may have a logP lower than 0.1, a charge of at least positive 1, one or more positively charged amino acids, and one or more of Arg(R) and / or Lys(K) residues. Still further, in embodiments a gerotherapeutic CPP may have a length greater than four amino acids and fewer than 60 amino acids.

[0156] Cardiolipin Binding Affinity of Gerotherapeutic Peptides

[0157] In embodiments, gerotherapeutic peptides and / or gerotherapeutic compositions may have high binding affinity for normal cardiolipin. Binding affinity was evaluated in a cardiolipin binding competition assay (in vitro) in which a cardiolipin-specific fluorescent probe only fluoresces when bound to cardiolipin. Displacement of the cardiolipin-specific probe results in diminished fluorescent signal (relative fluorescence units, RFU). Compositions that have higher binding affinity will displace a greater percentage of the cardiolipin-specific probe and will demonstrate a greater reduction in fluorescent signal.

[0158] FIG. 4 shows cardiolipin binding competition assay results for a negative control, elamipretide, and exemplary gerotherapeutic peptide P5. Elamipretide is a 4-amino acid peptide known to bind cardiolipin. As shown in FIG. 4, elamipretide demonstrates a modest RFU reduction compared to the negative control. Exemplary gerotherapeutic peptide P5 demonstrates much higher reduction, for example, approximately 60.3% reduction at 0.5 pM and 71.9% reduction at 5.0 pM.ATTORNEY DOCKET: 05336.0008W001

[0159] RFU reduction binding affinity results for exemplary peptides (5 uM) are presented in the following table:

[0160] Peptide at 5 uM RFU Reduction

[0161] P5 71.9%

[0162] P11 47.9%

[0163] P16 39.3%

[0164] P6 3.04%

[0165] P15 29.6%

[0166] P17 0%

[0167] P9 39.6%

[0168] P13 5.6%

[0169] P14 88.9%

[0170] P10 41.7%

[0171] P12 92.8%

[0172]

[0173] These results demonstrate a high binding affinity of gerotherapeutic peptides for cardiolipin.

[0174] Selective Stabilization / Destabilization

[0175] Due to this high binding affinity to normal cardiolipin, gerotherapeutic peptides may provide selective stabilization and / or destabilization of complexes formed between cardiolipin and cytochrome C within mitochondrial cells.

[0176] In embodiments, gerotherapeutic peptides and / or gerotherapeutic compositions may stabilize complexes comprising cytochrome C and normal cardiolipin while destabilizing complexes comprising cytochrome C and oxidized cardiolipin. Reference is made to FIG.

[0177] 3A and FIG. 3B discussed above which schematically depict stabilization / destabilization of cytochrome C complexes within senescent and non-senescent (aging) cells.

[0178] This selective stabilization / destabilization was evaluated by co-localization studies between mitochondrial marker TOM20 and cytochrome C in proliferating and senescent IMR90 lungATTORNEY DOCKET: 05336.0008W001

[0179] fibroblasts treated with exemplary gerotherapeutic peptide P5. Results are shown in FIG.

[0180] 5. As depicted therein, fluorescent microscopy revealed an increase in TOM20 / cytochrome C co-localization in proliferating cells evidencing stabilization of the mitochondrial membrane in non-senescent cells and a decrease in co-localization in senescent cells evidencing destabilization of the mitochondrial membrane in senescent cells. Further, dose-dependent changes were observed, with higher respective increase and decrease at 5 pM than 0.5 pM. Accordingly, gerotherapeutic peptides provide dose-dependent, selective stabilization / destabilization of the mitochondrial membrane.

[0181] Gerotherapeutic Peptides Provide ROS Reduction and ATP Production Improvement in Non-Senescent Cells (Mechanism #1)

[0182] As discussed above, in embodiments the protective effect of Mechanism #1 may involve stabilization of the cytochrome C and cardiolipin complex via cardiolipin binding by the gerotherapeutic peptide. Stabilization prevents cytochrome C-mediated oxidation of cardiolipin, thereby stabilizing the mitochondrial membrane, reducing ROS levels, providing more efficient electron transport, and leading to increased ATP production.

[0183] These effects were evaluated in proliferating IMR90 fibroblasts. As shown in FIG. 6A and FIG. 6B, proliferating IMR90 fibroblasts treated with exemplary gerotherapeutic peptide P5 exhibit reduced levels of ROS generation and increased production of ATP.

[0184] FIG. 6A shows reduction in ROS generation in proliferating IMR90 lung fibroblasts treated with 0.5 pM and 5.0 pM doses of P5. A horseradish peroxidase (HRP) enzyme-based colorimetric assay was used to quantify the levels of ROS in IMR90 lung fibroblasts treated 0.5 pM and 5.0 pM doses of P5, where the level of fluorescence (RFU) corelated to the levels of ROS within the cells. As shown, substantial RFU reduction was exhibited in treated cells compared with control.

[0185] FIG. 6B shows increase in ATP production relative to control in IMR90 lung fibroblasts treated with 0.5 pM and 5.0 pM doses of P5. As shown, cells treated with 0.5 pM doses of P5 demonstrated an approximately 75% increase in ATP production relative to control. Cells treated with 5.0 pM doses of P5 demonstrated greater than 100% increase in ATP production relative to control.ATTORNEY DOCKET: 05336.0008W001

[0186] Together FIG. 6A and FIG. 6B display the protective therapeutic effect (Mechanism #1 ) provided by gerotherapeutic peptides in non-senescent cells (for example, aging cells that have not yet become senescent).

[0187] Gerotherapeutic Peptides Provide MOMP induction and Apoptotic / Senolytic Effect (Mechanism #2)

[0188] As discussed above, in embodiments the apoptotic / senolytic effect of Mechanism #2 may involve destabilization of the cytochrome C and cardiolipin complex via oxidized cardiolipin binding ultimately leading to elimination of cells, for example, senescent cells and / or cancer cells. For example, in senescent cells a gerotherapeutic peptide and / or gerotherapeutic composition may bind to oxidized cardiolipin, which has a lower affinity for cytochrome C, and displace cytochrome C. The displaced cytochrome C may transit to the cytosol, resulting in reduced mitochondrial calcein levels, increased caspase-3 induction, and apoptosis. Similar processes may occur in cancer cells.

[0189] For example, gerotherapeutic peptides and / or gerotherapeutic compositions such as those described herein may selectively eliminate senescent cells via mitochondrial-mediated apoptosis as is now described in more detail. Likewise, gerotherapeutic peptides and / or gerotherapeutic compositions such as those described herein may selectively eliminate cancer cells via mitochondrial-mediated apoptosis.

[0190] The loss of mitochondrial membrane potential, or MMP (A'-Pm) is a critical event in the process of apoptosis and may be referred to as Mitochondrial Outer Membrane Permeabilization (MOMP). A representative diagram of mitochondrial-mediated apoptosis is shown in FIG. 7 in which the following steps are depicted:

[0191] Opening of mPTP: Pathological conditions such as oxidative stress, calcium overload, or ischemia can trigger the opening of the mPTP.

[0192] Loss of A 'Pm: The opening of the mPTP disrupts the proton gradient across the inner mitochondrial membrane, leading to a loss of A^Pm. This gradient is essential for ATP production through oxidative phosphorylation.

[0193] Release of Pro-apoptotic Factors: The loss of A'-Pm causes the mitochondria to swell and the outer mitochondrial membrane to become permeable. This permeability allows the release of pro-apoptotic factors such as cytochrome c, apoptosis-inducing factor (AIF), and Smac / DIABLO into the cytosol.ATTORNEY DOCKET: 05336.0008W001

[0194] Activation of Caspases Leading to Apoptosis: Once in the cytosol, cytochrome c binds to Apaf-1 (apoptotic protease activating factor-1) and dATP, forming the apoptosome. This complex then activates caspase-9, which in turn activates executioner caspases like caspase-3, leading to the proteolytic cleavage of cellular components. The activation of executioner caspases results in the systematic dismantling of the cell, in the process of apoptosis.

[0195] In embodiments, when administered to senescent cells and / or cancer cells, gerotherapeutic peptides and / or gerotherapeutic compositions such as those described herein may selectively trigger apoptosis via a reduction in the Mitochondrial Membrane Potential (MMP) (A’-Pm), leading to prolonged mitochondrial transition pore opening and permeabilization of these cells, and ultimately leading to apoptosis and selective elimination of these senescent cells and / or cancer cells.

[0196] Apoptotic and / or senolytic effect of gerotherapeutic peptides was evaluated by comparison of mitochondrial calcein levels, co-localization effects, and caspase-3 induction in proliferating and senescent IMR90 cells treated with exemplary peptide P5.

[0197] FIG. 8A depicts mitochondrial calcein levels in proliferating and senescent IMR90 cells treated with exemplary peptide P5 at doses of 0.5 pM and 5.0 pM. Reduced mitochondrial calcein levels can indicate formation of pores in mitochondria. As shown in FIG. 8A, PS-treated cells displayed reduction in mitochondrial calcein levels.

[0198] FIG. 8B depicts co-localization of TOM20 and mitochondrial transcription factor A (TFAM) in proliferating and senescent IMR90 cells treated with exemplary P5 at doses of 0.5 pM and 5.0 pM. Decreases in co-localization of TOM20 and TFAM may indicate mitochondrial DNA export, for example, leakage. As shown, co-localization is unchanged or even improved in proliferating cells treated with P5, indicating reduced leakage. However, colocalization decreases relative to control in senescent cells treated with P5, indicating increased leakage. Thus, while treated proliferating and senescent cells showed similar calcein levels (and would be expected to have similar pore openings), senescent cells treated with gerotherapeutic peptide demonstrated decreased co-localization and corresponding increased leakage.

[0199] FIG. 8C depicts respective caspase-3 induction levels in proliferating and senescent IMR90 cells treated with exemplary peptide P5 at doses of 0.5 pM, 5.0 pM, and 50 pM.ATTORNEY DOCKET: 05336.0008W001

[0200] Results are shown as change relative to control. As discussed above, caspase-3 may be considered an executioner caspase, leading to proteolytic cleavage of cellular components. The activation of executioner caspases such as caspase-3 results in systematic dismantling of the cell as part of the apoptosis process. As shown in FIG. 8C, proliferating cells treated with P5 demonstrate minimal change in caspase-3 induction relative to control even at a dose 50 pM. However, senescent cells treated with gerotherapeutic peptide show substantial increase in caspase-3 induction relative to control, for example, approximately 20% increase at doses of 0.5 pM and 5.0 pM and over 70% increase at a dose of 50 pM.

[0201] Accordingly, treatment with gerotherapeutic peptides such as those described herein shows selective induction of the apoptotic process in senescent cells without a corresponding induction in proliferating cells, i.e., cells that have not yet aged sufficiently to reach senescence. Gerotherapeutic peptides may therefore provide a selective senolytic effect as discussed in further detail below. As discussed in more detail below, treatment with gerotherapeutic peptides such as those described herein may provide selective induction of the apoptotic process in cancer cells as well and may provide a selective oncolytic effect.

[0202] Therapeutic Window for Senolytic Activity (Mechanism #2)

[0203] Senescent cells are balanced on a "hair-trigger” between anti-apoptotic (BCL-2 family) and pro-apoptotic (BAX / BAK) states. For example, some mitochondria in senescent cells have minority outer membrane permeabilization (miMOMP), with elevated cytochrome C, mtDNA, and caspase-3 levels; these apoptotic conditions may be loosely held in check by anti-apoptotic proteins and factors. Similar conditions may be present in cancer cells.

[0204] Gerotherapeutic peptides and gerotherapeutic compositions such as those described herein may exploit this hair-trigger, for example, by binding cardiolipin / oxidized cardiolipin, triggering cytochrome C and mtDNA release / leakage, and caspase-3 activation to push senescent cells into apoptosis (Mechanism #2). However, as discussed above, in proliferating cells any gerotherapeutic peptide-induced cytochrome C and / or mtDNA release remains well below apoptotic levels.

[0205] This hair-trigger and selective senolytic effect is schematically depicted in FIG. 9. As shown therein, proliferating cells require a much larger magnitude of mitochondrial insult toATTORNEY DOCKET: 05336.0008W001

[0206] trigger apoptosis, while senescent cells quickly reach an apoptotic threshold even with a relatively low mitochondrial insult. This disparity provides a therapeutic window in which treatment with gerotherapeutic peptides and gerotherapeutic compositions provide effective senolytic effect (Mechanism #2) without undesirable apoptosis of proliferating cells. As discussed in more detail below, for example, with respect to FIG. 12 and FIG. 30, gerotherapeutic peptides and / or gerotherapeutic compositions provide a selective senolytic effect.

[0207] Dual-Action Therapeutic Effect of Gerotherapeutic Peptides and Compositions As evidenced by the discussion and figures above, gerotherapeutic peptides and / or gerotherapeutic compositions such as those described herein provide a dual-action therapeutic effect including both a protective effect for healthy / normal aging cells that have yet to proceed to senescence (Mechanism #1) and an apoptotic effect for removing / eliminating cells (Mechanism #2), for example, a senolytic effect removing / eliminating unhealthy / senescent cells (Mechanism #2) and / or an oncolytic effect removing / eliminating cancer cells (Mechanism #2).

[0208] In some embodiments, treatment with gerotherapeutic peptides and / or gerotherapeutic compositions may provide improved mitochondrial function, i.e., mitochondrial rejuvenation, by increasing the mitochondrial membrane potential (MMP or Δψm) in healthy aging cells as part of Mechanism #1.

[0209] For example, treatment with exemplary peptide P5 increases MMP / Δψm in proliferating cells when administered at sub-nanomolar doses. FIG. 10 depicts MMP / Ai m levels in proliferating and senescent IMR90 human fibroblasts treated with P5. As shown, proliferating cells demonstrated a dose-dependent increase in MMP / Δψm levels. As discussed above, improved mitochondrial membrane potential in healthy aging cells may lead to improved efficiency, improved ATP production, and other benefits.

[0210] By providing mitochondrial rejuvenation or restoration, gerotherapeutic peptides and / or gerotherapeutic compositions may target a fundamental mechanism of aging that is present across various species.

[0211] For example, P5 treatment was administered to C. elegans along with known mitochondrial uncoupler FCCP (10 μM). As shown in FIG. 11, while administration of FCCP reduced locomotor activity in C. elegans, this reduction was avoided in groups that were alsoATTORNEY DOCKET: 05336.0008W001

[0212] administered P5, even at lower doses such as 3 μM. Instead, P5 treatment reversed the negative effects of the FCCP mitochondrial uncoupler on activity and provided improved healthspan.

[0213] These results provide direct evidence that gerotherapeutic peptides target the inner mitochondrial membrane, reduce leakage, increase MMP / Δψm levels, and increase oxidative phosphorylation coupling in C. elegans. This is a fundamental mechanism of aging that is present across species, including but not limited to, C. elegans, mice, and likely humans. Accordingly, gerotherapeutic peptides and gerotherapeutic compositions may provide a universal protective effect in healthy / aging cells by Mechanism #1.

[0214] Further, as discussed above, treatment with gerotherapeutic peptides and / or gerotherapeutic compositions selectively induces apoptotic elimination of senescent cells and / or of cancer cells as part of Mechanism #2.

[0215] For example, as shown in FIG. 12, treatment with exemplary peptide P5 demonstrated a selective senolytic effect (calculated as apoptosis increase in senescent IMR90 cells divided by apoptosis increase in proliferating IMR90 cells, both relative to saline-treated cells), especially at sub-nanomolar doses. The selective senolytic effect demonstrates effective induction of apoptosis in senescent cells and low collateral apoptotic effect in healthy aging cells (proliferative cells). Similar selective senolytic effect was seen with treatment of P6 as evidenced by FIG. 30 below.

[0216] Senolytic effect was also evaluated in naturally aged mice. For example, naturally aged 75 week old mice are analogous to approximately 50-55 year old humans. In naturally aged mice treated with gerotherapeutic peptides, senescent cell numbers showed dose-dependently reduction across various tissue types as analyzed by multiple senescent cell markers such as senescence-associated p-galactosidase (SA-p-gal), urokinase-type plasminogen activator receptor (uPAR), and p16INK4a(p16). SA-p-gal is a well-established biomarker of cellular senescence. uPAR is a cell surface marker associated with senescence. p16 is a regulator of the cell cycle and is a well-established biomarker of cellular senescence. Exemplary results are shown in FIG. 13, FIG. 14, and FIG. 15.

[0217] FIG. 13 shows quantification of senescent cells as measured by percent SA-β-gal+ area in the spleen for mice treated with P6 and control (saline). As shown, treatment with 50ATTORNEY DOCKET: 05336.0008W001

[0218] mg / kg of P6 (3x per week for 20 weeks) resulted in an approximately 51 % reduction in percent area SA-p-gal compared with control.

[0219] FIG. 14 shows quantification of senescent cells as measured by percent uPAR area for mice treated with P1, P5, and control (saline). As shown, treatment with 5 mg / kg of P1 (3x per week for 8 weeks) resulted in an approximately 48% reduction in percent area uPAR compared with control and treatment with 5 mg / kg of P5 (3x per week for 8 weeks) resulted in an approximately 67% reduction in percent area uPAR compared with control.

[0220] FIG. 15 shows quantification of senescent cells as measured by percent p16 area for mice treated with P1, P5, and control (saline). As shown, treatment with 5 mg / kg of P1 (3x per week for 8 weeks) resulted in an approximately 58% reduction in percent area p16 compared with control and treatment with 5 mg / kg of P5 (3x per week for 8 weeks) resulted in an approximately 56% reduction in percent area p16 compared with control.

[0221] Further, gerotherapeutic peptides demonstrate senescent cell elimination in naturally aged mice after approximately 8 weeks of treatment. FIG. 16 shows post-treatment senescent cell elimination measured by percent SA-£-gal+ area in mice treated with P5 relative to control (saline). P5 was dosed at 3.3 mg / kg of P5 (3x per week) in naturally aged mice. Spleens were analyzed at 4, 6, and 8 weeks post-treatment and percentage senescent cell reduction relative to saline is plotted. P5 treatment resulted in substantial reduction of senescent cell burden in spleen tissue observable by 8 weeks of treatment.

[0222] Physiological and Metabolic Benefits of Gerotherapeutic Peptides and Compositions As a result of, or in addition to, Mechanism #1 and / or Mechanism #2, gerotherapeutic peptides and / or gerotherapeutic compositions may provide various physiological, metabolic, and / or phenotypic benefits, including, for example, tissue remodeling, body weight control, increased endurance, weight reduction, improved body composition, and anti-cancer effect.

[0223] Gerotherapeutic Peptides Provide Tissue Remodeling

[0224] For example, a method to assess pathological effect of aging on muscle tissue is to measure an intermyocyte space. Lean mass increase results from a reduction in intermyocyte space, a sign of younger, healthier muscle tissue. Intermyocyte space (gastrocnemius) was measured in naturally aged mice treated with P6 (50 mg / kg 3X per week) and with saline as a control. FIG. 17 shows results after 20 weeks of treatment.ATTORNEY DOCKET: 05336.0008W001

[0225] The treatment group showed a 26% reduction in intermyocyte space, a sign of improved muscle health, a sign of improved heath.

[0226] Another method to assess tissue health is to measure adipocyte area. Fat mass loss occurs along with reduction in adipocyte area, a sign of younger, healthier fat tissue.

[0227] Adipocyte area in white adipose tissue (IAT) was measured in naturally aged mice treated with P6 (50 mg / kg 3X per week) and with saline as a control. FIG. 18 shows results after 20 weeks of treatment. The treatment group showed a 52% reduction in adipocyte area, demonstrating younger, healthier fat tissue.

[0228] Gerotherapeutic peptide treatment resulted in reduced gastrocnemius intermyocyte space and IAT adipocyte area, demonstrating improved tissue morphology (i.e., tissue remodeling from aged to younger) and health with peptide treatment compared with control.

[0229] Gerotherapeutic Peptides Provide Body Weight Control

[0230] Gerotherapeutic peptide treatment also resulted in improved body weight control beginning at 8 weeks of treatment. Improved body weight control is seen using gerotherapeutic peptides as a monotherapy and also as a combination therapy with semaglutide.

[0231] For example, naturally aged diet-induced obesity (DIO) mice (90 weeks old at start of treatment) were treated with P5 alone, semaglutide (SMG) alone, combination of P5 and semaglutide, and control (saline). Results are reported in FIG. 19 and in the graph below. As noted in FIG. 19, SMG dose was increased from 0.2 mg / kg, 3X / week to 0.4 mg / kg 3X / week after four weeks of the initial dose, as is required by GLP1 RA to maintain effectiveness. As shown, the P5 group demonstrated improved weight loss compared to the saline group, and the combination of P5 and SMG group demonstrated Improved weight loss compared to semaglutide alone group, with the effect in both comparisons beginning at 8 weeks (when senescent-cell elimination has occurred as (see FIG. 16)). Improved weight loss in the P5 and combination group compared to control and SMG treatment alone, respectively, was maintained throughout the study (37 weeks).

[0232] % Body Weight Change

[0233] Relative to Initial Relative to Saline, ASMG, Latest Time Timepoint Latest Time Point Point Group %Change P Relative% p Relative% P

[0234]

[0235] Saline 22.63% 0.0109 - - 12.98% 0.0826ATTORNEY DOCKET: 05336.0008W001

[0236] P5 -0.40% 0.3863 -23.03% 0.0063 -10.05% 0.1044 SMG 9.66% 0.4015 -12.98% 0.0826 - -

[0237]

[0238] P5 + SMG -8.07% 0.1406 -30.71% 0.0019 -17.73% 0.0142

[0239] Accordingly, gerotherapeutic peptide treatment as a monotherapy or combination therapy can provide improved body weight compared to conventional treatments like semaglutide. Gerotherapeutic Peptides Provide Improved Endurance

[0240] Gerotherapeutic peptide treatment also results in increased endurance, with results seen as early as 5 weeks (or less) after beginning treatment. Increased endurance was seen using gerotherapeutic peptides as a monotherapy and also as a combination therapy with semaglutide.

[0241] For example, naturally aged mice treated with high-dose P5 showed similar, sustained endurance gains in rotarod testing (latency) as naturally-aged diet-induced obesity (DIO) mice treated with low-dose P5 in combination with semaglutide. This demonstrates high-dose P5 has similar efficacy as a combined semaglutide / low-dose P5 treatment.

[0242] Results are reported in FIG. 20 and FIG. 21. As shown, after 5 weeks of treatment both the group receiving high-dose (25 mg / kg 1X per week) P5 and the group receiving a combination of low-dose (3.3 mg / kg 3X per week) and SMG demonstrated approximately 25% increase in rotarod endurance (latency). Improvements in these groups exceeded improvement of SMG treatment alone and were maintained throughout the study (17 and 20 weeks, respectively).

[0243] Gerotherapeutic Peptides Provide Aging-Specific Targets and Benefits Gerotherapeutic peptide treatment may also provide aging-specific targets and benefits such as aging-specific body weight control, body composition, and physical function.

[0244] For example, gerotherapeutic peptides reduce body weight in aged mice (75 weeks old) but not young mice (20 weeks old) indicating an age-specific therapeutic response for body weight reduction.

[0245] FIG. 22A depicts results of P5 treatment (25 mg / kg 1X per week) compared with control treatment (saline) in 20 week old naturally aged mice. FIG. 22B depicts results of P5 treatment (25 mg / kg 1X per week) compared with control treatment (saline) in 75 week old naturally aged mice. As shown in FIG. 22A, in 20 week old mice, peptide treatment resultsATTORNEY DOCKET: 05336.0008W001

[0246] in minimal reduction of weight compared with the control group. However, as shown in FIG. 22B, in 75 week old mice, peptide treatment results in more substantial reduction of weight (lower weight gain), particularly after approximately 10 weeks of treatment.

[0247] As another example, gerotherapeutic peptides improve body composition in aged mice (75 weeks old) but not young mice (20 weeks old) indicating an age-specific therapeutic response for body composition.

[0248] FIG. 23A depicts fat mass results of 5 weeks of P5 treatment (25 mg / kg 1X per week) compared with control (saline) treatment in both 20 week old naturally aged mice and 75 week old naturally aged mice. FIG. 23B depicts lean mass results of 5 weeks of P5 treatment (25 mg / kg 1X per week) compared with control (saline) treatment in both 20 week old naturally aged mice and 75 week old naturally aged mice.

[0249] As shown in FIG. 23A, both 20 week old and 75 week old control groups gained fat mass, as did the 20 week old treatment group. However, the 75 week old P5 treatment group showed reduction In fat mass.

[0250] As shown in FIG. 23B, for younger 20 week old mice, both the treatment and control group showed slight reduction in lean mass after 5 weeks. For aged 75 week old mice, both the treatment and control group showed increase in lean mass; however, the P5 treatment group showed greater increase.

[0251] As a still further example, gerotherapeutic peptides improve function (rotarod latency) in aged mice (75 weeks old) but not young mice (20 weeks old) indicating an age-specific therapeutic response for function.

[0252] FIG. 24 depicts rotarod latency after 15 weeks of P5 treatment (25 mg / kg 1X per week) compared with control (saline) treatment in both 20 week old naturally aged mice and 75 week old naturally aged mice.

[0253] As shown in FIG. 24, the 20 week old treatment group showed no change and the 20 week old control group showed a decrease in rotarod latency after 15 weeks. Likewise, the 75 week old control group showed no change after 15 weeks. However, the 75 week old P5 treatment group showed a substantial improvement in rotarod latency, indicating an age¬ specific response.ATTORNEY DOCKET: 05336.0008W001

[0254] Accordingly, gerotherapeutic peptide treatment may be used to provide targeted improvements in aging subjects, helping aging subjects reduce fat mass, increase lean mass, and regain functionality expected from younger subjects.

[0255] Gerotherapeutic Peptides Reverse Age-Associated Decline in Physical Function

[0256] As discussed above, gerotherapeutic peptide treatment provides aging-specific targets and benefits, including in physical function.

[0257] Physical function in naturally aged mice was also evaluated using smart cage-based continuous activity monitoring. An overview of a smart cage or smart lid system is provided in FIG. 25. As shown, smart cages or smart lids are provided with cameras, sensors, and / or other equipment for tracking movement and other features of mice.

[0258] Activity metrics such as climbing events, average acceleration, average speed, and distance traveled were tracked. Climbing activity is representative of strength and declines with age. The other activity metrics are representative of physical function and endurance and also decline with age.

[0259] Naturally aged (75 week old) P5-treated (0.625 mg / kg 1X per week) mice were monitored for 8 weeks. FIG. 26 shows baseline change in average speed in P5-treated naturally aged mice monitored by a smart cage. As shown, even at this low dosage, P5 treated mice showed increased speed, indicative of an increase in physical function. Data normalized to baseline measurements show an increase of +132% (p = 0.0015) in average speed after 8 weeks of dosing. Similar improvements compared to baseline measurements were seen for average acceleration (+242%, p=0.0097) and total distance (+119%, p<0.0043). FIG. 27A shows baseline change in average acceleration in peptide-treated naturally aged mice monitored by a smart cage and FIG. 27B shows baseline change in total distance traveled in peptide-treated naturally aged mice monitored by a smart cage.

[0260] Accordingly, gerotherapeutic peptide treatment provides an increase in physical function, energy, and endurance for naturally aged subjects.

[0261] Gerotherapeutic Peptides Provide Favorable Weight Loss Composition without Affecting Food Consumption

[0262] GLP-1 based therapies, for example, treatment with semaglutide, present serious Gl side effects. For example, much of the weight loss, which includes loss of both fat and muscle,ATTORNEY DOCKET: 05336.0008W001

[0263] from GLP-1 based treatment is due to a reduction in appetite and in food consumption, partly due to these side effects.

[0264] However, gerotherapeutic peptides and gerotherapeutic compositions reduce body weight, relative to saline, without affecting food consumption, in a dose-response manner. Further, body weight reduction is solely from fat loss, as evidenced by a reduction in fat mass and an increase in lean mass, as analyzed by DEXA full body composition scanner. For example, naturally aged mice that were 75 weeks old at initiation of treatment were fed a standard diet of 10% fat, 20% protein, and 70% carbohydrate (by kcal%) and were treated with low-dose P5 (2.5 mg / kg 1X per week), with high-dose P5 (25 mg / kg 1X per week), or with control (saline).

[0265] FIG. 28A shows moralized body weights over time for treatment and control groups. As shown, the control group and iow-dose P5 group showed an increase in normalized body weight over 6 weeks, while the high-dose P5 group showed a reduction in normalized body weight.

[0266] FIG. 28B shows food consumption over time for all three groups. As shown, none of the groups showed a decline in food consumption. Further, the high-dose P5 group actually showed the highest food consumption.

[0267] FIG. 28C shows post-treatment (5 weeks) change in fat mass for all three groups. As shown, the control group fed this diet showed an almost 20% increase in fat mass after 5 weeks. However, both the low-dose P5 group and the high-dose P5 group showed reduction in fat mass, with the high-dose group showing higher reduction.

[0268] FIG. 28D shows post-treatment change in lean mass for all three groups. As shown, all three groups had an increase in lean mass after 5 weeks.

[0269] As demonstrated by these results, gerotherapeutic peptides and gerotherapeutic compositions reduce body weight without affecting food consumption and without sacrificing lean mass. Instead, reduction in body weight comes solely from reduction in fat mass fat, leading to better body composition and overall health.ATTORNEY DOCKET: 05336.0008W001

[0270] Differential Gene Expression and Phenotypical Results from Gerotherapeutic Peptides and Compositions

[0271] Gerotherapeutic peptides and / or gerotherapeutic compositions affect numerous biological processes, either through Mechanism #1 and / or Mechanism #2 described above, or through additional biological mechanisms.

[0272] For example, P6 treatment in naturally aged mice (75 weeks old at study initiation) affected 1,260 biological processes including fatty acid metabolism, T cell immunity, and muscle development. Genes in the table below represent those most prevalent in those processes revealed by RNAseq pathway analysis from mouse splenocytes.

[0273] Gene Fold- Primary Function Relevance to Enrichment Phenotypic Change (Median)

[0274] Inflammatory

[0275] Anti-inflammatory Prostaglandin enzyme,

[0276] effects may improve PTGS2 G / H synthase 7.30 mitochondrial

[0277] muscle function and 2 (COX-2) dysfunction

[0278] body composition marker

[0279] Enhanced protein Heat shock Protein folding, quality control HSPA8 protein family 7.06 mitochondrial supports muscle A member 8 protein import function and metabolic health lnsulin / IGF-1 Improved insulin Insulin

[0280] signaling, sensitivity drives fat IRS2 receptor 5.44

[0281] metabolic loss and lean mass substrate 2

[0282] regulation gain Transcription Coordinates adaptive Early growth

[0283] EGR1 8.15 factor, stress responses to improve response 1

[0284] response cellular function Jagged Notch signaling, Promotes tissue JAG1 canonical 7.15 cell fate regeneration and Notch ligand 1 determination muscle development Mitochondrial Direct mitochondrial PHB2 Prohibitin 2 5.54 chaperone, cristae target improving

[0285]

[0286] structure energy metabolism Representative connections between these biological processes, associated genes, and phenotypic effect are shown in the table above and in FIG. 29 and FIG. 30 in addition to the discussion provided above.ATTORNEY DOCKET: 05336.0008W001

[0287] The phenotypic changes of PTGS2, HSPA8, IRS2, EGR1, and JAG1 are associated with the data of FIG. 29. As shown therein, gerotherapeutic peptide treatment, here P6 treatment, provided dose dependent reduction of fat mass, increase in lean mass, improved rotarod latency, and SASP reduction.

[0288] The phenotypic changes of PHB2 is associated with FIG. 30. As shown, gerotherapeutic peptide treatment, here P6 treatment, provided selective senolytic effect by selectively inducing apoptosis in senescent cells. These results were consistent with those discussed above in FIG. 12 (P5 treatment), further confirming Mechanism #2. Likewise, gerotherapeutic peptide treatment, here P6 treatment, provided selective protective effect by increasing membrane potential in healthy cells as opposed to senescent cells. These results were consistent with those discussed above in FIG. 10 (P5 treatment), further confirming Mechanism #1.

[0289] Gerotherapeutic Peptide Co-Precipitation

[0290] Protein binding of gerotherapeutic peptides was evaluated using a co-precipitation study. Study schema is shown in FIG. 31 and includes providing biotinylated peptides, incubating peptides with proliferating IMR90 cells, preparing lysate, capturing bound complexes using streptavidin, and analyzing complexes using mass spectrometry. The co-precipitation study was designed to identify unique protein interactors with gerotherapeutic peptides and infer pathway modulation based on fold-change analysis.

[0291] Proliferating IMR-90 cells were treated with biotinylated and non-biotinylated P5 in vitro at 0.5 pM and 50 pM for 24 hours. Proliferating IMR-90 cells were also treated with biotinylated and non-biotinylated elamipreiide in vitro at 0.5 pM and 50 pM for 24 hours for comparison. Cells were lysed and bound complexes were captured and analyzed following the schema discussed above and shown in FIG. 31.

[0292] Fold-change analysis for select genes / proteins is shown in FIG. 32. Fold-change increase or decrease is mapped for 0.5 pM P5 (Group A), 50 pM P5 (Group B), 0.5 pM elamipretide (Group C), and 50 pM elamipretide (Group C).

[0293] As shown in FIG. 32 and in the table below, at least 7 genes / proteins in the metabolism and bioenergetics pathway demonstrated

[0294]

[0295] 10-fold increases in the amount of protein detected after co-precipitation with low dose P5 (0.5 pM) (group A), compared to negativeATTORNEY DOCKET: 05336.0008W001

[0296] controls. The table below shows representative gene / proteins that demonstrated

[0297]

[0298] 10-fold increases. Corresponding categories of functions are provided for these genes / proteins. Gene / Protein Category of Function

[0299] COX4I1 ETC Complex IV subunit

[0300] COX7A2 ETC Complex IV subunit

[0301] UQCRC2 ETC Complex III subunit

[0302] TOMM70 Mitochondrial protein import receptor

[0303] SFXN1 Inner membrane serine / one-carbon transporter

[0304] MT-CO2 ETC Complex IV mtDNAOencoded subunit

[0305] FH TCA cycle-fumarase

[0306]

[0307] For example, COX4I1 and COX7A2, both components of the Electron Transport Chain (ETC) Complex IV subunit, demonstrated a

[0308]

[0309] 10-fold increased amount of co-precipitation with P5 at both the low (0.5uM) and high (50uM) concentrations, compared to nonbiotinylated controls.

[0310] These results for gerotherapeutic peptide are in contrast to results for elamipritide. As shown in groups C and D of FIG. 32, most of the genes / proteins in the mitochondrial metabolism and bioenergetics pathway do not significantly co-precipitate with elamipretide at either low (0.5uM) or high (50 uM) concentrations, with the exception of COX4I1 at 50uM.

[0311] FIG. 33A depicts a schematic representation of portions of the electron transport chain including the role of COX4I1 and COX7A2. Arrows indicate functional flow for efficient oxidative phosphorylation. FIG. 33B shows a schematic representation of how membrane stabilization due to gerotherapeutic peptide binding to cardiolipin triggers improved efficiency of nuclear-encoded subunits (TOMM70), supports metabolic integration for Complex IV (SFXN1), and reduces ROS by improving electron flow between Complex III and IV (UQCRC2 - COX4I1 - COX7A2 - mt-CO2). Through these pathways, gerotherapeutic peptides may improve bioenergetic function in high-demand tissues (such as heart and skeletal muscle) and activities (during exercise) and reduce ROS. Further, gerotherapeutic peptides may mitigate mitochondrial dysfunction of aging.ATTORNEY DOCKET: 05336.0008W001

[0312] Gerotherapeutic Peptides Provide Anti-Cancer Effect

[0313] As discussed above, gerotherapeutic peptide treatment also provides anti-cancer effect. Without intended to be bound by theory, cancer cells may also have a decreased capacity to maintain MMP compared with normal cells. Cancer cells may thus also be exposed to prolonged mPTP opening and possibly, to minority MOMP. Accordingly, MMP may provide a selective functional target for cancer cells, for example, a functional target for gerotherapeutic CPPs such as those described herein to target cancer cells. In embodiments, Mechanism #2 may thus provide an oncolytic effect in addition to a senolytic effect.

[0314] Gerotherapeutic Peptides Provide increased Cancer-Specific Survival Gerotherapeutic peptide treatment also provides increased cancer-specific survival in naturally aged mice.

[0315] Cancer-specific survival was evaluated in naturally aged C57BL / 6J male mice. Animals fed a normal diet were treated with P5, P6, and control (saline) beginning at 75 weeks old. After approximately 50 weeks of treatment with P5 (18 weeks of low-dose of 6.6 mg / kg 3X per week and then increased to high-dose of 25 mg / kg 1 X per week) and P6 (18 weeks of low-dose of 10 mg / kg 3X per week and increased to high-dose of 50 mg / kg 1X per week) treated animals showed a developing trend towards increased cancer-specific survival relative to saline treated animals.

[0316] FIG. 34A shows probability of survival (overall survival) over time for naturally aged male mice treated with gerotherapeutic peptide and control (saline). As shown, both the P5 and P6 treatment groups showed greater probability of survival compared with control.

[0317] FIG. 34B shows cancer-specific probability of survival over time for naturally aged male mice treated with gerotherapeutic peptide and control (saline). As shown, both the P5 and P6 treatment groups showed greater probability of cancer-specific survival compared with control. Further, the improvement in cancer-specific survival was greater than the improvement in general survival, indicating a cancer-specific therapeutic benefit to gerotherapeutic peptide treatment.

[0318] FIG. 34C shows survival (percent survival) of C57BL / 6J mice (male and female) for comparison. This data reflects normal lifespan of C57BL / 6J mice (male and female). Based on this data, saline control mice will continue to die at an accelerating rate.ATTORNEY DOCKET: 05336.0008W001

[0319] Gerotherapeutic Peptides Provide In Vitro Cancer Effect

[0320] Exemplary gerotherapeutic peptides were analyzed against leukemias and lymphomas. EC50values are shown in the table below (values given in μM).

[0321] Cell

[0322] Cell Type P6 P8 P9 P13 P14 P16 P17 P18 Line

[0323] Acute monocy tic

[0324] THP-1

[0325] leukemia 100 100 66.4 100 100 100 100 Acute

[0326] HL-60 promyelocytic

[0327] leukemia 149.3 100 88.6 97.4 100 100 100 100 Acute

[0328] HL- myeloblastic

[0329] 60 / S4

[0330] leukemia 100 100 100 100 100 100 100 100 Mantle cell (B

[0331] JeKo-1

[0332] cell) lymphoma 100 100 81.1 8.3 6.3 100 too 100 B cell (Burkitt’s

[0333] Raji

[0334] lymphoma) 2.0 100 267.5 100 100 100 100 KCL-22- CML KM 100 100 100 100 100 100 100 100 KU-812 CML 100 125.8 76.2 100 100 130.8 100 51.5 Acute myeloid

[0335] HNT-34

[0336] leukemia 100 100 100 100 76.489 100 100 Acute T cell

[0337] Loucy

[0338] leukemia 100 100 100 100 100 100 100 100 Acute T cell

[0339] Jurkat

[0340] leukemia 100 100 100 100 84.31 100 100 100 MHH- Ph “like” B cell

[0341] CALL 4 precursor leukemia 63.5 70.4 51.7 100 100 100 100 100 MUTZ-5 Ph “like” B-ALL 100 12.4

[0342] MOLM- 1

[0343] HAL-01 Ph “like” B-ALL 15.7 100 6.1 31.0 17.1 37.3 17.9 RCH- Ph “like” B-ALL

[0344] ACV 59.2 9.4 5.4 41.7 7.9 75.1 10.6 NALM- Ph + B-ALL

[0345] 21 100 100 100 100 100 100 100 100 TOM-1 Ph + B-ALL 2.4 15.8 4.054 100 100 100 100 100 SD-1 Ph + B-ALL 143.9 100 92.4 81.2 100 61.0 88.4

[0346] Bladder, TCC

[0347] RT4

[0348] papilloma 5.0 95.0 86.8

[0349] T24 Bladder cancer 10.9 63.8 115.2 29.1 5.8 38.5 9.8 TCCSUP Bladder cancer

[0350] 13.4

[0351]

[0352] UMUC3 Bladder cancer 22.9 100 45.8 18.8 1.8 116.2 2.0ATTORNEY DOCKET: 05336.0008W001

[0353] Cell

[0354] Cell Type P6 P8 P9 Pl 3 P14 Pl 6 Pl 7 P18 Line

[0355] T-47D Breast cancer 7.1 12.7 100.0 59.4 0.6 66.1 1.3

[0356] ZR-75- Breast cancer

[0357] 30 100 100 62.5 100 100 100 100 HCT116 Colon carcinoma 10.9 100.0 14.8 17.1 1.9 77.4 3.9 SW620 Colon cancer 100 100 100 27.1 1.6 100 3.4 100 LS123 Colorectal cancer 86.0 60.9

[0358] Epidermoid

[0359] A431 carcinoma of the

[0360] skin

[0361] SK- Malignant

[0362] MEL-28 Melanoma 100 100 too 17.4 0.4 100 0.7

[0363] SK- Malignant

[0364] MEL-1 Melanoma

[0365] Malignant

[0366] A-375

[0367] Melanoma

[0368] Malignant

[0369] G-361

[0370] Melanoma

[0371] HepG2 Liver carcinoma 3.0 147.0 100

[0372] SNU- Liver carcinoma

[0373] 475 too 68.2

[0374] Extrahepatic bile

[0375] TFK-1

[0376] duct carcinoma 100 100 100 39.9 1.8 46.8 2.6 HCC-78 Lung carcinoma 8.8 22.5 12.4 20.5 3.9 60.4 3.1 A549 Lung carcinoma 100 136.2 72.4 100 100 100 100

[0377] Prostate cancer

[0378] 22RV1

[0379] (AR+) 5.5 16.6 11.7 25.8 1.6 100 100 Prostate cancer

[0380] LnCAP

[0381] (AR+) 62.9 100 too 49.1 4.5

[0382] MDA Prostate cancer

[0383] Pea 2 b (AR+) 100 100 100 100 100 100 100

[0384] Prostate cancer

[0385] DU145

[0386] (AR-) 100 6.2 15.9 7.9 1.5 89.4 3.4 Prostate cancer

[0387] PC3

[0388]

[0389] (AR-) 100 100 100 100 100 100 100

[0390] Gerotherapeutic Peptides Provide In Vitro Cancer Effect

[0391] Gerotherapeutic peptide treatment also provides in vitro cancer effect.

[0392] Peptide treatment against colorectal cancer was evaluated in female NSG mice. Mice were 8 weeks old at initiation of study and were injected with SW620, 4E6 SC. PeptideATTORNEY DOCKET: 05336.0008W001

[0393] treatment was initiated 14 days following injection. The experimental schema is shown in FIG. 35A. Treatment groups are shown in the table below.

[0394] Treatment Dose ROA Frequency No. of Animals

[0395] Saline IP QD, M-F 5

[0396] P9 50 mg / kg SC 1X / Week 5

[0397] P14 50 mg / kg sc 1 X / Week 5

[0398]

[0399] Normalized SW620 tumor volumes (mean) for all three groups are shown in FIG. 35B. As shown, both P9 and P14 showed lower normalized tumor volumes throughout the study. Normalized SW620 tumor volumes (individual) for control are shown in FIG. 35C.

[0400] Normalized SW620 tumor volumes (individual) for P9 are shown in FIG. 35D. Normalized SW620 tumor volumes (individual) for P14 are shown in FIG. 35E. As shown, both P9 and P14 treatment groups demonstrated lower normalized tumor volumes compared with control.

[0401] FIG. 36A shows normalized tumor volumes for control-treated mice with data tracked by individual subject. FIG. 36B shows normalized tumor volumes for P9-treated mice with data tracked by individual subject. FIG. 36D shows normalized tumor volumes for P14-treated mice with data tracked by individual subject. Tumors were processed using RPMIc buffer containing mixture of Collagenase IV and Dnase I on the day of necropsy, stained with anti-human VEGFR2 and anti-mouse neutrophil (mCD11b and mLy6G) antibodies, and analyzed by flow cytometry

[0402] FIG. 36D through FIG. 36H show tumor cell, neutrophil, and tumor volume data tracked by individual subject. FIG. 36D shows tumor cells per subject across the three treatment groups. FIG. 36E shows neutrophils per subject across the three treatment groups. FIG.

[0403] 36F shows ratio of tumor cells to tumor infiltrating neutrophils per subject across the three treatment groups. FIG. 36G shows ratio of tumor cells to normalized tumor volume per subject across the three treatment groups. FIG. 36H shows ratio of neutrophils to normalized tumor volume per subject across the three treatment groups.

[0404] Tumor volume in mice dosed with gerotherapeutic peptides P9 and P14 decreased moderately compared to saline-dosed controls as shown in FIG. 35B, indicative of tumor growth control. Due to previous studies establishing a robust immune response fromATTORNEY DOCKET: 05336.0008W001

[0405] gerotherapeutic peptide treatment in mice, it was hypothesized that tumor infiltrating neutrophils were making up a significant proportion of the tumor volume. Flow cytometry was used to measure the number of tumor cells and neutrophils in each individual tumor as shown in FIG. 36D through FIG. 36H. Flow cytometry analysis revealed that tumors in mice treated with P9 and P14 contained a much higher proportion of neutrophils than tumors in mice treated with saline controls as shown in FIG. 36E and FIG. 36H. These results indicate that tumor caliper measurements obfuscated the efficacy of P9 and P14, due to added tumor volume from immune cell infiltration.

[0406] In summary, gerotherapeutic peptide treatment provides anti-cancer effect including increased cancer-specific survival, in vitro effect against cancer cell lines, and in vivo effect against colorectal tumor cells in mice. Accordingly, gerotherapeutic peptides demonstrate an oncolytic effect.

[0407] Summary of Dual-Action Therapeutic Effect Provided by Gerotherapeutic Peptides and Compositions

[0408] Gerotherapeutic peptides and gerotherapeutic compositions provide a single age-specific target, namely, mitochondria, more specifically inner mitochondrial membrane potential (Δψm), and even more specifically reduced inner mitochondrial membrane potential that develops in the mitochondria of all living organisms as they age. Gerotherapeutic peptides and gerotherapeutic compositions described herein target this inner mitochondrial membrane potential (Δψm) resulting in two mechanisms of therapeutic effect.

[0409] Mechanism #1 provides enhancement / improvement of mitochondrial efficiency in all aging cells by increasing the Δψm (protective effect). This protective effect provides improved energy metabolism, for example, via reduced proton leak, increased coupling efficiency, and increased mitochondrial ATP production. This protective effect also provides increased exercise endurance, for example, on treadmill and / or rotarod testing, with no drop off in improvement while treatment continues. Mechanism #1 can be used to provide improved healthspan and possibly increased lifespan in subjects treated with gerotherapeutic peptides.

[0410] Mechanism #2 provides apoptotic elimination of senescent cells via mitochondrial-mediated apoptosis (senolytic effect) and / or of cancer cells via mitochondrial-mediated apoptosis (oncolytic effect). This apoptotic effect provides reduction in systemicATTORNEY DOCKET: 05336.0008W001

[0411] inflammation, tissue remodeling, improved muscle strength, improved body composition including loss of fat accompanied by increase in lean body mass, and improvement in age- related cognitive decline, and reduction of cancer incidence. Mechanism #2 can be used to provide improved healthspan and possibly increased lifespan in subjects treated with gerotherapeutic peptides.

[0412] Overview of Gerotherapeutic CPPs and CPP Compositions

[0413] In certain embodiments, a gerotherapeutic CPP in a composition is in an amount sufficient to reduce a senescent cell population in vitro, eliminate cancer cells, and / or to increase inner mitochondrial membrane potential in vitro. In certain instances, a gerotherapeutic CPP in a composition is in an amount sufficient to reduce the senescent cell population in vivo, in a tissue or organ, eliminate cancer cells in vivo, in a tissue or organ, and / or to increase inner mitochondrial membrane potential in vivo, in a tissue or organ. In certain embodiments, a gerotherapeutic CPP in a composition is in an amount sufficient to reduce the senescent cell population in a subject, eliminate cancer cells in a subject, and / or to increase inner mitochondrial membrane potential in a subject.

[0414] A gerotherapeutic CPP can contain naturally occurring amino acids. There are different amino acid isomers, and a gerotherapeutic CPP can contain D-amino acids, L-amino acids, or a combination of D-amino acids and L-amino acids. In certain embodiments, all amino acids of a gerotherapeutic CPP are L-amino acids or D-amino acids. A gerotherapeutic CPP in certain embodiments can contain a peptidomimetic portion and an amino acid portion. In certain instances, a gerotherapeutic CPP is a peptidomimetic containing no naturally occurring amino acids.

[0415] In certain embodiments, a gerotherapeutic CPP contains:

[0416] WEARLARALARALARHLARALARALRACEA (SEQ ID NO: 5).

[0417] In certain embodiments, a gerotherapeutic CPP contains:

[0418] WEARLARALARALARLARALARALRACEA (SEQ ID NO: 6);

[0419] WEARLARALARALARELARALARALRACEA (SEQ ID NO: 8);

[0420] WEAHLAHALARALARHLARALARALRACEA (SEQ ID NO: 17) WEARLARALARALARHLARALAHALHACEA (SEQ ID NO: 18) WEAHLAHALARALARHLARALARALRACEA (SEQ ID NO: 19) WEARLARALARALARHLARALAHALHACEA (SEQ ID NO: 20)ATTORNEY DOCKET: 05336.0008W001

[0421] REARLARALARALARLARALARALRACEA (SEQ ID NO: 9);

[0422] REARLARALARALARLARALARALRAREA (SEQ ID NO: 10); or REARLARALARALARELARALARALRAREA (SEQ ID NO: 11).

[0423] In certain embodiments, a gerotherapeutic CPP contains: LLIILRRRIRKQAHAHSK (SEQ ID NO: 13), derived from murine VE-Cadherin and referred to as murine pVEC (“m-pVEC”), or LLIFLRRRLRKQARAHGK (SEQ ID NO: 14), derived from human VE-Cadherin and referred to as a human pVEC (“hu-pVEC”).

[0424] In certain embodiments, a gerotherapeutic CPP contains RKKRRQRRR (SEQ ID NO: 21), or RRRRRRRR (SEQ ID NO: 22), or RKKRRRESRKKRRRES (SEQ ID NO: 23), or GRPRESGKKRKRKRLKP (SEQ ID NO: 24), or GRRRRRRRRRPPQ (SEQ ID NO: 25), or RVRVFVVHIPRLT (SEQ ID NO: 26), or GALFLGFLGAAGSTMGAWSQPKKKRKV (SEQ ID NO: 27), or KLALKLALKALKAALKLA (SEQ ID NO: 28), or GWTLNSAGYLLGKINLKALAALAKKIL (SEQ ID NO: 29), or VSALK (SEQ ID NO: 30), or CSIPPEVKFNPFVYLI (SEQ ID NO: 31), or GIGAVLKVLTTGLPALISWIKRKRQQ (SEQ ID NO: 32) or HGLASTLTRWAHYNALIRAF (SEQ ID NO: 33).

[0425] In certain embodiments, a gerotherapeutic CPP contains kshahaqkrirrrlilll (SEQ ID NO: 1009), kgharaqkrlrrrlfill (SEQ ID NO: 1010), aecahlahalahalhralaralaralraew (SEQ ID NO: 1077), Wearlaralaralarhlahalahalhacea (SEQ ID NO: 1078), aecahlahalaralhralaralaralraew (SEQ ID NO: 1079), lliilrrrirkqahahsk (SEQ ID NO: 1080), wearlaralaralarhlaralahalhacea (SEQ ID NO: 1081), or lliflrrrlrkqarahgk (SEQ ID NO: 1084). In certain embodiments a gerotherapeutic CPP may be selected from those in Table 1 included below.

[0426] As discussed above, in the conventional art, cell penetrating peptides have been used to provide a carrier or transporter function, for example, to deliver a different active component into a call, across a cell membrane, etc.

[0427] In embodiments of the present invention, a gerotherapeutic CPP may itself provide a senolytic effect irrespective of any carrier function. That is, the gerotherapeutic CPP may provide the senolytic effect separate and apart from acting as carrier or transporter for a different active component. Likewise, in embodiments of the present invention, a gerotherapeutic CPP may itself provide an oncolytic effect irrespective of any carrier function. That is, the gerotherapeutic CPP may provide the oncolytic effect separate andATTORNEY DOCKET: 05336.0008W001

[0428] apart from acting as carrier or transporter for a different active component. Still further, in embodiments a gerotherapeutic CPP may itself provide a protective effect (increasing inner mitochondrial membrane potential) irrespective of any carrier function. That is, the gerotherapeutic CPP may provide the protective effect separate and apart from acting as carrier or transporter for a different active component. Thus, in certain embodiments, a gerotherapeutic CPP composition contains no cargo nucleic acid. In certain embodiments, a gerotherapeutic CPP composition contains no nucleic acid. In certain instances, a gerotherapeutic CPP composition contains no cargo component that reduces a senescent cell population, eliminates a cancer cell population, or increases the inner mitochondrial membrane potential. In certain embodiments, a gerotherapeutic CPP composition contains no component (for example, no cargo component) having one or more of the following activities: (i) having JAK2 protein kinase inhibition activity; (ii) having proinflammatory molecule reduction activity; (iii) having interleukin reduction activity (for example, having IL-6 reduction activity); (iv) having senomorphic activity; or (v) a combination of (i) and (ii); (i) and (iii); (i) and (iv); (ii) and (iii); (ii) and (iv); (iii) and (iv); (i), (ii) and (iii); (i), (iii) and (iv); (ii), (ill) and (iv); or (i), (ii), (iii) and (iv). In certain instances, a gerotherapeutic CPP composition contains no cargo agent. In certain embodiments, a gerotherapeutic CPP composition contains no additive capable of reducing a senescent cell population, eliminating cancer cells, or increasing the inner mitochondrial membrane potential. In certain embodiments, a gerotherapeutic CPP composition contains no fluorescent labels, fluorescein, fluorescein derivatives, GFP, or EGFP. In certain embodiments, a gerotherapeutic CPP composition contains no biotin.

[0429] In certain embodiments, a gerotherapeutic CPP composition contains an active ingredient, and the active ingredient contains, consists essentially of, or consists of the gerotherapeutic CPP. The term “consists essentially of” with reference to an active ingredient containing a gerotherapeutic CPP means there is no other component in the active ingredient that materially affects the characteristics of the active ingredient. An active ingredient, for example, can include one or more components other than the gerotherapeutic CPP that enhance senescent cell population reduction activity by not more than 5%, that enhances cancer cell elimination activity by not more than 5%, or that increases the inner mitochondrial membrane potential by not more than 5%. For example, an active ingredient can contain another component so long as the senescent cellATTORNEY DOCKET: 05336.0008W001

[0430] population reduction activity, cancer elimination activity, and / or inner mitochondrial membrane increase activity of the active ingredient containing the gerotherapeutic CPP and other component is increased by no more than 5% compared to the active ingredient containing the gerotherapeutic CPP but not containing the other component.

[0431] Senescent cell population reduction activity of an active ingredient can be assessed by determining the amount of (i) SA-beta-galactosidase; or (ii) p16 (p16INK4a for example); or (iii) urokinase plasminogen activator receptor (uPAR); or (iv) a p-21 positive cell population; or (v) a combination of one or more of (i), (ii), (iii), and (iv) or other markers as discussed above. Senescent cell population reduction activity of an active ingredient can be assessed by a process described in the Examples disclosed herein. In embodiments, a senescent cell population reduced by a gerotherapeutic CPP composition contains cells located in any and / or every organ in a body of the patient. As examples and without limitation, a senescent cell population reduced by a gerotherapeutic CPP composition contains cells in one or more organs, including but not limited to the brain, kidneys, liver, lungs, eyes, inguinal adipose tissue, gastrocnemius, skin and spleen. In certain embodiments, a senescent cell population reduced by a gerotherapeutic CPP composition is the skin, containing skin cells, and the skin cells can include epidermis cells, dermis cells, or epidermis cells and dermis cells. In certain embodiments, a senescent cell population reduced by a gerotherapeutic CPP composition are in any organ of the body, containing the cells located in those organs. In certain embodiments, a senescent cell population reduced by a gerotherapeutic CPP composition contains fibroblast cells. In certain embodiments, a gerotherapeutic CPP composition contains a senescent cell population in addition to a gerotherapeutic CPP, and sometimes a senescent cell population contains one or more skin cells and / or system cells, including cell types described herein.

[0432] A gerotherapeutic CPP composition can be prepared as a pharmaceutically acceptable composition containing a gerotherapeutic CPP as described herein along with one or more pharmaceutically acceptable excipients, referred to as a gerotherapeutic CPP pharmaceutical composition. A gerotherapeutic CPP pharmaceutical composition can be prepared for a suitable route of administration, including topical or systemic administration, for example. In certain embodiments, a gerotherapeutic CPP pharmaceutical composition is formulated as a topical cream. In certain instances, a gerotherapeutic CPP pharmaceutical composition is prepared for injection (for example, for subcutaneous,ATTORNEY DOCKET: 05336.0008W001

[0433] intramuscular or intravenous administration). In certain instances, a gerotherapeutic CPP cosmetic composition is prepared for application topically or by penetration of the skin using microneedles, intradermal or subcutaneous injection or other methods of skin penetration.

[0434] Gerotherapeutic CPP Compositions

[0435] A gerotherapeutic CPP sometimes contains about 50 or fewer amino acids, or about 45 or fewer amino acids, or about 40 or fewer amino acids, or about 35 or fewer amino acids, or about 30 or fewer amino acids, or about 25 or fewer amino acids, or about 20 or fewer amino acids, or about 15 or fewer amino acids. In an embodiment, a gerotherapeutic CPP may contain 18 amino acids.

[0436] In embodiments, a gerotherapeutic CPP may be categorized by its net charge, for example, the sum or total charge of individual amino acids in the gerotherapeutic CPP may be used to categorize the gerotherapeutic CPP. Certain amino acids can have a net positive charge at pH 7.0 (positively charged amino acid) or net negative charge at pH 7.0 (negatively charged amino acid), and certain amino acids are hydrophobic or hydrophilic. Amino acids are referred to herein by representative single-letter codes. Positively-charged amino acids at pH 7.0 include arginine (R), lysine (K) and histidine (H). Negatively-charged amino acids at pH 7.0 include aspartate (D) and glutamate (E). Hydrophilic amino acids include arginine (R), asparagine (N), aspartate (D), glutamine (Q), glutamate (E), histidine (H), lysine (K), serine (S) and threonine (T). Hydrophobic amino acids include glycine (G), alanine (A), leucine (L), isoleucine (I), valine (V), tryptophan (W), tyrosine (Y), phenylalanine (F), methionine (M), cysteine (C) and proline (P).

[0437] In embodiments, a gerotherapeutic CPP may be a cationic peptide. A cationic peptide may have an overall charge at a pH of 7.0, for example, an overall positive charge. For example, in embodiments, the cationic peptide may have a charge of greater than 3 at a pH of 7.0, a charge of greater than 4 at a pH of 7.0, a charge of greater than 5 at a pH of 7.0, a charge of greater than 6 at a pH of 7.0, a charge of greater than 7 at a pH of 7.0, or a charge of greater than 8 at a pH of 7.0.

[0438] Additionally or alternatively, a cationic peptide may have a percentage of charged amino acids with respect to a total number of amino acids. For example, in embodiments the percentage of charged amino acids may be within a specified range, for example, betweenATTORNEY DOCKET: 05336.0008W001

[0439] 25% and 50%. In embodiments, the percentage of charged amino acids may be greater than 40%. In embodiments, the percentage of charged amino acids may be 44% or greater.

[0440] Due at least in part to the overall positive charge and / or the percentage of charged amino acids, a cationic peptide may effectively interact with a cell membrane (for example, a negatively charged cell membrane).

[0441] In embodiments, a gerotherapeutic GPP can be an amphipathic peptide. An amphipathic peptide may have both hydrophilic (water-attracting) and hydrophobic (water-repelling) regions. Amphipathic peptides may effectively insert into lipid bilayers and may be effective at disrupting and / or crossing cell membranes.

[0442] In embodiments, a gerotherapeutic GPP can be both cationic and amphipathic. Such a gerotherapeutic CPP may be referred to as a cationic-amphipathic gerotherapeutic CPP. Other means of categorizing a gerotherapeutic CPP may also be used, for example, whether the gerotherapeutic CPP is polar or nonpolar, hydrophobic or hydrophilic, etc. Still further, a gerotherapeutic CPP may also be categorized based on an amount of one or more specific amino acids. For example, a gerotherapeutic CPP may be categorized as arginine rich, cysteine rich, etc. An arginine rich gerotherapeutic CPP comprises multiple arginine residues. For example, greater than 10% of total residues or greater than 20% of total residues may be arginine. Likewise, a cysteine rich gerotherapeutic CPP comprises multiple cysteine residues. For example, greater than 10% of total residues or greater than 20% of total residues may be cysteine.

[0443] in certain embodiments, a gerotherapeutic CPP contains hydrophobic amino acids, and a gerotherapeutic CPP can contain leucine (L) amino acids, or alanine amino acids (A), or a combination of L amino acids and A amino acids. In certain embodiments, a gerotherapeutic CPP contains a greater proportion of hydrophobic amino acids than hydrophilic amino acids. A gerotherapeutic CPP in certain embodiments contains a ratio of hydrophilic amino acids to hydrophobic amino acids at pH 7.0 of at least about 30:70 to about 40:60 or about 30:67 to about 40:60.

[0444] In certain embodiments, a gerotherapeutic CPP contains one or more negatively-charged amino acids at pH 7.0, and a gerotherapeutic CPP can contain one or more glutamate (E) amino acids. In certain embodiments, a gerotherapeutic CPP contains at least two but noATTORNEY DOCKET: 05336.0008W001

[0445] more than three negatively-charged amino acids. In certain embodiments, a gerotherapeutic GPP contains a ratio of positively-charged amino acids to negatively- charged amino acids of at least about 6:2 to about 9:2 or about 6:2 to about 8:2. In certain embodiments, a ratio of R amino acids to E amino acids is at least about 6:2 to about 9:2 or about 6:2 to about 8:2.

[0446] In certain embodiments, a gerotherapeutic GPP contains six or more R amino acids, twelve or more A amino acids, and six or more L amino acids. In certain instances, a gerotherapeutic GPP contains two or more segments containing RALA (SEQ ID NO: 1 ). In certain embodiments, a gerotherapeutic GPP contains EARLARALARALAR (SEQ ID NO: 2); or LARALARALRA (SEQ ID NO: 3); or EARLARALARALAR (SEQ ID NO: 2) and LARALARALRA (SEQ ID NO: 3). In certain instances, a gerotherapeutic GPP contains X1-EARLARALARALAR-X2-LARALARALRA-X3-EA (SEQ ID NO: 4), where: X1is W or R; X2is selected from H or E; and X3is C or R. In certain instances, a gerotherapeutic CPP contains X1-EARLARALARALARLARALARALRA-X3-EA (SEQ ID NO: 7), where: X1is W or R; and X3is C or R.

[0447] In certain embodiments, a gerotherapeutic CPP contains an amino acid sequence at least about 80% or more identical to X1-EARLARALARALAR-X2-LARALARALRA-X3-EA (SEQ ID NO: 4).

[0448] In certain embodiments, a gerotherapeutic CPP may have a logP measure lower than 0.1 (with log P measurements extending into the negative range).

[0449] In certain embodiments, a gerotherapeutic CPP may have a net positive charge, a logP measure lower than 0.1, one or more positively charged amino acids, an Arg (R) or Lys(K) residue, and combinations thereof.

[0450] In certain embodiments a gerotherapeutic CPP may be selected from those in Table 1. In certain embodiments a gerotherapeutic CPP may be a retro-inverso peptide of any of the SEQ IDs or peptides disclosed herein, for example a D-retro-inverso peptide.

[0451] Uses of Compositions

[0452] In certain embodiments, a gerotherapeutic CPP composition is used to selectively reduce a senescent cell population. In certain embodiments, provided is a method for reducing a senescent cell population, which includes administering a gerotherapeutic CPPATTORNEY DOCKET: 05336.0008W001

[0453] composition to cells in an amount sufficient to selectively reduce the senescent cell population. In certain embodiments, a gerotherapeutic CPP composition is used to selectively reduce a senescent cell population in a tissue, organ or subject. In certain embodiments, provided is a method for selectively reducing a senescent cell population, which includes administering a gerotherapeutic CPP composition to a tissue, organ or subject in an amount sufficient to selectively reduce the senescent cell population in the tissue, organ or subject. In certain embodiments, a gerotherapeutic CPP composition is used to treat a medical condition associated with a senescent cell population. In certain embodiments, provided is a method for treating a medical condition, which includes administering a gerotherapeutic CPP composition to a tissue, organ or subject in an amount sufficient to selectively reduce a senescent cell population in the subject.

[0454] In certain instances, the cells, tissue, organ or subject contain, and optionally have been detected to contain, a senescent cell population. For example, senescent cells may be found to accumulate in various cells, tissue, and / or organs. Representative examples of senescent cell accumulation in humans and other mammals may include within the eyes, lung, liver, pancreas, fat cells, skeletal muscle, skeletal structure including bone, brain, heart, kidneys, and skin. Representative examples of disease / conditions, for example, age-related diseases and conditions, that may be caused or exacerbated by senescent cell accumulation include cataracts, age-associated macular degeneration (both wet and dry), idiopathic pulmonary fibrosis, obesity, glucose intolerance, diabetes, sarcopenia, reduced exercise capacity, frailty, osteoporosis, bone fracture, cognitive decline, memory impairment, Alzheimer’s disease, Parkinson’s disease, chronic traumatic encephalopathy, age-related cardiomyocyte hypertrophy, loss of cardiac stress tolerance, heart failure, arrhythmias, glomerulosclerosis, renal RAAS hyperactivity, kidney failure, dermal thinning, and subdermal adipose layer thinning. In embodiments, a gerotherapeutic CPP composition as described herein may be used to treat or prevent one or more of these age- related diseases and conditions. Representative examples of the effects of a gerotherapeutic CPP composition as described herein may include delayed cataract formation, reduction of idiopathic pulmonary fibrosis, alleviation of metabolic and adipose tissue dysfunction, improved glucose tolerance, enhanced insulin sensitivity, amelioration of inflammation, increase muscle strength and exercise capacity, improved body weight and composition, higher bone mass and strength, better microarchitecture, reduction inATTORNEY DOCKET: 05336.0008W001

[0455] lordokyphosis, improved cognition and memory, reduced incidence of neurodegenerative disease, improved cardiac diastolic function, reduced cardiac hypertrophy, reduced arrhythmias, improved kidney function (for example, as measured by albumin / Creatinine Ratio), increased thickness of dermis and subdermal adipose layer, reduction of cancer and cancer-related death, extension of lifespan, extension of healthspan.

[0456] In further embodiments, senescent cells may accumulate in tissue as a result of other injury, for example, senescent cells may accumulate in the brain as a result of mild traumatic brain injury or other damage. Some examples of sources of such damage include contact sports, especially football, military operations, firing weapons, etc. These senescent cells may contribute to a host of symptoms, including but not limited to cognitive difficulties, low testosterone levels, headache, concussion signs and symptoms, depressive / emotional and behavioral dyscontrol symptoms, pain, suicidal thoughts, insomnia, paranoia, and the like. Representative examples of the effects of a gerotherapeutic CPP composition as described herein may include eliminating such senescent cells and preventing progression to persistent symptoms and neurodegenerative disease. As an example, post-concussive syndrome may be treated and / or prevented. Similarly, chronic traumatic encephalopathy may be treated and / or prevented.

[0457] In further embodiments, senescent cells may accumulate in tissue as a result of treatment with radiation therapy for cancer or other diseases or conditions, for example, senescent cells may accumulate in or around the treated tissue. Representative examples of the effects of a gerotherapeutic CPP composition as described herein may include eliminating such senescent cells and preventing progression to further diseases or conditions.

[0458] Methods for detecting senescent cells are known, including determining presence, absence and / or amount of (I) SA-beta-galactosidase; or (ii) p16 (p16INK4a for example); or (iii) urokinase plasminogen activator receptor (uPAR); or (iv) a p-21 positive cell population; or (v) a combination of one or more of (I), (ii), (iii), and (iv).). In certain embodiments, the senescent cell population is (i) a SA-beta-galactosidase-positive cell population; or (ii) a p16-positive cell population (a p16INK4a-positive cell population for example); or (iii) a urokinase plasminogen activator receptor (uPAR)-positivecell population; or (iv) a p-21 positive cell population; or (v) a combination of one or more of (i), (ii), (iii), and (iv).. In certain embodiments, presence, absence and / or amount of a senescent cells in aATTORNEY DOCKET: 05336.0008W001

[0459] population is detected in vitro, ex vivo and / or in vivo, in certain instances, presence, absence and / or amount of a senescent cells in a population is detected in a sample containing cells, tissue and / or organ of subject, and / or sometimes in a subject. In certain embodiments, a gerotherapeutic CPP composition is administered based on the presence, absence or amount of senescent cells detected.

[0460] In embodiments, the senescent cell population includes cells throughout the body and in various organs. For example and without limitation, a senescent cell population may be located in one or more of the brain, kidneys, liver, lungs, eyes, inguinal adipose tissue, gastrocnemius, and spleen. In certain embodiments, the senescent cell population contains skin cells, and the skin cells sometimes include epidermis cells, dermis cells, or epidermis cells and dermis cells. In certain implementations, a gerotherapeutic CPP composition is administered to skin tissue (for example, skin tissue of a subject) topically or by injection. In certain embodiments, the senescent cell population contains systemic cells. In certain embodiments, a gerotherapeutic CPP composition is administered topically or by injection. In certain embodiments, a device described herein is used to administer a gerotherapeutic CPP composition, which sometimes is for topical administration or administration by injection.

[0461] In some embodiments, the disclosed method treats the whole Individual’s body, including the skin. Such embodiments may apply the conditions internally (e.g., injection such as IV injection) and also topically.

[0462] In certain embodiments, a gerotherapeutic CPP composition has a detectable senolytic activity, and sometimes does not have a detectable senomorphic activity.

[0463] In certain embodiments, a medical condition treated by a gerotherapeutic CPP composition is actinic keratosis, Bowen’s disease, in situ carcinoma, atopic dermatitis, non-segmental vitiligo, psoriasis, ultraviolet (UV) damaged skin or aged skin. The UV damaged skin sometimes is severely UV damaged skin, and sometimes the psoriasis is plaque psoriasis. In certain instances, a medical condition is treated in a human subject.

[0464] In some embodiments, the gerotherapeutic CPP composition is administered to treat a medical condition including delaying or preventing age-related disorders and maximizing healthy lifespan, infertility, lordokyphosis, sarcopenia, age-related cataracts, fat loss, age- related cardiomyocyte hypertrophy and loss of cardiac stress tolerance, heart failure,ATTORNEY DOCKET: 05336.0008W001

[0465] cardiac arrhythmias, glomerulosclerosis, renal RAAS hyperactivity, kidney failure, lungs - idiopathic pulmonary fibrosis, skeletal muscle - exercise capacity, frailty, skeleton - femur and spine - osteoporosis, fracture, arterial wall stiffening, impaired wound healing, dermal thinning (dermis and subdermal adipose layer thickness), physical fitness and exercise ability (e.g. time to exhaustion in a treadmill exercise test), amelioration of metabolic dysfunction and alleviation of age-related brain inflammation and cognitive impairment. Examples of ameliorating metabolic disfunction include decreased fasting glucose levels and improved glucose tolerance when on a high-fat diet. This induces metabolic syndrome in even young animals fed a high fat diet. Metabolic syndrome is effectively reduced by elimination of senescent cells as measured by lower body weight, lower fasting blood glucose levels and improvements in both glucose and insulin tolerance. Also lower basal insulin levels after fasting that is followed by a significant increase in insulin levels 15 min after a glucose load in a Glucose Tolerance Test (GTT), indicative of improved pancreatic beta cell function.

[0466] In certain embodiments, a gerotherapeutic CPP composition is used to provide a senolytic effect by inducing apoptosis in senescent cells.

[0467] In certain embodiments, a gerotherapeutic CPP composition is used to provide an oncolytic effect by inducing apoptosis in cancer cells.

[0468] In certain embodiments, a gerotherapeutic CPP composition is used to selectively reduce or eliminate a cancer cell population. In certain embodiments, provided is a method for reducing or eliminating a cancer cell population, which includes administering a gerotherapeutic CPP composition to cells in an amount sufficient to selectively reduce or eliminate the cancer cell population. In certain embodiments, a gerotherapeutic CPP composition is used to selectively reduce or eliminate a cancer cell population in a tissue, organ or subject. In certain embodiments, provided is a method for selectively reducing or eliminating a cancer cell population, which includes administering a gerotherapeutic CPP composition to a tissue, organ or subject in an amount sufficient to selectively reduce or eliminate the cancer cell population in the tissue, organ or subject. In certain embodiments, a gerotherapeutic CPP composition is used to treat a medical condition associated with cancer. In certain embodiments, provided is a method for treating a medical condition, which includes administering a gerotherapeutic CPP composition to a tissue, organ or subject in an amount sufficient to selectively reduce or eliminate a cancer cell population inATTORNEY DOCKET: 05336.0008W001

[0469] the subject. In certain embodiments, a gerotherapeutic CCP composition is used to provide a protective effect by increasing inner mitochondrial membrane potential in aging cells. In certain embodiments, a gerotherapeutic CPP composition is used to bind to cardiolipin. In certain embodiments, a gerotherapeutic CPP composition is used to bind to normal cardiolipin and stabilize a cytochrome C-cardiolipin complex and / or to is used to bind to oxidized cardiolipin and destabilize a cytochrome C-oxidized cardiolipin complex. In certain embodiments, a gerotherapeutic CPP composition is used to bind to normal cardiolipin and stabilize the inner mitochondrial membrane potential and / or is used to bind to oxidized cardiolipin and induce apoptosis.

[0470] In certain embodiments, a gerotherapeutic CPP composition is used to increase an inner mitochondrial membrane potential. In certain embodiments, provided is a method for increasing inner mitochondrial membrane potential, which includes administering a gerotherapeutic CPP composition to cells in an amount sufficient to increase the inner mitochondrial membrane potential.

[0471] In certain embodiments, a gerotherapeutic CPP composition is used to increase inner mitochondrial membrane potential in a tissue, organ or subject. In certain embodiments, provided is a method for increasing inner mitochondrial membrane potential, which includes administering a gerotherapeutic CPP composition to a tissue, organ or subject in an amount sufficient to increase the inner mitochondrial membrane potential in the tissue, organ or subject.

[0472] In certain embodiments, a gerotherapeutic CPP composition is used to treat a medical condition associated with decreased inner mitochondrial membrane potential. In certain embodiments, provided is a method for treating a medical condition, which includes administering a gerotherapeutic CPP composition to a tissue, organ or subject in an amount sufficient to increase an inner mitochondrial membrane potential in the subject. In certain embodiments, a gerotherapeutic CPP composition is used to provide improved mitochondrial function. In certain embodiments, a gerotherapeutic CPP composition is administered in an amount sufficient to cause improved mitochondrial function.

[0473] In certain embodiments, a gerotherapeutic CPP composition is used to provide improved increased ATP production. In certain embodiments, a gerotherapeutic CPP composition is administered in an amount sufficient to cause increased ATP production.ATTORNEY DOCKET: 05336.0008W001

[0474] In certain embodiments, a gerotherapeutic CPP composition is used to provide tissue remodeling. In certain embodiments, a gerotherapeutic CPP composition is administered in an amount sufficient to cause reduction of intermyocyte space, reduction in adipocyte area, and / or reduction in fat mass.

[0475] In certain embodiments, a gerotherapeutic CPP composition is used to provide weight loss. In certain embodiments, a gerotherapeutic CPP composition is administered in an amount sufficient to cause weight loss in a subject.

[0476] In certain embodiments, a gerotherapeutic CPP composition is used to provide improved endurance or function. In certain embodiments, a gerotherapeutic CPP composition is administered in an amount sufficient to cause increased endurance or function.

[0477] In certain embodiments, a gerotherapeutic CPP composition is used to provide an anti¬ tumor effect in a subject. In certain embodiments, a gerotherapeutic CPP composition is administered in an amount sufficient to cause an increased cancer-specific probability of survival in a subject. In certain embodiments, a gerotherapeutic CPP composition is administered in an amount sufficient to cause selective apoptosis of cancer cells.

[0478] In certain embodiments, a gerotherapeutic CPP in a composition is administered at a dose of about 0.1 mg / kg to about 50 mg / kg. A CPP composition can be administered about one (1X) to about five times (5X) weekly, or three times (3X) weekly, and in certain instances is administered intraperitoneally, subcutaneously, intravenously or topically.

[0479] Certain Implementations

[0480] Following are non-limiting examples of certain implementations of the technology. These implementations may be used in connection with one or more of the models and / or examples described above.

[0481] A1. A method of eliminating senescent cells, eliminating cancer cells, and / or improving mitochondrial efficiency in non-senescent cells by administering a gerotherapeutic cell penetrating peptide (“CPP”).

[0482] A2. The method according to the embodiment of A1, wherein the gerotherapeutic CPP is an amphipathic gerotherapeutic CPP.

[0483] A3. The method according to the embodiment of A2, wherein the amphipathic gerotherapeutic CPP triggers apoptosis of senescent cells through disruption of either anATTORNEY DOCKET: 05336.0008W001

[0484] external cell membrane or a mitochondrial membrane and / or improves mitochondrial efficiency in non-senescent cells through stabilization of an inner mitochondrial membrane. A4, The method according to the embodiment of A1, wherein the gerotherapeutic CPP is a cationic CPP.

[0485] A5. The method according to the embodiment of A4, wherein the cationic gerotherapeutic CPP triggers apoptosis of senescent cells and / or cancer cells through disruption of either an external cell membrane or a mitochondrial membrane and / or improves mitochondrial efficiency in non-senescent cells through stabilization of an inner mitochondrial membrane.

[0486] A6. The method according to the embodiment of A1, wherein the gerotherapeutic CPP is a cationic-amphipathic gerotherapeutic CPP.

[0487] A7. The method according to the embodiment of A6, wherein the cationic-amphipathic gerotherapeutic CPP triggers apoptosis of senescent cells and / or cancer cells through disruption of either an external cell membrane or a mitochondrial membrane and / or improves mitochondrial efficiency in non-senescent cells through stabilization of an inner mitochondrial membrane.

[0488] A8. The method according to the embodiment of A1, wherein the gerotherapeutic CPP is an arginine-rich CPP.

[0489] A9. The method according to the embodiment of A8, wherein the arginine-rich gerotherapeutic CPP comprises arginine in an amount of at least 10% of a total number of residues.

[0490] A10. The method according to the embodiment of A1, wherein the gerotherapeutic CPP is a positively charged gerotherapeutic CPP.

[0491] A11. The method according to the embodiment of A10, wherein the positively charged gerotherapeutic CPP binds to phosphatidylserine.

[0492] A12. The method according to the embodiment of A10, wherein the positively charged gerotherapeutic CPP preferentially binds to phosphatidylserine.

[0493] A13. The method according to the embodiment of A10, wherein the positively charged gerotherapeutic CPP preferentially binds to phosphatidylserine in a membrane of a senescent cell.

[0494] A14. The method according to the embodiment of A10, wherein the positively charged gerotherapeutic CPP triggers apoptosis of senescent cells and / or cancer cells through disruption of either an external cell membrane or a mitochondrial membrane and / orATTORNEY DOCKET: 05336.0008W001

[0495] improves mitochondrial efficiency in non-senescent cells through stabilization of an inner mitochondrial membrane.

[0496] A15. The method according to the embodiment of A10, wherein the positively charged gerotherapeutic CPP triggers apoptosis of senescent cells and / or cancer cells through disruption of either the external cell membrane or the mitochondrial membrane and / or improves mitochondrial efficiency in non-senescent cells through stabilization of an inner mitochondrial membrane as a result of binding cardiolipin.

[0497] A16. The method according to the embodiment of A10, wherein the positively charged gerotherapeutic CPP binds oxidized cardiolipin in a senescent cell or a cancer cell and binds native form cardiolipin in a non-senescent cell.

[0498] A17. The method according to the embodiment of A1, wherein the gerotherapeutic CPP is selected from the group consisting of: SEQ ID NO: 5, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 1009, SEQ ID NO: 1010, SEQ ID NO: 1077, SEQ ID NO: 1078, SEQ ID NO:1079, SEQ ID NO: 1080, SEQ ID NO: 1081, and SEQ ID NO: 1084.

[0499] A18. The method according to the embodiment of A1, wherein the gerotherapeutic cell penetrating peptide has a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to at least one sequence selected from the group consisting: SEQ ID NO: 5, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 1009, SEQ ID NO: 1010, SEQ ID NO: 1077, SEQ ID NO: 1078, SEQ ID NO:1079, SEQ ID NO: 1080, SEQ ID NO: 1081, and SEQ ID NO: 1084.

[0500] A19. The method according to the embodiment of A1, wherein the gerotherapeutic cell penetrating peptide is selected from the group consisting of: SEQ ID NO: 028 and any of SEQ ID NO: 557-SEQ ID NO: 742.

[0501] A20. The method according to the embodiment of A1, wherein the gerotherapeutic cell penetrating peptide is selected from the group consisting of: any of SEQ ID NO: 513-SEQ ID NO: 556.

[0502] A21. The method according to the embodiment of A1, wherein the gerotherapeutic cell penetrating peptide is selected from the group consisting of: SEQ ID NO: 1- SEQ ID NO.

[0503] 11, SEQ ID NO: 13-SEQ ID NO: 20, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 26, SEQ ID NO: 27, and any of SEQ ID NO: 29-SEQ ID NO: 64.ATTORNEY DOCKET: 05336.0008W001

[0504] A22. The method according to the embodiment of A1, wherein the gerotherapeutic ceil penetrating peptide is selected from the group consisting of: SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 25, any of SEQ ID NO: 65-498, and SEQ ID NO: 504.

[0505] A23. The method according to the embodiment of A1, wherein the gerotherapeutic cell penetrating peptide is selected from the group consisting of: any of SEQ ID NO: 743-SEQ ID NO: 779.

[0506] A24. The method according to the embodiment of A1, wherein the gerotherapeutic cell penetrating peptide is derived from murine vascular endothelial cadherin.

[0507] A25. The method according to the embodiment of A1, wherein the gerotherapeutic cell penetrating peptide is derived from human vascular endothelial cadherin.

[0508] A26. The method according to the embodiment of A1, wherein the gerotherapeutic cell penetrating peptide comprises SEQ ID NO: 607.

[0509] B1. A composition, comprising a gerotherapeutic cell penetrating peptide in an amount sufficient to selectively reduce a senescent cell population, selectively reduce a cancer cell population, and / or improve mitochondrial efficiency in a non-senescent cell population. B2. The composition of embodiment B1, wherein the senescent cell population is (i) a SA- beta-galactosidase-positive cell population; or (ii) a p16-positive cell population; or (iii) a urokinase plasminogen activator receptor (uPAR)-positivecell population; or (iv) a p-21 positive cell population; or (v) a combination of one or more of (i), (ii), (iii), and (iv).

[0510] B3. The composition of embodiment B1 or B2, wherein the gerotherapeutic cell penetrating peptide contains about 50 or fewer amino acids.

[0511] B4. The composition of any one of embodiments B1-B3, wherein the gerotherapeutic cell penetrating peptide is an amphipathic gerotherapeutic peptide.

[0512] B5. The composition of any one of embodiments B1-B4, wherein the gerotherapeutic cell penetrating peptide has a net positive charge at pH 7.0.

[0513] B6. The composition of any one of embodiments B1-B5, wherein the gerotherapeutic cell penetrating peptide comprises hydrophilic amino acids.

[0514] B7. The composition of any one of embodiments B1-B6, wherein the gerotherapeutic cell penetrating peptide comprises positively-charged amino acids at pH 7.0.

[0515] B8. The composition of embodiment B7, wherein the positively-charged amino acids comprise arginine (R) amino acids.ATTORNEY DOCKET: 05336.0008W001

[0516] B9. The composition of embodiment B7 or B8, wherein the positively-charged amino acids are evenly distributed along the length of the gerotherapeutic peptide.

[0517] B10. The composition of any one of embodiments B1-B9, wherein the gerotherapeutic cell penetrating peptide comprises hydrophobic amino acids.

[0518] B11. The composition of embodiment B10, wherein the hydrophobic amino acids comprise leucine (L) amino acids, or alanine amino acids (A), or a combination of L amino acids and A amino acids.

[0519] B12. The composition of embodiment B10 or B11, wherein the gerotherapeutic cell penetrating peptide comprises a greater proportion of hydrophobic amino acids than hydrophilic amino acids.

[0520] B13. The composition of any one of embodiments B10-B12, wherein the gerotherapeutic cell penetrating peptide comprises a ratio of hydrophilic amino acid residues to hydrophobic amino acid residues at pH 7.0 of at least about 30:70 to about 40:60 or about 30:67 to about 40:60.

[0521] B14. The composition of any one of embodiments B1-B13, wherein the gerotherapeutic cell penetrating peptide comprises one or more negatively-charged amino acids at pH 7.0. B15. The composition of embodiment B14, wherein the negatively-charged amino acids comprise a glutamate (E) amino acid.

[0522] B16. The composition of embodiment B14 or B15, wherein the gerotherapeutic cell penetrating peptide comprises at least two but no more than three negatively-charged amino acids.

[0523] B17. The composition of any one of embodiments B7-B16 the ratio of positively-charged amino acids to negatively-charged amino acids is at least about 6:2 to about 9:2 or about 6:2 to about 8:2.

[0524] B18. The composition of embodiment B17, wherein the ratio of R amino acids to E amino acids is at least about 6:2 to about 9:2 or about 6:2 to about 8:2.

[0525] B19. The composition of any one of embodiments B15-B18, wherein the gerotherapeutic cell penetrating peptide comprises six or more R amino acids, twelve or more A amino acids, and six or more L amino acids.ATTORNEY DOCKET: 05336.0008W001

[0526] B20. The composition of any one of embodiments B8-B19, wherein the gerotherapeutic cell penetrating peptide comprises two or more segments comprising RALA (SEQ ID NO: 1).B21. The composition of embodiment B20, wherein the gerotherapeutic cell penetrating peptide comprises EARLARALARALAR (SEQ ID NO: 2); or LARALARALRA (SEQ ID NO: 3); or EARLARALARALAR and LARALARALRA.

[0527] B22-1. The composition of embodiment B21, wherein the gerotherapeutic cell penetrating peptide comprises X1-EARLARALARALAR-X2-LARALARALRA-X3-EA (SEQ ID NO: 4), wherein: X1is W or R; X2is selected from H or E; and X3is C or R, or an amino acid sequence at least about 80% or more identical to X1-EARLARALARALAR-X2-LARALARALRA-X3-EA (SEQ ID NO: 4).

[0528] B22-2. The composition of embodiment B21, wherein the gerotherapeutic cell penetrating peptide comprises X1-EARLARALARALARLARALARALRA-X3-EA (SEQ ID NO: 7), where: X1is W or R; and X3is C or R, or an amino acid sequence at least 80% or more identical to X1-EARLARALARALARLARALARALRA-X3-EA (SEQ ID NO: 7).

[0529] B23. The composition of any one of embodiments B1-B22-2, wherein the gerotherapeutic cell penetrating peptide comprises WEARLARALARALARHLARALARALRACEA (SEQ ID NO: 5).

[0530] B24. The composition of any one of embodiments B1-B22-2, wherein the gerotherapeutic cell penetrating peptide comprises:

[0531] WEARLARALARALARLARALARALRACEA (SEQ ID NO: 6);

[0532] WEARLARALARALARELARALARALRACEA (SEQ ID NO: 8);

[0533] WEAHLAHALARALARHLARALARALRACEA (SEQ ID NO: 17);

[0534] WEARLARALARALARHLARALAHALHACEA (SEQ ID NO: 18);

[0535] WEAHLAHALAHALARHLARALARALRACEA (SEQ ID NO: 19);

[0536] WEARLARALARALARHLAHALAHALHACEA (SEQ ID NO: 20);

[0537] REARLARALARALARLARALARALRACEA (SEQ ID NO: 9);

[0538] REARLARALARALARLARALARALRAREA (SEQ ID NO: 10); or REARLARALARALARELARALARALRAREA (SEQ ID NO: 11).

[0539] B24.1. The composition of any one of embodiments B1-B8, B10, B11 and B14-B16, wherein the gerotherapeutic cell penetrating peptide comprises:ATTORNEY DOCKET: 05336.0008W001

[0540] LLIILRRRIRKQAHAHSK (SEQ ID NO: 13), or

[0541] LLIFLRRRLRKQARAHGK (SEQ ID NO: 14).

[0542] B25. The composition of any one of embodiments B1-B24.1, wherein the gerotherapeutic cell penetrating peptide comprises D-amino acids, L-amino acids, or a combination of D- amino acids and L-amino acids.

[0543] B25.1. The composition of any one of embodiments B1-B25, wherein the gerotherapeutic cell penetrating peptide comprises a peptidomimetic portion or is a peptidomimetic.

[0544] B26. The composition of any one of embodiments B1-B25.1, wherein the gerotherapeutic cell penetrating peptide is in an amount sufficient to selectively reduce the senescent cell population in vitro and / or the cancer cell population in vitro.

[0545] B27. The composition of any one of embodiments B1-B26, wherein the gerotherapeutic cell penetrating peptide is in an amount sufficient to selectively reduce the senescent cell population and / or the cancel cell population in a tissue or organ.

[0546] B28. The composition of any one of embodiments B1-B27, wherein the gerotherapeutic cell penetrating peptide is in an amount sufficient to selectively reduce the senescent cell population and / or the cancer cell population in cells, tissue and / or organ of subject.

[0547] B29. The composition of any one of embodiments B1-B22-2, wherein the gerotherapeutic cell penetrating peptide has at least 80% sequence identify to a sequence selected from the group consisting of:

[0548] WEARLARALARALARLARALARALRACEA (SEQ ID NO: 6);

[0549] WEARLARALARALARELARALARALRACEA (SEQ ID NO: 8);

[0550] WEAHLAHALARALARHLARALARALRACEA (SEQ ID NO: 17);

[0551] WEARLARALARALARHLARALAHALHACEA (SEQ ID NO: 18);

[0552] WEAHLAHALARALARHLARALARALRACEA (SEQ ID NO: 19);

[0553] WEARLARALARALARHLARALAHALHACEA (SEQ ID NO: 20);

[0554] REARLARALARALARLARALARALRACEA (SEQ ID NO: 9);

[0555] REARLARALARALARLARALARALRAREA (SEQ ID NO: 10); and REARLARALARALARELARALARALRAREA (SEQ ID NO: 11).

[0556] B30. The composition of any one of embodiments B1-B22-2, wherein the gerotherapeutic cell penetrating peptide has at least 85% sequence identify to a sequence selected from the group consisting of:ATTORNEY DOCKET: 05336.0008W001

[0557] WEARLARALARALARLARALARALRACEA (SEQ ID NO: 6);

[0558] WEARLARALARALARELARALARALRACEA (SEQ ID NO: 8);

[0559] WEAHLAHALARALARHLARALARALRACEA (SEQ ID NO: 17);

[0560] WEARLARALARALARHLARALAHALHACEA (SEQ ID NO: 18);

[0561] WEAHLAHALAHALARHLARALARALRACEA (SEQ ID NO: 19);

[0562] WEARLARALARALARHLAHALAHALHACEA (SEQ ID NO: 20);

[0563] REARLARALARALARLARALARALRACEA (SEQ ID NO: 9);

[0564] REARLARALARALARLARALARALRAREA (SEQ ID NO: 10); and REARLARALARALARELARALARALRAREA (SEQ ID NO: 11).

[0565] B31. The composition of any one of embodiments B1-B22-2, wherein the gerotherapeutic cell penetrating peptide has at least 90% sequence identify to a sequence selected from the group consisting of:

[0566] WEARLARALARALARLARALARALRACEA (SEQ ID NO: 6);

[0567] WEARLARALARALARELARALARALRACEA (SEQ ID NO: 8);

[0568] WEAHLAHALARALARHLARALARALRACEA (SEQ ID NO: 17);

[0569] WEARLARALARALARHLARALAHALHACEA (SEQ ID NO: 18);

[0570] WEAHLAHALAHALARHLARALARALRACEA (SEQ ID NO: 19);

[0571] WEARLARALARALARHLAHALAHALHACEA (SEQ ID NO: 20);

[0572] REARLARALARALARLARALARALRACEA (SEQ ID NO: 9);

[0573] REARLARALARALARLARALARALRAREA (SEQ ID NO: 10); and REARLARALARALARELARALARALRAREA (SEQ ID NO: 11).

[0574] B32. The composition of any one of embodiments B1-B22-2, wherein the gerotherapeutic cell penetrating peptide has at least 95% sequence identify to a sequence selected from the group consisting of:

[0575] WEARLARALARALARLARALARALRACEA (SEQ ID NO: 6);

[0576] WEARLARALARALARELARALARALRACEA (SEQ ID NO: 8);

[0577] WEAHLAHALARALARHLARALARALRACEA (SEQ ID NO: 17);

[0578] WEARLARALARALARHLARALAHALHACEA (SEQ ID NO: 18);

[0579] WEAHLAHALAHALARHLARALARALRACEA (SEQ ID NO: 19);

[0580] WEARLARALARALARHLAHALAHALHACEA (SEQ ID NO: 20);

[0581] REARLARALARALARLARALARALRACEA (SEQ ID NO: 9);

[0582] REARLARALARALARLARALARALRAREA (SEQ ID NO: 10); andATTORNEY DOCKET: 05336.0008W001

[0583] REARLARALARALARELARALARALRAREA (SEQ ID NO: 11).

[0584] B33. The composition according to the embodiment of B1, wherein the gerotherapeutic cell penetrating peptide comprises SEQ ID NO: 607.

[0585] C1. The composition of any one of embodiments B1-B33, comprising no cargo nucleic acid.

[0586] C2. The composition of any one of embodiments B1-B33, comprising no nucleic acid.

[0587] C3. The composition of any one of embodiments B1-B33, comprising no cargo agent that selectively reduces the senescent cell population or that selectively reduces the cancer cell population.

[0588] C4. The composition of any one of embodiments B1-B33, comprising no cargo agent.

[0589] C5. The composition of any one of embodiments B1-B33, comprising no additive that selectively reduces the senescent cell population or that selectively reduces the cancer cell population.

[0590] C6. The composition of any one of embodiments B1-B33, wherein the composition comprises an active ingredient, and the active ingredient consists essentially of or consists of the gerotherapeutic cell penetrating peptide.

[0591] D1. A method for selectively reducing a senescent cell population, selectively reducing a cancer cell population, and / or improving mitochondrial efficiency in a non-senescent cell population, comprising administering a composition comprising an active ingredient comprising a gerotherapeutic cell penetrating peptide to cells in an amount sufficient to selectively reduce the senescent cell population, to selectively reduce the cancer cell population, and / or to improve mitochondrial efficiency in the non-senescent cell population. D2. A method for selectively reducing a senescent cell population, selectively reducing a cancer cell population, and / or improving mitochondrial efficiency in a non-senescent cell population, comprising administering a composition comprising an active ingredient comprising a gerotherapeutic cell penetrating peptide to a tissue, organ or subject in an amount sufficient to selectively reduce the senescent cell population, reduce the cancer cell population, and / or improve mitochondrial efficiency in the non-senescent cell population.ATTORNEY DOCKET: 05336.0008W001

[0592] D3. A method for treating a medical condition, comprising administering a composition comprising an active ingredient comprising a gerotherapeutic cell penetrating peptide to a tissue, organ or subject in an amount sufficient to selectively reduce a senescent cell population, to selectively reduce a cancer cell population, and / or to improve mitochondrial efficiency in a non-senescent cell population.

[0593] D4. The method of any one of embodiments D1-D3, wherein the cells, tissue, organ or subject contain a senescent cell population.

[0594] D5. The method of any one of embodiments D1-D4, wherein the senescent cell population is (i) a SA-beta-galactosidase-positive cell population; or (ii) a p16-positive cell population: or (Hi) a urokinase plasminogen activator receptor (uPAR)-positivecell population; or (iv) a p-21 positive cell population; or (v) a combination of one or more of (i), (ii), (iii), and (iv).. D6. The method of any one of embodiments D1-D5, wherein the senescent cell population comprises skin cells.

[0595] D7. The method of embodiment D6, wherein the skin cells comprise epidermis cells, dermis cells, or epidermis cells and dermis cells.

[0596] D8. The method of any one of embodiments D1-D7, wherein the senescent cell population comprises systemic cells.

[0597] D9. The method of embodiment D8, wherein the systemic cells comprise kidney cells, liver cells, spleen cells, or a combination thereof.

[0598] D10. The method of any one of embodiments D1 -D9, wherein the composition is of any one of embodiments A1 -A26 and B1 -B33.

[0599] D11. The method of any one of embodiments D3-D10, wherein the medical condition is actinic keratosis, Bowen's disease, in situ carcinoma, atopic dermatitis, non-segmental vitiligo, psoriasis, ultraviolet (UV) damaged skin or aged skin.

[0600] D12. The method of embodiment D11, wherein the UV damaged skin is severely UV damaged skin.

[0601] D13. The method of embodiment D12, wherein the psoriasis is plaque psoriasis.

[0602] D14. The method of any one of embodiments D1 -D13, wherein the composition comprises about 0.1 mg / kg to about 50 mg / kg of the cell penetrating peptide.ATTORNEY DOCKET: 05336.0008W001

[0603] D15. The method of embodiment D14, wherein the composition comprises about 5 mg / kg of the gerotherapeutic cell penetrating peptide.

[0604] D16. The method of any one of embodiments D1 -D15, wherein the composition is administered about one (1X) to about five times (5X) per week.

[0605] D17. The method of embodiment D16, wherein the composition is administered about three times per week.

[0606] D18. The method of any one of embodiments DI -D17, wherein the composition is administered intraperitoneally, subcutaneously, intravenously or topically.

[0607] E1. A method for selectively reducing a senescent cell population and improving mitochondrial efficiency in a patient, comprising administering to the patient a composition comprising an active ingredient in an amount sufficient to selectively reduce the senescent cell population and / or improve mitochondrial efficiency in a non-senescent cell population, wherein the active ingredient comprises a gerotherapeutic cell penetrating peptide.

[0608] E2. The method of the embodiment of E1, wherein the active ingredient consists essentially of the gerotherapeutic cell penetrating peptide.

[0609] E3. The method of any one of embodiments E1-E2, wherein the gerotherapeutic cell penetrating peptide is a gerotherapeutic cationic cell penetrating peptide.

[0610] E4. The method of any one of embodiments E1 -E3, wherein the gerotherapeutic cell penetrating peptide is an amphipathic gerotherapeutic cell penetrating peptide.

[0611] E5. The method of any one of embodiments E1-E4, wherein the gerotherapeutic cell penetrating peptide is a hydrophobic gerotherapeutic cell penetrating peptide.

[0612] E6. The method of any one of embodiments E1-E5, wherein the gerotherapeutic cell penetrating peptide is selected from the group consisting of: SEQ ID NO: 5, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, and SEQ ID NO: 20. E7. The method of any one of embodiments E1-E6, wherein the gerotherapeutic cell penetrating peptide has a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to at least one sequence selected from the group consisting: SEQ ID NO: 5, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO:ATTORNEY DOCKET: 05336.0008W001

[0613] 20, SEQ ID NO: 1009, SEQ ID NO: 1010, SEQ ID NO: 1077, SEQ ID NO: 1078, SEQ ID NO:1079, SEQ ID NO: 1080, SEQ ID NO: 1081, and SEQ ID NO: 1084.

[0614] E8. The method according to the embodiment of E1, wherein the gerotherapeutic cell penetrating peptide comprises SEQ ID NO: 607.

[0615] F1. A method for treating a condition in a patient, comprising administering to the patient a composition comprising an active ingredient in an amount sufficient to selectively reduce a senescent cell population, selectively reduce a cancer cell population, and / or improve mitochondrial efficiency in a non-senescent cell population, wherein the active ingredient comprises a gerotherapeutic cell penetrating peptide.

[0616] F2. The method of the embodiment of F1, wherein the active ingredient consists essentially of the gerotherapeutic cell penetrating peptide.

[0617] F3. The method of any one of embodiments F1-F2, wherein the gerotherapeutic cell penetrating peptide is a cationic gerotherapeutic cell penetrating peptide.

[0618] F4. The method of any one of embodiments F1-F3, wherein the gerotherapeutic cell penetrating peptide is an amphipathic gerotherapeutic cell penetrating peptide.

[0619] F5. The method of any one of embodiments F1-F4, wherein the gerotherapeutic cell penetrating peptide is a hydrophobic gerotherapeutic cell penetrating peptide.

[0620] F6. The method of any one of embodiments F1-F5, wherein the gerotherapeutic cell penetrating peptide is selected from the group consisting of: SEQ ID NO: 5, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 1009, SEQ ID NO: 1010, SEQ ID NO: 1077, SEQ ID NO: 1078, SEQ ID NO:1079, SEQ ID NO: 1080, SEQ ID NO: 1081, SEQ ID NO: 1084.

[0621] F7. The method of any one of embodiments F1-F6, wherein the gerotherapeutic cell penetrating peptide has a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to at least one sequence selected from the group consisting: SEQ ID NO: 5, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 1009, SEQ ID NO: 1010, SEQ ID NO: 1077, SEQ ID NO: 1078, SEQ ID NO:1079, SEQ ID NO: 1080, SEQ ID NO: 1081, SEQ ID NO: 1084.ATTORNEY DOCKET: 05336.0008W001

[0622] F8. The method of any one of embodiments F1-F7, wherein the condition is an age- related disease.

[0623] F9. The method of any one of embodiments F1-F8, wherein the condition is selected from the group consisting of: dementia, Alzheimer's, sarcopenia, frailty, diabetes, pre¬ diabetes, cataracts, Infertility, lordokyphosis, geographic atrophy of the macula, age- associated macular degeneration, wet age-associated macular degeneration, dry age- associated macular degeneration, uveitis, fat loss, age-related cardiomyocyte hypertrophy, age-related loss of cardiac stress tolerance, heart failure, cardiac arrythmias, glomerulosclerosis, renal RAAS hyperactivity, kidney failure, lung disease, idiopathic pulmonary fibrosis, skeletal muscle decline, osteoporosis, bone fracture, arterial wall stiffening, impaired wound healing, dermal thinning, subdermal adipose layer thinning, physical fitness, exercise ability, metabolic dysfunction, metabolic syndrome, age-related brain inflammation, cognitive impairment, and post-concussive syndrome.

[0624] F10. The method of any one of embodiments F1 -F8, wherein the condition is diabetes and / or pre-diabetes.

[0625] F11. The method of any one of embodiments F10, wherein the gerotherapeutic cell penetrating peptide has a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 18.

[0626] F12. The method of any one of embodiments F1 -F8, wherein the gerotherapeutic condition is sarcopenia and / or frailty.

[0627] F13. The method of the embodiment F12, wherein the gerotherapeutic cell penetrating peptide has a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 18.

[0628] F14. The method of any one of embodiments F1-F8, wherein the condition is post- concussive syndrome.

[0629] F15. The method of embodiment F14, wherein the gerotherapeutic cell penetrating peptide has a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 13.ATTORNEY DOCKET: 05336.0008W001

[0630] F16. The method according to the embodiment of F1, wherein the gerotherapeutic cell penetrating peptide comprises SEQ ID NO: 607.

[0631] G1. A method of treating an animal, the method comprising:

[0632] administering to the animal the composition of any one of embodiments A1 -A26, B1 -33, and C1-6.

[0633] G2. The method of any one of embodiments G1, wherein the animal is a human.

[0634] H1. A method preventing and / or treating a condition in a patient, comprising: identifying a mild traumatic brain injury in the patient,

[0635] administering a gerotherapeutic cell penetrating peptide to the patient.

[0636] H2. The method of embodiment H1, wherein the gerotherapeutic cell penetrating peptide is capable of crossing the blood brain barrier.

[0637] H3. The method of any one of embodiments H1-H2, wherein the gerotherapeutic cell penetrating peptide comprises SEQ ID NO: 13.

[0638] H4. The method of any one of embodiments H1-H2, wherein the gerotherapeutic cell penetrating peptide has at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 13.

[0639] H5. The method of any one of embodiments H1-H4, wherein the condition is selected from the group comprising: post-concussive syndrome, chronic traumatic encephalopathy, and a neurodegenerative disease.

[0640] 11. A method comprising: administering a gerotherapeutic cell penetrating peptide to a patient in an amount sufficient to selectively eliminate senescent cells, selectively eliminating cancer cells, and / or improve mitochondrial efficiency in non-senescent cells. J1. A method comprising: administering a gerotherapeutic cell penetrating peptide to a patient In an amount sufficient to reduce inflammation and improve tissue and organ health by the elimination of senescent cells.

[0641] K1. A method comprising: administering a gerotherapeutic cell penetrating peptide to a patient in an amount sufficient to reduce effects of aging and improve overall health andATTORNEY DOCKET: 05336.0008W001

[0642] functioning of the patient by elimination of senescent cells and / or improvement in mitochondrial efficiency.

[0643] L1. A method comprising: administering a gerotherapeutic cell penetrating peptide to a patient in an amount sufficient to reduce the effects of aging and improve the overall health and functioning of the patient by the elimination of senescent cells and / or improvement in mitochondrial efficiency, wherein administering comprises topical administration and / or administration by microneedle.

[0644] M1. A method comprising: administering a gerotherapeutic cell penetrating peptide to a patient in an amount sufficient to trigger apoptosis through disruption of a mitochondrial membrane and / or improved mitochondrial efficiency through stabilization of the mitochondrial membrane.

[0645] M2. The method of O1, wherein the gerotherapeutic cell penetrating peptide has a net positive charge, a logP measure lower than 0.1, one or more positively charged amino acids, an Arg (R) or Lys(K) residue, or combinations thereof.

[0646] N1. A method comprising: administering a gerotherapeutic cell penetrating peptide to a patient in an amount sufficient to selectively eliminate cancer cells.

[0647] N2. The method of N1, wherein the cancer cells are human leukemia cells.

[0648] O. A method comprising: administering a gerotherapeutic cell penetrating peptide to a patient in an amount sufficient to reduce late radiation-induced toxicity.

[0649] P1. A method comprising: administering a gerotherapeutic cell penetrating peptide to a patient in an amount sufficient to reduce therapy-induced senescence and / or to eliminate therapy induced senescent cells.

[0650] P2. The method of P1, wherein the patient is receiving radiotherapy and / or chemotherapy. The entirety of each patent, patent application, publication and document referenced herein is incorporated by reference. Citation of patents, patent applications, publications and documents is not an admission that any of the foregoing is pertinent prior art, nor does it constitute any admission as to the contents or date of these publications or documents. Their citation is not an indication of a search for relevant disclosures. All statements regarding the date(s) or contents of the documents are based on available information and is not an admission as to their accuracy or correctness.ATTORNEY DOCKET: 05336.0008W001

[0651] The technology has been described with reference to specific examples and implementations. The terms and expressions that have been utilized herein to describe the technology are descriptive and not necessarily limiting. Certain modifications made to the disclosed implementations can be considered within the scope of the technology. Certain aspects of the disclosed implementations suitably may be practiced in the presence or absence of certain elements not specifically disclosed herein.

[0652] Each of the terms “comprising,” “consisting essentially of,” and “consisting of” may be replaced with either of the other two terms. The term “a” or “an” can refer to one of or a plurality of the elements it modifies (e.g., “a reagent” can mean one or more reagents) unless it is contextually clear either one of the elements or more than one of the elements is described. The term “about” as used herein refers to a value within 10% of the underlying parameter (i.e., plus or minus 10%; e.g., a weight of “about 100 grams” can include a weight between 90 grams and 110 grams). Use of the term “about” at the beginning of a listing of values modifies each of the values (e.g., “about 1, 2 and 3” refers to "about 1, about 2 and about 3"). When a listing of values is described, the listing includes all intermediate values and all fractional values thereof (e.g., the listing of values "80%, 85% or 90%" includes the intermediate value 86% and the fractional value 86.4%). When a listing of values is followed by the term "or more," the term "or more" applies to each of the values listed (e.g., the listing of ”80%, 90%, 95%, or more" or ”80%, 90%, 95% or more" or "80%, 90%, or 95% or more" refers to "80% or more, 90% or more, or 95% or more”). When a listing of values is described, the listing includes all ranges between any two of the values listed (e.g., the listing of "80%, 90% or 95%" includes ranges of "80% to 90%, " "80% to 95%" and "90% to 95%").

[0653] TABLE 1: Examples of Gerotherapeutic CPPs

[0654] Ch

[0655] N- C- em Linear Peptide See SEQ

[0656] Category termi term / Cycli LogP Sequence ID NO:

[0657] nus inus Mo c

[0658] d

[0659] RRR Cationic n / a Free NA NA Linear -2.37

[0660] Acet

[0661] amid

[0662] RKC Arginine-rich n / a ylatio NA Linear

[0663] ation

[0664]

[0665] ATTORNEY DOCKET: 05336.0008W001

[0666] Cationic

[0667] SEQ ID RALA and Linear NO: 0001

[0668] amphipathic -0.53 Cationic

[0669] EARLARALARAL SEQ ID

[0670] and Linear AR NO: 0002

[0671] amphipathic -3.38 Cationic

[0672] SEQ ID LARALARALRA and Linear NO: 0003

[0673] amphipathic -1.32 XEARLARALARA Cationic

[0674] SEQ ID LARXLARALARA and Linear NO: 0004

[0675] LRAXEA amphipathic

[0676] -5.97 WEARLARALAR Cationic

[0677] SEQ ID ALARHLARALAR and Free Free NA Linear NO: 0005

[0678] ALRACEA amphipathic

[0679] -3.99 WEARLARALAR Cationic

[0680] SEQ ID ALARLARALARA and Linear NO: 0006

[0681] LRACEA amphipathic

[0682] -3.68 XEARLARALARA Cationic

[0683] SEQ ID LARLARALARAL and Linear NO: 0007

[0684] RAXEA amphipathic

[0685] -5.97 WEARLARALAR Cationic

[0686] SEQ ID ALARELARALAR and Linear NO: 0008

[0687] ALRACEA amphipathic

[0688] -4.68 REARLARALARA Cationic

[0689] SEQ ID LARLARALARAL and Linear NO: 0009

[0690] RACEA amphipathic

[0691] -5.93 REARLARALARA Cationic

[0692] SEQ ID LARLARALARAL and Linear NO: 0010

[0693] RAREA amphipathic

[0694] -7.55 REARLARALARA Cationic

[0695] SEQ ID LARELARALARA and Linear NO: 0011

[0696] LRAREA amphipathic

[0697] -8.55 Cationic

[0698] LLIILRRRIRKQA SEQ ID

[0699] and Linear HAHSK NO: 0013

[0700] amphipathic -0.27 Cationic

[0701] LLIFLRRRLRKQ SEQ ID

[0702] and Linear ARAHGK NO: 0014

[0703]

[0704] amphipathic 0.04ATTORNEY DOCKET: 05336.0008W001

[0705] Cationic

[0706] CRRLRHLRHHY SEQ ID

[0707] and Free Free NA Linear RRRWHRFRC NO: 0015

[0708] amphipathic -1.92 Cationic Acet Ami

[0709] RQIKIWFQNRRM SEQ ID

[0710] and ylatio datio NA Linear KWKK NO: 0016

[0711] amphipathic n n 4.72 Cationic Ami

[0712] RQIKIWFQNRRM SEQ ID

[0713] and Free datio NA Linear KWKK NO: 0016

[0714] amphipathic n 3.29 Cationic

[0715] RQIKIWFQNRRM SEQ ID

[0716] and Free Free NA Linear KWKK NO: 0016

[0717] amphipathic 2.64 Cationic Ami

[0718] RQIKIWFQNRRM SEQ ID

[0719] and NA datio NA Linear KWKK NO: 0016

[0720] amphipathic n 3.29 Cationic

[0721] RQIKIWFQNRRM SEQ ID

[0722] and NA NA NA Linear KWKK NO: 0016

[0723] amphipathic 2.64 WEAHLAHALAR Cationic

[0724] SEQ ID ALARHLARALAR and Linear NO: 0017

[0725] ALRACEA amphipathic

[0726] -3.03 WEARLARALAR Cationic

[0727] SEQ ID ALARHLARALAH and Linear NO: 0018

[0728] ALHACEA amphipathic

[0729] -3.03 WEAHLAHALAR Cationic

[0730] SEQ ID ALARHLARALAR and Linear NO: 0019

[0731] ALRACEA amphipathic

[0732] -2.55 WEARLARALAR Cationic

[0733] SEQ ID ALARHLAHALAH and Linear NO: 0020

[0734] ALHACEA amphipathic

[0735] -2.55 Acet Ami

[0736] SEQ ID RKKRRQRRR Cationic ylatio datio NA Linear NO: 0021

[0737] n n -2.66 SEQ ID RKKRRQRRR Cationic Free Free NA Linear NO: 0021 -4.74

[0738] 12- am

[0739] ino

[0740] do

[0741] RGD-ADDA- Amphipathi SEQ ID

[0742] NA Free de Linear RRRRRRRR c NO: 0022

[0743] ca

[0744] noi

[0745] c

[0746]

[0747] aci -4.11ATTORNEY DOCKET: 05336.0008W001

[0748] d

[0749] (A

[0750] DD

[0751] A)

[0752] link

[0753] ed

[0754] RG

[0755] D

[0756] mo

[0757] tif

[0758] to

[0759] R1

[0760] RG

[0761] D

[0762] mo

[0763] tif

[0764] is

[0765] link

[0766] ed

[0767] by

[0768] P2

[0769] thr

[0770] ou

[0771] RGD-Ahx- Amphipathi SEQ ID

[0772] NA Free gh Linear RRRRRRRR c NO: 0022

[0773] 6- am

[0774] ino

[0775] he

[0776] xa

[0777] noi

[0778] c

[0779] aci

[0780] d

[0781] (Ah

[0782] X). -10.3 Acet Ami

[0783] SEQ ID RRRRRRRR Cationic ylatio datio NA Linear NO: 0022

[0784] n n -4.24 Ami

[0785] SEQ ID RRRRRRRR Cationic Free datio NA Linear NO: 0022

[0786] n -5.67 SEQ ID RRRRRRRR Cationic Free Free NA Linear NO: 0022 -6.32

[0787] Stear Ami

[0788] SEQ ID RRRRRRRR Cationic ylatio datio NA Linear NO: 0022

[0789]

[0790] n n 2.83ATTORNEY DOCKET: 05336.0008W001

[0791] Cationic

[0792] RKKRRRESRKK SEQ ID

[0793] and Linear RRRES NO: 0023

[0794] amphipathic -8.54 Cationic

[0795] GRPRESGKKRK SEQ ID

[0796] and Linear RKRLKP NO: 0024

[0797] amphipathic -3.89 GRRRRRRRRRP SEQ ID

[0798] Cationic Free Free NA Linear

[0799] PQ NO: 0025 -7.37

[0800] Cationic

[0801] RVRVFVVHIPRL SEQ ID

[0802] and Linear

[0803] T NO: 0026

[0804] amphipathic 1.15

[0805] Cyst GALFLGFLGAAG Cationic Acet eami

[0806] SEQ ID STMGAWSQPKK and ylatio de NA Linear NO: 0027

[0807] KRKV amphipathic n grou

[0808] P 5.1 Cyst GALFLGFLGAAG Cationic Acet eami

[0809] SEQ ID STMGAWSQPKK and ylatio de NA Linear NO: 0027

[0810] KRKV amphipathic n grou

[0811] P 5.1 Acet Ami

[0812] KLALKLALKALK Amphipathi SEQ ID

[0813] ylatio datio NA Linear AALKLA c NO: 0028

[0814] n n 6.91 Ami

[0815] KLALKLALKALK Amphipathi SEQ ID

[0816] Free datio NA Linear AALKLA c NO: 0028

[0817] n 5.48 KLALKLALKALK Amphipathi SEQ ID

[0818] Free NA NA Linear AALKLA c NO: 0028 4.83 GWTLNSAGYLL Cationic Ami

[0819] SEQ ID GKINLKALAALA and Free datio NA Linear NO: 0029

[0820] KKIL amphipathic n 5.66 GWTLNSAGYLL Cationic

[0821] SEQ ID GKINLKALAALA and Free Free NA Linear NO: 0029

[0822] KKIL amphipathic 5.01 GWTLNSAGYLL Cationic

[0823] SEQ ID GKINLKALAALA and Linear NO: 0029

[0824] KKIL amphipathic 5.01

[0825] Cationic

[0826] SEQ ID VSALK and Linear NO: 0030

[0827] amphipathic 0.57 Cationic

[0828] CSIPPEVKFNPF SEQ ID

[0829] and Linear VYLI NO: 0031

[0830] amphipathic 4.73 GIGAVLKVLTTG Cationic

[0831] SEQ ID LPALISWIKRKR and Linear NO: 0032

[0832]

[0833] QQ amphipathic 3.63ATTORNEY DOCKET: 05336.0008W001

[0834] Cationic

[0835] HGLASTLTRWA SEQ ID

[0836] and Linear HYNALIRAF NO: 0033

[0837] amphipathic 0.82 Cationic Stear Ami AGYLLGKLLOOL SEQ ID

[0838] and ylatio datio NA Linear AAAALOOLL NO: 0034

[0839] amphipathic n n 14.48 Cationic

[0840] AYRIKPTFRRLK SEQ ID

[0841] and Free Free NA Linear WKYKGKFW NO: 0035

[0842] amphipathic 5.72 Cationic Ami CRQIKIWFQNRR SEQ ID

[0843] and Free datio NA Linear MKWKK NO: 0036

[0844] amphipathic n 4.12 Cationic Acet Ami CRQIKIWFQNRR SEQ ID

[0845] and ylatio datio NA Linear MKWKK NO: 0036

[0846] amphipathic n n 5.55 Cationic Ami

[0847] GLRKRLRKFRN SEQ ID

[0848] and Free datio NA Linear KIKEK NO: 0037

[0849] amphipathic n -0.4 Cationic Ami GRKKRRQRRRP SEQ ID

[0850] and Free datio NA Linear PQC NO: 0038

[0851] amphipathic n -3.52 Cationic

[0852] GRKKRRQRRRP SEQ ID

[0853] and Free Free NA Linear PQC NO: 0038

[0854] amphipathic -4.17 Cationic Ami GRKKRRQRRRP SEQ ID

[0855] and NA datio NA Linear PQC NO: 0038

[0856] amphipathic n -3.52 Cationic Cys

[0857] GRKKRRQRRRP SEQ ID

[0858] and additi Free NA Linear PQC NO: 0038

[0859] amphipathic on -4.17 Cationic

[0860] HARIKPTFRRLK SEQ ID

[0861] and Free Free NA Linear WKYKGKFW NO: 0039

[0862] amphipathic 4.86 Cationic

[0863] HYRIKPTARRLK SEQ ID

[0864] and Free Free NA Linear WKYKGKFW NO: 0040

[0865] amphipathic 4.25 Cationic

[0866] HYRIKPTFRRLA SEQ ID

[0867] and Free Free NA Linear WKYKGKFW NO: 0041

[0868] amphipathic 5.24 Cationic

[0869] HYRIKPTFRRLK SEQ ID

[0870] and Free Free NA Linear WKYKGKFA NO: 0042

[0871] amphipathic 3.95 Cationic Ami

[0872] KKWKMRRNQF SEQ ID

[0873] and Free datio NA Linear WIKIQR NO: 0043

[0874]

[0875] amphipathic n 3.29ATTORNEY DOCKET: 05336.0008W001

[0876] Cationic Acet

[0877] KKWKMRRNQF SEQ ID

[0878] and ylatio Free NA Linear WIKIQR NO: 0043

[0879] amphipathic n 4.07 Cationic

[0880] KKWKMRRNQF SEQ ID

[0881] and Free Free NA Linear WIKIQR NO: 0043

[0882] amphipathic 2.64 Cationic Ami

[0883] SEQ ID

[0884] lliilrrri rkqahahsk and Free datio NA Linear NO: 0044

[0885] amphipathic n 0.38 Cationic Ami

[0886] LLIILRRRIRKQa SEQ ID

[0887] and Free datio NA Linear HAHSK NO: 0045

[0888] amphipathic n 0.38 Cationic Ami

[0889] LLIILRRRIRKQA SEQ ID

[0890] and Free datio NA Linear HaHSK NO: 0046

[0891] amphipathic n 0.38 Cationic

[0892] RKKRRQRRRGG Ami

[0893] and SEQ ID

[0894] GKLLKLLLKLLLK Free datio NA Linear Amphipathi NO: 0047

[0895] LLK n

[0896] c 4.1 Cationic Ami

[0897] SEQ ID

[0898] rqikiwfqnrrmkwkk and Free datio NA Linear NO: 0048

[0899] amphipathic n 3.29 Cationic

[0900] SEQ ID

[0901] rqikiwfqnrrmkwkk and Free Free NA Linear NO: 0048

[0902] amphipathic 2.64 Cationic

[0903] RQIKIWFQNRRM SEQ ID

[0904] and Free Free NA Linear KWKKK NO: 0049

[0905] amphipathic 2.81 Cationic Ami

[0906] RQIRIWFQNRR SEQ ID

[0907] and Free datio NA Linear MRWRR NO: 0050

[0908] amphipathic n -0.55 Cationic

[0909] RQIRIWFQNRR SEQ ID

[0910] and NA NA NA Linear MRWRR NO: 0050

[0911] amphipathic -1.2 Cationic Cycli

[0912] SEQ ID

[0913] [RRRRWWWW] and Free zatio NA Cyclic NO: 0051

[0914] amphipathic n 2.68 WEAKLAKALAKA Cationic

[0915] SEQ ID LAKHLAKALAKA and Free Free NA Linear NO: 0052

[0916] LKACEA amphipathic

[0917] 2.73 Cationic Ami

[0918] SEQ ID YGRKKRRQRRR and Free datio NA Linear NO: 0053

[0919] amphipathic n -3.76 Cationic

[0920] SEQ ID YGRKKRRQRRR and Free Free NA Linear NO: 0053

[0921]

[0922] amphipathic -4.41ATTORNEY DOCKET: 05336.0008W001

[0923] ac

[0924] P,

[0925] Ep

[0926] silo

[0927] n- Cationic

[0928] YGRKKRRQRRR SEQ ID am

[0929] and Free Free Linear -acp-OH NO: 0053 ino

[0930] amphipathic

[0931] ca

[0932] pro

[0933] ic

[0934] aci

[0935] d -7.42 ac

[0936] P,

[0937] Ep

[0938] silo

[0939] SEQ ID

[0940] n- NO: 0053 Ami YGRKKRRQRRR am

[0941] Cationic and SEQ Free datio Linear -acp-DYQQD ino

[0942] ID NO: n

[0943] ca

[0944] 0509

[0945] pro

[0946] ic

[0947] aci

[0948] d -7.15 ac

[0949] P,

[0950] Ep

[0951] silo

[0952] SEQ ID

[0953] n- NO: 0053 Ami YGRKKRRQRRR am

[0954] Cationic and SEQ Free datio Linear -acp-ENAEYLR ino

[0955] ID NO: n

[0956] ca

[0957] 0510

[0958] pro

[0959] ic

[0960] aci

[0961] d -9.15 ac

[0962] P,

[0963] Ep

[0964] silo

[0965] SEQ ID

[0966] n- NO: 0053 Ami YGRKKRRQRRR am

[0967] Cationic and SEQ Free datio Linear -acp-NYQQN ino

[0968] ID NO: n

[0969] ca

[0970] 0511

[0971] pro

[0972] ic

[0973] aci

[0974]

[0975] d -8.55ATTORNEY DOCKET: 05336.0008W001

[0976] ac

[0977] P,

[0978] Ep

[0979] silo

[0980] SEQ ID

[0981] n- NO: 0053 Ami YGRKKRRQRRR am

[0982] Cationic and SEQ Free datio Linear -acp-QNAQYLR ino

[0983] ID NO: n

[0984] ca

[0985] 0512

[0986] pro

[0987] ic

[0988] aci

[0989] d -7.83 Cyst

[0990] Cationic

[0991] RQIKIWFQNRRM SEQ ID eine

[0992] and Free NA Linear KWKKC NO: 0054 addit

[0993] amphipathic

[0994] ion 3.47 Cationic

[0995] RQIKIWFQNRRM SEQ ID

[0996] and NA NA NA Linear KWKKC NO: 0054

[0997] amphipathic 3.47 Nbtg-Nbtg-Nbtg- Cationic Ami

[0998] SEQ ID

[0999] Nbtg-Nbtg-Nbtg- and Free datio NA Linear NO: 0055

[1000] Nbtg-Nbtg amphipathic n

[1001] 4 Nbtg-Nbtg-Nspe- Cationic Ami

[1002] Nbtg-Nbtg-Nspe- SEQ ID

[1003] and Free datio NA Linear Nbtg-Nbtg-Nspe- NO: 0056

[1004] amphipathic n

[1005] Nbtg-Nbtg-Nspe

[1006] 8.64 Nbtg-Nspe-Nspe- Cationic Ami

[1007] Nbtg-Nspe-Nspe- SEQ ID

[1008] and Free datio NA Linear Nbtg-Nspe-Nspe- NO: 0057

[1009] amphipathic n

[1010] Nbtg-Nspe-Nspe

[1011] 11.28 NLys-NLys-NLys- NLys-NLys-NLys- Cationic Ami

[1012] SEQ ID NLys-NLys-NLeu- and Free datio NA Linear NO: 0058

[1013] NLeu-NLeu- amphipathic n

[1014] NLeu-NLeu

[1015]

[1016] 0ATTORNEY DOCKET: 05336.0008W001

[1017] NLys-NLys-NLys- Cationic Ami

[1018] NLys-NLys-NLys- SEQ ID

[1019] and Free datio NA Linear NLys-NLys-Nspe- NO: 0059

[1020] amphipathic n

[1021] Nspe-Nspe-Nspe

[1022] 4.64 NLys-NLys-Nspe- Cationic Ami

[1023] NLys-NLys-Nspe- SEQ ID

[1024] and Free datio NA Linear NLys-NLys-Nspe- NO: 0060

[1025] amphipathic n

[1026] NLys-NLys-Nspe

[1027] 4.64 NLys-Npm-Npm- Cationic Ami

[1028] NLys-Npm-Npm- SEQ ID

[1029] and Free datio NA Linear NLys-Npm-Npm- NO: 0061

[1030] amphipathic n

[1031] NLys-Npm-Npm

[1032] 2.4 NLys-Nspe-Nspe- Cationic Ami

[1033] SEQ ID NLys-Nspe-Nspe- and Free datio NA Linear NO: 0062

[1034] NLys-Nspe-Nspe amphipathic n

[1035] 6.96 NLys-Nspe-Nspe- Cationic Ami

[1036] NLys-Nspe-Nspe- SEQ ID

[1037] and Free datio NA Linear NLys-Nspe-Nspe- NO: 0063

[1038] amphipathic n

[1039] NLys-Nspe-Nspe

[1040] 9.28 NLys-Nssb-Nssb- Cationic Ami

[1041] NLys-Nssb-Nssb- SEQ ID

[1042] and Free datio NA Linear NLys-Nssb-Nssb- NO: 0064

[1043] amphipathic n

[1044] NLys-Nssb-Nssb

[1045] 3.2 Acet

[1046] Ac-WELVVL- SEQ ID

[1047] Cationic ylatio Free NA Linear YGRKKRRQRRR NO: 0065

[1048] n 1.15 WELVVLYGRKK SEQ ID

[1049] Cationic Free Free NA Linear nnUnnn NO: 0065 -1.71

[1050] Ami

[1051] AGYLLGHINLHH SEQ ID

[1052] Cationic Free datio NA Linear LAHLHHIL NO: 0066

[1053] n 3.58 AGYLLGHINLHH SEQ ID

[1054] Cationic Free Free NA Linear LAHLHHILC NO: 0067

[1055]

[1056] 3.76ATTORNEY DOCKET: 05336.0008W001

[1057] Ami

[1058] AGYLLGKINLKK SEQ ID

[1059] Cationic Free datio NA Linear LAKLLLIL NO: 0068

[1060] n 7.72 B,

[1061] Bet

[1062] Ami

[1063] SEQ ID a- B-[KrrrrrrrrE] Cationic Free datio Cyclic NO: 0069 Ala

[1064] n

[1065] nin

[1066] e -9.2 Ah

[1067] x,

[1068] 6- am

[1069] Ami ino

[1070] Ahx- SEQ ID

[1071] Cationic Free datio he Linear RRRRRRRRR NO: 0070

[1072] n xa

[1073] noi

[1074] c

[1075] aci

[1076] d -9.16 Acet Ami

[1077] SEQ ID RRRRRRRRR Cationic ylatio datio NA Linear NO: 0070

[1078] n n -5.03 Ami

[1079] SEQ ID RRRRRRRRR Cationic Free datio NA Linear NO: 0070

[1080] n -6.46 SEQ ID RRRRRRRRR Cationic Free NA NA Linear NO: 0070 -7.11 SEQ ID RRRRRRRRR Cationic Free Free NA Linear NO: 0070 -7.11 SEQ ID AKKRRQRRR Cationic Free Free NA Linear NO: 0071 -4.22 AKKRRQRRRAK SEQ ID

[1081] Cationic Free Free NA Linear KRRQRRR NO: 0072

[1082] -8.44 ALALALALALALA Ami

[1083] SEQ ID LALKIKKIKKIKKI Cationic Free datio NA Linear NO: 0073

[1084] KKLAKLAKKIK n

[1085] 11.66 Cyst

[1086] AYGRKKRRQRR SEQ ID eine

[1087] Cationic Free NA Linear

[1088] R NO: 0074 additi

[1089] on -4.68 AYGRKKRRQRR SEQ ID

[1090] Cationic Free Free NA Linear

[1091] R NO: 0074 -4.68

[1092] Ami B,

[1093] SEQ ID

[1094] B-[KRrRrRrE] Cationic Free datio Bet Cyclic NO: 0075

[1095]

[1096] n a- -7.62ATTORNEY DOCKET: 05336.0008W001

[1097] Ala

[1098] nin

[1099] e

[1100] B,

[1101] Bet

[1102] Ami

[1103] SEQ ID a- B-[KRRRRRRE] Cationic Free datio Cyclic NO: 0076 Ala

[1104] n

[1105] nin

[1106] e -7.62 B,

[1107] Bet

[1108] Ami

[1109] SEQ ID a- B-R[KRRRRRRE] Cationic Free datio Cyclic NO: 0076 Ala

[1110] n

[1111] nin

[1112] e -8.41 B,

[1113] Bet

[1114] Ami

[1115] SEQ ID a- B-[KrRrRrRrE] Cationic Free datio Cyclic NO: 0077 Ala

[1116] n

[1117] nin

[1118] e -8.41 B,

[1119] Bet

[1120] Ami

[1121] SEQ ID a- B-[KRRRRRRRE] Cationic Free datio Cyclic NO: 0078 Ala

[1122] n

[1123] nin

[1124] e -8.41 B,

[1125] Bet

[1126] Ami

[1127] SEQ ID a- B-[KrrrrrrrE] Cationic Free datio Cyclic NO: 0079 Ala

[1128] n

[1129] nin

[1130] e -8.41 B,

[1131] Bet

[1132] Ami

[1133] SEQ ID a- B-[KRrRrRrRrE] Cationic Free datio Cyclic NO: 0080 Ala

[1134] n

[1135] nin

[1136] e -9.2 B,

[1137] Bet

[1138] Ami

[1139] B- SEQ ID a- Cationic Free datio Cyclic [KRRRRRRRRE] NO: 0081 Ala

[1140] n

[1141] nin

[1142] e -9.2 Ami B,

[1143] SEQ ID

[1144] B-[KrrrrrrrrE] Cationic Free datio Bet Cyclic NO: 0082

[1145]

[1146] n a- -9.2ATTORNEY DOCKET: 05336.0008W001

[1147] Ala

[1148] nin

[1149] e

[1150] B,

[1151] Bet

[1152] B- Ami

[1153] SEQ ID a- [KRRRRRRRRR Cationic Free datio Cyclic NO: 0083 Ala

[1154] E] n

[1155] nin

[1156] e -9.99 Ami GGGGRRFFRRF SEQ ID

[1157] Cationic Free datio NA Linear RR NO: 0084

[1158] n -1.49 Ami

[1159] GGGGRRFFRR SEQ ID

[1160] Cationic Free datio NA Linear WRR NO: 0085

[1161] n -1.19 Ami

[1162] GGGGRRFWRR SEQ ID

[1163] Cationic Free datio NA Linear FRR NO: 0086

[1164] n -1.19 Ami

[1165] GGGGRRFWRR SEQ ID

[1166] Cationic Free datio NA Linear WRR NO: 0087

[1167] n -0.89 Ami

[1168] GGGGRRWFRR SEQ ID

[1169] Cationic Free datio NA Linear FRR NO: 0088

[1170] n -1.19 Ami

[1171] GGGGRRWFRR SEQ ID

[1172] Cationic Free datio NA Linear WRR NO: 0089

[1173] n -0.89 Ami GGGGRRWWRR SEQ ID

[1174] Cationic Free datio NA Linear FRR NO: 0090

[1175] n -0.89 Ami GGGGRRWWRR SEQ ID

[1176] Cationic Free datio NA Linear WRR NO: 0091

[1177] n -0.59 B,

[1178] Bet

[1179] Ami

[1180] SEQ ID a- BRR[KRRRRRE] Cationic Free datio Cyclic NO: 0092 Ala

[1181] n

[1182] nin

[1183] e -8.41 B,

[1184] Bet

[1185] Ami

[1186] SEQ ID a- B[KRRRRE] Cationic Free datio Cyclic NO: 0093 Ala

[1187] n

[1188] nin

[1189] e -6.04 Ami B,

[1190] SEQ ID BRRRRRR Cationic Free datio Bet Linear NO: 0094

[1191]

[1192] n a- -6.79ATTORNEY DOCKET: 05336.0008W001

[1193] Ala

[1194] nin

[1195] e

[1196] B,

[1197] Bet

[1198] Ami

[1199] SEQ ID a- BRRRRRRR Cationic Free datio Linear NO: 0095 Ala

[1200] n

[1201] nin

[1202] e -7.58 B,

[1203] Bet

[1204] Ami

[1205] SEQ ID a- B-RRRRRRR Cationic NA datio Linear NO: 0095 Ala

[1206] n

[1207] nin

[1208] e -7.58 B,

[1209] Bet

[1210] Ami

[1211] SEQ ID a- BRRRRRRRR Cationic Free datio Linear NO: 0096 Ala

[1212] n

[1213] nin

[1214] e -8.37 CALNNYGRKKR SEQ ID

[1215] Cationic Free Free NA Linear RQRRR NO: 0097 -5.01

[1216] Cyst

[1217] CAYGGQQGGQ SEQ ID eine

[1218] Cationic NA NA Linear GGG NO: 0098 additi

[1219] on -1.45 CCTGRKKRRQR SEQ ID

[1220] Cationic Free Free NA Linear RR NO: 0099 -3.56 CELAGIGILTVKK SEQ ID

[1221] Cationic Free Free NA Linear KKKQKKK NO: 0100 3.2 CELAGIGILTVRK SEQ ID

[1222] Cationic Free Free NA Linear KRRQRRR NO: 0101

[1223] -2.56 CGGGARKKAAK AARKKAAKAAR SEQ ID

[1224] Cationic Free Free NA Linear KKAAKAARKKAA NO: 0102

[1225] KA

[1226] -5.27 CGGGGYGRKKR SEQ ID

[1227] Cationic Free Free NA Linear RQRRR NO: 0103 -4.46 CGGGRRRRRR SEQ ID

[1228] Cationic Free Free NA Linear RRRLLLL NO: 0104 -3.74 CGGGYGRKKRR SEQ ID

[1229] Cationic NA NA NA Linear

[1230]

[1231] QRRR NO: 0105 -4.24ATTORNEY DOCKET: 05336.0008W001

[1232] CGGKDCERRFS Ami

[1233] SEQ ID RSDQLKRHQRR Cationic Free datio NA Linear NO: 0106

[1234] HTGVKPFQ n

[1235] -3.35 CGRKKRAARQR SEQ ID

[1236] Cationic Free Free NA Linear AARAARPPQ NO: 0107

[1237] -5.79 CGRKKRAARQR SEQ ID

[1238] Cationic Free Free NA Linear RRPPQ NO: 0108 -4.71 CGRKKRLLRQR SEQ ID

[1239] Cationic Free Free NA Linear LLRLLRPPQ NO: 0109

[1240] 0.63 CGRKKRLLRQR SEQ ID

[1241] Cationic Free Free NA Linear RRPPQ NO: 0110 -2.57 CGRKKRRQRAA SEQ ID

[1242] Cationic Free Free NA Linear RRPPQ NO: 0111 -4.71 CGRKKRRQRLL SEQ ID

[1243] Cationic Free Free NA Linear RRPPQ NO: 0112 -2.57 CGRKKRRQRRA SEQ ID

[1244] Cationic Free Free NA Linear ARPPQ NO: 0113 -4.71 CGRKKRRQRRL SEQ ID

[1245] Cationic Free Free NA Linear LRPPQ NO: 0114 -2.57

[1246] Acet Ami CGRKKRRQRRR SEQ ID

[1247] Cationic ylatio datio NA Linear PPQ NO: 0115

[1248] n n -2.09 CGRKKRRQRRR SEQ ID

[1249] Cationic Free Free NA Linear PPQ NO: 0115 -4.17

[1250] Palm Ami CGRKKRRQRRR SEQ ID

[1251] Cationic itoyla datio NA Linear PPQ NO: 0115

[1252] tion n -3.52 CGRKKRRQRR SEQ ID

[1253] Cationic Free Free NA Linear WWRPPQ NO: 0116

[1254] -1.25 CGRKKRRQRW SEQ ID

[1255] Cationic Free Free NA Linear WRRPPQ NO: 0117

[1256] -1.25 CGRKKRWWRQ SEQ ID

[1257] Cationic Free Free NA Linear RRRPPQ NO: 0118

[1258] -1.25 CGRKKRWWRQ SEQ ID

[1259] Cationic Free Free NA Linear RWWRWWRPPQ NO: 0119

[1260] 4.59 CGYGRKKRRQR SEQ ID

[1261] Cationic Free Free NA Cyclic RRGC NO: 0120 -3.19 CHHHHHRRRRR SEQ ID

[1262] Cationic NA NA NA Linear RRRRHHHHHC NO: 0122

[1263]

[1264] -8.55ATTORNEY DOCKET: 05336.0008W001

[1265] CKDEPQRRSAR SEQ ID LSAKPAPPKPEP Cationic Free Free NA Linear NO: 0123

[1266] KPKKAPAKK

[1267] -3.05 SEQ ID

[1268] ckkkkkkkkk Cationic Free Free NA Linear NO: 0124 2.36

[1269] Acet

[1270] CKYGRKKRRQR SEQ ID

[1271] Cationic amid Free NA Linear RR NO: 0125

[1272] ation -3.41 CKYGRKKRRQR SEQ ID

[1273] Cationic Free Free NA Linear RR NO: 0125 -3.41

[1274] Ami CREKAKKLFKKI SEQ ID

[1275] Cationic Free datio NA Linear LKKL NO: 0126

[1276] n 4.87 SEQ ID

[1277] [CRGDKGPDC] Cationic Free Free NA Cyclic NO: 0127 0.19

[1278] Cyst

[1279] CRKARYRGRKR SEQ ID eine

[1280] Cationic NA NA Linear QR NO: 0128 additi

[1281] on -3.85 SEQ ID

[1282] crkkrrqrrr Cationic Free Free NA Linear NO: 0129 -3.91

[1283] Cyst

[1284] SEQ ID eine

[1285] CRRRRRRRR Cationic NA NA Linear NO: 0130 additi

[1286] on -5.49 SEQ ID

[1287] crrrrrrrrr Cationic Free Free NA Linear NO: 0131 -6.28

[1288] Ami

[1289] CSSLDEPGRGG SEQ ID

[1290] Cationic Free datio NA Linear FSSESKV NO: 0132

[1291] n -1.9 CVSRRRRRRGG SEQ ID

[1292] Cationic Free Free NA Linear RRRR NO: 0133 -7.64

[1293] Acet

[1294] SEQ ID CWKKK Cationic ylatio Free NA Linear NO: 0134

[1295] n 4.23 Acet

[1296] SEQ ID CWKKKKKKKK Cationic ylatio Free NA Linear NO: 0135

[1297] n 5.08 Acet

[1298] CWKKKKKKKKK SEQ ID

[1299] Cationic ylatio Free NA Linear KKKK NO: 0136

[1300] n 5.93 Acet

[1301] CWKKKKKKKKK SEQ ID

[1302] Cationic ylatio Free NA Linear KKKKKKKKK NO: 0137

[1303] n 6.78 CYGRKKRRQRR SEQ ID

[1304] Cationic Free Free NA Linear

[1305]

[1306] R NO: 0138 -3.58ATTORNEY DOCKET: 05336.0008W001

[1307] Ami

[1308] DRRRRGSRPSG SEQ ID

[1309] Cationic Free datio NA Linear AERRRR NO: 0139

[1310] n -9.2 Ami

[1311] DRRRRGSRPSG SEQ ID

[1312] Cationic Free datio NA Linear AERRRRRAAAA NO: 0140

[1313] n -11.1 ELVVLGKLYGRK SEQ ID

[1314] Cationic Free Free NA Linear KRRQRRR NO: 0141

[1315] -2.42 Ami

[1316] SEQ ID ERKKRRRE Cationic Free datio NA Linear NO: 0142

[1317] n -4.17 LoUUUUorUnn SEQ ID

[1318] Cationic Free Free NA Linear RRRRRRRRR NO: 0143

[1319] -11.5 FFFAAGRKRKK SEQ ID

[1320] Cationic Free Free NA Linear

[1321] RT NO: 0144 0.6

[1322] Ami

[1323] FFFFFFGRRRRR SEQ ID

[1324] Cationic NA datio NA Linear RRRGC NO: 0145

[1325] n 1.68 Ami

[1326] SEQ ID

[1327] ffffgrrrrrrrrgc Cationic NA datio NA Linear NO: 0146

[1328] n -0.64 Ami

[1329] FFFFGRRRRRR SEQ ID

[1330] Cationic NA datio NA Linear RRGC NO: 0147

[1331] n -0.64 Ami

[1332] FFGRRRRRRRG SEQ ID

[1333] Cationic NA datio NA Linear

[1334] C NO: 0148

[1335] n -2.17 Ami

[1336] FFLIGRRRRRRR SEQ ID

[1337] Cationic NA datio NA Linear RGC NO: 0149

[1338] n -1.46 Ami

[1339] SEQ ID

[1340] fflipkgrrrrrrrr Cationic NA datio NA Linear NO: 0150

[1341] n -1.75 Ami

[1342] FFLIPKGRRRRR SEQ IDCationic NA datio NA Linear RRRGC NO: 0151

[1343] n -1.14 FFLIPKGRRRRR SEQ IDCationic NA NA NA Linear RRRR NO: 0152 -3.19 FITKALGISYGRK SEQ ID

[1344] Cationic Free Free NA Linear KRR NO: 0153 0.63 FITKALGISYGRK SEQ ID

[1345] Cationic Free Free NA Linear KRRQRRRPPQ NO: 0154

[1346]

[1347] -2.12ATTORNEY DOCKET: 05336.0008W001

[1348] Ami

[1349] SEQ ID FKKFRKF Cationic Free datio NA Linear NO: 0155

[1350] n 3.85 x,

[1351] eye

[1352] loh

[1353] SEQ ID FXrFXrFXr Cationic NA NA exy Linear NO: 0156

[1354] lala

[1355] nin

[1356] e 1.11 x,

[1357] eye

[1358] loh

[1359] SEQ ID FXrFXrFXrFXr Cationic NA NA exy Linear NO: 0157

[1360] lala

[1361] nin

[1362] e 1.48 x,

[1363] eye

[1364] loh

[1365] SEQ ID FXrFXrFXrFXrFXr Cationic NA NA exy Linear NO: 0158

[1366] lala

[1367] nin

[1368] e 1.85 x,

[1369] eye

[1370] loh FXrFXrFXrFXrFXr SEQ ID

[1371] Cationic NA NA exy Linear FXr NO: 0159

[1372] lala

[1373] nin

[1374] e 2.22 Cyst GALFLAFLAAAL Acet earn!

[1375] SEQ ID SLMGLWSQPKK Cationic ylatio de NA Linear NO: 0160

[1376] KRKV n grou

[1377] P 8.15 GCGGGYGRKKR SEQ ID

[1378] Cationic NA NA NA Linear RQRRR NO: 0161 -4.46

[1379] Ab

[1380] u,

[1381] iso

[1382] Cyst ste GD(Abu)LPHLKL SEQ ID eine ric

[1383] Cationic Free Linear

[1384] C NO: 0162 addit 2- ion am

[1385] ino

[1386] but

[1387]

[1388] yric 2.47ATTORNEY DOCKET: 05336.0008W001

[1389] aci

[1390] d

[1391] Malei

[1392] GGGGRRRRRR SEQ ID mide

[1393] Cationic Free NA Linear RRRLLLL NO: 0163 additi

[1394] on -4.79 GGGRRRRRRY SEQ ID

[1395] Cationic Free Free NA Linear GRKKRRQRR NO: 0164

[1396] -9.02 [GGVCPKILKKC

[1397] RRDSDCPGACI SEQ ID

[1398] Cationic Free Free NA Cyclic CRGNGWCGSG NO: 0165

[1399] SD]

[1400] 2.42 [GGVCPKILKKC

[1401] RRDSDCPGACI SEQ ID

[1402] Cationic Free Free NA Cyclic CRGNGYCGSGS NO: 0166

[1403] D] 1.51 [GGVCPKILRRC

[1404] RRDSDCPGACI SEQ ID

[1405] Cationic Free Free NA Cyclic CRGNGWCGSG NO: 0167

[1406] SD]

[1407] 0.5 [GGVCPKILRRC

[1408] RRDSDCPGACI SEQ ID

[1409] Cationic Free Free NA Cyclic CRGNGYCGSGS NO: 0168

[1410] D] -0.41 [GGVCPKILRRC

[1411] RRDSDCPGACI SEQ ID

[1412] Cationic Free Free NA Cyclic CRGNGYCGSGS NO: 0169

[1413] R] -0.92 [GGVCPRILRRC

[1414] RRDSDCPGACI SEQ ID

[1415] Cationic Free Free NA Cyclic CRGNGYCGSGS NO: 0170

[1416] K] -0.92 GKHRHERGHHR SEQ ID

[1417] Cationic Free Free NA Linear DRRER NO: 0171 -8.53

[1418] SEQ ID GKKKKKKKKK Cationic Free Free NA Linear NO: 0172 1.31

[1419] Ami

[1420] SEQ ID GKKKKRKREKL Cationic Free datio NA Linear NO: 0173

[1421] n -0.33 GKKKRKLSNRE SEQ ID

[1422] Cationic Free Free NA Linear

[1423]

[1424] SAKRSR NO: 0174 -5.33ATTORNEY DOCKET: 05336.0008W001

[1425] GKKTNLFSALIK SEQ ID

[1426] Cationic Free Free NA Linear KKKTA NO: 0175 1.77 GKRARNTEAAR SEQ ID

[1427] Cationic Free Free NA Linear RSRARKL NO: 0176 -7.59 GKRRRRATAKY SEQ ID

[1428] Cationic Free Free NA Linear RSAH NO: 0177 -5.11 GKRVAKRKLIEQ SEQ ID

[1429] Cationic Free Free NA Linear NRERRR NO: 0178 -6.22

[1430] Cyst

[1431] earn! GLWRALWRLLR SEQ ID

[1432] Cationic Free de NA Linear SLWRLLWKA NO: 0179

[1433] grou

[1434] P _ 7.54 [GRCTKSIPPICF SEQ ID

[1435] Cationic Free Free NA Cyclic PA] NO: 0180 2.85 [GRCTKSIPPICW SEQ ID

[1436] Cationic Free Free NA Cyclic PK] NO: 0181 3.59 [GRCTRSIPPKC SEQ ID

[1437] Cationic Free Free NA Cyclic WPD] NO: 0182 1.65 GRGDGPRRKKK Acet

[1438] SEQ ID KGPRRKKKKGP Cationic ylatio Free NA Linear NO: 0183

[1439] RR n -3.67

[1440] Ph

[1441] OS

[1442] Acet

[1443] SEQ ID ph GRGDSPRR Cationic ylatio Free Linear NO: 0184 ory

[1444] n

[1445] lati

[1446] on -1.96 Ph

[1447] os GRGDSPRRKKK Acet

[1448] SEQ ID ph KSPRRKKKKSP Cationic ylatio Free Linear NO: 0185 ory

[1449] RR n

[1450] lati

[1451] on -4.36 Ph

[1452] os

[1453] Acet

[1454] GRGDSPRRSPR SEQ ID ph

[1455] Cationic ylatio Free Linear

[1456] R NO: 0186 ory

[1457] n

[1458] lati

[1459] on -3.84 GRKKRRERRRP SEQ ID

[1460] Cationic Free Free NA Linear PERKC NO: 0187 -6.11 GRKKRRQARAP SEQ ID

[1461] Cationic Free Free NA Linear PQC NO: 0188 -3.13

[1462] SEQ ID GRKKRRQPPQC Cationic Free Free NA Linear

[1463]

[1464] NO: 0189 -1.8ATTORNEY DOCKET: 05336.0008W001

[1465] GRKKRRQRARP SEQ ID

[1466] Cationic Free Free NA Linear PQC NO: 0190 -3.65 GRKKRRQRPPQ SEQ ID

[1467] Cationic Free Free NA Linear

[1468] C NO: 0191 -2.59 GRKKRRQRRRP SEQ ID

[1469] Cationic Free Free NA Linear QC NO: 0192 -3.38

[1470] SEQ ID GRKKRRQRRR Cationic Free Free NA Linear NO: 0193 -4.96 SEQ ID GRKKRRQRRRC Cationic Free Free NA Linear NO: 0194 -4.13 GRKKRRQRRRC SEQ ID

[1471] Cationic Free Free NA Linear

[1472] G NO: 0195 -4.35

[1473] Ami

[1474] SEQ ID GRKKRRQRRRG Cationic Free datio NA Linear NO: 0196

[1475] n -4.53 GRKKRRQRRRM SEQ ID

[1476] Cationic NA NA NA Linear VSAL NO: 0197 -4.05 GRKKRRQRRRP SEQ ID

[1477] Cationic Free Free NA Linear

[1478] P NO: 0198 -4.66

[1479] Ami GRKKRRQRRRP SEQ ID

[1480] Cationic Free datio NA Linear

[1481] PQ NO: 0199

[1482] n -4.35 GRKKRRQRRRP SEQ ID

[1483] Cationic Free Free NA Linear

[1484] PQ NO: 0199 -5 GRKKRRQRRRP SEQ ID

[1485] Cationic Free Free NA Linear PQK NO: 0200 -4.83 GRKKRRQRRRP SEQ ID

[1486] Cationic Free Free NA Linear PQRKC NO: 0201 -4.79

[1487] Ami

[1488] [GRKKRRQRRR SEQ ID

[1489] Cationic Free datio NA Cyclic PPQY] NO: 0202

[1490] n -3.8 Ami GRKKRRQRRRP SEQ ID

[1491] Cationic Free datio NA Linear WQ NO: 0203

[1492] n -3.04 GRKLKKKKNEK SEQ ID

[1493] Cationic Free Free NA Linear EDKRPRT NO: 0204 -3.97

[1494] Ami

[1495] SEQ ID GRKRKKRT Cationic Free datio NA Linear NO: 0205

[1496] n -1.69 SEQ ID GRKRKKRT Cationic Free Free NA Linear NO: 0205 -2.34

[1497] Ami GRQLRIAGKRLE SEQ ID

[1498] Cationic Free datio NA Linear GRSK NO: 0206

[1499] n -2.59 Ami GRQLRIAGKRLR SEQ ID

[1500] Cationic Free datio NA Linear GRSK NO: 0207

[1501]

[1502] n -2.38ATTORNEY DOCKET: 05336.0008W001

[1503] Ami GRQLRIAGRRLR SEQ ID

[1504] Cationic Free datio NA Linear GRSR NO: 0208

[1505] n -4.3 Ami GRQLRIAGRRLR SEQ ID

[1506] Cationic Free datio NA Linear RRSR NO: 0209

[1507] n -4.87 Ami GRQLRRAGRRL SEQ ID

[1508] Cationic Free datio NA Linear RGRSR NO: 0210

[1509] n -5.79 Ami GRQLRRAGRRL SEQ ID

[1510] Cationic Free datio NA Linear RRRSR NO: 0211

[1511] n -6.36 GRRERNKMAAA SEQ ID

[1512] Cationic Free Free NA Linear KCRNRRR NO: 0212

[1513] -7.84 GRRRRATAKYR SEQ ID

[1514] Cationic Free Free NA Linear TAH NO: 0213 -5.09 GRRRRKRLSHR SEQ ID

[1515] Cationic Free Free NA Linear

[1516] T NO: 0214 -5.01

[1517] SEQ ID GRRRRRERNK Cationic Free Free NA Linear NO: 0215 -6.77

[1518] Ami

[1519] SEQ ID GRRRRRRRRR Cationic Free datio NA Linear NO: 0216

[1520] n -6.68 GSVSRRRRRRG SEQ ID

[1521] Cationic Free Free NA Linear GRRRR NO: 0217 -9.14

[1522] Carri

[1523] es

[1524] GYGRKKRRQRR SEQ ID an

[1525] Cationic Free NA Linear RG NO: 0218 extra

[1526] glyci

[1527] ne -4.85 GYGYGYGYGYG

[1528] Acet Ami

[1529] YGYGYKKRKKR SEQ ID

[1530] Cationic ylatio datio NA Linear KKRKKRKQQKQ NO: 0219

[1531] n n

[1532] QKRRK

[1533] 0.66 GYGYGYGYGYG

[1534] Ami

[1535] YGYGYKKRKKR SEQ ID

[1536] Cationic Free datio NA Linear KKRKKRKQQKQ NO: 0219

[1537] n

[1538] QKRRK

[1539] -0.77 HEHEHEHEHEH EHEHEEFGGGG SEQ ID

[1540] Cationic Free Free NA Linear GYGRGRGRGR NO: 0220

[1541] GRGRG

[1542]

[1543] -17.2ATTORNEY DOCKET: 05336.0008W001

[1544] HEHEHEHEHEH EHEHEEFGGGG SEQ ID

[1545] Cationic Free Free NA Linear GYGRRRRRRG NO: 0221

[1546] GGGGG

[1547] -17.2 HEHEHEHEHEH EHEHEHEHEEF SEQ ID

[1548] Cationic Free Free NA Linear GGGGGYGRGR NO: 0222

[1549] GRGRGRGRG

[1550] -19.8 HEHEHEHEHEH EHEHEHEHEEF SEQ ID

[1551] Cationic Free Free NA Linear GGGGGYGRRR NO: 0223

[1552] RRRGGGGGG

[1553] -19.8 HEHEHEHEHEH EHEHEHEHEHE SEQ ID HEEFGGGGGYG Cationic Free Free NA Linear NO: 0224

[1554] RGRGRGRGRG RG

[1555] -22.4 HEHEHEHEHEH EHEHEHEHEHE SEQ ID

[1556] Cationic Free Free NA Linear HEEFGGGGGYG NO: 0225

[1557] RKKRRQRRR

[1558] -21.1 HEHEHEHEHEH EHEHEHEHEHE SEQ ID HEEFGGGGGYG Cationic Free Free NA Linear NO: 0226

[1559] RRRRRRGGGG GG

[1560] -22.4 SEQ ID HEHEHEHEHE Cationic Free Free NA Linear NO: 0227 -6.55 SEQ ID HEHEHEHEHE Cationic Free Free NA Linear NO: 0227 -6.55 HHHHHHHHHHH

[1561] Stear Ami

[1562] HHHHHHHHHRR SEQ ID

[1563] Cationic ylatio datio NA Linear RRRRRRRRRRR NO: 0228

[1564] n n

[1565] RR

[1566] -8.9 HHHHHHHHHHH Acet Ami

[1567] SEQ ID HHHHHRRRRRR Cationic ylatio datio NA Linear NO: 0229

[1568] RRRRRRRRR n n

[1569]

[1570] -14.7ATTORNEY DOCKET: 05336.0008W001

[1571] HHHHHHHHHHH Stear Ami

[1572] SEQ ID HHHHHRRRRRR Cationic ylatio datio NA Linear NO: 0229

[1573] RRRRRRRRR n n

[1574] -7.66 HHHHHHHHHHH Stear Ami

[1575] SEQ ID HRRRRRRRRRR Cationic ylatio datio NA Linear NO: 0230

[1576] RRRRR n n

[1577] -6.42 Stear Ami

[1578] HHHHHHHHRRR SEQ ID

[1579] Cationic ylatio datio NA Linear RRRRR NO: 0231

[1580] n n 0.35 HHHHHHHHRRR Acet Ami

[1581] SEQ ID RRRRRRRRRRR Cationic ylatio datio NA Linear NO: 0232

[1582] R n n -12.3 HHHHHHHHRRR Stear Ami

[1583] SEQ ID RRRRRRRRRRR Cationic ylatio datio NA Linear NO: 0232

[1584] R n n -5.18

[1585] SEQ ID HHHRRRRRRRR Cationic Free Free NA Linear NO: 0233 -7.25 HILPWKWPWWP SEQ ID

[1586] Cationic Free Free NA Linear WRR NO: 0234 7.53 HSDAVFTDNYTA LRKQMAVKKYL SEQ ID

[1587] Cationic Free Free NA Linear NSILNYGRKKRR NO: 0235

[1588] QRRR

[1589] -4.56 HSDGIFTDSYSR

[1590] Ami

[1591] YRKQMAVKKYL SEQ ID

[1592] Cationic Free datio NA Linear AAVLGKRYKQR NO: 0236

[1593] n

[1594] VKNK

[1595] 0.42 X,

[1596] am

[1597] ino

[1598] Ami

[1599] HXRHXRILFQYH SEQ ID he

[1600] Cationic Free datio Linear XRHXR NO: 0237 xyl

[1601] n

[1602] res

[1603] idu

[1604] e -0.88 IKIKIKIKIKIKIKIK Acet Ami

[1605] SEQ ID KLAKLAKLAKLA Cationic ylatio datio NA Linear NO: 0238

[1606] KLAKLAKKIK n n

[1607] 14.45 IKIKIKIKIKIKIKIK Ami

[1608] SEQ ID KLAKLAKLAKLA Cationic Free datio NA Linear NO: 0238

[1609] KLAKLAKKIK n

[1610]

[1611] 13.02ATTORNEY DOCKET: 05336.0008W001

[1612] IPLVVPLRRRRR SEQ ID

[1613] Cationic Free Free NA Linear RRRC NO: 0239 -2.25

[1614] SEQ ID IRQRRRR Cationic Free Free NA Linear NO: 0240 -3.59 IYLATALAKWAL SEQ ID KQGFGGRRRRR Cationic Free Free NA Linear NO: 0241

[1615] RR -1.26 IYLATALAKWAL SEQ ID

[1616] Cationic Free Free NA Linear KQGGRRRRRRR NO: 0242

[1617] -2.2 Ami

[1618] KCFQWQRNMR SEQ ID

[1619] Cationic Free datio NA Linear KVRGPPVSCIKR NO: 0243

[1620] n 2.1 Ami

[1621] SEQ ID KCPSRRPKR Cationic Free datio NA Linear NO: 0244

[1622] n -0.7 KDCERRFSRSD SEQ ID QLKRHQRRHTG Cationic Free NA NA Linear NO: 0245

[1623] VKPFQK

[1624] -4.22 KETWWETWWT SEQ ID EWSQPKKKRKV Cationic Free Free NA Linear NO: 0246

[1625] C 4.09

[1626] SEQ ID KFFKFFKFFK Cationic Free Free NA Linear NO: 0247 7.64 KFLNRFWHWLQ SEQ ID

[1627] Cationic Free Free NA Linear LKPGQPMY NO: 0248

[1628] 6.36 Acet Ami

[1629] KGRKKRRQRRR SEQ ID

[1630] Cationic ylatio datio NA Linear PPQ NO: 0249

[1631] n n -2.75 KGRTPIKFGKAD Ami

[1632] SEQ ID CDRPPKHSQNG Cationic Free datio NA Linear NO: 0250

[1633] MGK n

[1634] -0.48 hey

[1635] ho

[1636] mo

[1637] K-Hcy- cys

[1638] Ami

[1639] FQWQRNMRKV SEQ ID tei

[1640] Cationic Free datio Linear RGPPVS-Hcy- NO: 0251 ne

[1641] n

[1642] IKR in

[1643] whi

[1644] ch

[1645] the

[1646]

[1647] sid 2.58ATTORNEY DOCKET: 05336.0008W001

[1648] e

[1649] ch

[1650] ain

[1651] is

[1652] on

[1653] e

[1654] me

[1655] thyl

[1656] en

[1657] e

[1658] gro

[1659] up

[1660] Ion

[1661] ger

[1662] tha

[1663] n

[1664] in

[1665] cys

[1666] tei

[1667] ne KHKHKHKHKHK SEQ ID HKHKHKHKKLFK Cationic Free Free NA Linear NO: 0252

[1668] KILKYL

[1669] 4.4 SEQ ID KKKKKKKK Cationic Free Free NA Linear NO: 0253 1.36

[1670] Ami

[1671] SEQ ID KKKKKKKKK Cationic Free datio NA Linear NO: 0254

[1672] n 2.18 KKKKKKNKKLQ SEQ ID

[1673] Cationic Free Free NA Linear QRGD NO: 0255 -0.79

[1674] Ami

[1675] SEQ ID KKLFKKILKKL Cationic Free datio NA Linear NO: 0256

[1676] n 5.93 Ami

[1677] KKPGKKTTTKPT SEQ ID

[1678] Cationic Free datio NA Linear KK NO: 0257

[1679] n 0.88 Ami

[1680] KKPGKKTTTKPT SEQ ID

[1681] Cationic Free datio NA Linear KKPTIKTTKK NO: 0258

[1682] n 1.46 Ami

[1683] SEQ ID KKPTIKTTKK Cationic Free datio NA Linear NO: 0259

[1684] n 1.57 SEQ ID KKRRQRRR Cationic Free Free NA Linear NO: 0260 -3.95

[1685] Ami

[1686] SEQ ID KKTTTKPTKK Cationic Free datio NA Linear NO: 0261

[1687]

[1688] n 0.61ATTORNEY DOCKET: 05336.0008W001

[1689] X,

[1690] am

[1691] ino

[1692] Ami

[1693] KKWKMRILFQY SEQ ID he

[1694] Cationic Free datio Linear RXRRXR NO: 0262 xyl

[1695] n

[1696] res

[1697] idu

[1698] e 2.05 KLAKLAKKLAKL SEQ ID

[1699] Cationic Free Free NA Linear AKGGRRRRRRR NO: 0263

[1700] -2.83 KLAKLAKKLAKL SEQ ID AKGRKKRRQRR Cationic Free Free NA Linear NO: 0264

[1701] RP -1.67 KLAKLAKKLAKL SEQ ID AKNYRWRCKNQ Cationic Free Free NA Linear NO: 0265

[1702] N 1.29

[1703] Ami

[1704] SEQ ID KLIKGRTPIKFGK Cationic Free datio NA Linear NO: 0266

[1705] n 3.35 KLIKGRTPIKFGK Ami

[1706] SEQ ID ADCDRPPKHSG Cationic Free datio NA Linear NO: 0267

[1707] K n 2.22 KLIKGRTPIKFGK Ami

[1708] SEQ ID ADCDRPPKHSQ Cationic Free datio NA Linear NO: 0268

[1709] NGK n

[1710] 0.9 KLIKGRTPIKFGK Ami

[1711] SEQ ID ADCDRPPKHSQ Cationic Free datio NA Linear NO: 0269

[1712] NGM n

[1713] 1.24 KLIKGRTPIKFGK Ami

[1714] SEQ ID ADCDRPPKHSQ Cationic Free datio NA Linear NO: 0270

[1715] NGMGK n

[1716] 1.19 KLIKGRTPIKFGK Ami

[1717] SEQ ID ARCRRPPKHSG Cationic Free datio NA Linear NO: 0271

[1718] K n 1.2

[1719] SEQ ID KLPVM Cationic Free Free NA Linear NO: 0272 1.95 KLTRAQRRAAA SEQ ID

[1720] Cationic Free Free NA Linear RKNKRNTRGC NO: 0273

[1721] -6.72 KMTRAQRRAAA SEQ ID

[1722] Cationic Free Free NA Linear RRNRWTARGC NO: 0274

[1723]

[1724] -5.97ATTORNEY DOCKET: 05336.0008W001

[1725] Ami

[1726] KPRSKNPPKKP SEQ ID

[1727] Cationic Free datio NA Linear

[1728] K NO: 0275

[1729] n -0.12 KRARNTEAARR SEQ ID SRARKLQRMKQ Cationic Free Free NA Linear NO: 0276

[1730] GC -7.55

[1731] Ami

[1732] SEQ ID KRIPNKKPGKK Cationic Free datio NA Linear NO: 0277

[1733] n 0.51 Ami

[1734] SEQ ID KRIPNKKPGKKT Cationic Free datio NA Linear NO: 0278

[1735] n 0.25 Ami

[1736] KRIPNKKPGKKT SEQ ID

[1737] Cationic Free datio NA Linear TTKPTKK NO: 0279

[1738] n 0.13 Ami

[1739] KRIPNKKPGKKT SEQ ID

[1740] Cationic Free datio NA Linear TTKPTKKPTIK NO: 0280

[1741] n 0.89 KRIPNKKPGKKT Ami

[1742] SEQ ID TTKPTKKPTIKTT Cationic Free datio NA Linear NO: 0281

[1743] KK n 0.71 KRIPNKKPGKKT Ami

[1744] SEQ ID TTKPTKKPTIKTT Cationic Free datio NA Linear NO: 0282

[1745] KKDLK n

[1746] 1.4 KRIPNKKPGKKT Ami

[1747] SEQ ID TTKPTKKPTIKTT Cationic Free datio NA Linear NO: 0283

[1748] KKDLKPQTTKPK n

[1749] 1.18 Ami

[1750] SEQ ID KRIPNKKPKK Cationic Free datio NA Linear NO: 0284

[1751] n 0.73 SEQ ID KRKRWHW Cationic Free Free NA Linear NO: 0285 1.37 SEQ ID KRKRWHW Cationic NA Free NA Linear NO: 0285 1.37

[1752] Ami

[1753] KRPAAIKKAGQA SEQ ID

[1754] Cationic Free datio NA Linear KKKK NO: 0286

[1755] n 0.26 KRRIRRERNKM SEQ ID AAAKSRNRRRE Cationic Free Free NA Linear NO: 0287

[1756] LTDTGC

[1757] -10 SEQ ID KRRQRRR Cationic Free Free NA Linear NO: 0288 -4.12 KRVSRNKSEKK SEQ ID

[1758] Cationic Free NA NA Linear

[1759]

[1760] RR NO: 0289 -5.04ATTORNEY DOCKET: 05336.0008W001

[1761] Ami KSICKTIPSNKPK SEQ ID

[1762] Cationic Free datio NA Linear KK NO: 0290

[1763] n 2.06 KSTGKANKITITN SEQ ID

[1764] Cationic Free Free NA Linear DKGRLSK NO: 0291

[1765] -2.37 Ami

[1766] SEQ ID KTIPSNKPKKK Cationic Free datio NA Linear NO: 0292

[1767] n 0.81 X,

[1768] am

[1769] ino

[1770] Ami

[1771] KXRKXRILFQYK SEQ ID he

[1772] Cationic Free datio Linear XRKXR NO: 0293 xyl

[1773] n

[1774] res

[1775] idu

[1776] e 1.04 LALALALALALAL Ami

[1777] SEQ ID AKLAKLAKLAKL Cationic Free datio NA Linear NO: 0294

[1778] AKIKKIKKKIK n

[1779] 10.45 LALALALALALAL Ami

[1780] SEQ ID ALAKIKKIKKIKKI Cationic Free datio NA Linear NO: 0295

[1781] KKLAKLAKKIK n

[1782] 11.66 LALALALALALAL

[1783] Acet Ami

[1784] ALAKKLKKLKKL SEQ ID

[1785] Cationic ylatio datio NA Linear KKLKKLKKLKYA NO: 0296

[1786] n n

[1787] K 13.78 LALALALALALAL

[1788] Ami

[1789] ALAKKLKKLKKL SEQ ID

[1790] Cationic Free datio NA Linear KKLKKLKKLKYA NO: 0296

[1791] n

[1792] K 12.35 LALALALALALAL Ami

[1793] SEQ ID ALAKLAKLAKLA Cationic Free datio NA Linear NO: 0297

[1794] KLAKLAKKIK n

[1795] 9.6 B,

[1796] Bet

[1797] Laur Ami

[1798] SEQ ID a- Lauroyl-B-rrrrrrr Cationic oylati datio Linear NO: 0298 Ala

[1799] on n

[1800] nin

[1801] e -6.49 B,

[1802] Laur Ami

[1803] Lauroyl-B- SEQ ID Bet

[1804] Cationic oylati datio Linear RRRRRRRRR NO: 0299 a- on n

[1805]

[1806] Ala -8.07ATTORNEY DOCKET: 05336.0008W001

[1807] nin

[1808] e

[1809] B,

[1810] Bet

[1811] Laur Ami

[1812] Lauroyl-B-rrrrr- SEQ ID a- Cationic oylati datio Linear RRRR NO: 0300 Ala

[1813] on n

[1814] nin

[1815] e -8.07 B,

[1816] Bet

[1817] Laur Ami

[1818] Lauroyl-B-RRRR- SEQ ID a- Cationic oylati datio Linear rrrrr NO: 0301 Ala

[1819] on n

[1820] nin

[1821] e -8.07 LGISYGRKKRRQ SEQ ID

[1822] Cationic Free Free NA Linear RRRPPQ NO: 0302

[1823] -3.62 Ami

[1824] LILIGRRRRRRR SEQ ID

[1825] Cationic NA datio NA Linear RGC NO: 0303

[1826] n -2.28 LILILILILILILILIKR Acet Ami

[1827] SEQ ID KKRKKRKKRKK Cationic ylatio datio NA Linear NO: 0304

[1828] RAKRAKHSK n n

[1829] 10.08 LILILILILILILILIKR Ami

[1830] SEQ ID KKRKKRKKRKK Cationic Free datio NA Linear NO: 0304

[1831] RAKRAKHSK n

[1832] 8.65 Acet Ami

[1833] LKKLCKLLKKLC SEQ ID

[1834] Cationic ylatio datio NA Linear KLAG NO: 0305

[1835] n n 9.07 Acet Ami

[1836] LKKLLKLLKKLLK SEQ ID

[1837] Cationic ylatio datio NA Linear LAG NO: 0306

[1838] n n 9.01 LKRWGTIKKSKA SEQ ID INVLRGFRKEIG Cationic Free Free NA Linear NO: 0307

[1839] RMLNILNRRRR

[1840] -1.6 LLRARWRRRRS SEQ ID

[1841] Cationic Free Free NA Linear RRFR NO: 0308 -3.61 LVVLGKL- SEQ ID

[1842] Cationic Free Free NA Linear YGRKKRRQRRR NO: 0309

[1843] -1.42 MDAQTRRRERR SEQ ID AEKQAQWKAAN Cationic Free Free NA Linear NO: 0310

[1844]

[1845] ATTORNEY DOCKET: 05336.0008W001

[1846] SEQ ID MLLLTRRRST Cationic Free Free NA Linear NO: 0311 -0.43 SEQ ID RGRGRGRGRG Cationic Free Free NA Linear NO: 0312 -5.05 SEQ ID RGRGRGRGRG Cationic Free Free NA Linear NO: 0312 -5.05 MRRIRPRPPRLP SEQ ID RPRPRPLPFPRP Cationic Free Free NA Linear NO: 0313

[1847] GGCYPG

[1848] -0.77 B,

[1849] Bet

[1850] Myrsi Ami

[1851] Myristoyl-B- SEQ ID a- Cationic toylat datio Linear rrrrrrrrrrr NO: 0314 Ala

[1852] ion n

[1853] nin

[1854] e -9.13 B,

[1855] Bet

[1856] Myrsi Ami

[1857] Myristoyl-B- SEQ ID a- Cationic toylat datio Linear RRRRRRRRRRR NO: 0315 Ala

[1858] ion n

[1859] nin

[1860] e -9.13 NAKTRRHERRR SEQ ID

[1861] Cationic Free Free NA Linear KLAIERGC NO: 0316

[1862] -6.38 NNNAAGRKRKK SEQ ID

[1863] Cationic Free Free NA Linear

[1864] RT NO: 0317 -5.82

[1865] Ami

[1866] SEQ ID NRARRNRRRVR Cationic Free datio NA Linear NO: 0318

[1867] n -6.79 SEQ ID NYQRRCKNQN Cationic Free Free NA Linear NO: 0319 -3.65 SEQ ID NYQWRCKNQN Cationic Free Free NA Linear NO: 0320 -1.4 SEQ ID NYRRRCKNQN Cationic Free Free NA Linear NO: 0321 -4.1 SEQ ID NYRWRCK Cationic Free Free NA Linear NO: 0322 0.45 SEQ ID NYRWRCKN Cationic Free Free NA Linear NO: 0323 -0.53 SEQ ID NYRWRCKNQ Cationic Free Free NA Linear NO: 0324 -0.87 SEQ ID NYRWRCKNQN Cationic Free Free NA Linear NO: 0325 -1.85

[1868] Ami

[1869] SEQ ID PKKKRKV Cationic Free datio NA Linear NO: 0326

[1870]

[1871] n 1.01ATTORNEY DOCKET: 05336.0008W001

[1872] PKKKRKVAGYLL GKINLKALAALA SEQ ID KKILPQMQQNVF Cationic Free Free NA Linear NO: 0327

[1873] QYPGAGMVPQG EANF

[1874] 4.14 PKKKRKVRRRR RRRPQMQQNVF SEQ ID

[1875] Cationic Free Free NA Linear QYPGAGMVPQG NO: 0328

[1876] EANF

[1877] -6.05 PKKKRKVRRRR SEQ ID RRRYSQTSHKL Cationic Free Free NA Linear NO: 0329

[1878] VQLLTTAEQQ

[1879] -6.35 Ami

[1880] PKKKRKVWKLL SEQ ID

[1881] Cationic Free datio NA Linear QQFFGLM NO: 0330

[1882] n 6.97 Stear Ami

[1883] PKKKRKVWKLL SEQ ID

[1884] Cationic ylatio datio NA Linear QQFFGLM NO: 0330

[1885] n n 15.47 Ami

[1886] QTRRRERRAEK SEQ ID

[1887] Cationic Free datio NA Linear QAQW NO: 0331

[1888] n -5.49 SEQ ID RAKRRQRRR Cationic Free Free NA Linear NO: 0332 -5.18 RGDGPRRRPRK SEQ ID

[1889] Cationic Free Free NA Linear RRGR NO: 0333 -6.79 RGPRRQPRRHR SEQ ID

[1890] Cationic Free Free NA Linear RPRR NO: 0334 -7.53 RIKAERKRMRN SEQ ID RIAASKSRKRKL Cationic Free Free NA Linear NO: 0335

[1891] ERIARGC

[1892] -7.2 SEQ ID RKARRQRRR Cationic Free Free NA Linear NO: 0336 -5.18 SEQ ID RKKAAA Cationic Free Free NA Linear NO: 0337 -1.26 SEQ ID RKKARQRRR Cationic Free Free NA Linear NO: 0338 -4.22 SEQ ID RKKNPNCRRH Cationic Free Free NA Linear NO: 0339 -3.32 SEQ ID RKKRAQRRR Cationic Free Free NA Linear NO: 0340 -4.22 SEQ ID RKKRRARRR Cationic Free Free NA Linear

[1893]

[1894] NO: 0341 -4.67ATTORNEY DOCKET: 05336.0008W001

[1895] SEQ ID RKKRRQARR Cationic Free Free NA Linear NO: 0342 -4.22 SEQ ID RKKRRQR Cationic Free Free NA Linear NO: 0343 -3.16 SEQ ID RKKRRQRAR Cationic Free Free NA Linear NO: 0344 -4.22 SEQ ID RKKRRQRR Cationic Free Free NA Linear NO: 0345 -3.95 SEQ ID RKKRRQRRA Cationic Free Free NA Linear NO: 0346 -4.22 SEQ ID

[1896] rkkrrqrrr Cationic Free Free NA Linear NO: 0347 -4.74

[1897] Ami

[1898] SEQ ID RKKRRQRRRGC Cationic Free datio NA Linear NO: 0348

[1899] n -3.48 Ami

[1900] RKKRRQRRRGG SEQ ID

[1901] Cationic Free datio NA Linear

[1902] G NO: 0349

[1903] n -4.75 RKKRRQRRRHR SEQ ID

[1904] Cationic NA NA NA Linear RKKR NO: 0350 -7.08 RKKRRQRRRRK SEQ ID

[1905] Cationic Free Free NA Linear KRRQRRR NO: 0351

[1906] -9.48 SEQ ID RKKWFW Cationic Free Free NA Linear NO: 0352 3.63

[1907] Ami

[1908] SEQ ID RLLRLLRLL Cationic Free datio NA Linear NO: 0353

[1909] n 3.08 X,

[1910] 1- am

[1911] ino

[1912] eye

[1913] lop

[1914] ent

[1915] an

[1916] Ami

[1917] SEQ ID e- RLLRLLRLX Cationic Free datio Linear NO: 0354 1- n

[1918] car

[1919] bo

[1920] xyli

[1921] c

[1922] aci

[1923] ds

[1924] (Ac

[1925]

[1926] 5c) 2.28ATTORNEY DOCKET: 05336.0008W001

[1927] X,

[1928] 1- am

[1929] ino

[1930] eye

[1931] lop

[1932] ent

[1933] an

[1934] Ami

[1935] SEQ ID e- RLLRLXRLX Cationic Free datio Linear NO: 0355 1- n

[1936] car

[1937] bo

[1938] xyli

[1939] c

[1940] aci

[1941] ds

[1942] (Ac

[1943] 5c) 1.48 RLRLRLRLRLRL

[1944] Ami RLRLKLLKLLKLL SEQ ID

[1945] Cationic Free datio NA Linear KLLKKKKKKKGY NO: 0356

[1946] n

[1947] K 9.5 RLRLRLRLRLRL

[1948] Ami

[1949] RLRLKNNKNNK SEQ ID

[1950] Cationic Free datio NA Linear NNKNNKKKKKK NO: 0357

[1951] n

[1952] KGYK

[1953] -4.74 RLRLRLRLRLRL

[1954] Ami

[1955] RLRLKRLKRLKR SEQ ID

[1956] Cationic Free datio NA Linear LKRLKKKKKKKG NO: 0358

[1957] n

[1958] YK

[1959] 3.14 X,

[1960] 1- am

[1961] ino

[1962] eye

[1963] lop

[1964] ent

[1965] Ami

[1966] SEQ ID an RLXRLXRLX Cationic Free datio Linear NO: 0359 e- n

[1967] 1- car

[1968] bo

[1969] xyli

[1970] c

[1971] aci

[1972]

[1973] ds 0.68ATTORNEY DOCKET: 05336.0008W001

[1974] (Ac

[1975] 5c)

[1976] X,

[1977] 1- am

[1978] ino

[1979] eye

[1980] lop

[1981] ent

[1982] an

[1983] Ami

[1984] SEQ ID e- RLXRLXRXX Cationic Free datio Linear NO: 0360 1- n

[1985] car

[1986] bo

[1987] xyli

[1988] c

[1989] aci

[1990] ds

[1991] (Ac

[1992] 5c) -0.12 X,

[1993] 1- am

[1994] ino

[1995] eye

[1996] lop

[1997] ent

[1998] an

[1999] Ami

[2000] SEQ ID e- RLXRXRXX Cationic Free datio Linear NO: 0361 1- n

[2001] car

[2002] bo

[2003] xyli

[2004] c

[2005] aci

[2006] ds

[2007] (Ac

[2008] 5c) -0.92 X,

[2009] am

[2010] Ami

[2011] RMKWKKILFQY SEQ ID ino

[2012] Cationic Free datio Linear RXRRXR NO: 0362 he

[2013] n

[2014] xyl

[2015]

[2016] res 2.05ATTORNEY DOCKET: 05336.0008W001

[2017] idu

[2018] e

[2019] Ami

[2020] SEQ ID RNRSRHRR Cationic Free datio NA Linear NO: 0363

[2021] n -5.04 Ami

[2022] SEQ ID RQARRNRRRC Cationic Free datio NA Linear NO: 0364

[2023] n -4.85 RQGAARVTSWL Ami

[2024] SEQ ID GRQLRIAGKRLE Cationic Free datio NA Linear NO: 0365

[2025] GRSK n -3.4

[2026] Ami

[2027] RQIKIFFQNRRM SEQ ID

[2028] Cationic Free datio NA Linear KFKK NO: 0366

[2029] n 2.69 RQIKIQFQNRRK SEQ ID

[2030] Cationic Free Free NA Linear WKK NO: 0367 0.33

[2031] Ami

[2032] RQIKIWFQNRRM SEQ ID

[2033] Cationic NA datio NA Linear KWKKGC NO: 0368

[2034] n 3.9 RQIKIWFQNRRM SEQ ID

[2035] Cationic Free Free NA Linear KWKKGG NO: 0369

[2036] 2.2 Ami

[2037] RQLRIAGRRLRG SEQ ID

[2038] Cationic Free datio NA Linear RSR NO: 0370

[2039] n -4.08 RRARRPRRLRP SEQ ID

[2040] Cationic Free Free NA Linear APGR NO: 0371 -5.83

[2041] Ami

[2042] SEQ ID RRGC Cationic NA datio NA Linear NO: 0372

[2043] n -0.32 Ami

[2044] SEQ ID RRGRRG Cationic Free datio NA Linear NO: 0373

[2045] n -2.95 Ami

[2046] SEQ ID RRIPNRRPRR Cationic Free datio NA Linear NO: 0374

[2047] n -4.07 RRIRPRPPRLPR SEQ ID PRPRPLPFPRP Cationic Free Free NA Linear NO: 0375

[2048] G -2.37

[2049] Ami

[2050] SEQ ID RRLLRRLRR Cationic Free datio NA Linear NO: 0376

[2051] n -1.69 Ami

[2052] SEQ ID RRLLRRLRR Cationic NA datio NA Linear NO: 0376

[2053]

[2054] n -1.69ATTORNEY DOCKET: 05336.0008W001

[2055] SEQ ID RRLSYSRRRF Cationic Free Free NA Linear NO: 0377 -2.34

[2056] Ami

[2057] SEQ ID RRRERRAEK Cationic Free datio NA Linear NO: 0378

[2058] n -5.4 SEQ ID

[2059] [rRrGrKkRr] Cationic Free Free NA Cyclic NO: 0379 -4.62 RRRQKRIVVRR SEQ ID

[2060] Cationic Free Free NA Linear RLIR NO: 0380 -3.65

[2061] SEQ ID

[2062] rrrqrrkkr Cationic Free Free NA Linear NO: 0381 -4.74 SEQ ID RRRQRRKKR Cationic Free Free NA Linear NO: 0382 -4.74 RRRQRRKKRGY SEQ ID CKCKYGRKKRR Cationic Free Free NA Linear NO: 0383

[2063] QRRR

[2064] -6.82 SEQ ID RRRR Cationic Free Free NA Linear NO: 0384 -3.16 RRRRNRTRRNR SEQ ID

[2065] Cationic Free Free NA Linear RRVRGC NO: 0385

[2066] -9.98 SEQ ID RRRRR Cationic Free Free NA Linear NO: 0386 -3.95 SEQ ID

[2067] rrrrr Cationic Free Free NA Linear NO: 0387 -3.95 SEQ ID

[2068] rrrrrr Cationic Free Free NA Linear NO: 0388 -4.74

[2069] Ami

[2070] SEQ ID RRRRRR Cationic Free datio NA Linear NO: 0389

[2071] n -4.09 SEQ ID RRRRRR Cationic Free Free NA Linear NO: 0389 -4.74 SEQ ID RRRRRRHHH Cationic Free NA NA Linear NO: 0390 -5.67 SEQ ID

[2072] rrrrrrr Cationic Free Free NA Linear NO: 0391 -5.53 SEQ ID RRRRRRR Cationic Free Free NA Linear NO: 0392 -5.53 RRRRRRRGGIY SEQ ID

[2073] Cationic Free Free NA Linear LATALAKWALKQ NO: 0393

[2074] -2.2 RRRRRRRGGIY SEQ ID LATALAKWALKQ Cationic Free Free NA Linear NO: 0394

[2075]

[2076] GF -1.26ATTORNEY DOCKET: 05336.0008W001

[2077] RRRRRRRGGKL SEQ ID

[2078] Cationic Free Free NA Linear AKLAKKLAKLAK NO: 0395

[2079] -2.83 SEQ ID RRRRRRRHHH Cationic Free NA NA Linear NO: 0396 -6.46 RRRRRRRQIKIL SEQ ID FQNRRMKWKK Cationic Free Free NA Linear NO: 0397

[2080] GGC -2.37

[2081] SEQ ID

[2082] rRrRRRRR Cationic NA NA NA Linear NO: 0398 -6.32 SEQ ID

[2083] rrrRrRrR Cationic NA NA NA Linear NO: 0399 -6.32 SEQ ID

[2084] rRrRrRrR Cationic NA NA NA Linear NO: 0400 -6.32 SEQ ID RRRRRRRRC Cationic Free Free NA Linear NO: 0401 -5.49

[2085] Cy

[2086] stei

[2087] ne

[2088] mo

[2089] difi

[2090] ed

[2091] oct

[2092] a- arg

[2093] inin

[2094] e

[2095] RRRRRRRR- SEQ ID

[2096] Cationic Free Free co Linear c(RGDfK) NO: 0402

[2097] nju

[2098] gat

[2099] ed

[2100] to

[2101] the

[2102] bra

[2103] nc

[2104] h

[2105] of

[2106] lysi

[2107] ne -5.45 Ami

[2108] SEQ ID RRRRRRRRGC Cationic NA datio NA Linear NO: 0403

[2109] n -5.06 Ami

[2110] SEQ ID

[2111] rrrrrrrrGC Cationic NA datio NA Linear NO: 0404

[2112] n -5.06 SEQ ID RRRRRRRRHHH Cationic Free NA NA Linear

[2113]

[2114] NO: 0405 -7.25ATTORNEY DOCKET: 05336.0008W001

[2115] SEQ ID RRRRRRRRK Cationic Free Free NA Linear NO: 0406 -6.15

[2116] Ami

[2117] SEQ ID

[2118] rRRRRRRRr Cationic Free datio NA Linear NO: 0407

[2119] n -6.46 Ami

[2120] SEQ ID

[2121] rRrRrRrRr Cationic Free datio NA Linear NO: 0408

[2122] n -6.46 Ami

[2123] SEQ ID

[2124] rrrrrrrrr Cationic Free datio NA Linear NO: 0409

[2125] n -6.46 SEQ ID

[2126] rrrrrrrrr Cationic Free Free NA Linear NO: 0409 -7.11

[2127] Cyst

[2128] SEQ ID eine

[2129] RRRRRRRRRC Cationic Free NA Linear NO: 0410 addit

[2130] ion -6.28 SEQ ID

[2131] rrrrrrrrrcqcrrkn Cationic Free Free NA Linear NO: 0411 -8.18 SEQ ID RRRRRRRRRGD Cationic Free Free NA Linear NO: 0412 -7.61 RRRRRRRRRHH SEQ ID

[2132] Cationic Free NA NA Linear

[2133] H NO: 0413 -8.04

[2134] Acet

[2135] SEQ ID

[2136] rrrrrrrrrk Cationic ylatio Free NA Linear NO: 0414

[2137] n -5.51 Ami

[2138] SEQ ID RRRRRRRRRR Cationic NA datio NA Linear NO: 0415

[2139] n -7.25 Ami

[2140] SEQ ID RRRRRRRRRRR Cationic Free datio NA Linear NO: 0416

[2141] n -8.04 SEQ ID RRRRRRRRRRR Cationic Free Free NA Linear NO: 0416 -8.69

[2142] Ami

[2143] SEQ ID

[2144] rrrrrrrrrrrr Cationic NA datio NA Linear NO: 0417

[2145] n -8.83 RRRRRRRRRRR SEQ ID

[2146] Cationic Free Free NA Linear

[2147] R NO: 0418 -9.48

[2148] Ami

[2149] RRRRRRRRRRR SEQ ID

[2150] Cationic NA datio NA Linear RGC NO: 0419

[2151] n -8.22 Ami

[2152] SEQ ID

[2153] rrrrrrrrrrrrGC Cationic NA datio NA Linear NO: 0420

[2154] n -8.22 Acet Ami

[2155] RRRRRRRRRRR SEQ ID

[2156] Cationic ylatio datio NA Linear RRRR NO: 0421

[2157]

[2158] n n -9.77ATTORNEY DOCKET: 05336.0008W001

[2159] RRRRRRRRRRR SEQ ID

[2160] Cationic Free Free NA Linear RRRRR NO: 0422 -12.6

[2161] Ami

[2162] RRRRRRRRRRR SEQ ID

[2163] Cationic NA datio NA Linear RRRRRGC NO: 0423

[2164] n -11.4 Ami

[2165] SEQ ID RRRRRRRW Cationic Free datio NA Linear NO: 0424

[2166] n -3.42 Ami

[2167] RRRRWWWWR SEQ ID

[2168] Cationic Free datio NA Linear RRR NO: 0425

[2169] n 0.17 Ami

[2170] RRVTSWLGRQL SEQ ID

[2171] Cationic Free datio NA Linear RIAGKRLEGRSK NO: 0426

[2172] n -2.3 RRVWRRYRRQ SEQ ID

[2173] Cationic Free Free NA Linear RWCRR NO: 0427 -2.83 RRWRRWNRFN SEQ ID

[2174] Cationic Free Free NA Linear RRRCR NO: 0428 -4.16

[2175] Ami

[2176] SEQ ID

[2177] rsrgrlrrgairlqrg Cationic Free datio NA Linear NO: 0429

[2178] n -4.3 Ami

[2179] SEQ ID RTRRNRRRVR Cationic Free datio NA Linear NO: 0430

[2180] n -5.8 Ami

[2181] RVRSWLGRQLR SEQ ID

[2182] Cationic Free datio NA Linear IAGKRLEGRSK NO: 0431

[2183] n -2.04 Ami RVTSWLGRQLRI SEQ ID

[2184] Cationic Free datio NA Linear AGKRLEGRSK NO: 0432

[2185] n -1.51 SEQ ID RWRCKNQN Cationic Free Free NA Linear NO: 0433 -1.42

[2186] Ami

[2187] RWRRWRRWRR SEQ ID

[2188] Cationic Free datio NA Linear WR NO: 0434

[2189] n 0.17 SEQ ID RWRWRWRW Cationic Free Free NA Linear NO: 0435 2.68

[2190] X,

[2191] 6- am

[2192] ino

[2193] he RXRRBRRXRRB SEQ ID

[2194] Cationic NA NA xa Linear RXB NO: 0436

[2195] noi

[2196] c

[2197] aci

[2198] d

[2199]

[2200] (Ah -9.02ATTORNEY DOCKET: 05336.0008W001

[2201] x)

[2202] an

[2203] d

[2204] B,

[2205] Bet

[2206] a- Ala

[2207] nin

[2208] e

[2209] X,

[2210] am

[2211] ino

[2212] Ami

[2213] RXRRXRAAAAA SEQ ID he

[2214] Cationic Free datio Linear RXRRXR NO: 0437 xyl

[2215] n

[2216] res

[2217] idu

[2218] e -7.02 X,

[2219] am

[2220] ino

[2221] Ami

[2222] RXRRXRFLQIYR SEQ ID he

[2223] Cationic Free datio Linear XRRXR NO: 0438 xyl

[2224] n

[2225] res

[2226] idu

[2227] e -2.8 X,

[2228] am

[2229] ino

[2230] Ami

[2231] RXRRXRIEFQYR SEQ ID he

[2232] Cationic Free datio Linear XRRXR NO: 0439 xyl

[2233] n

[2234] res

[2235] idu

[2236] e -4.6 X,

[2237] am

[2238] ino

[2239] Ami

[2240] RXRRXRIKFQYR SEQ ID he

[2241] Cationic Free datio Linear XRRXR NO: 0440

[2242] n xyl

[2243] res

[2244] idu

[2245] e -3.43 X,

[2246] am

[2247] ino

[2248] Ami

[2249] RXRRXRILFQYK SEQ ID he

[2250] Cationic Free datio Linear KWKMR NO: 0441 xyl

[2251] n

[2252] res

[2253] idu

[2254]

[2255] e 2.05ATTORNEY DOCKET: 05336.0008W001

[2256] X,

[2257] am

[2258] ino

[2259] Ami

[2260] RXRRXRILFQYR SEQ ID he

[2261] Cationic Free datio Linear MKWKK NO: 0442 xyl

[2262] n

[2263] res

[2264] idu

[2265] e 2.05 X,

[2266] am

[2267] ino

[2268] Ami

[2269] RXRRXRILFQYR SEQ ID he

[2270] Cationic Free datio Linear XRRXR NO: 0443 xyl

[2271] n

[2272] res

[2273] idu

[2274] e -2.8 X,

[2275] am

[2276] ino

[2277] Ami

[2278] RXRRXRIPFQYR SEQ ID he

[2279] Cationic Free datio Linear XRRXR NO: 0444 xyl

[2280] n

[2281] res

[2282] idu

[2283] e -3.45 X,

[2284] am

[2285] ino

[2286] Ami

[2287] RXRRXRIWFQY SEQ ID he

[2288] Cationic Free datio Linear RXRRXR NO: 0445

[2289] n xyl

[2290] res

[2291] idu

[2292] e -2.14 X,

[2293] 6- am

[2294] ino

[2295] he

[2296] xa

[2297] noi

[2298] c RXRRXRRXRRX SEQ ID

[2299] Cationic NA NA aci Linear RXB NO: 0446

[2300] d

[2301] (Ah

[2302] x)

[2303] an

[2304] d

[2305] B,

[2306] Bet

[2307]

[2308] a- -9.02ATTORNEY DOCKET: 05336.0008W001

[2309] Ala

[2310] nin

[2311] e

[2312] X,

[2313] am

[2314] ino

[2315] Ami

[2316] RXRRXRYQFLIR SEQ ID he

[2317] Cationic Free datio Linear XRRXR NO: 0447 xyl

[2318] n

[2319] res

[2320] idu

[2321] e -2.8 X,

[2322] 6- am

[2323] ino

[2324] he

[2325] xa

[2326] noi

[2327] c

[2328] aci RXRXRXRXRXR SEQ ID d

[2329] Cationic NA NA Linear XRXRXB NO: 0448 (Ah

[2330] x)

[2331] an

[2332] d

[2333] B,

[2334] Bet

[2335] a- Ala

[2336] nin

[2337] e -9.02 X,

[2338] 1- am

[2339] ino

[2340] eye

[2341] lop

[2342] Ami

[2343] SEQ ID ent RXXRXRXX Cationic Free datio Linear NO: 0449 an

[2344] n

[2345] e- 1- car

[2346] bo

[2347] xyli

[2348]

[2349] c -1.72ATTORNEY DOCKET: 05336.0008W001

[2350] aci

[2351] ds

[2352] (Ac

[2353] 5c)

[2354] Ami

[2355] SEQ ID SKKKKTKV Cationic Free datio NA Linear NO: 0450

[2356] n 1.11 SQMTRQARRLY SEQ ID

[2357] Cationic Free Free NA Linear BGC NO: 0451 -1.56

[2358] SEQ ID SRRRRRRRRR Cationic NA NA NA Linear NO: 0452 -7.56

[2359] X,

[2360] am

[2361] ino

[2362] Ami

[2363] SXRSXRILFQYS SEQ ID he

[2364] Cationic Free datio Linear XRSXR NO: 0453 xyl

[2365] n

[2366] res

[2367] idu

[2368] e -1.44 TAKTRYKARRAE SEQ ID

[2369] Cationic Free Free NA Linear LIAERRGC NO: 0454

[2370] -4.55 TRQARRNRRRR SEQ ID

[2371] Cationic Free Free NA Linear WRERQR NO: 0455

[2372] -9.63 TRQARRNRRRR SEQ ID

[2373] Cationic Free Free NA Linear WRERQRGC NO: 0456

[2374] -9.02 TRRQRTRRARR SEQ ID

[2375] Cationic Free Free NA Linear NRGC NO: 0457 -7.82

[2376] Ami

[2377] TRRSKRRSHRK SEQ ID

[2378] Cationic Free datio NA Linear

[2379] F NO: 0458

[2380] n -3.27 SEQ ID VQLRRRWC Cationic Free Free NA Linear NO: 0459 0.7

[2381] Ami

[2382] SEQ ID VQRKRQKLMP Cationic Free datio NA Linear NO: 0460

[2383] n 0.51 VSRRRRRRGGR SEQ ID

[2384] Cationic Free Free NA Linear RRR NO: 0461 -8.47

[2385] Sul

[2386] Sulfh fhy VSRRRRRRGGR SEQ ID

[2387] Cationic ydryl Free dry Linear RRR NO: 0461

[2388] ation lati

[2389]

[2390] on -8.47ATTORNEY DOCKET: 05336.0008W001

[2391] VSRRRRRRGGR SEQ ID

[2392] Cationic Free Free NA Linear RRRK NO: 0462 -8.3 VVLGKLYGRKK SEQ ID

[2393] Cationic Free Free NA Linear RRQRRR NO: 0463 -2.22 WEAVVAYGRKK SEQ ID

[2394] Cationic Free Free NA Linear RRQRRR NO: 0464 -3.85 WEAVVLYGRKK SEQ ID

[2395] Cationic Free Free NA Linear RRQRRR NO: 0465 -2.78 WELVVAYGRKK SEQ ID

[2396] Cationic Free Free NA Linear RRQRRR NO: 0466 -2.78 WELVVLGKLYG SEQ ID

[2397] Cationic Free Free NA Linear RKKRRQRRR NO: 0467

[2398] -0.96 WELVVLGKYGR SEQ ID

[2399] Cationic Free Free NA Linear KKRRQRRR NO: 0468

[2400] -1.76 WELVVLGYGRK SEQ ID

[2401] Cationic Free Free NA Linear KRRQRRR NO: 0469

[2402] -1.93 WELVVYGRKKR SEQ ID

[2403] Cationic Free Free NA Linear RQRRR NO: 0470 -2.51 WELVYGRKKRR SEQ ID

[2404] Cationic Free Free NA Linear QRRR NO: 0471 -2.83 WELYGRKKRRQ SEQ ID

[2405] Cationic Free Free NA Linear RRR NO: 0472 -3.15 WEYGRKKRRQR SEQ ID

[2406] Cationic Free Free NA Linear RR NO: 0473 -3.95

[2407] Ami

[2408] SEQ ID WRRRRRRRR Cationic Free datio NA Linear NO: 0474

[2409] n -4.21 SEQ ID

[2410] [WRWKKKKA] Cationic NA NA NA Cyclic NO: 0475 2.54

[2411] Ami

[2412] SEQ ID WWRRRRRRRR Cationic Free datio NA Linear NO: 0476

[2413] n -2.75 Ami WWWRRRRRRR SEQ ID

[2414] Cationic Free datio NA Linear

[2415] R NO: 0477

[2416] n -1.29 Ami

[2417] WWWWRRRRR SEQ ID

[2418] Cationic Free datio NA Linear RRR NO: 0478

[2419] n 0.17 SEQ ID YARVRRRGPRR Cationic Free Free NA Linear NO: 0479 -4.21 YGDCLPHLKLCK SEQ ID ENKDCCSKKCK Cationic Free Free NA Linear NO: 0480

[2420] RRGTNIEKRCR

[2421]

[2422] 0.83ATTORNEY DOCKET: 05336.0008W001

[2423] YGRGGRRGRR SEQ ID

[2424] Cationic Free Free NA Linear

[2425] R NO: 0481 -5.07 YGRKKKRRQRR SEQ ID

[2426] Cationic Free Free NA Linear

[2427] R NO: 0482 -4.24

[2428] SEQ ID YGRKKRPQRRR Cationic NA NA NA Linear NO: 0483 -3.47 YGRKKRRQRRR SEQ ID AYFNGCSSPTA Cationic Free Free NA Linear NO: 0484

[2429] PLSPMSP

[2430] -3.76 Cyst YGRKKRRQRRR SEQ ID eine

[2431] Cationic Free NA Linear

[2432] C NO: 0485 addit

[2433] ion -3.58 YGRKKRRQRRR SEQ ID

[2434] Cationic Free Free NA Linear

[2435] G NO: 0485 -3.58 YGRKKRRQRRR DPYHATSGALSP SEQ ID AKDCGSQKYAY Cationic Free Free NA Linear NO: 0486

[2436] FNGCSSPTLSP MSP

[2437] -4.34 Ami YGRKKRRQRRR SEQ ID

[2438] Cationic Free datio NA Linear GO NO: 0487

[2439] n -3.15 YGRKKRRQRRR SEQ ID

[2440] Cationic Free Free NA Linear PPQG NO: 0488 -4.67 YGRKKRRQRRR SEQ ID QRRRPTAPLSP Cationic Free Free NA Linear NO: 0489

[2441] MSP -6.64

[2442] SEQ ID YRWRCKNQ Cationic Free Free NA Linear NO: 0490 0.11 SEQ ID YRWRCKNQN Cationic Free Free NA Linear NO: 0491 -0.87 YYYAAGRKRKK SEQ ID

[2443] Cationic Free Free NA Linear

[2444] RT NO: 0492 -1.23

[2445] SEQ ID RRRRRHHH Cationic Free NA NA Linear NO: 0493 -4.88 SEQ ID

[2446] rrrrrrrr Cationic Free Free NA Linear NO: 0494 -6.32 SEQ ID

[2447] rRrRrRRR Cationic NA NA NA Linear NO: 0495 -6.32 SEQ ID

[2448] rRRRRRRR Cationic NA NA NA Linear NO: 0496 -6.32 CAYGRKKRRQR SEQ ID Cyst

[2449] Cationic Free NA Linear

[2450]

[2451] RR NO: 0497 eine -3.85ATTORNEY DOCKET: 05336.0008W001

[2452] additi

[2453] on

[2454] CAYGRKKRRQR SEQ ID

[2455] Cationic Free Free NA Linear RR NO: 0497 -3.85

[2456] SEQ ID

[2457] rRrGrKkRr Cationic Free Free NA Linear NO: 0498 -4.62

[2458] B,

[2459] SEQ ID

[2460] Bet

[2461] NO: 0499 Ami

[2462] B-[ERRRK]-(B)2- a- Cationic and SEQ Free datio Cyclic [KRRRE] Ala

[2463] ID NO: n

[2464] nin

[2465] 0500

[2466] e -8.45 B,

[2467] SEQ ID

[2468] Bet

[2469] NO: 0499 Ami

[2470] B-[ERRRK]-(B)3- a- Cationic and SEQ Free datio Cyclic [KRRRE] Ala

[2471] ID NO: n

[2472] nin

[2473] 0500

[2474] e -8.45 B,

[2475] SEQ ID

[2476] Bet

[2477] NO: 0499 Ami

[2478] B-[ERRRK]- a- Cationic and SEQ Free datio Cyclic [KRRRE] Ala

[2479] ID NO: n

[2480] nin

[2481] 0500

[2482] e -8.45 B,

[2483] SEQ ID

[2484] Bet

[2485] NO: 0499 Ami

[2486] B-[ERRRK]-B- a- Cationic and SEQ Free datio Cyclic [KRRRE] Ala

[2487] ID NO: n

[2488] nin

[2489] 0500

[2490] e -11.2 B,

[2491] SEQ ID

[2492] Bet

[2493] n ODD NO: 0501 Ami

[2494] B-RRR- a- Cationic and SEQ Free datio Cyclic [KRRRRE] Ala

[2495] ID NO: n

[2496] nin

[2497] 0093

[2498] e -8.41 B,

[2499] SEQ ID

[2500] Bet

[2501] NO: 0502 Ami

[2502] B-RRRR- a- Cationic and SEQ Free datio Cyclic [KRRRE] Ala

[2503] ID NO: n

[2504] nin

[2505] 0500

[2506] e -8.41 X,

[2507] SEQ ID

[2508] 6- CGRKKR-Ahx- NO: 0504

[2509] am

[2510] RQR-Ahx-R-ahx- Cationic and SEQ Free Free Linear

[2511] ino

[2512] RPPQ ID NO:

[2513] he

[2514] 0503

[2515]

[2516] xa -12.3ATTORNEY DOCKET: 05336.0008W001

[2517] noi

[2518] c

[2519] aci

[2520] d

[2521] (Ah

[2522] x)

[2523] X,

[2524] 6- am

[2525] ino

[2526] SEQ ID

[2527] he

[2528] NO: 0504

[2529] CGRKKR-Ahx- xa

[2530] Cationic and SEQ Free Free Linear RQRRRPPQ noi

[2531] ID NO:

[2532] c

[2533] 0505

[2534] aci

[2535] d

[2536] (Ah

[2537] x) -6.87 X,

[2538] 6- am

[2539] ino

[2540] SEQ ID

[2541] he

[2542] NO: 0506

[2543] CGRKKRRQR- xa

[2544] Cationic and SEQ Free Free Linear Ahx-RRPPQ noi

[2545] ID NO:

[2546] c

[2547] 0507

[2548] aci

[2549] d

[2550] (Ah

[2551] x) -6.87 X,

[2552] 6- am

[2553] ino

[2554] SEQ ID

[2555] he

[2556] NO: 0508

[2557] CGRKKRRQRR- xa

[2558] Cationic and SEQ Free Free Linear Ahx-RPPQ noi

[2559] ID NO:

[2560] c

[2561] 0503

[2562] aci

[2563] d

[2564] (Ah

[2565] x) -6.87 Probably Ami

[2566] ALIILRRRIRKQA SEQ ID

[2567] Amphipathi Free datio NA Linear HAHSK NO: 0513

[2568] c n -0.69 Probably Ami

[2569] AQIKIWFQNRRM SEQ ID

[2570] Amphipathi Free datio NA Linear KWKK NO: 0514

[2571]

[2572] c n 3.81ATTORNEY DOCKET: 05336.0008W001

[2573] Probably Ami

[2574] SEQ ID FQNRRMKWKK Amphipathi Free datio NA Linear NO: 0515

[2575] c n 1.39 Probably Ami

[2576] IKIWFQNRRMK SEQ ID

[2577] Amphipathi Free datio NA Linear WKK NO: 0516

[2578] c n 4.42 Probably Ami

[2579] IWFQNRRMKWK SEQ ID

[2580] Amphipathi Free datio NA Linear

[2581] K NO: 0517

[2582] c n 3.55 Probably Ami

[2583] KIWFQNRRMKW SEQ ID

[2584] Amphipathi Free datio NA Linear KK NO: 0518

[2585] c n 3.72 Probably Ami KSHAHAQKRIRR SEQ ID

[2586] Amphipathi Free datio NA Linear RLIILL NO: 0519

[2587] c n 0.38 Probably Ami

[2588] LAIILRRRIRKQA SEQ ID

[2589] Amphipathi Free datio NA Linear HAHSK NO: 0520

[2590] c n -0.69 Probably Ami

[2591] LLAILRRRIRKQA SEQ ID

[2592] Amphipathi Free datio NA Linear HAHSK NO: 0521

[2593] c n -0.59 Probably Ami

[2594] LLIALRRRIRKQA SEQ ID

[2595] Amphipathi Free datio NA Linear HAHSK NO: 0522

[2596] c n -0.59 Probably Ami

[2597] LLIIARRRIRKQA SEQ ID

[2598] Amphipathi Free datio NA Linear HAHSK NO: 0523

[2599] c n -0.69 Probably Ami

[2600] LLIILARRIRKQA SEQ ID

[2601] Amphipathi Free datio NA Linear HAHSK NO: 0524

[2602] c n 0.9 Probably Ami

[2603] LLIILRARIRKQA SEQ ID

[2604] Amphipathi Free datio NA Linear HAHSK NO: 0525

[2605] c n 0.9 Probably Ami

[2606] LLIILRRAIRKQA SEQ ID

[2607] Amphipathi Free datio NA Linear HAHSK NO: 0526

[2608] c n 0.9 Probably Ami

[2609] LLIILRRRARKQA SEQ ID

[2610] Amphipathi Free datio NA Linear HAHSK NO: 0527

[2611] c n -0.59 Probably Ami

[2612] LLIILRRRIARKQ SEQ ID

[2613] Amphipathi Free datio NA Linear AHAHSK NO: 0528

[2614] c n 0.11 Probably Ami

[2615] LLIILRRRIRAQA SEQ ID

[2616] Amphipathi Free datio NA Linear HAHSK NO: 0529

[2617] c n -0.06 Probably Ami

[2618] LLIILRRRIRKAA SEQ ID

[2619] Amphipathi Free datio NA Linear HAHSK NO: 0530

[2620]

[2621] c n 0.45ATTORNEY DOCKET: 05336.0008W001

[2622] Probably Ami

[2623] LLIILRRRIRKQA SEQ ID

[2624] Amphipathi Free datio NA Linear AAHSK NO: 0531

[2625] c n 0.42 Probably Ami

[2626] LLIILRRRIRKQA SEQ ID

[2627] Amphipathi Free datio NA Linear HAASK NO: 0532

[2628] c n 0.42 Probably Ami

[2629] LLIILRRRIRKQA SEQ ID

[2630] Amphipathi Free datio NA Linear HAHAK NO: 0533

[2631] c n 0.56 Probably Ami

[2632] LLIILRRRIRKQA SEQ ID

[2633] Amphipathi Free datio NA Linear HAHSA NO: 0534

[2634] c n -0.06 Probably Ami QIKIWFQNRRMK SEQ ID

[2635] Amphipathi Free datio NA Linear WKK NO: 0535

[2636] c n 4.08 Probably Ami

[2637] RAIKIWFQNRRM SEQ ID

[2638] Amphipathi Free datio NA Linear KWKK NO: 0536

[2639] c n 3.36 Probably Ami

[2640] RQAKIWFQNRR SEQ ID

[2641] Amphipathi Free datio NA Linear MKWKK NO: 0537

[2642] c n 2.32 Probably Ami

[2643] RQIAIWFQNRRM SEQ ID

[2644] Amphipathi Free datio NA Linear KWKK NO: 0538

[2645] c n 2.85 Probably Ami

[2646] RQIKAWFQNRR SEQ ID

[2647] Amphipathi Free datio NA Linear MKWKK NO: 0539

[2648] c n 2.32 Probably Ami

[2649] RQIKIAFQNRRM SEQ ID

[2650] Amphipathi Free datio NA Linear KWKK NO: 0540

[2651] c n 1.56 Probably Ami

[2652] RQIKIWAQNRR SEQ ID

[2653] Amphipathi Free datio NA Linear MKWKK NO: 0541

[2654] c n 1.86 Probably Ami

[2655] RQIKIWFANRRM SEQ ID

[2656] Amphipathi Free datio NA Linear KWKK NO: 0542

[2657] c n 3.36 Probably Ami

[2658] RQIKIWFQARRM SEQ ID

[2659] Amphipathi Free datio NA Linear KWKK NO: 0543

[2660] c n 4 Probably Ami

[2661] RQIKIWFQNARM SEQ ID

[2662] Amphipathi Free datio NA Linear KWKK NO: 0544

[2663] c n 3.81 Probably Ami

[2664] RQIKIWFQNRAM SEQ ID

[2665] Amphipathi Free datio NA Linear KWKK NO: 0545

[2666] c n 3.81 Probably Ami

[2667] SEQ ID RQIKIWFQNRR Amphipathi Free datio NA Linear NO: 0546

[2668]

[2669] c n 0.81ATTORNEY DOCKET: 05336.0008W001

[2670] Probably Ami

[2671] RQIKIWFQNRRA SEQ ID

[2672] Amphipathi Free datio NA Linear KWKK NO: 0547

[2673] c n 2.51 Probably Ami

[2674] SEQ ID RQIKIWFQNRRM Amphipathi Free datio NA Linear NO: 0548

[2675] c n 1.32 Probably Ami

[2676] RQIKIWFQNRRM SEQ ID

[2677] Amphipathi Free datio NA Linear AWKK NO: 0549

[2678] c n 2.85 Probably Ami

[2679] RQIKIWFQNRRM SEQ ID

[2680] Amphipathi Free datio NA Linear

[2681] K NO: 0550

[2682] c n 1.49 Probably Ami

[2683] RQIKIWFQNRRM SEQ ID

[2684] Amphipathi Free datio NA Linear KAKK NO: 0551

[2685] c n 1.56 Probably Ami

[2686] RQIKIWFQNRRM SEQ ID

[2687] Amphipathi Free datio NA Linear

[2688] KW NO: 0552

[2689] c n 2.95 Probably Ami

[2690] RQIKIWFQNRRM SEQ ID

[2691] Amphipathi Free datio NA Linear KWAK NO: 0553

[2692] c n 2.85 Probably Ami

[2693] RQIKIWFQNRRM SEQ ID

[2694] Amphipathi Free datio NA Linear KWK NO: 0554

[2695] c n 3.12 Probably Ami

[2696] RQIKIWFQNRRM SEQ ID

[2697] Amphipathi Free datio NA Linear KWKA NO: 0555

[2698] c n 2.85 Probably Ami WFQNRRMKWK SEQ ID

[2699] Amphipathi Free datio NA Linear

[2700] K NO: 0556

[2701] c n 2.85

[2702] L- CF

[2703] 3- Bp

[2704] g,

[2705] Trit

[2706] luo

[2707] ro

[2708] Ami

[2709] a-CF3-Bpg- Amphipathi SEQ ID me

[2710] Free datio Linear lyllgkinlkalaalakkil c NO: 0557 thyl

[2711] n

[2712] bic

[2713] ycl

[2714] op

[2715] ent

[2716] [1 -

[2717]

[2718] 1.1 8.25ATTORNEY DOCKET: 05336.0008W001

[2719] ]-1- yigi

[2720] yci

[2721] ne

[2722] L- CF

[2723] 3- Bp

[2724] g,

[2725] Trif

[2726] luo

[2727] ro

[2728] me

[2729] thyl

[2730] A-CF3-Bpg- Ami

[2731] Amphipathi SEQ ID

[2732] LYLLGKINLKALA Free datio Linear

[2733] c NO: 0558 bic

[2734] ALAKKIL n

[2735] ycl

[2736] op

[2737] ent

[2738] [1 - 1.1

[2739] H- yigi

[2740] yci

[2741] ne 8.25 Ph

[2742] os

[2743] Stear Ami AGY(PO3)LLGKI Amphipathi SEQ ID ph

[2744] yiatio datio Linear NLKALAALAKKIL c NO: 0559 ory

[2745] n n

[2746] lati

[2747] on 13.96 Ph

[2748] os AGY(PO3)LLGKT Stear Ami

[2749] Amphipathi SEQ ID ph (PO3)NLKALAAL yiatio datio Linear

[2750] c NO: 0560 ory

[2751] AKKIL n n

[2752] lati

[2753] on 13.15 Ph

[2754] os

[2755] Stear Ami AGY(PO3)LLGKT Amphipathi SEQ ID ph

[2756] yiatio datio Linear NLKALAALAKKIL c NO: 0561 ory

[2757] n n

[2758] lati

[2759]

[2760] on 13ATTORNEY DOCKET: 05336.0008W001

[2761] L- CF

[2762] 3- Bp

[2763] g,

[2764] Trif

[2765] luo

[2766] ro

[2767] me

[2768] thyi

[2769] Ami

[2770] agy-CF3-Bpg- Amphipathi SEQ ID

[2771] Free datio Linear Igkinlkalaalakkil c NO: 0562 bic

[2772] n

[2773] ycl

[2774] op

[2775] ent

[2776] [1 - 1.1

[2777] ]-1- ylgl

[2778] yci

[2779] ne 6.43 L- CF

[2780] 3- Bp

[2781] g,

[2782] Trit

[2783] luo

[2784] ro

[2785] me

[2786] thyi

[2787] AGY-CF3-Bpg- Ami

[2788] Amphipathi SEQ ID

[2789] LGKINLKALAALA Free datio Linear

[2790] c NO: 0563 bic

[2791] KKIL n

[2792] ycl

[2793] op

[2794] ent

[2795] [1 - 1.1

[2796] ]-1- W

[2797] yci

[2798] ne 6.43 0,

[2799] AGYLLG)5- Stear Or Amphipathi SEQ ID

[2800] OINLKALAALAK ylatio Free nit Linear

[2801] c NO: 0564

[2802] KIL n hin

[2803]

[2804] e 12.99ATTORNEY DOCKET: 05336.0008W001

[2805] O.

[2806] Stear Ami Or AGYLLGOINLKA Amphipathi SEQ ID

[2807] ylatio datio nit Linear LAALAKKIL c NO: 0564

[2808] n n hin

[2809] e 13.64 O,

[2810] 5 - (Stearyl- Stear Ami Or

[2811] AGYLLG) Amphipathi SEQ ID

[2812] ylatio datio nit Linear OINLKALAALAK c NO: 0564

[2813] n n hin

[2814] KIL

[2815] e 12.22 Ort

[2816] ho

[2817] go

[2818] nail AGYLLGK(Steary Stear Ami y

[2819] Amphipathi SEQ ID ste l)INLKALAALAKK ylatio datio Linear

[2820] c NO: 0565 ary

[2821] IL n n

[2822] I at

[2823] ed

[2824] on

[2825] Lys

[2826] > 12.39 sa:

[2827] sue

[2828] cini

[2829] cc

[2830] aci

[2831] d,

[2832] qn:

[2833] no

[2834] vel

[2835] 2-4

[2836] rin

[2837] g AGYLLGK[KK2sa Stear Ami sys Amphipathi SEQ ID

[2838] 4qn4]INLKALAAL ylatio datio te Linear

[2839] c NO: 0566

[2840] AKKIL n n ms

[2841] sue

[2842] h

[2843] as

[2844] qui

[2845] noli

[2846] ne

[2847] an

[2848] d

[2849] na

[2850] pht

[2851] hal

[2852]

[2853] en 12.11ATTORNEY DOCKET: 05336.0008W001

[2854] e

[2855] an

[2856] alo

[2857] gu

[2858] es

[2859] Acet Ami

[2860] AGYLLGKINLKA Amphipathi SEQ ID

[2861] ylatio datio NA Linear LAALAKKIL c NO: 0567

[2862] n n 6.74 Ami

[2863] AGYLLGKINLKA Amphipathi SEQ ID

[2864] Free datio NA Linear LAALAKKIL c NO: 0567

[2865] n 5.31 AGYLLGKINLKA Amphipathi SEQ ID

[2866] Free Free NA Linear LAALAKKIL c NO: 0567

[2867] 4.66 Stear Ami

[2868] AGYLLGKINLKA Amphipathi SEQ ID

[2869] ylatio datio NA Linear LAALAKKIL c NO: 0567

[2870] n n 13.81 Stear

[2871] AGYLLGKINLKA Amphipathi SEQ ID

[2872] ylatio Free NA Linear LAALAKKIL c NO: 0567

[2873] n 13.16 £ - (Steary- Stear Ami

[2874] Amphipathi SEQ ID

[2875] AGYLLG)KINLKA ylatio datio NA Linear

[2876] c NO: 0567

[2877] LAALAKKIL n n

[2878] 11.59 AGYLLGKINLKA Amphipathi SEQ ID

[2879] Free Free NA Linear LAALAKKILGGC c NO: 0568

[2880] 5.05 AGYLLGKLKALA Amphipathi SEQ ID

[2881] Free Free NA Linear ALAKKIL c NO: 0569 4.94

[2882] Ph

[2883] os

[2884] Stear Ami AGYLLGKT(PO3) Amphipathi SEQ ID ph

[2885] ylatio datio Linear NLKALAALAKKIL c NO: 0570 ory

[2886] n n

[2887] lati

[2888] on 13 AHALCLTERQIKI

[2889] Amphipathi SEQ ID

[2890] WFQNRRMKWK Free Free NA Linear

[2891] c NO: 0571

[2892]

[2893] KEN 0.98ATTORNEY DOCKET: 05336.0008W001

[2894] AHALCPPERQIKI

[2895] Amphipathi SEQ ID

[2896] WFQNRRMKWK Free Free NA Linear

[2897] c NO: 0572

[2898] KEN 0.74 ALWMRWYSPTT Amphipathi SEQ ID

[2899] Free Free NA Linear RRYG c NO: 0573 1.65 AYALCLTERQIKI

[2900] Amphipathi SEQ ID

[2901] WFANRRMKWK Free Free NA Linear

[2902] c NO: 0574

[2903] KEN 1.91

[2904] Ami AYLLGKINLKALA Amphipathi SEQ ID

[2905] Free datio NA Linear ALAKKIL c NO: 0575

[2906] n 5.53 B,

[2907] Bet

[2908] a- Ala

[2909] nin

[2910] e;

[2911] Ami X,

[2912] Amphipathi SEQ ID

[2913] BrrXrrXrrX Free datio a- Linear

[2914] c NO: 0576

[2915] n am

[2916] ino

[2917] iso

[2918] but

[2919] yric

[2920] aci

[2921] d -6.79 B,

[2922] Bet

[2923] a- Ala

[2924] nin

[2925] e;

[2926] Ami X,

[2927] Amphipathi SEQ ID

[2928] BRRXRRXRRX Free datio 0- Linear

[2929] c NO: 0577

[2930] n am

[2931] ino

[2932] iso

[2933] but

[2934] yric

[2935] aci

[2936] d -6.79 B,

[2937] Bet

[2938] Ami a- Amphipathi SEQ ID

[2939] BRrXRrXRrX Free datio Ala Linear

[2940] c NO: 0578

[2941] n nin

[2942] e;

[2943]

[2944] X, -6.79ATTORNEY DOCKET: 05336.0008W001

[2945] flam

[2946] ino

[2947] iso

[2948] but

[2949] yric

[2950] aci

[2951] d

[2952] B,

[2953] Bet

[2954] a- Ala

[2955] nin

[2956] e;

[2957] Ami X, BXRXRXXRXRX Amphipathi SEQ ID

[2958] Free datio n Linear XRXRX c NO: 0579

[2959] n am

[2960] ino

[2961] iso

[2962] but

[2963] yric

[2964] aci

[2965] d -6.79 CIGAVLKVLTTG

[2966] Amphipathi SEQ ID

[2967] LPALISWIKRKR Free Free NA Linear

[2968] c NO: 0580

[2969] QQ 4.68 CLLYWFRRRHR Amphipathi SEQ ID

[2970] Free Free NA Linear HHRRRHRRC c NO: 0581

[2971] -1.92 Unk

[2972] CRQIKIWFPNRR Amphipathi SEQ ID

[2973] Free now NA Linear MKWKKC c NO: 0582

[2974] n 4.79 CRQIKIWFQNRR Acet Ami

[2975] Amphipathi SEQ ID

[2976] MKWKKKLAKLA yiatio datio NA Linear

[2977] c NO: 0583

[2978] KKLAKLAK n n

[2979] 8.69 Ami

[2980] Amphipathi SEQ ID

[2981] [FRRRRQ] Free datio NA Cyclic

[2982] c NO: 0584

[2983] n 1.32 DAATARGRGRS AASRPTERPRA Amphipathi SEQ ID

[2984] Free Free NA Linear PARSASRPRRP c NO: 0585

[2985] VD -13.3 DPKGDPKGVTV

[2986] Amphipathi SEQ ID

[2987] TVTVTVTGKGDP Free NA NA Linear

[2988] c NO: 0586

[2989] KPD -0.42 DSLKSYWYLQK Amphipathi SEQ ID

[2990] Free Free NA Linear

[2991]

[2992] FSWR c NO: 0587 4.36ATTORNEY DOCKET: 05336.0008W001

[2993] EKRPRTAFSSE QLARLKREFNEN RYLTTERRRQQ Amphipathi SEQ ID

[2994] Free Free NA Linear LSSELGLNEAQI c NO: 0588

[2995] KIWFQNKRAKIK KST

[2996] -10.6 Ami

[2997] ELALELALEALE Amphipathi SEQ ID

[2998] Free datio NA Linear AALELA c NO: 0589

[2999] n -0.37 FFKKLALHALHL

[3000] Amphipathi SEQ ID

[3001] LALLWLHLAHLA Free Free NA Linear

[3002] c NO: 0590

[3003] LKK 10.67 FKKLALHALHLL

[3004] Amphipathi SEQ ID

[3005] ALLWLHLAHLAL Free Free NA Linear

[3006] c NO: 0591

[3007] KK 9.51

[3008] Stear Ami

[3009] FLKLLKKFLKLFK Amphipathi SEQ ID

[3010] ylatio datio NA Linear KLLKLF c NO: 0592

[3011] n n 21.38 Cyst GALFLAFLAAAL Acet eami

[3012] Amphipathi SEQ ID

[3013] SLMGLWSQPKK ylatio de NA Linear

[3014] c NO: 0593

[3015] KRRV n grou

[3016] P _ 7.19 Cyst GALFLGFLGAAG Acet eami

[3017] Amphipathi SEQ ID

[3018] STMGAWSQPKS ylatio de NA Linear

[3019] c NO: 0594

[3020] KRKV n grou

[3021] P 4.48 GALFLGWLGAA

[3022] Amphipathi SEQ ID

[3023] GSTMGAPKKKR Free Free NA Linear

[3024] c NO: 0595

[3025] KV 3 GKKALKLAAKLL Amphipathi SEQ ID

[3026] Free Free NA Linear KKC c NO: 0596 4.02 GLFEALLELLESL Amphipathi SEQ ID

[3027] NA NA NA Linear WELLLEA c NO: 0597

[3028] 3.61 GLFKALLKLLKSL Amphipathi SEQ ID

[3029] NA NA NA Linear WKLLLKA c NO: 0598

[3030] 9.46 GLFRALLRLLRS Amphipathi SEQ ID

[3031] Free Free NA Linear LWRLLLRA c NO: 0599

[3032] 4.66 Ami GLKKLAELAHKL Amphipathi SEQ ID

[3033] Free datio NA Linear LKLGC c NO: 0600

[3034]

[3035] n 4.67ATTORNEY DOCKET: 05336.0008W001

[3036] Ami

[3037] GLKKLAELFHKL Amphipathi SEQ ID

[3038] Free datio NA Linear LKLGC c NO: 0601

[3039] n 6.1 Ami GLKKLARLAHKL Amphipathi SEQ ID

[3040] Free datio NA Linear LKLGC c NO: 0602

[3041] n 4.88 Ami GLKKLARLFHKL Amphipathi SEQ ID

[3042] Free datio NA Linear LKLGC c NO: 0603

[3043] n 6.31 Cyst

[3044] Acet earn! GLWRALWRLLR Amphipathi SEQ ID

[3045] ylatio de NA Linear SLWRLLWRA c NO: 0604

[3046] n grou

[3047] P _ 8.01 Acet

[3048] GLWRALWRLLR Amphipathi SEQ ID

[3049] ylatio Free NA Linear SLWRLLWRA c NO: 0604

[3050] n 7.71 GLWWKAWWKA

[3051] Amphipathi SEQ ID

[3052] WWKSLWWRKR NA NA NA Linear

[3053] c NO: 0605

[3054] KRKA

[3055] 10.45 Acet

[3056] GLWWRLWWRL Amphipathi SEQ ID

[3057] ylatio Free NA Linear RSWFRLWFRA c NO: 0606

[3058] n 10.82 Amphipathi SEQ ID

[3059] GRKKRRQRRRP Free Free NA Linear

[3060] c NO: 0607 -4.81 GWTLNPAGYLL

[3061] Amphipathi SEQ ID

[3062] GKINLKALAALA Free Free NA Linear

[3063] c NO: 0608

[3064] KKIL 5.61 GWTLNPPGYLL

[3065] Amphipathi SEQ ID

[3066] GKINLKALAALA Free Free NA Linear

[3067] c NO: 0609

[3068] KKIL 6.03 GWTLNSAGYLL

[3069] Amphipathi SEQ ID

[3070] GKFLPLILRKIVT Free Free NA Linear

[3071] c NO: 0610

[3072] AL 7.04 GWTLNSAGYLL

[3073] Amphipathi SEQ ID

[3074] GKINLKALAALA Free Free NA Linear

[3075] c NO: 0611

[3076] KKLL 5.11 GWTLNSAGYLL

[3077] Amphipathi SEQ ID

[3078] GKINLKAPAALA Free Free NA Linear

[3079] c NO: 0612

[3080] KKIL 4.36 GWTLNSAGYLL

[3081] Amphipathi SEQ ID

[3082] GKLKALAALAKKI Free Free NA Linear

[3083] c NO: 0613

[3084] L 5.29 GWTLNSKINLKA Amphipathi SEQ ID

[3085] Free Free NA Linear LAALAKKIL c NO: 0614

[3086]

[3087] 3.57ATTORNEY DOCKET: 05336.0008W001

[3088] GYGNCRHFKQK Amphipathi SEQ ID

[3089] Free Free NA Linear PRRD c NO: 0615 -1.69 HEHEHEHEHEH EHEHEHEHEGG Amphipathi SEQ ID

[3090] Free NA NA Linear GGGKLALKLALK c NO: 0616

[3091] ALKAALKLA

[3092] -9.37 IPSRWKDQFWK Amphipathi SEQ ID

[3093] Free Free NA Linear RWHY c NO: 0617 4.32

[3094] Ami

[3095] KALAALLKKLAK Amphipathi SEQ ID

[3096] Free datio NA Linear LLAALK c NO: 0618

[3097] n 5.48 Ami KALAALLKKWAK Amphipathi SEQ ID

[3098] Free datio NA Linear LLAALK c NO: 0619

[3099] n 6.14 Ami KALAKALAKLWK Amphipathi SEQ ID

[3100] Free datio NA Linear ALAKAA c NO: 0620

[3101] n 4 Ami

[3102] KALKKLLAKWLA Amphipathi SEQ ID

[3103] Free datio NA Linear AAKALL c NO: 0621

[3104] n 6.14 Acet

[3105] KETWFETWFTE Amphipathi SEQ ID

[3106] ylatio Free NA Linear WSQPKKKRKV c NO: 0622

[3107] n 4.09 Acet

[3108] KETWWETWWT Amphipathi SEQ ID

[3109] ylatio Free NA Linear EWSQPKKKRKV c NO: 0623

[3110] n 4.69 KETWWETWWT Amphipathi SEQ ID

[3111] Free Free NA Linear EWSQPKKKRKV c NO: 0623

[3112] 3.26 KHKALHALHLLA

[3113] Amphipathi SEQ ID

[3114] LLWLHLAHLAKH Free Free NA Linear

[3115] c NO: 0624

[3116] K 6.13 KHKLLHLLHLLAL Amphipathi SEQ ID

[3117] Free Free NA Linear LWLHLLHLLKHK c NO: 0625

[3118] 10.41 Ami KIAAKSIAKIWKSI Amphipathi SEQ ID

[3119] Free datio NA Linear LKIA c NO: 0626

[3120] n 5.28 Ami

[3121] KITLKLAIKAWKL Amphipathi SEQ ID

[3122] Free datio NA Linear ALKAA c NO: 0627

[3123] n 5.95 KKALLAHALHLL

[3124] Amphipathi SEQ ID

[3125] ALLALHLAHALK Free Free NA Linear

[3126] c NO: 0628

[3127]

[3128] KA 5.28ATTORNEY DOCKET: 05336.0008W001

[3129] KKLALHALHLLA

[3130] Amphipathi SEQ ID

[3131] LLWLHLAHLALK Free Free NA Linear

[3132] c NO: 0629

[3133] K 8.35

[3134] Ami KLAAALLKKWKK Amphipathi SEQ ID

[3135] Free datio NA Linear LAAALL c NO: 0630

[3136] n 6.14 KLAKLAKKLAKL Amphipathi SEQ ID

[3137] Free Free NA Linear AK c NO: 0631 3.14

[3138] Ami KLALKAAAKAWK Amphipathi SEQ ID

[3139] Free datio NA Linear AAAKAA c NO: 0632

[3140] n 1.86 Ami KLALKAALKAWK Amphipathi SEQ ID

[3141] Free datio NA Linear AAAKLA c NO: 0633

[3142] n 4 Ami

[3143] KLALKALKAALK Amphipathi SEQ ID

[3144] Free datio NA Linear

[3145] LA c NO: 0634

[3146] n 3.98 Ami

[3147] KLALKLALKALK Amphipathi SEQ ID

[3148] Free datio NA Linear AA c NO: 0635

[3149] n 3.98 Ami

[3150] KLALKLALKALK Amphipathi SEQ ID

[3151] Free datio NA Linear AALK c NO: 0636

[3152] n 4.95 Ami

[3153] Amphipathi SEQ ID

[3154] klalklalkalkaalkla Free datio NA Linear

[3155] c NO: 0637

[3156] n 5.48 Ami

[3157] KLALKLALKALQ Amphipathi SEQ ID

[3158] Free datio NA Linear AALQLA c NO: 0638

[3159] n 4.46 Ami

[3160] KLALKLALKAWK Amphipathi SEQ ID

[3161] Free datio NA Linear AALKLA c NO: 0639

[3162] n 6.14 Ami

[3163] KLALKLALKWAK Amphipathi SEQ ID

[3164] Free datio NA Linear LALKAA c NO: 0640

[3165] n 6.14 Ami

[3166] KLALQLALQALQ Amphipathi SEQ ID

[3167] Free datio NA Linear AALQLA c NO: 0641

[3168] n 3.44 Ami

[3169] KLGLKLGLKGLK Amphipathi SEQ ID

[3170] Free datio NA Linear GGLKLG c NO: 0642

[3171] n 5.78 Ami KLLAKAAKKWLL Amphipathi SEQ ID

[3172] Free datio NA Linear LALKAA c NO: 0643

[3173] n 6.14 Ami

[3174] KLLAKAALKWLL Amphipathi SEQ ID

[3175] Free datio NA Linear KALKAA c NO: 0644

[3176]

[3177] n 6.14ATTORNEY DOCKET: 05336.0008W001

[3178] U,

[3179] exam

[3180] ino

[3181] Acet Ami iso KLULKLULKULK Amphipathi SEQ ID

[3182] ylatio datio but Linear AULKLU c NO: 0645

[3183] n n yric

[3184] aci

[3185] d

[3186] (Ai

[3187] b) 8.26 Acet

[3188] KLULKLULKULK Amphipathi SEQ ID

[3189] ylatio Free NA Linear AULKLUGC c NO: 0646

[3190] n 8.22 KLWMRWYSATT Amphipathi SEQ ID

[3191] Free Free NA Linear RRYG c NO: 0647 1.67 KLWMRWYSPTT Amphipathi SEQ ID

[3192] Free Free NA Linear RRYG c NO: 0648 2.09 KLWMRWYSPW Amphipathi SEQ ID

[3193] Free Free NA Linear TRRYG c NO: 0649 3.81 KNAWKHSSCHH Amphipathi SEQ ID

[3194] Free Free NA Linear RHQI c NO: 0650 -1.19

[3195] Acet

[3196] KWFETWFTEWP Amphipathi SEQ ID

[3197] ylatio Free NA Linear KKRK c NO: 0651

[3198] n 5.65 LGTYTQDFNKFH Amphipathi SEQ ID

[3199] Free Free NA Linear TFPQTAIGVGAP c NO: 0652

[3200] 1.83 Ami

[3201] LIRLWSHLIHIWF Amphipathi SEQ ID

[3202] NA datio NA Linear QNRRLKWKKK c NO: 0653

[3203] n 7.41 LIRLWSHLIHIWF

[3204] Amphipathi SEQ ID

[3205] QNRRLKWKKKG Free Free NA Linear

[3206] c NO: 0654

[3207] GO 7.15

[3208] Ami LKTLATALTKLAK Amphipathi SEQ ID

[3209] Free datio NA Linear TLTTL c NO: 0655

[3210] n 3.59 Ami

[3211] LKTLTETLKELTK Amphipathi SEQ ID

[3212] Free datio NA Linear TLTEL c NO: 0656

[3213] n 1.4 LLGKINLKALAAL Amphipathi SEQ ID

[3214] Free Free NA Linear AKKIL c NO: 0657 4.6 LLHILRRSIRKQA Amphipathi SEQ ID

[3215] NA NA NA Linear HAIRK c NO: 0658 -0.27 LLHILRRSIRRQA Amphipathi SEQ ID

[3216] NA NA NA Linear

[3217]

[3218] HAIRR c NO: 0659 -2.19ATTORNEY DOCKET: 05336.0008W001

[3219] LLIILRRRIRRRA Amphipathi SEQ ID

[3220] NA NA NA Linear RARSR c NO: 0660 -3.6

[3221] Stear Ami

[3222] LLKLLKKLLKLLK Amphipathi SEQ ID

[3223] ylatio datio NA Linear KLLKLL c NO: 0661

[3224] n n 19.94

[3225] O.

[3226] Stear Ami Or LLOOLAAAALOO Amphipathi SEQ ID

[3227] ylatio datio nit Linear

[3228] LL c NO: 0662

[3229] n n hin

[3230] e 12.87 LLRHLRRHIRRA Amphipathi SEQ ID

[3231] NA NA NA Linear RRHIRR c NO: 0663 -4.51 LLRILRRSIRRAR Amphipathi SEQ ID

[3232] NA NA NA Linear RAIRR c NO: 0664 -3.6 LLYWFRRRHRH Amphipathi SEQ ID

[3233] Free Free NA Linear HRRRHRR c NO: 0665

[3234] -3.58 LNSAGYLLGKAL Amphipathi SEQ ID

[3235] Free Free NA Linear AALAKKIL c NO: 0666

[3236] 3.34 LNSAGYLLGKIN Amphipathi SEQ ID

[3237] Free Free NA Linear LKALAALAKKIL c NO: 0667

[3238] 4.03 LNSAGYLLGKLK Amphipathi SEQ ID

[3239] Free Free NA Linear ALAALAK c NO: 0668 2.64 LNSAGYLLGKLK Amphipathi SEQ ID

[3240] Free Free NA Linear ALAALAKIL c NO: 0669

[3241] 4.14 MANLGCWMLVL Ami

[3242] Amphipathi SEQ ID

[3243] FVATWSDLGLC Free datio NA Linear

[3244] c NO: 0670

[3245] KKRPKP n

[3246] 9.12 MANLGYWLLAL Ami

[3247] Amphipathi SEQ ID

[3248] FVTMWTDVGLC Free datio NA Linear

[3249] c NO: 0671

[3250] KKRPKP n

[3251] 9.03 Cyst

[3252] Acet eami MGLGLHLLVLAA Amphipathi SEQ ID

[3253] ylatio de NA Linear ALQGAKKKRKV c NO: 0672

[3254] n grou

[3255] _ 5.18 Cyst MGLGLHLLVLAA Acet eami

[3256] Amphipathi SEQ ID

[3257] ALQGAWSQPKK ylatio de NA Linear

[3258] c NO: 0673

[3259] KRKV n grou

[3260]

[3261] P _ 6ATTORNEY DOCKET: 05336.0008W001

[3262] MVKSKIGSWILV Ami

[3263] Amphipathi SEQ ID

[3264] LFVAMWSDVGL Free datio NA Linear

[3265] c NO: 0674

[3266] CKKRPKP n

[3267] 9.68 Ami

[3268] MVTVLFRRLRIR Amphipathi SEQ ID

[3269] Free datio NA Linear RACGPPRVRV c NO: 0675

[3270] n 0.75 Amphipathi SEQ ID

[3271] PLSSIFSRIGDP Free Free NA Linear

[3272] c NO: 0676 1.02

[3273] Ami QLALQLALQALQ Amphipathi SEQ ID

[3274] Free datio NA Linear AALQLA c NO: 0677

[3275] n 2.93 QQHLLIAINGYP Amphipathi SEQ ID

[3276] Free Free NA Linear RYN c NO: 0678 0.02 RAWMRWYSPTT Amphipathi SEQ ID

[3277] Free Free NA Linear RRYG c NO: 0679 0.06

[3278] RG

[3279] D

[3280] mo

[3281] tif

[3282] Amphipathi SEQ ID

[3283] RGDRRRRRRRR NA Free is Linear

[3284] c NO: 0680

[3285] link

[3286] ed

[3287] to

[3288] P3 -7.61 RGGRLSYSRRR Amphipathi SEQ ID

[3289] Free Free NA Linear FSTSTGRA c NO: 0681

[3290] -5.48 RHIKIWFQNRRM Amphipathi SEQ ID

[3291] Free Free NA Linear KWKK c NO: 0682 2.67 RLAMRWYSPTT Amphipathi SEQ ID

[3292] Free Free NA Linear RRYG c NO: 0683 -0.6 RLFMRFYSPTTR Amphipathi SEQ ID

[3293] Free Free NA Linear RYG c NO: 0684 0.53 RLIMRIYSPTTRR Amphipathi SEQ ID

[3294] Free Free NA Linear YG c NO: 0685 -0.39 RLLMRLYSPTTR Amphipathi SEQ ID

[3295] Free Free NA Linear RYG c NO: 0686 -0.19

[3296] Acet Ami

[3297] RLLRLLLRLWRR Amphipathi SEQ ID

[3298] ylatio datio NA Linear LLRLLR c NO: 0687

[3299] n n 6.01 RLVMRVYSPTT Amphipathi SEQ ID

[3300] Free Free NA Linear RRYG c NO: 0688 -1.15 RLWARWYSPTT Amphipathi SEQ ID

[3301] Free Free NA Linear RRYG c NO: 0689 0.35 RLWMAWYSPTT Amphipathi SEQ ID

[3302] Free Free NA Linear

[3303]

[3304] RRYG c NO: 0690 1.65ATTORNEY DOCKET: 05336.0008W001

[3305] RLWMRAYSPTT Amphipathi SEQ ID

[3306] Free Free NA Linear RRYG c NO: 0691 -0.6 RLWMRWASPTT Amphipathi SEQ ID

[3307] Free Free NA Linear RRYG c NO: 0692 0.31 RLWMRWYAPTT Amphipathi SEQ ID

[3308] Free Free NA Linear RRYG c NO: 0693 1.31 RLWMRWYSPAT Amphipathi SEQ ID

[3309] Free Free NA Linear RRYG c NO: 0694 1.12 RLWMRWYSPTA Amphipathi SEQ ID

[3310] Free Free NA Linear RRYG c NO: 0695 1.12 RLWMRWYSPTT Amphipathi SEQ ID

[3311] Free Free NA Linear ARYG c NO: 0696 1.65 RLWMRWYSPTT Amphipathi SEQ ID

[3312] Free Free NA Linear RAYG c NO: 0697 1.65 RLWMRWYSPTT Amphipathi SEQ ID

[3313] Free Free NA Linear RRAG c NO: 0698 0.31 RLWMRWYSPTT Amphipathi SEQ ID

[3314] Free Free NA Linear RRYA c NO: 0699 1.08 RLWMRWYSPTT Amphipathi SEQ ID

[3315] Free Free NA Linear RRYG c NO: 0700 1.13 RLWMRWYSPW Amphipathi SEQ ID

[3316] Free Free NA Linear TRRWG c NO: 0701 3.76 RLWMRWYSPW Amphipathi SEQ ID

[3317] Free Free NA Linear TRRYG c NO: 0702 2.85 RLYMRYYSPTT Amphipathi SEQ ID

[3318] Free Free NA Linear RRYG c NO: 0703 -0.69

[3319] Di- Ami

[3320] Amphipathi SEQ ID palmi

[3321] RPARPAR datio NA Linear

[3322] c NO: 0704 tilysa

[3323] n

[3324] tion -1.96 Di- Amphipathi SEQ ID palmi

[3325] RPARPAR Free NA Linear

[3326] c NO: 0704 tilysa

[3327] tion -2.61 Ami

[3328] Amphipathi SEQ ID

[3329] RPARPAR Free datio NA Linear

[3330] c NO: 0704

[3331] n -1.96 Amphipathi SEQ ID

[3332] RPARPAR Free Free NA Linear

[3333] c NO: 0704 -2.61

[3334] Ami

[3335] RQIKIFFQNRRM Amphipathi SEQ ID

[3336] Free datio NA Linear KWKK c NO: 0705

[3337] n 2.99 Ami

[3338] RQIKIWFPNRRM Amphipathi SEQ ID

[3339] Free datio NA Linear KWKK c NO: 0706

[3340] n 3.78 RQIKIWFQNMRR Amphipathi SEQ ID

[3341] NA NA NA Linear

[3342]

[3343] KWKK c NO: 0707 2.64ATTORNEY DOCKET: 05336.0008W001

[3344] RQIKIWFQNRRM

[3345] Amphipathi SEQ ID

[3346] KWKKRQIKIWFQ Free Free NA Linear

[3347] c NO: 0708

[3348] NRRMKWK

[3349] 5.11 RRLRHLRHHYR Amphipathi SEQ ID

[3350] Free Free NA Linear RRWHRFR c NO: 0709

[3351] -3.58 RRRRRRRRRGP

[3352] Amphipathi SEQ ID

[3353] GVTWTPQAWFQ NA NA NA Linear

[3354] c NO: 0710

[3355] WV -2.54 RRWRRWWRR Amphipathi SEQ ID

[3356] Free Free NA Linear WWRRWRR c NO: 0711

[3357] 0.86 RTLVNEYKNTLK Amphipathi SEQ ID

[3358] Free Free NA Linear FSK c NO: 0712 -0.58

[3359] Ami

[3360] RVIRVWFQNKR Amphipathi SEQ ID

[3361] Free datio NA Linear CKDKK c NO: 0713

[3362] n 2.15 RVREWWYTITLK Amphipathi SEQ ID

[3363] Free Free NA Linear QES c NO: 0714 0.57

[3364] Amphipathi SEQ ID

[3365] RWRRWWRRW Free Free NA Linear

[3366] c NO: 0715 1.89 SKRTRQTYTRY QTLELEKEFHFN

[3367] Amphipathi SEQ ID

[3368] RYITRRRRIDIAN Free Free NA Linear

[3369] c NO: 0716

[3370] ALSLSERQIKIWF QNRRMKSKKDR

[3371] -7.47 VELPPPVELPPP Amphipathi SEQ ID

[3372] Free Free NA Linear VELPPP c NO: 0717 1.71

[3373] Amphipathi SEQ ID

[3374] VHLPPP Free Free NA Linear

[3375] c NO: 0718 1.26 Amphipathi SEQ ID

[3376] VHLPPPVHLPPP Free Free NA Linear

[3377] c NO: 0719 2.52 VHLPPPVHLPPP Amphipathi SEQ ID

[3378] Free Free NA Linear VHLPPP c NO: 0720 3.78

[3379] Amphipathi SEQ ID

[3380] VKLPPP Free Free NA Linear

[3381] c NO: 0721 1.74 Amphipathi SEQ ID

[3382] VKLPPPVKLPPP Free Free NA Linear

[3383] c NO: 0722 3.48 VKLPPPVKLPPP Amphipathi SEQ ID

[3384] Free Free NA Linear VKLPPP c NO: 0723 5.22

[3385] Amphipathi SEQ ID

[3386] VRLPPP Free Free NA Linear

[3387] c NO: 0724 0.78 Amphipathi SEQ ID

[3388] VRLPPPVRLPPP Free Free NA Linear

[3389]

[3390] c NO: 0725 1.56ATTORNEY DOCKET: 05336.0008W001

[3391] vrlpppvrlpppvrlpp Amphipathi SEQ ID

[3392] Free Free NA Linear

[3393] P c NO: 0726 2.34 VRLPPPVRLPPP Amphipathi SEQ ID

[3394] Free Free NA Linear VRLPPP c NO: 0727 2.34 WEAALAEALAEA

[3395] Amphipathi SEQ ID

[3396] LAEHLAEALAEA Free NA NA Linear

[3397] c NO: 0728

[3398] LEALAA

[3399] -4.03 WEARLARALAR

[3400] Amphipathi SEQ ID

[3401] ALARHLARALAR Free Free NA Linear

[3402] c NO: 0729

[3403] A -3.29 WKCRRQCFRVL Amphipathi SEQ ID

[3404] Free Free NA Linear HHWN c NO: 0730 2.72

[3405] Stear Ami

[3406] WLKLLKKWLKL Amphipathi SEQ ID

[3407] ylatio datio NA Linear WKKLLKLW c NO: 0731

[3408] n n 22.58 Stear Ami WLKLWKKWLKL Amphipathi SEQ ID

[3409] ylatio datio NA Linear

[3410] W c NO: 0732

[3411] n n 18.87 WLKY(PO3)LLKK Stear Ami

[3412] Amphipathi SEQ ID

[3413] WLKLWKKLLKL ylatio datio NA Linear

[3414] c NO: 0733

[3415] W n n 23.28

[3416] O,

[3417] Stear Ami Or WLOLLOOWLOL Amphipathi SEQ ID

[3418] ylatio datio nit Linear WOOLLOLW c NO: 0734

[3419] n n hin

[3420] e 21.39 O.

[3421] Stear Ami Or WLOLLROWLRL Amphipathi SEQ ID

[3422] ylatio datio nit Linear WORLLOLW c NO: 0735

[3423] n n hin

[3424] e 19.02 O.

[3425] Stear Ami Or WLRLLORWLOL Amphipathi SEQ ID

[3426] ylatio datio nit Linear WROLLRLW c NO: 0736

[3427] n n hin

[3428] e 18.23 Y(PO3)WLKLLKK Stear Ami

[3429] Amphipathi SEQ ID

[3430] WLKLWKKLLKL ylatio datio NA Linear

[3431] c NO: 0737

[3432] W n n 23.28 YGRKKRRQRRR

[3433] Amphipathi SEQ ID

[3434] YGRKKRRQRRR Free Free NA Linear

[3435] c NO: 0738

[3436] YGRKKRRQRRR

[3437]

[3438] -13.2ATTORNEY DOCKET: 05336.0008W001

[3439] α, ε (Stearyl- Stear Ami

[3440] Amphipathi SEQ ID

[3441] AGYLLG)2KINLK ylatio datio NA Linear

[3442] c NO: 0739

[3443] ALAALAKKIL n n

[3444] 12.39 Stear Ami AGYLLGKTNLKA Amphipathi SEQ ID

[3445] ylatio datio NA Linear LAALAKKIL c NO: 0740

[3446] n n 12.85 Stear

[3447] AGYLLGKTNLKA Amphipathi SEQ ID

[3448] ylatio Free NA Linear LAALAKKIL c NO: 0740

[3449] n 12.2 Acet

[3450] KLALKLALKALK Amphipathi SEQ ID

[3451] ylatio Free NA Linear AALKLAGC c NO: 0741

[3452] n 6.87 KKALLALALHHL

[3453] Amphipathi SEQ ID

[3454] AHLALHLALALK Free Free NA Linear

[3455] c NO: 0742

[3456] KA 5.28

[3457] Ami

[3458] ACGRGRGRCG Arginine SEQ ID

[3459] Free datio NA Cyclic RGRGRCG rich NO: 0743

[3460] n -3.41 Ami

[3461] ACGRGRGRCR Arginine SEQ ID

[3462] Free datio NA Cyclic GRGRGCG rich NO: 0744

[3463] n -3.41 Ami

[3464] ACHGRRWGCG Arginine SEQ ID

[3465] Free datio NA Cyclic RHRGRCG rich NO: 0745

[3466] n -1.34 Ami

[3467] ACRDRFRNCPA Arginine SEQ ID

[3468] Free datio NA Cyclic DEALCG rich NO: 0746

[3469] n -0.69 Ami

[3470] ACRDRFRNCPA Arginine SEQ ID

[3471] Free datio NA Cyclic DERLCG rich NO: 0747

[3472] n -1.21 Ami

[3473] ACRDRFRRCPA Arginine SEQ ID

[3474] Free datio NA Cyclic DERLCG rich NO: 0748

[3475] n -1.02 Ami

[3476] ACRDRFRRCPA Arginine SEQ ID

[3477] Free datio NA Cyclic DRRLCG rich NO: 0749

[3478] n -0.81 Ami

[3479] ACRGRGRGCG Arginine SEQ ID

[3480] Free datio NA Cyclic RGRGRCG rich NO: 0750

[3481] n -3.41 Ami ACRGRGRGCGS Arginine SEQ ID

[3482] Free datio NA Cyclic GSGSCG rich NO: 0751

[3483] n -2.39 Ami ACRGRGRGCGS Arginine SEQ ID

[3484] Free datio NA Cyclic GSRSCG rich NO: 0752

[3485]

[3486] n -2.96ATTORNEY DOCKET: 05336.0008W001

[3487] Ami

[3488] ACRGRGRGCR Arginine SEQ ID

[3489] Free datio NA Cyclic GRGRGCG rich NO: 0753

[3490] n -3.41 Ami ACRGRGRRCGS Arginine SEQ ID

[3491] Free datio NA Cyclic GRRSCG rich NO: 0754

[3492] n -3.87 All

[3493] cys

[3494] tei

[3495] ne

[3496] s

[3497] we

[3498] re

[3499] Ami ca ACRGRGRRCGS Arginine SEQ ID

[3500] Free datio Cyclic GRRSCG rich NO: 0755 PP

[3501] n ed

[3502] wit

[3503] h

[3504] iod

[3505] oa

[3506] cet

[3507] am

[3508] ide -3.87 Ami ACRGRGRRCGS Arginine SEQ ID

[3509] Free datio NA Cyclic GSRSCG rich NO: 0756

[3510] n -3.53 Ami ACRGRRRGCGR Arginine SEQ ID

[3511] Free datio NA Cyclic RRGRCG rich NO: 0757

[3512] n -4.55 Ami ACRGSGRGCGR Arginine SEQ ID

[3513] Free datio NA Cyclic GSGRCG rich NO: 0758

[3514] n -2.73 Ami ACRRSRRGCGR Arginine SEQ ID

[3515] Free datio NA Cyclic RSRRCG rich NO: 0759

[3516] n -5.01 All

[3517] cys

[3518] tei

[3519] ne

[3520] s

[3521] Ami we ACRRSRRGCGR Arginine SEQ ID

[3522] Free datio re Cyclic RSRRCG rich NO: 0760

[3523] n ca

[3524] PP

[3525] ed

[3526] wit

[3527] h

[3528]

[3529] iod -5.01ATTORNEY DOCKET: 05336.0008W001

[3530] oa

[3531] cet

[3532] am

[3533] ide

[3534] Ami

[3535] ACSDRFRNCPA Arginine SEQ ID

[3536] Free datio NA Cyclic DEALCG rich NO: 0761

[3537] n -0.35 ACSDRFRNCPA Ami

[3538] Arginine SEQ ID

[3539] DEALCGRRRRR Free datio NA Cyclic

[3540] rich NO: 0762

[3541] RRR n -6.67

[3542] All

[3543] cys

[3544] tei

[3545] ne

[3546] s

[3547] we

[3548] re ACSDRFRNCPA Ami ca

[3549] Arginine SEQ ID

[3550] DEALCGRRRRR Free datio Cyclic

[3551] rich NO: 0763 PP

[3552] RRR n ed

[3553] wit

[3554] h

[3555] iod

[3556] oa

[3557] cet

[3558] am

[3559] ide -6.67 Ami ACSGRGRGCGR Arginine SEQ ID

[3560] Free datio NA Cyclic GRGSCG rich NO: 0764

[3561] n -2.73 Ami ACSGRGRGCGS Arginine SEQ ID

[3562] Free datio NA Cyclic GSGSCG rich NO: 0765

[3563] n -2.05 Ami ACSGRGSGCGS Arginine SEQ ID

[3564] Free datio NA Cyclic GRGSCG rich NO: 0766

[3565] n -2.05 Ami ACSGSGSGCGS Arginine SEQ ID

[3566] Free datio NA Cyclic GSGSCG rich NO: 0767

[3567] n -1.37 ACSGSGSGCGS Ami

[3568] Arginine SEQ ID

[3569] GSGSCGRRRRR Free datio NA Cyclic

[3570] rich NO: 0768

[3571] RRR n

[3572]

[3573] -7.69ATTORNEY DOCKET: 05336.0008W001

[3574] All

[3575] cys

[3576] tei

[3577] ne

[3578] s

[3579] we

[3580] re ACSGSGSGCGS Ami ca

[3581] Arginine SEQ ID

[3582] GSGSCGRRRRR Free datio Cyclic

[3583] rich NO: 0769 PP

[3584] RRR n ed

[3585] wit

[3586] h

[3587] iod

[3588] oa

[3589] cet

[3590] am

[3591] ide -7.69 ACSHSGHGCGH Ami

[3592] Arginine SEQ ID

[3593] GSHSCGRRRRR Free datio NA Cyclic

[3594] rich NO: 0770

[3595] RRR n

[3596] -7.59 ACSHSGWGCG Ami

[3597] Arginine SEQ ID

[3598] HGSWSCGRRR Free datio NA Cyclic

[3599] rich NO: 0771

[3600] RRRRR n

[3601] -4.05 Ami

[3602] ARCSDRFRNCP Arginine SEQ ID

[3603] Free datio NA Cyclic ADEALCGR rich NO: 0772

[3604] n -1.93 Ami ARCSGSGSGCG Arginine SEQ ID

[3605] Free datio NA Cyclic SGSGSCGR rich NO: 0773

[3606] n -2.95 Ami

[3607] ARRCSDRFRNC Arginine SEQ ID

[3608] Free datio NA Cyclic PADEALCGRR rich NO: 0774

[3609] n -3.51 Ami ARRCSGSGSGC Arginine SEQ ID

[3610] Free datio NA Cyclic GSGSGSCGRR rich NO: 0775

[3611] n -4.53 ARRRCSDRFRN Ami

[3612] Arginine SEQ ID

[3613] CPADEALCGRR Free datio NA Cyclic

[3614] rich NO: 0776

[3615] R n -5.09 ARRRCSGSGSG Ami

[3616] Arginine SEQ ID

[3617] CGSGSGSCGRR Free datio NA Cyclic

[3618] rich NO: 0777

[3619] R n -6.11 ARRRRCSDRFR Ami

[3620] Arginine SEQ ID

[3621] NCPADEALCGR Free datio NA Cyclic

[3622] rich NO: 0778

[3623]

[3624] RRR n -6.67ATTORNEY DOCKET: 05336.0008W001

[3625] ARRRRCSGSGS Ami

[3626] Arginine SEQ ID

[3627] GCGSGSGSCGR Free datio NA Cyclic

[3628] rich NO: 0779

[3629] RRR n

[3630] -7.69 Re

[3631] sid

[3632] lie

[3633] 2 is

[3634] 2,6

[3635] Ami

[3636] SEQ ID

[3637] rXKF Cationic Free datio Linear NO: 0780 di

[3638] n

[3639] me

[3640] thyl

[3641] tyr

[3642] osi

[3643] ne 1.19 Malei

[3644] AAVALLPAVLLA Ami

[3645] Amphipathi SEQ ID mide

[3646] LLAPRKKRRQR datio NA Linear

[3647] c NO: 0781 additi

[3648] RRPPQ n

[3649] on -0.01 Malei

[3650] AAVALLPAVLLA Ami

[3651] Amphipathi SEQ ID mide

[3652] LLAPRKKRRQR datio NA Linear

[3653] c NO: 0781 additi

[3654] RRPPQ n

[3655] on -0.01 AAVALLPAVLLA Ami

[3656] Amphipathi SEQ ID

[3657] LLAPRKKRRQR Free datio NA Linear

[3658] c NO: 0781

[3659] RRPPQ n

[3660] -0.01 AAVACRICMRNF Ami

[3661] Amphipathi SEQ ID

[3662] STRQARRNHRR Free datio NA Linear

[3663] c NO: 0782

[3664] RHRR n

[3665] -7.61 Ami

[3666] AAVALLPAVLLA Amphipathi SEQ ID

[3667] Free datio NA Linear LLAPRRRRRR c NO: 0783

[3668] n 0.03 Amphipathi SEQ ID

[3669] ACSSSPSKHCG Free Free NA Linear

[3670] c NO: 0784 -0.62 ACSSSPSKHCG

[3671] Arginine SEQ ID

[3672] GGGRRRRRRR Free Free NA Linear rich NO: 0785

[3673] RR -8.39 AEAEAEAEAKAK

[3674] Arginine SEQ ID

[3675] AKAKAGGGHRR Free Free NA Linear rich NO: 0786

[3676] RRRRR

[3677]

[3678] -12.3ATTORNEY DOCKET: 05336.0008W001

[3679] AKKAKAAKKAKA SEQ ID AKKAKAAKKAKA Cationic Free Free NA Linear NO: 0787

[3680] AKKAKA

[3681] -1.5 AKKKAAKAAKKK SEQ ID

[3682] Cationic Free Free NA Linear AAKAAKKKAAKA NO: 0788

[3683] -1.2 AKKKAAKAAKKK SEQ ID AAKAAKKKAAKA Cationic Free Free NA Linear NO: 0789

[3684] AKKKAAKA

[3685] -1.6 AKVKDEPQRRS

[3686] Amphipathi SEQ ID

[3687] ARLSAKPAPPKP Free Free NA Linear

[3688] c NO: 0790

[3689] EPKPKKAPAKK

[3690] -3.66 akvkdepqrrsarlsa

[3691] Amphipathi SEQ ID

[3692] kpappkpepkpkkap Free Free NA Linear

[3693] c NO: 0791

[3694] akk -3.66 APWHLSSQYSR Amphipathi SEQ ID

[3695] Free Free NA Linear

[3696] T c NO: 0792 -0.36 APWHLSSQYSR Amphipathi SEQ ID

[3697] Free Free NA Linear

[3698] T c NO: 0792 -0.36 ARRARAARRAR

[3699] Arginine SEQ ID

[3700] AARRARAARRA Free Free NA Linear rich NO: 0793

[3701] RAARRARA

[3702] -15.9 ARRRAARAARR

[3703] Arginine SEQ ID

[3704] RAARAARRRAA Free Free NA Linear rich NO: 0794

[3705] RA -12.7 ARRRAARAARR

[3706] Arginine SEQ ID

[3707] RAARAARRRAA Free Free NA Linear rich NO: 0795

[3708] RAARRRAARA

[3709] -17 Conj

[3710] ugati

[3711] on

[3712] with

[3713] hca

[3714] Ami

[3715] ASMWERVKSIIK Amphipathi SEQ ID (4-(7- datio NA Linear SSLAAASNI c NO: 0796 hydr

[3716] n

[3717] oxyc

[3718] oum

[3719] aryl)- acety

[3720]

[3721] l) 0.08ATTORNEY DOCKET: 05336.0008W001

[3722] ASMWERVKSIIK Amphipathi SEQ ID

[3723] NA NA NA Linear SSLAAASNI c NO: 0796

[3724] -0.57 Amphipathi SEQ ID

[3725] AVPAKKRZKSV NA NA NA Linear

[3726] c NO: 0797 -0.48

[3727] B,

[3728] Bet

[3729] a- Ala

[3730] nin

[3731] e;

[3732] Nl

[3733] A,

[3734] 2- B- (2- Amphipathi SEQ ID Amid

[3735] GLRK(NIA)RLRK NA nitr Linear

[3736] c NO: 0798 ation

[3737] FRNKIKEK oi

[3738] mi

[3739] da

[3740] zol

[3741] .1.

[3742] yl)

[3743] ac

[3744] etic

[3745] aci

[3746] d -4.3 B,

[3747] Bet

[3748] a- Ala

[3749] nin

[3750] e;

[3751] Nl

[3752] A,

[3753] 2- (2- B- Amphipathi SEQ ID Amid nitr GLRK(NIA)RLRK NA Linear

[3754] c NO: 0798 ation oi

[3755] FRNKIKEK

[3756] mi

[3757] da

[3758] zol

[3759] -1- yl)

[3760] ac

[3761] etic

[3762] aci

[3763] d;

[3764]

[3765] N -4.3ATTORNEY DOCKET: 05336.0008W001

[3766] ter

[3767] mi

[3768] nal

[3769] ch

[3770] ela

[3771] tor

[3772] DO TA

[3773] (1,

[3774] 4,7

[3775] ,10

[3776] tetr

[3777] aa

[3778] za- cyc

[3779] lod

[3780] od

[3781] ec

[3782] an

[3783] e- 1,4

[3784] ,7,

[3785] 10- tetr

[3786] aa

[3787] ceti

[3788] c

[3789] aci

[3790] d)

[3791] B,

[3792] Bet

[3793] a- Ala

[3794] nin

[3795] e;

[3796] N

[3797] ter

[3798] B- mi Amphipathi SEQ ID Amid

[3799] GLRKRLRKFRN NA nal Linear

[3800] c NO: 0799 ation

[3801] KIKEK ch

[3802] ela

[3803] tor

[3804] DO TA

[3805] (1,

[3806] 4,7

[3807] ,10

[3808]

[3809] -3.75ATTORNEY DOCKET: 05336.0008W001

[3810] tetr

[3811] aa

[3812] za- cyc

[3813] lod

[3814] od

[3815] ec

[3816] an

[3817] e- 1,4

[3818] ,7,

[3819] 10- tetr

[3820] aa

[3821] ceti

[3822] c

[3823] aci

[3824] d)

[3825] Amphipathi SEQ ID

[3826] CARSKNKDC Free Free NA Linear

[3827] c NO: 0800 -0.77 CGAYDLRRRER

[3828] Arginine SEQ ID

[3829] QSRLRRRERQS NA NA NA Linear rich NO: 0801

[3830] R -9.27 CGGMVTVLFRR Ami

[3831] Arginine SEQ ID

[3832] LRIRRASGPPRV Free datio NA Linear rich NO: 0802

[3833] RV n -0.14

[3834] SEQ ID CGNKRTR Cationic NA NA NA Linear NO: 0803 -2.04

[3835] Ami

[3836] SEQ ID CGNKRTRGC Cationic Free datio NA Linear NO: 0804

[3837] n -0.78 CGNVVRQGCGY SEQ ID GRKKRRQRRRG Cationic NA NA NA Linear NO: 0805

[3838] TALDWSWLQTE

[3839] -3.44 Stear

[3840] Arginine SEQ ID

[3841] CHHRRRRHHC ylatio Free NA Cyclic

[3842] rich NO: 0806

[3843] n 5.76 Succi

[3844] nimid

[3845] yl-4- CLLIILRRRIRKQ (N- Ami

[3846] Amphipathi SEQ ID

[3847] AHAHSKNHQQQ mal- datio NA Linear

[3848] c NO: 0807

[3849] NPHQPPM eimid n

[3850] omet

[3851] hyl)

[3852]

[3853] cyclo -1.77ATTORNEY DOCKET: 05336.0008W001

[3854] hexa

[3855] ne-1- carb

[3856] oxyla

[3857] te

[3858] (SM

[3859] CC)

[3860] Amphipathi SEQ ID

[3861] CNGRC Free Free NA Linear

[3862] c NO: 0808 -0.33 Amphipathi SEQ ID

[3863] CRGDK Free Free NA Linear

[3864] c NO: 0809 -0.29 Amphipathi SEQ ID

[3865] CRNGRGPDC Free Free NA Linear

[3866] c NO: 0810 -1.47

[3867] Addit

[3868] CTSTTAKRKKRK SEQ ID ion of

[3869] Cationic Free NA Linear

[3870] LK NO: 0811 cyste

[3871] ine -0.6 CVKRGLKLRHV SEQ ID

[3872] Cationic NA NA NA Linear RPRVTRDV NO: 0812

[3873] -0.82 DAATATRGRSA ASRPTQRPRAP Amphipathi SEQ ID

[3874] NA NA NA Linear ARSASRPRRPV c NO: 0813

[3875] E -12.6 DPATNPGPHFP Amphipathi SEQ ID

[3876] NA NA NA Linear

[3877] R c NO: 0814 -1.35 DPVDTPNPTRR Amphipathi SEQ ID

[3878] Free NA NA Linear KPGK c NO: 0815 -2.6 EEEAAGRKRKK SEQ ID

[3879] Cationic Free Free NA Linear

[3880] RT NO: 0816 -5.88

[3881] Malei

[3882] Ami

[3883] FKQQQQQQQQ Amphipathi SEQ ID mide

[3884] datio NA Linear QQ c NO: 0817 additi

[3885] n

[3886] on -1.42 FQFNFQFNGGG Arginine SEQ ID

[3887] Free Free NA Linear HRRRRRRR rich NO: 0818

[3888] -4.5 Ami

[3889] FQWQRNMRKV Amphipathi SEQ ID

[3890] Free datio NA Linear RGPPVS c NO: 0819

[3891] n 0.19 Cys

[3892] GAYDLRRRERQ Arginine SEQ ID

[3893] additi Free NA Linear SRLRRRERQSR rich NO: 0820

[3894] on -10.1 GGAYVTRSSAV Ami

[3895] Amphipathi SEQ ID

[3896] RLRSSVPGVRLL Free datio NA Linear

[3897] c NO: 0821

[3898]

[3899] Q n -1.73ATTORNEY DOCKET: 05336.0008W001

[3900] GGGARKKAAKA ARKKAAKAARK SEQ ID

[3901] Cationic Free Free NA Linear KAAKAARKKAAK NO: 0822

[3902] A -6.1

[3903] Arginine SEQ ID

[3904] GGRRARRRRRR Free Free NA Linear rich NO: 0823 -7.03

[3905] Cys

[3906] GKRKKKGKLGK SEQ ID

[3907] Cationic additi Free NA Linear KRDP NO: 0824

[3908] on -0.38 Cys

[3909] GKRKKKGKLGK SEQ ID

[3910] Cationic additi Free NA Linear KRPRSR NO: 0825

[3911] on -2.13 GKYVSLTTPKNP Amphipathi SEQ ID

[3912] Free Free NA Linear TKRRITPKDV c NO: 0826

[3913] -0.73 Bio

[3914] tiny

[3915] lati GLFEAIEGFIENG on

[3916] Bioti

[3917] WEGMIDGWYG Amphipathi SEQ ID at

[3918] Free nylat Linear GGGRRRRRRR c NO: 0827 iysi

[3919] ion

[3920] RRK ne

[3921] res

[3922] idu

[3923] e -5.25 GLLEALAELLEG Ami

[3924] Amphipathi SEQ ID

[3925] LRKRLRKFRNKI Free datio NA Linear

[3926] c NO: 0828

[3927] KEK n -0.16

[3928] Lipid

[3929] GLPRRRRRRRR Arginine SEQ ID Peg

[3930] Free NA Linear

[3931] R rich NO: 0829 deriv

[3932] ative -6.38 GNYAHRVGAGA Amphipathi SEQ ID

[3933] Free Free NA Linear PVWL c NO: 0830 0.05

[3934] Bioti

[3935] GRKGKHKRKKL SEQ ID

[3936] Cationic nylati Free NA Linear

[3937] P NO: 0831

[3938] on -0.53 GRKKRRQRRRP PQGRKKRRQRR Arginine SEQ ID

[3939] NA NA NA Linear RPPQGRKKRRQ rich NO: 0832

[3940] RRRPPQ

[3941] -15 GRKKRRQRRRP

[3942] Arginine SEQ ID

[3943] PQTYADFIASGR Free Free NA Linear rich NO: 0833

[3944] TGRRNAI

[3945]

[3946] -7.74ATTORNEY DOCKET: 05336.0008W001

[3947] GRKKRRQRRRP SEQ ID

[3948] Cationic Free Free NA Linear

[3949] Q NO: 0834 -5.15

[3950] Bioti

[3951] GRRHHCRSKAK Amphipathi SEQ ID

[3952] nyiati Free NA Linear RSRHH c NO: 0835

[3953] on -5.41 GSPWGLQHHPP Amphipathi SEQ ID

[3954] Free Free NA Linear

[3955] RT c NO: 0836 -0.19

[3956] Amphipathi SEQ ID

[3957] GSRHPSLIIPRQ NA NA NA Linear

[3958] c NO: 0837 -0.85 GSRVQIRCRFR Amphipathi SEQ ID

[3959] Free Free NA Linear NSTR c NO: 0838 -3.64

[3960] Bioti

[3961] nyl- Giy- GWTLNSAGYLL

[3962] Amphipathi SEQ ID Gly- GPHAVGNHRSF Free NA Linear

[3963] c NO: 0839 N

[3964] SDKNGLTS

[3965] 25gal

[3966] anin(

[3967] 1-29) -1.58 GYGRKKRRGRR

[3968] Arginine SEQ ID

[3969] RTHRLPRRRRR Free Free NA Linear rich NO: 0840

[3970] R -9.66

[3971] Amphipathi SEQ ID

[3972] HATKSQNINF Free Free NA Linear

[3973] c NO: 0841 -1.56

[3974] Conj Lin

[3975] ugati ker

[3976] on (E HHHHHHESGGG

[3977] Arginine SEQ ID with SG GSPGRRRRRRR NA Linear rich NO: 0842 6- GG

[3978] RRRR

[3979] histid GS

[3980] ine PG

[3981] tag ) -13.4 HHHHHHRRRRR Arginine SEQ ID

[3982] Free Free NA Linear RRRR rich NO: 0843 -8.97 HHHHHHRRRRR Arginine SEQ ID

[3983] Free Free NA Linear RRRR rich NO: 0844 -8.97 HHHHHHTKRRIT

[3984] Amphipathi SEQ ID

[3985] PKDVIDVRSVTT Free Free NA Linear

[3986] c NO: 0845

[3987] EINT -4.97 HHHRRRRRRRR Arginine SEQ ID

[3988] Free Free NA Linear RHHH rich NO: 0846 -8.97 HPGSPFPPEHR Amphipathi SEQ ID

[3989] NA NA NA Linear

[3990] P c NO: 0847 -1.17 HQHKPPPLTNN Amphipathi SEQ ID

[3991] NA NA NA Linear

[3992] W c NO: 0848 -0.3 HQHKPPPLTNN Amphipathi SEQ ID

[3993] NA NA NA Linear

[3994]

[3995] W c NO: 0848 -0.3ATTORNEY DOCKET: 05336.0008W001

[3996] Amphipathi SEQ ID

[3997] HRHIRRQSLIML NA NA NA Linear

[3998] c NO: 0849 -0.27 KETWWETWWT Ami

[3999] Arginine SEQ ID

[4000] EWSQPGRKKRR Free datio NA Linear rich NO: 0850

[4001] QRRRPPQ n

[4002] -1.3 KGSKKAVTKAQ

[4003] Ami

[4004] KKDGKKRKRSR SEQ ID

[4005] Cationic Free datio NA Linear KESYSVYVYKVL NO: 0851

[4006] n

[4007] KQ

[4008] -0.95 KGSKKAVTKAQ

[4009] Ami

[4010] KKDGKKRKRSR SEQ ID

[4011] Cationic Free datio NA Linear KESYSVYVYKVL NO: 0851

[4012] n

[4013] KQ

[4014] -0.95 KHHWHHVRLPP

[4015] Amphipathi SEQ ID

[4016] PVRLPPPGNHH Free Free NA Linear

[4017] c NO: 0852

[4018] HHHH -1.11

[4019] Ami KKAAQIRSQVMT Amphipathi SEQ ID

[4020] Free datio NA Linear HLRVI c NO: 0853

[4021] n 0.52 KKDGKKRKRSR Ami

[4022] SEQ ID KESYSVYVYKVL Cationic Free datio NA Linear NO: 0854

[4023] KQ n -0.14

[4024] Ami

[4025] KKKEERADLIAY SEQ ID

[4026] Cationic Free datio NA Linear LKKA NO: 0855

[4027] n 0.47 KKWKMRRGAG Arginine SEQ ID

[4028] NA Free NA Linear RRRRRRRRR rich NO: 0856

[4029] -6.92 Amphipathi SEQ ID

[4030] KRIHPRLTRSIR NA NA NA Linear

[4031] c NO: 0857 -1.66 Amphipathi SEQ ID

[4032] KRIIQRILSRNS NA NA NA Linear

[4033] c NO: 0858 -1.52 Amphipathi SEQ ID

[4034] KTIEAHPPYYAS NA NA NA Linear

[4035] c NO: 0859 -0.29

[4036] Bioti

[4037] KWSFRVSYRGIS SEQ ID

[4038] Cationic nylati Free NA Linear YRRSRGK NO: 0860

[4039] on -1.11 LAELLAELLAEL

[4040] Arginine SEQ ID

[4041] GGGGRRRRRR Free Free NA Linear rich NO: 0861

[4042] RRR -7 LAELLAELLAEL

[4043] Arginine SEQ ID

[4044] GGGGRRRRRR Free Free NA Linear rich NO: 0862

[4045]

[4046] RRR -7ATTORNEY DOCKET: 05336.0008W001

[4047] LAQLLAQLLAQL

[4048] Arginine SEQ ID

[4049] GGGGRRRRRR Free Free NA Linear rich NO: 0863

[4050] RRR -5.02 LLETLLKPFQCRI Ami

[4051] SEQ ID CMRNFSTRQAR Cationic Free datio NA Linear NO: 0864

[4052] RNHRRRHRR n

[4053] -4.04 LLIILRRRIRKQA Ami

[4054] Amphipathi SEQ ID

[4055] HAHSKNHQQQN Free datio NA Linear

[4056] c NO: 0865

[4057] PHQPPM n

[4058] -2.6 LRHHLRHLLRHL

[4059] Amphipathi SEQ ID

[4060] RHLLRHLRHHLR Free Free NA Linear

[4061] c NO: 0866

[4062] HLLRH

[4063] -0.62 Cys

[4064] LRRERQSRLRR Amphipathi SEQ ID

[4065] additi Free NA Linear ERQSR c NO: 0867

[4066] on -8.3 Amphipathi SEQ ID

[4067] MAARL Free Free NA Linear

[4068] c NO: 0868 -0.02 MAMPGEPRRAN

[4069] Amphipathi SEQ ID

[4070] VMAHKLEPASL Free NA NA Linear

[4071] c NO: 0869

[4072] QLRNSCA

[4073] -3.75 MAPQRDTVGGR

[4074] Amphipathi SEQ ID

[4075] TTPPSWGPAKA Free NA NA Linear

[4076] c NO: 0870

[4077] QLRNSCA

[4078] -3.04 Me MERKKRRRESW

[4079] Amphipathi SEQ ID me VHLPPPVHLPPP Free Free Linear

[4080] c NO: 0871 thyl GGHHHHHH

[4081] gro

[4082] up -3.08 MGVADLIKKFESI

[4083] Arginine SEQ ID

[4084] SKEEGGGGKGG Free Free NA Linear rich NO: 0872

[4085] RRRRRRRR

[4086] -7.44 MHKRPTTPSRK Amphipathi SEQ ID

[4087] NA NA NA Linear

[4088] M c NO: 0873 -1.2 NHQQQNPHQPP Ami

[4089] Amphipathi SEQ ID

[4090] MLLIILRRRIRKQ Free datio NA Linear

[4091] c NO: 0874

[4092] AHAHSK n

[4093] -2.6 NRHFRFFFNFTN Amphipathi SEQ ID

[4094] Free Free NA Linear

[4095]

[4096] R c NO: 0875 -0.08ATTORNEY DOCKET: 05336.0008W001

[4097] Bioti

[4098] nylati

[4099] on

[4100] (Lab

[4101] eled Ami

[4102] SEQ ID NRRMKWKK Cationic with datio NA Linear NO: 0876

[4103] Bioti n

[4104] nyl- beta- Alani

[4105] ne) 0.57 NSGTMQSASRA Amphipathi SEQ ID

[4106] NA NA NA Linear

[4107] T c NO: 0877 -4.23 NYTTYKSHFQD Amphipathi SEQ ID

[4108] NA NA NA Linear

[4109] R c NO: 0878 -1.24

[4110] Fusi

[4111] on

[4112] Arginine SEQ ID

[4113] PARAARRAARR Free with NA Linear rich NO: 0879

[4114] beta

[4115] -Gal -5.15 Arginine SEQ ID

[4116] PIRRRKKLRRLK NA NA NA Linear rich NO: 0880 -0.99 Amphipathi SEQ ID

[4117] PNTRVRPDVSF NA NA NA Linear

[4118] c NO: 0881 -1.45 PPHNRIQRRLN Amphipathi SEQ ID

[4119] NA NA NA Linear

[4120] M c NO: 0882 -2.67 PPRLPRPRPRPL SEQ ID

[4121] Cationic Free Free NA Linear PFPRPG NO: 0883 -0.06 PPRLRKRRQLN SEQ ID

[4122] Cationic NA NA NA Linear

[4123] M NO: 0884 -1.9

[4124] SEQ ID PQNRLQIRRHSK Cationic NA NA NA Linear NO: 0885 -2.97 PRPPRLPRPRP Amphipathi SEQ ID

[4125] Free Free NA Linear RPLPFPRPG c NO: 0886

[4126] -0.7 PRPRPRPLPFPR Amphipathi SEQ ID

[4127] Free Free NA Linear

[4128] PG c NO: 0887 -0.37

[4129] Amphipathi SEQ ID

[4130] PSKRLLHNNLRR NA NA NA Linear

[4131] c NO: 0888 -2.37 QAASRVENYMH Amphipathi SEQ ID

[4132] NA NA NA Linear

[4133] R c NO: 0889 -3.82

[4134] Bioti

[4135] nylati

[4136] Ami

[4137] SEQ ID on

[4138] QNRRMKWKK Cationic datio NA Linear NO: 0890 (Lab

[4139] n

[4140] eled

[4141]

[4142] with 0.23ATTORNEY DOCKET: 05336.0008W001

[4143] Bioti

[4144] nyl- beta- Alani

[4145] ne)

[4146] SEQ ID QRIRKSKISRTL Cationic NA NA NA Linear NO: 0891 -1.33

[4147] Ami

[4148] SEQ ID QWQRNMRKVR Cationic Free datio NA Linear NO: 0892

[4149] n -0.92 Ami

[4150] QWQRNMRKVR SEQ ID

[4151] Cationic Free datio NA Linear GPPVSCIKR NO: 0893

[4152] n -0.06 Bioti Ami

[4153] RAGLQFPVGRV Amphipathi SEQ ID

[4154] nylati datio NA Linear HRLLRK c NO: 0894

[4155] on n 0.65 RARARARARAR

[4156] Arginine SEQ ID

[4157] ARARARARARA Free Free NA Linear rich NO: 0895

[4158] RARARARARA

[4159] -17 RFTFHFRFEFTF

[4160] Arginine SEQ ID

[4161] HFEGGGRRRRR Free Free NA Linear rich NO: 0896

[4162] RR -2.79

[4163] Cycli Cycli

[4164] Amphipathi SEQ ID

[4165] RGDFK clizat zatio NA Cyclic

[4166] c NO: 0897

[4167] ion n 0.04 RGDRGDRRDLR SEQ ID

[4168] Cationic Free Free NA Linear LDRGDLRC NO: 0898

[4169] -4.36 RGDRLDRRDLR SEQ ID

[4170] Cationic Free Free NA Linear LDRRDLRC NO: 0899

[4171] -3.91 RGERGERRELR SEQ ID

[4172] Cationic Free Free NA Linear LERGELRC NO: 0900

[4173] -7.96 RGERLERRELRL SEQ ID

[4174] Cationic Free Free NA Linear ERRELRC NO: 0901

[4175] -7.51 Conj

[4176] ugati

[4177] on

[4178] RGGRLAYLRRR SEQ ID with

[4179] Cationic Free NA Linear WAVLGR NO: 0902 NBD

[4180] and

[4181] TAM

[4182]

[4183] RA -1.21ATTORNEY DOCKET: 05336.0008W001

[4184] Conj

[4185] ugati

[4186] on

[4187] RGGRLSYSRRR SEQ ID with

[4188] Cationic Free NA Linear FSTSTGR NO: 0903 NBD

[4189] and

[4190] TAM RA -5.21 RGGRLSYSRRR SEQ ID

[4191] Cationic Free Free NA Linear FSTSTGR NO: 0903 -5.21 RGGRLSYSRRR SEQ ID

[4192] Cationic Free Free NA Linear FSTSTGR NO: 0903 -5.21 RGGRLSYSRRR SEQ ID

[4193] Cationic Free Free NA Linear FSTSTGR NO: 0903 -5.21

[4194] Conj

[4195] ugati

[4196] RGGRLSYSRRR SEQ ID

[4197] Cationic on Free NA Linear FSTSTGR NO: 0904

[4198] with

[4199] NBD -5.21 RGSRRAVTRAQ

[4200] Ami

[4201] RRDGRRRRRSR SEQ ID

[4202] Cationic Free datio NA Linear RESYSVYVYRVL NO: 0905

[4203] n

[4204] RQ

[4205] -12.5 Arginine SEQ ID

[4206] RHHLRHLRRHL Free Free NA Linear rich NO: 0906 -2 RHHLRHLRRHL Arginine SEQ ID

[4207] Free Free NA Linear RHLLRHLRHHL rich NO: 0907

[4208] -2.41 RHHLRHLRRHL Arginine SEQ ID

[4209] Free Free NA Linear RHLLRHLRHHL rich NO: 0908

[4210] -2.41 RHHLRHLRRHL

[4211] Arginine SEQ ID

[4212] RHLLRHLRHHLR Free Free NA Linear rich NO: 0910

[4213] HLRRHLRHLL

[4214] -3.3 RHHRRHHRRHR Arginine SEQ ID

[4215] Free Free NA Linear RHHRRHHRHHR rich NO: 0911

[4216] -12.1 RHNFRFFFNFRT Arginine SEQ ID

[4217] Free Free NA Linear NR rich NO: 0912 -0.87 RHNHRFNFRFF Arginine SEQ ID

[4218] Free Free NA Linear FNFRFNTRTN rich NO: 0913

[4219] -1.87 RHRHRRHRHRR Arginine SEQ ID

[4220] Free Free NA Linear

[4221]

[4222] HRHR rich NO: 0914 -8.97ATTORNEY DOCKET: 05336.0008W001

[4223] X,

[4224] 4- am

[4225] ino

[4226] Stear Ami

[4227] RKKRKKKRXRH SEQ ID

[4228] Cationic ylatio datio Linear XRHXRHXR NO: 0915 but

[4229] n n

[4230] an

[4231] oic

[4232] aci

[4233] d 3.54 RKKRRRESRKK SEQ ID

[4234] Cationic NA NA NA Linear RRRESC NO: 0916

[4235] -7.71 Cys

[4236] RKKRRRESRRA SEQ ID

[4237] Cationic additi Free NA Linear RRSPRHL NO: 0917

[4238] on -8.3 RKKRRRESWVH SEQ ID LPPPVHLPPPGG Cationic Free Free NA Linear NO: 0918

[4239] HHHHHH

[4240] -2.59 RLALRLALRALR Amphipathi SEQ ID

[4241] Free Free NA Linear AALRLA c NO: 0919 0.03 RLHHRLHRRLH Amphipathi SEQ ID

[4242] Free Free NA Linear RLHR c NO: 0920 -3.09 RLHHRLHRRLH

[4243] Amphipathi SEQ ID

[4244] RLHRRLHRLHH Free Free NA Linear

[4245] c NO: 0921

[4246] RLHRRLH

[4247] -5.39 RLHLRLHLRHLR Amphipathi SEQ ID

[4248] Free Free NA Linear HHLRLH c NO: 0922 -0.21 RLHRRLHRRLH Amphipathi SEQ ID

[4249] Free Free NA Linear RLHR c NO: 0923 -3.57 RLHRRLHRRLH

[4250] Amphipathi SEQ ID

[4251] RLHRRLHRLHR Free Free NA Linear

[4252] c NO: 0924

[4253] RLHRRLH

[4254] -6.35 RLIMRIYAPTTRR Amphipathi SEQ ID

[4255] NA NA NA Linear YG c NO: 0925 -0.21 RLPRPRPRPLPF Amphipathi SEQ ID

[4256] Free Free NA Linear PRPG c NO: 0926 -0.36

[4257] Ami

[4258] RQARRNRRRAL SEQ ID

[4259] Cationic Free datio NA Linear WKTLLKKVLKA NO: 0927

[4260] n -0.82 RQIKIWFQNRRM

[4261] Amphipathi SEQ ID

[4262] KWKKTYADFIAS Free Free NA Linear

[4263] c NO: 0928

[4264] GRTGRRNAI

[4265]

[4266] -0.1ATTORNEY DOCKET: 05336.0008W001

[4267] Cy

[4268] stei

[4269] ne RQIRIWFQNRR Amphipathi SEQ ID

[4270] NA NA mo Linear MRWRRC c NO: 0929

[4271] difi

[4272] cati

[4273] on -0.37 SEQ ID RQRSRRRPLNIR Cationic NA NA NA Linear NO: 0930 -4.86

[4274] Bioti

[4275] RRHHCRSKAKR SEQ ID

[4276] Cationic nylati Free NA Linear SR NO: 0931

[4277] on -4.57 RRHLRRHLRHL Amphipathi SEQ ID

[4278] Free Free NA Linear RRHLRRHLRHL c NO: 0932

[4279] -4.96 Arginine SEQ ID

[4280] RRIRPRP Free Free NA Linear rich NO: 0933 -2.16 RRIRPRPPRLPR Arginine SEQ ID

[4281] Free Free NA Linear PRP rich NO: 0934 -3.13 RRIRPRPPRLPR Arginine SEQ ID

[4282] Free Free NA Linear PRPRP rich NO: 0935 -3.77

[4283] Ami

[4284] SEQ ID RRKLSQQKEKK Cationic Free datio NA Linear NO: 0936

[4285] n -1.58 RRQRRTSKLMK SEQ ID

[4286] Cationic NA NA NA Linear

[4287] R NO: 0937 -3.35 RRRQRRKRGGD Ami

[4288] Amphipathi SEQ ID

[4289] IMGEWGNEIFGA Free datio NA Linear

[4290] c NO: 0938

[4291] IAGFLG n

[4292] -2.41 Brom

[4293] RRRQRRKRGGD Ami

[4294] Amphipathi SEQ ID oacet

[4295] IMGEWGNEIFGA datio NA Linear

[4296] c NO: 0938 ylatio

[4297] IAGFLG n

[4298] n -2.41

[4299] Aib

[4300] , a- am RRRRRRRRRGG ino

[4301] Arginine SEQ ID

[4302] LAA(AIB)SGWKH Free Free iso Linear rich NO: 0939

[4303] HHHHH but

[4304] yric

[4305] aci

[4306] d -7.76 RRRRRRRRRRR

[4307] Arginine SEQ ID

[4308] TYADFIASGRTG Free Free NA Linear rich NO: 0940

[4309] RRNAI

[4310]

[4311] -11.4ATTORNEY DOCKET: 05336.0008W001

[4312] Malei

[4313] Ami

[4314] RVIRWFQNKRS SEQ ID mide

[4315] Cationic datio NA Linear KDKK NO: 0941 additi

[4316] n

[4317] on 0.55 Conj

[4318] ugati

[4319] on Ami

[4320] RVRILARFLRTR SEQ ID

[4321] Cationic with datio NA Linear

[4322] V NO: 0942

[4323] fluor n

[4324] escei

[4325] n 0.27

[4326] B,

[4327] Bet

[4328] a- Ala

[4329] nin

[4330] e

[4331] an

[4332] d

[4333] X,

[4334] Acet

[4335] RXRRBRRXRYQ SEQ ID 6- Cationic ylatio Free Linear FLIRXRBRXRB NO: 0943 am

[4336] n

[4337] ino

[4338] he

[4339] xa

[4340] noi

[4341] c

[4342] aci

[4343] d

[4344] (Ah

[4345] x) -6.3 X,

[4346] 6- am

[4347] ino

[4348] he

[4349] Ami

[4350] RXRRXRRXRRX Arginine SEQ ID xa

[4351] Free datio Linear

[4352] R rich NO: 0944 noi

[4353] n

[4354] c

[4355] aci

[4356] d

[4357] (Ah

[4358] x) -5.67 Ah

[4359] x, RXRRXRRXRRX Arginine SEQ ID 6- NA NA Linear

[4360] R rich NO: 0944 am

[4361] ino

[4362]

[4363] he -6.32ATTORNEY DOCKET: 05336.0008W001

[4364] xa

[4365] noi

[4366] c

[4367] aci

[4368] d

[4369] Ah

[4370] x,

[4371] 6- am

[4372] ino RXRRXRRXRRX Arginine SEQ ID

[4373] NA NA he Linear

[4374] R rich NO: 0944

[4375] xa

[4376] noi

[4377] c

[4378] aci

[4379] d -6.32 X,

[4380] ae

[4381] LP,

[4382] Ami am RXRRXRRXRRX Arginine SEQ ID

[4383] Free datio ino Linear

[4384] R rich NO: 0945

[4385] n eth

[4386] yip

[4387] rop

[4388] yi -5.67 X,

[4389] ap

[4390] LP,

[4391] Ami am RXRRXRRXRRX Arginine SEQ ID

[4392] Free datio ino Linear

[4393] R rich NO: 0945

[4394] n pro

[4395] pyl

[4396] pro

[4397] pyl -5.67 Bioti

[4398] SARHHCRSKAK Amphipathi SEQ ID

[4399] nylati Free NA Linear RSRHH c NO: 0946

[4400] on -5.12 Amphipathi SEQ ID

[4401] SFHQFARATLAS NA NA NA Linear

[4402] c NO: 0947 -0.29 SGRGKQGGKAR Malei

[4403] Ami AKAKTRSSRAGL Amphipathi SEQ ID mide

[4404] datio NA Linear QFPVGRVHRLL c NO: 0948 aditio

[4405] n

[4406] RKG n

[4407]

[4408] -4.9ATTORNEY DOCKET: 05336.0008W001

[4409] SGRGKQGGKAR

[4410] Ami AKAKTRSSRAGL Amphipathi SEQ ID

[4411] Free datio NA Linear QFPVGRVHRLL c NO: 0949

[4412] n

[4413] RKGC

[4414] -4.07 SMLKRNHSTSN SEQ ID

[4415] Cationic NA NA NA Linear

[4416] R NO: 0950 -3.98

[4417] Bioti

[4418] SRAHHCRSKAK SEQ ID

[4419] Cationic nylati Free NA Linear RSRHH NO: 0951

[4420] on -5.12 Bioti

[4421] SRRAHCRSKAK SEQ ID

[4422] Cationic nylati Free NA Linear RSRHH NO: 0952

[4423] on -5.6 Cys

[4424] SRRARRSPRES SEQ ID

[4425] Cationic additi Free NA Linear GKKRKRKR NO: 0953

[4426] on -8.33 Cys

[4427] SRRARRSPRHL SEQ ID

[4428] Cationic additi Free NA Linear GSG NO: 0954

[4429] on -5.37 Bioti

[4430] SRRHACRSKAK SEQ ID

[4431] Cationic nylati Free NA Linear RSRHH NO: 0955

[4432] on -5.6 Bioti

[4433] SRRHHARSKAK SEQ ID

[4434] Cationic nylati Free NA Linear RSRHH NO: 0956

[4435] on -6.74 Bioti

[4436] SRRHHCRAKAK SEQ ID

[4437] Cationic nylati Free NA Linear RSRHH NO: 0957

[4438] on -5.46 Bioti

[4439] SRRHHCRSAAK SEQ ID

[4440] Cationic nylati Free NA Linear RSRHH NO: 0958

[4441] on -6.08 Bioti

[4442] SRRHHCRSKAA SEQ ID

[4443] Cationic nylati Free NA Linear RSRHH NO: 0959

[4444] on -6.08 Bioti

[4445] SRRHHCRSKAK SEQ ID

[4446] Cationic nylati Free NA Linear ASRHH NO: 0960

[4447] on -5.12 Bioti

[4448] SRRHHCRSKAK SEQ ID

[4449] Cationic nylati Free NA Linear RARHH NO: 0961

[4450] on -5.46 Bioti

[4451] SRRHHCRSKAK SEQ ID

[4452] Cationic nylati Free NA Linear RSAHH NO: 0962

[4453] on -5.12 SRRKRQRSNMR SEQ ID

[4454] Cationic NA NA NA Linear

[4455] I NO: 0963 -4.79

[4456] SEQ ID SYIQRTPSTTLP Cationic NA NA NA Linear

[4457]

[4458] NO: 0964 -0.46ATTORNEY DOCKET: 05336.0008W001

[4459] TARRITPKDVIDV Amphipathi SEQ ID

[4460] Free Free NA Linear RSVTTEINT c NO: 0965

[4461] -3.55 TKAARITPKDVID Amphipathi SEQ ID

[4462] Free Free NA Linear VRSVTTEINT c NO: 0966

[4463] -2.86 Amphipathi SEQ ID

[4464] TKRRITPKDVIDV Free Free NA Linear

[4465] c NO: 0967 -0.13 TKRRITPKDVIDV Amphipathi SEQ ID

[4466] Free Free NA Linear RSVTTEINT c NO: 0968

[4467] -3.11 TKRRITPKDVIDV Amphipathi SEQ ID

[4468] Free Free NA Linear RSVTTEINT c NO: 0968

[4469] -3.11 TKRRITPKDVIDV Amphipathi SEQ ID

[4470] Free Free NA Linear RSVTTKINT c NO: 0969

[4471] -1.94 TKRRITPKKVIDV Amphipathi SEQ ID

[4472] Free Free NA Linear RSVTTEINT c NO: 0970

[4473] -2.66 Conj

[4474] ugati TRSSRAGLQWP on

[4475] Amphipathi SEQ ID

[4476] VGRVHRLLRKG Free with NA Linear

[4477] c NO: 0971

[4478] GC Texa

[4479] s

[4480] Red -1.26 Amphipathi SEQ ID

[4481] TSHTDAPPARSP NA NA NA Linear

[4482] c NO: 0972 -2.89

[4483] Ami

[4484] Amphipathi SEQ ID

[4485] TSPLNIHNGQKL Free datio NA Linear

[4486] c NO: 0973

[4487] n -0.27 TVDNPASTTNKD Amphipathi SEQ ID

[4488] Free Free NA Linear KLFAVRK c NO: 0974

[4489] -1.82 Cys

[4490] VKRGLKLRHVR Amphipathi SEQ ID

[4491] additi Free NA Linear PRVTRMDV c NO: 0975

[4492] on -1.14 Ami

[4493] VQAILRRNWNQ Amphipathi SEQ ID

[4494] Free datio NA Linear YKIQ c NO: 0976

[4495] n 0.52 Ami

[4496] VRRFLVTLRIRR SEQ ID

[4497] Cationic Free datio NA Linear

[4498] A NO: 0977

[4499] n 0.27 SEQ ID VSGKK Catioinic Free Free NA Linear

[4500]

[4501] NO: 0978 -0.01ATTORNEY DOCKET: 05336.0008W001

[4502] WKQSHKKGGKK SEQ ID

[4503] Cationic Free Free NA Linear GSG NO: 0979 -0.12 WKQSHKKGGKK SEQ ID

[4504] Cationic Free Free NA Linear GSG NO: 0979 -0.12

[4505] FITC

[4506] linke

[4507] d to

[4508] a

[4509] SEQ ID YARAAARQARA Cationic beta- NA NA Linear NO: 0980

[4510] Alani

[4511] ne

[4512] resid

[4513] ue -3.78 YARAAARQARA SEQ ID

[4514] Cationic Free Free NA Linear KALARQLGVAA NO: 0981

[4515] -4.12 Fusi

[4516] on

[4517] SEQ ID YARAARRAARR Cationic Free with NA Linear NO: 0982

[4518] beta

[4519] -Gal -4.75 Fusi

[4520] on

[4521] SEQ ID YAREARRAARR Cationic Free with NA Linear NO: 0983

[4522] beta

[4523] -Gal -5.48 Fusi

[4524] on

[4525] SEQ ID YARKARRAARR Cationic Free with NA Linear NO: 0984

[4526] beta

[4527] -Gal -4.31 Fusi

[4528] on

[4529] SEQ ID YEREARRAARR Cationic Free with NA Linear NO: 0985

[4530] beta

[4531] -Gal -6.21 Fusi

[4532] on

[4533] SEQ ID YGRAARRAARR Cationic Free with NA Linear NO: 0986

[4534] beta

[4535] -Gal -4.7 YGRKKRRQRRR Ami

[4536] SEQ ID GCYGRKKRRQR Cationic Free datio NA Linear NO: 0987

[4537] RRG n

[4538]

[4539] -7.78ATTORNEY DOCKET: 05336.0008W001

[4540] YGRKKRRQRRR.

[4541] GLFGAIAGFIEN Amphipathi SEQ ID

[4542] Free Free NA Linear GWEGMIDGWY c NO: 0988

[4543] G -0.55 YGRKKRRQRRR

[4544] Amphipathi SEQ ID

[4545] GTALDWSWLQT NA NA NA Linear

[4546] c NO: 0989

[4547] E -2.97 YGRKKRRQRRR Amphipathi SEQ ID

[4548] Free Free NA Linear YGRKKRRQRRR c NO: 0990

[4549] -8.82 YGRKKRRQRRT Amphipathi SEQ ID

[4550] Free NA NA Linear ALDASALQTE c NO: 0991

[4551] -5.42 Bio YGRKKRRQRRT Amphipathi SEQ ID tiny

[4552] Free NA Linear ALDWSWLQTE c NO: 0992 lati

[4553] on -1.96 Fusi

[4554] on

[4555] Arginine SEQ ID

[4556] YGRRARRAARR Free with NA Linear rich NO: 0993

[4557] beta

[4558] -Gal -5.22 Fusi

[4559] on

[4560] Arginine SEQ ID

[4561] YGRRARRRARR Free with NA Linear rich NO: 0994

[4562] beta

[4563] -Gal -5.74 Fusi

[4564] on

[4565] Arginine SEQ ID

[4566] YGRRARRRRRR Free with NA Linear rich NO: 0995

[4567] beta

[4568] -Gal -6.26 Fusi

[4569] on

[4570] Arginine SEQ ID

[4571] YGRRRRRRRRR Free with NA Linear rich NO: 0996

[4572] beta

[4573] -Gal -6.78 Ami YIVLRRRRKRVN Arginine SEQ ID

[4574] Free datio NA Linear TKRS rich NO: 0997

[4575] n -2.75 Amphipathi SEQ ID

[4576] YKQCHKKGG

[4577] c NO: 0998 0.8

[4578] Ah

[4579] SEQ ID

[4580] X,

[4581] NO: 0998

[4582] YKQCHKKGG- Amphipathi 6- and SEQ Free Free Linear AHX-KKGSG c am

[4583] ID NO:

[4584] ino

[4585] 0999

[4586]

[4587] he -2.45ATTORNEY DOCKET: 05336.0008W001

[4588] xa

[4589] noi

[4590] c

[4591] aci

[4592] d

[4593] Amphipathi SEQ ID

[4594] KKGSG

[4595] c NO: 0999 -0.55 YKQSHKKGGKK SEQ ID

[4596] Cationic Free Free NA Linear GSG NO: 1000 -1.03 YKQSHKKGGKK SEQ ID

[4597] Cationic Free Free NA Linear GSG NO: 1000 -1.03

[4598] Fusi

[4599] on

[4600] SEQ ID YKRAARRAARR Cationic Free with NA Linear NO: 1001

[4601] beta

[4602] -Gal -4.31 Fusi

[4603] on

[4604] SEQ ID YKRKARRAARR Cationic Free with NA Linear NO: 1002

[4605] beta

[4606] -Gal -3.87 Fusi

[4607] on

[4608] SEQ ID YPRAARRAARR Cationic Free with NA Linear NO: 1003

[4609] beta

[4610] -Gal -4.33 YPYDANHTRSP Amphipathi SEQ ID

[4611] NA NA NA Linear

[4612] T c NO: 1004 -2.2 YRQSHRRGGRR SEQ ID

[4613] Cationic Free Free NA Linear GSG NO: 1005 -5.83 YRQSHRRGGRR SEQ ID

[4614] Cationic Free Free NA Linear GSG NO: 1005 -5.83

[4615] Fusi

[4616] on

[4617] SEQ ID YRRAARRAARA Cationic Free with NA Linear NO: 1006

[4618] beta

[4619] -Gal -4.75 Fusi

[4620] on

[4621] Arginine SEQ ID

[4622] YRRRRRRRRRR Free with NA Linear rich NO: 1007

[4623] beta

[4624] -Gal -7.35 Bio YSSYSAPVSSSL

[4625] Amphipathi SEQ ID tiny SVRRSYSSSSG Free Free Linear

[4626] c NO: 1008 lati

[4627] S

[4628] on -4.68 Amphipathi SEQ ID

[4629] kshahaqkrirrrliill Free Free NA Linear

[4630]

[4631] c NO: 1009 -0.27ATTORNEY DOCKET: 05336.0008W001

[4632] Amphipathi SEQ ID

[4633] kgharaqkrlrrrlfill Free Free NA Linear

[4634] c NO: 1010 0.04 KKKKKKKKKKKK SEQ ID

[4635] Cationic Free Free NA Linear KKKKKKKK NO: 1011

[4636] 3.4 SEQ ID KKKKKKKKKK Cationic Free Free NA Linear NO: 1012 1.7 ACSSSPSKHCG SEQ ID

[4637] Arginine-rich Free Free NA Linear GRRRRRRRR NO: 1013

[4638] -7.16 RKKRRQRRRGG SEQ ID NVYTEIKCNSLL Arginine-rich Free Free NA Linear NO: 1014

[4639] PLAAIVRV

[4640] -3.72 3- nitro- 2- Ami

[4641] SEQ ID pyridi

[4642] CRRRRRRRRR Arginine-rich datio NA Linear NO: 1015 nesul

[4643] n

[4644] fenyl

[4645] (Npy

[4646] s) -5.63 YGRKKRRQRRR GGGENSFRFLA SEQ ID

[4647] Arginine-rich Free Free NA Linear DIFPAKAFPVRF NO: 1016

[4648] E

[4649] -3.08

[4650] GGSGSGPRHRD SEQ ID GVRRPQKRPSCI Arginine-rich Free Free NA Linear NO: 1017

[4651] GCKGTHGGTGA

[4652] -6.06 SEQ ID Stear

[4653] HHHHHHHH Cationic Free NA Linear NO: 1018 yl -2.48 SEQ ID CGRKKRRQRRR Arginine-rich Free Free NA Linear NO: 1019 -4.13

[4654] CGRLVQYRGEV QAMLGQSTEEL SEQ ID

[4655] Arginine-rich Free Free NA Linear RVRLASHLRKLR NO: 1020

[4656] KRLLRD

[4657]

[4658] -3.7ATTORNEY DOCKET: 05336.0008W001

[4659] CGGRGRRDRR SEQ ID GRYQFLIRGRDR Arginine-rich Free Free NA Linear NO: 1021

[4660] GRD

[4661] -6.36 YGRKKRRQRRR SEQ ID

[4662] Arginine-rich Free Free NA Linear KLSSIESDV NO: 1022

[4663] -5.05 CRQIKIWFQNRR SEQ ID

[4664] Arginine-rich Free Free NA Linear MKWKKGG NO: 1023

[4665] 3.03 RQIKIWFQNRRM SEQ ID

[4666] Arginine-rich Free Free NA Linear KWKKGGC NO: 1024

[4667] 3.03 CRQIRIWFQNRR SEQ ID

[4668] Arginine-rich Free Free NA Linear MRWRR NO: 1025 -0.37 LLGDFFRKSKEK SEQ ID IGKEFKRIVQRIK Arginine-rich Free Free NA Linear NO: 1026

[4669] DFLRNLVPRTES

[4670] 1.32 LLGDFFRKSKEK SEQ ID IGKEFKRIVQRIK Arginine-rich Free Free NA Linear NO: 1027

[4671] DFLRNLVPRTES

[4672] 1.32 FMHNLWKHLSS

[4673] Amphipathi SEQ ID amid MERVEWLRKKL Free NA Linear

[4674] c NO: 1028 ation

[4675] QDVHNY

[4676] 2.01 SEQ ID KKKKKKC Cationic Free Free NA Linear NO: 1029 1.85 AKAKASKPTTPP Amphipathi SEQ ID

[4677] Free Free NA Linear ENRPRH c NO: 1030 -4.54 KSGRPREDRVP HSRNSITLTNSG SEQ ID

[4678] Arginine-rich Free Free NA Linear SGSGSGSGRGD NO: 1031

[4679] SP

[4680] -11.5 YADAIFTNSYRK SEQ ID amid VLGQLSARKLLQ Arginine-rich Free NA Linear NO: 1032 ation

[4681] DIMSR

[4682] 0.8 MEVGWYRSPFS SEQ ID

[4683] Arginine-rich Free Free NA Linear RVVHLYRNGK NO: 1033

[4684] 0.31 GIGKFLHSAKKF SEQ ID

[4685] Amphipathic Free Free NA Linear GKAFVGEIMNS NO: 1034

[4686]

[4687] 2.58ATTORNEY DOCKET: 05336.0008W001

[4688] QMEPKMQSKTK SEQ ID

[4689] Amphipathic Free Free NA Linear IYRR NO: 1035 -1.04 RRDFYGCLLDLS SEQ ID LGVPSLGWRRR Arginine-rich Free Free NA Linear NO: 1036

[4690] CITA 3.4 LGKLSQELHKLQ SEQ ID amid

[4691] TYPRTNTGSGT Amphipathic Free NA Linear NO: 1037 ation

[4692] P -1.97

[4693] (Di

[4694] sulf

[4695] ide KCNTATCATQRL bri ANFLVRSSNNLG SEQ ID amid dg

[4696] Arginine-rich Free Linear PVLPPTNVGSNT NO: 1038 ation e: C

[4697] Y ys2

[4698] Gy

[4699] s7) -3.55 KCNTATCATQRL ANFLVHSSNNF SEQ ID

[4700] Amphipathic Free Free NA Linear GAILSSTNVGSN NO: 1039

[4701] TY -3.95

[4702] Glp

[4703] (pyro

[4704] SEQ ID amid

[4705] HWSYKLRPG Amphipathic gluta NA Linear NO: 1040 ation

[4706] mic

[4707] acid) 1.36 VHFFRNIVTART SEQ ID

[4708] Arginine-rich Free Free NA Linear

[4709] P NO: 1041 0.15 HLNILSTLWKYR SEQ ID

[4710] Amphipathic Free Free NA Linear

[4711] C NO: 1042 3.32 PLARTLSVAGLP SEQ ID

[4712] Amphipathic Free Free NA Linear GKK NO: 1043 0.88

[4713] Ac- Nle

[4714] SEQ ID

[4715] HfRWK Cationic (nori Free NA Linear NO: 1044

[4716] eucin

[4717] e) 1.69 SEQ ID CGGHAIYPRH Amphipathic Free Free NA Linear NO: 1045 0.11 SEQ ID CGGGRRR Arginine-rich Free Free NA Linear NO: 1046 -2.2

[4718] RRRGGGC SEQ ID

[4719] n n n U U U U Arginine-rich Free Free NA Linear NO: 1047 -2.2

[4720] VHHQKLVFFAED SEQ ID

[4721] Amphipathic NA Linear Free Free

[4722] 0.26 VGSNK NO: 1048

[4723]

[4724] ATTORNEY DOCKET: 05336.0008W001

[4725] HHQKLVFFAEDV SEQ ID

[4726] Amphipathic Free Free NA Linear GSNK NO: 1049 -0.06 WSHPQFEKCWS SEQ ID

[4727] Amphipathic Free Free NA Linear HPQFEK NO: 1050

[4728] 2.51 SEQ ID amid

[4729] HKTDSFVGLM Amphipathic Free NA Linear NO: 1051 ation 1.44 AKFVAAWTLKAA SEQ ID

[4730] Cationic Free Free NA Linear

[4731] A NO: 1052 2.2

[4732] Palm

[4733] SEQ ID itoyla

[4734] KTTKS Cationic Free NA Linear NO: 1053 tion

[4735] (Pal) -0.63 SEQ ID amid

[4736] FSLLRY Arginine-rich Free NA Linear NO: 1054 ation 2.07

[4737] Acet

[4738] SEQ ID amid

[4739] ACSSSPSKHCG Cationic ylatio NA Linear NO: 1055 ation

[4740] n 0.81 SEQ ID

[4741] hvfsr Arginine-rich Free Free NA Linear NO: 1056 -0.07 fmoc

[4742] SEQ ID FLPNSNHIKQGL Cationic -L-4- Free NA Linear NO: 1057

[4743] l-Phe 0.5 Fmo

[4744] SEQ ID c-D- flpnsnhikqGI Cationic Free NA Linear NO: 1058 4-I- Phe 0.5 SEQ ID CGGGGRR Arginine-rich Free Free NA Linear NO: 1059 -1.63 SEQ ID RRGGGGC Arginine-rich Free Free NA Linear NO: 1060 -1.63 YPSKPDNPGED APAEDMARYYS SEQ ID amid

[4745] Arginine-rich Free NA Linear ALRHYINLITRQR NO: 1061 ation

[4746] Y -4.04 MAADIISTIGDLV SEQ ID

[4747] Amphipathic Free Free NA Linear KWIIDTVNKFKK NO: 1062

[4748] 5.2 GCRDVPMSMR SEQ ID

[4749] Arginine-rich Free Free NA Linear GGDRCG NO: 1063 -1.11 ISQAVHAAHAEI SEQ ID amid

[4750] Amphipathic Free NA Linear NEAGR NO: 1064 ation -5.03

[4751] SEQ ID FEFKFEFKK Amphipathic Free Free NA Linear NO: 1065 3.15 EPGYSPTYKQD SEQ ID

[4752] Amphipathic Free Free NA Linear

[4753]

[4754] KHYGY NO: 1066 -0.24ATTORNEY DOCKET: 05336.0008W001

[4755] DFYGCLLDLSLG SEQ ID

[4756] Arginine-rich Free Free NA Linear VPSGVRRRCITA NO: 1067

[4757] 3.04 ETCHLSPNPYV SEQ ID

[4758] Cationic Free Free NA Linear GCTK NO: 1068 0.32

[4759] SEQ ID PKEK Cationic Free Free NA Linear NO: 1069 -0.51

[4760] Acet

[4761] ACESPLKRQCG SEQ ID amid

[4762] Arginine-rich ylatio NA Linear GGS NO: 1070 ation

[4763] n 0.25 YLRIVQCRSVEG SEQ ID

[4764] Arginine-rich Free Free NA Linear SCGF NO: 1071 1.25

[4765] SEQ ID RYLPT Arginine-rich Free Free NA Linear NO: 1072 0.45 AVVPVLAYAAAR SEQ ID

[4766] Arginine-rich Free Free NA Linear LLL NO: 1073 2.72

[4767] SEQ ID GGGK Cationic Free Free NA Linear NO: 1074 -0.49 SEQ ID CGGGGGR Arginine-rich Free Free NA Linear NO: 1075 -1.06 SEQ ID RGGGGGC Arginine-rich Free Free NA Linear NO: 1076 -1.06 aecahlahalahalhr Cationic and SEQ ID

[4768] Free Free NA Linear alaralaralraew amphipathic NO: 1077

[4769] -2.55 wearlaralaralarhla Cationic and SEQ ID

[4770] Free Free NA Linear halahalhacea amphipathic NO: 1078

[4771] -2.55 aecahlahalaralhra SEQ ID

[4772] Free Free NA Linear laralaralraew NO: 1079

[4773] Amphipathic -3.03 Amphipathi SEQ ID

[4774] lliilrrri rkqahahsk Free Free NA Linear

[4775] c NO: 1080 -0.27 wearlaralaralarhla SEQ ID

[4776] Free Free NA Linear ralahalhace NO: 1081

[4777] Amphipathic -3.03

[4778] Ami

[4779] SEQ ID RRWWRRWRR Cationic Free datio NA Linear NO: 1082

[4780] n 0.29 Re

[4781] sid

[4782] lie RXRRXRRXRRX Arginine SEQ ID 2

[4783] NA NA Linear

[4784] R rich NO: 1083 an

[4785] d 8

[4786] are

[4787]

[4788] 6- -6.32ATTORNEY DOCKET: 05336.0008W001

[4789] am

[4790] ino

[4791] he

[4792] xa

[4793] noi

[4794] c

[4795] aci

[4796] d;

[4797] Re

[4798] sid

[4799] ue

[4800] 5

[4801] an

[4802] d

[4803] 11

[4804] are

[4805] am

[4806] ino

[4807] pro

[4808] pio

[4809] nic

[4810] aci

[4811] d

[4812] Cationic

[4813] SEQ ID NO:

[4814] lliflrrrlrkqarahgk and NA NA NA

[4815] 1084 Linear amphipathic

[4816]

[4817] 0.04

[4818] Certain implementations of the technology are set forth in the claim(s) that follow(s).

Claims

ATTORNEY DOCKET: 05336.0008W001What is claimed is:

1. A method for selectively reducing a senescent cell population, selectively eliminating a cancer cell population, and / or improving mitochondrial efficiency in a non-senescent cell population, comprising administering a composition comprising an active ingredient to cells in an amount sufficient to selectively reduce the senescent cell population, to selectively eliminate the cancer cell population, and / or improve mitochondrial efficiency in the non-senescent cell population, wherein the active ingredient comprises a gerotherapeutic cell penetrating peptide.

2. The method as recited in claim 1, wherein the active ingredient consists essentially of SEQ ID NO: 13 or SEQ ID NO: 14.

3. The method as recited in claim 1, wherein the active ingredient consists essentially of SEQ ID NO: 13.

4. The method as recited in claim 1, wherein the composition is administered one or more times in a treatment time period of about 1 weeks to about 15 weeks.

5. The method as recited in claim 1, wherein the composition is administered two or more times in a treatment time period of about 1 weeks to about 15 weeks.

6. The method as recited in claim 1, wherein the active ingredient consists essentially of a gerotherapeutic cell penetrating peptide selected from the group consisting of SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 18 and SEQ ID NO: 1079.

7. The method as recited in claim 1, wherein the active ingredient consists essentially of a gerotherapeutic cell penetrating peptide selected from the group consisting of SEQ ID NO: 5, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 1009, SEQ ID NO: 1010, SEQ ID NO: 1077, SEQ ID NO: 1078, SEQ ID NO:1079, SEQ ID NO: 1080, SEQ ID NO: 1081, and SEQ ID NO: 1084.

8. The method as recited in claim 1, wherein the gerotherapeutic cell penetrating peptide binds to cardiolipin.

10. The method as recited in claim 1, wherein the gerotherapeutic cell penetrating peptide binds to native form cardiolipin in non-senescent cells and binds to oxidized cardiolipin in senescent cells and / or cancer cells.ATTORNEY DOCKET: 05336.0008W00111. The method as recited in claim 1, wherein the gerotherapeutic cell penetrating peptide binds to native form cardiolipin in non-senescent mitochondria and binds to oxidized cardiolipin in senescent mitochondria and / or cancer cells.

12. The method as recited in claim 1, wherein the gerotherapeutic cell penetrating peptide increases inner mitochondrial membrane potential in non-senescent mitochondria and induces apoptosis in senescent mitochondria and / or cancer cells.

13. A gerotherapeutic CPP composition, comprising: an active ingredient consisting essentially of a gerotherapeutic cell penetrating peptide.

14. The gerotherapeutic CPP composition as recited in claim 13, wherein the gerotherapeutic cell penetrating peptide binds to cardiolipin.

15. The gerotherapeutic CPP composition as recited in claim 13, wherein the gerotherapeutic cell penetrating peptide binds to native form cardiolipin in nonsenescent cells and binds to oxidized cardiolipin in senescent cells and / or cancer cells.

16. The gerotherapeutic CPP composition as recited in claim 13, wherein the gerotherapeutic cell penetrating peptide binds to native form cardiolipin in nonsenescent mitochondria and binds to oxidized cardiolipin in senescent mitochondria and / or cancer cells.

17. The gerotherapeutic CPP composition as recited in claim 13, wherein the gerotherapeutic cell penetrating peptide increases inner mitochondrial membrane potential in non-senescent mitochondria and induces apoptosis in senescent mitochondria and / or cancer cells.

18. The gerotherapeutic CPP composition as recited in claim 13, wherein the gerotherapeutic cell penetrating peptide is selected from the group consisting of SEQ ID NO: 5, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 1009, SEQ ID NO: 1010, SEQ ID NO: 1077, SEQ ID NO: 1078, SEQ ID NO:1079, SEQ ID NO: 1080, SEQ ID NO: 1081, and SEQ ID NO: 1084.

19. A method comprising: administering a gerotherapeutic cell penetrating peptide to a patient in an amount sufficient to reduce effects of aging and improve overall healthATTORNEY DOCKET: 05336.0008W001and functioning of the patient by elimination of senescent cells, elimination of cancer cells, and improvement of mitochondrial efficiency.

20. A method of inducing apoptosis in a cell population, comprising administering a gerotherapeutic cell penetrating peptide, wherein the gerotherapeutic cell penetrating peptide binds to cardiolipin and reduces inner mitochondrial membrane potential.

21. The method of claim 20, wherein the cell population is selected from the group consisting of: senescent cells and cancer cells.

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