STATEMENT REGARDING PRIOR DISCLOSURES BY THE INVENTOR OR A JOINT INVENTOR

The following disclosures are submitted under 35 U.S.C. 102(b)(1)(B):

A “grace period disclosure” was published on Sep. 19-22, 2015 by way of an abstract at the Radiation Research Society Annual Meeting held in Weston, Fla. This publication was entitle “Effects of Fibrinoplate-S in a Radiated Mice Model”. The applicant is a co-author of this publication. This Radiation Research Society Annual Meeting obtained the subject matter indirectly from the applicant not more than one year before the effective filing date of the claimed invention.

A “grace period disclosure” was published on Oct. 28, 2015 by the Basic Sciences Department School of Medicine at Loma Linda University. This publication was entitled “Fibrinoplate-S for the Treatment of Radiation-induced Skin Damage”. Loma Linda University obtained the subject matter indirectly from the applicant not more than one year before the effective filing date of the claimed invention.

BACKGROUND OF THE INVENTION

Field of the Invention

The present invention relates to using protein nanoparticles to augment the function or effectiveness of stem cells or precursor cells in vivo, including their production, mobilization and effectiveness in regenerative medicine and biology.

Description of the Prior Art

Stem cells are known to be the precursors of new cells formation or tissue regeneration. The field of studying stem cells in order to encourage their conversion into mature cells that can perform specific functions in the body is called regenerative biology or regenerative medicine. Some tissues and organs are more capable of regeneration after injury, e.g. the liver. It has been known now that the new liver cells are not necessarily all derived from already-formed mature liver cells that were there in the liver before the injury, but that stem cells from their sources in the body, having migrated there from the rest of the body, become “informed” of their location and then those stem cells become liver cells. Other cells or tissues are more difficult to regenerate, e.g. nerve cells. There is a dire need for methods to encourage stem cells production in vivo which can regenerate at specific sites into new and functional cells, e.g. functional nerve cells in patients with major spinal injury. Alternatively, even if there is no net gain in the production of stem cells, but they are mobilized from the site of production to the site where they are needed or do maximum benefit, the patient will benefit.

Numerous investigators have demonstrated that certain biological molecules, such as those produced by recombinant DNA methods (e.g. Neupogen, thrombopoietin, and erythropoietin) or naturally derived molecules can increase the production of white cells or platelets or red blood cells. However, these molecules all require the presence of a sufficient number of competent stem cells in the body and several days if not weeks for the stem cells to develop into mature and functional cells. There is a need for a product and a method to provide quicker and more effective remedies to patients who can be help by improved stem cell functions in a short time period.

In addition, small molecules can mimic the effect of such large biological products in stimulating the formation of mature blood cells. The small mimetic molecules can be peptide in nature (e.g. Romiplostim) or non-peptide in structure (e.g. Eltrombopag). But they have long-term problems such as “thrombosis, increased bone marrow reticulin, rebound worsening of thrombocytopenia upon discontinuation, and increased blast formation” (Kuter et al, Annu Rev Med; 2009, 60:193-206).

Efficacy of new molecules or compounds that can affect stem cell function is typically assessed by the resulting increase in cell concentrations in the blood. In the case of blood cells, they can easily be measured by the machines in the clinical laboratory. However, most stem cells regenerate into tissues that cannot be measured by the standard machines. Indeed, the effect of any method to augment the function of stem cells for regeneration of solid tissues or organs is difficult to measure. In addition, the improved functionality of stem cells may not necessarily be expressed in term of the number or the concentration of new progeny cells produced, it can be expressed in terms of a more robust or faster healing, or other measures. In order not to be restricted to “increase in cell number” we prefer to use the term augmentation. By augmentation in this disclosure, we mean any of the following: (a) increase in production in the number of stem cells capable of developing into functional mature cells; (b) increase in the speed with which stem cells mature; (c) increase in the functionality of either the stem cells or the mature cells in doing their job in the body; (d) decrease in the destruction of stem cells or their mature cells; (e) mobilization of stem cells from the site of production to the site of transformation where the stem cells become beneficial to the host; (f) any other mechanism leading to a decrease in the morbidity and mortality of the patient in a process in which stem cells are needed to restore health. Such methods are lacking in the prior arts.

For exemplary purposes, a model of burn to test the ability of stem cells to resolve the wound has been chosen. The model will consider the speedy resolution of a burn area to be a reflection of the augmentation of stem cell function regardless of its precise mechanism. Burn is a difficult topic for study. There are many reasons for the difficulties: (a) the degree of burn, particularly thermal burn, can vary from first degree which is superficial, to third degree which is very deep; (b) the size and the location of the burn affect not only the healing process but also the death rate—when the size is small it can be treated easily, whereas a large area burn or in critical locations in the body, it can be fatal; (c) each patient from the same incident will not have the same pattern of burns and therefore there is no standard “control” cases to evaluate if a particular method is better than another.

At the present time, burn patients are treated with pain medication, fluid support, nutritional support, and transfusion of plasma, platelet, red cells, anti-anxiety, anti-infection and anti-stomach-acid agents. Skin grafts are often needed when the patient is stabilized. There are no proven methods to stabilize the vasculature to decrease or stop leaky vessels in order to control extravasation of blood components from the intravascular compartment to the extravascular compartment, or to promote healing at the early stage of the body's response to the injury. Therefore there is need also for an evaluation method which is easy to conduct in the laboratory, is reliable, and which can predict the efficacy of stem cell augmentation in the treatment for a variety of diseases including burn in the clinical setting.

Therefore, a need exists for new and improved albumin nanoparticles that can be used for augmenting the function or effectiveness of stem cells or precursor cells in vivo, including their production, mobilization and effectiveness in regenerative medicine and biology. In this regard, the present invention substantially fulfills this need. In this respect, the albumin nanoparticles according to the present invention substantially departs from the conventional concepts and designs of the prior art, and in doing so provide an apparatus primarily developed for the purpose of augmenting the function or effectiveness of stem cells or precursor cells in vivo, including their production, mobilization and effectiveness in regenerative medicine and biology.

BRIEF SUMMARY OF THE INVENTION

In view of the foregoing disadvantages inherent in the prior art, the present invention provides improved albumin nanoparticles and method of augmenting the function or effectiveness of stem cells or precursor cells in vivo, including their production, mobilization and effectiveness in regenerative medicine and biology, and overcomes the above-mentioned disadvantages and drawbacks of the prior art. As such, the general purpose of the present invention, which will be described subsequently in greater detail, is to provide new and improved albumin nanoparticles and method which has all the advantages of the prior art mentioned heretofore and many novel features that result in augmenting the function or effectiveness of stem cells or precursor cells in vivo, including their production, mobilization and effectiveness in regenerative medicine and biology which is not anticipated, rendered obvious, suggested, or even implied by the prior art, either alone or in any combination thereof.

The present invention is a product and a method to augment the function or effectiveness of stem cells in vivo. It is also a laboratory method to evaluate the effectiveness of such augmentation towards an improvement in healing. The product is a suspension of protein nanometer-sized particles which will be administered intravenously to a patient who can be helped by improved stem cell function. An exemplary model of evaluation comprises of the creation of a non-lethal, non-painful and standardized burn on the skin, the administration of the to-be-evaluated stem-cell-augmenting agent, and the collection of efficacy data soon after administration of the stem-cell-augmentation agent.

To attain this, the present invention essentially comprises a product and method of using albumin nanoparticles for augmenting the function or effectiveness of stem cells or precursor cells in vivo. An albumin nanoparticle suspension containing submicron albumin spheres is prepared, with the albumin spheres being capable of augmenting a function and effectiveness of stem cells or precursor cells in vivo. A predetermined amount of the albumin nanoparticle suspension is administered to a patient before or after an onset of at least one condition. The condition is one that can benefit from a healing effect of the stem cells or precursor cells. A function of the stem cells or precursor cells are augmented or improved by the albumin spheres to repair cellular or tissue damage, resulting in decreasing mortality or morbidity of the patient. The albumin spheres can be bound with fibrinogen molecules in vitro or in vivo.

The patient is non-thrombocytopenic or thrombocytopenic.

There has thus been outlined, rather broadly, the more important features of the invention in order that the detailed description thereof that follows may be better understood and in order that the present contribution to the art may be better appreciated.

The invention may also include the stabilizing of blood vessels by attachment of the albumin spheres on appropriate receptors on an endothelium of the blood vessels.

The invention in addition or optionally may include the activating against extravasation of blood components from an intravascular compartment to an extravascular compartment, so that there is less free hemoglobin in the extravascular compartment.

Still in addition or optionally the invention may include the stimulating a conversion of the stem cells or precursor cells to mature cells.

There are, of course, additional features of the invention that will be described hereinafter and which will form the subject matter of the claims attached.

Numerous objects, features and advantages of the present invention will be readily apparent to those of ordinary skill in the art upon a reading of the following detailed description of presently preferred, but nonetheless illustrative, embodiments of the present invention when taken in conjunction with the accompanying drawings. In this respect, before explaining the current embodiment of the invention in detail, it is to be understood that the invention is not limited in its application to the details of construction and to the arrangements of the components set forth in the following description or illustrated in the drawings. The invention is capable of other embodiments and of being practiced and carried out in various ways. Also, it is to be understood that the phraseology and terminology employed herein are for the purpose of descriptions and should not be regarded as limiting.

As such, those skilled in the art will appreciate that the conception, upon which this disclosure is based, may readily be utilized as a basis for the designing of other structures, methods and systems for carrying out the several purposes of the present invention. It is important, therefore, that the claims be regarded as including such equivalent constructions insofar as they do not depart from the spirit and scope of the present invention.

It is therefore an object of the present invention to provide new and improved protein nanoparticles to augment the function or effectiveness of stem cells or precursor cells in vivo that has all of the advantages of the prior art and none of the disadvantages.

It is another object of the present invention to provide new and improved protein nanoparticles that may be easily and efficiently manufactured and marketed.

An even further object of the present invention is to provide new and improved protein nanoparticles that have a low cost of manufacture with regard to both materials and labor, and which accordingly is then susceptible of low prices of sale to the consuming public, thereby making such protein nanoparticles economically available to the buying public.

Still another object of the present invention is to provide new protein nanoparticles that provides in the products and methods of the prior art some of the advantages thereof, while simultaneously overcoming some of the disadvantages normally associated therewith.

These together with other objects of the invention, along with the various features of novelty that characterize the invention, are pointed out with particularity in the claims annexed to and forming a part of this disclosure. For a better understanding of the invention, its operating advantages and the specific objects attained by its uses, reference should be made to the accompanying drawings and descriptive matter in which there are illustrated embodiments of the invention.

