DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1, 3, 5, 7, 10-13, 16, 17, 19-21, 25, 276, 29, 30, 35, 37, 29, 30, 53-55, 57 and 68 are pending.
This application claims priority as a 371 filing of PCT/US2023/064831 filed 3/22/2023 which claims benefit of U.S. Provisional Patent Application No. 63/323280, filed March 24, 2022.
Information Disclosure Statement
Information disclosure statements filed 5/13/2025, 6/11/2025, 9/30/2025, 10/7/2025, 12/9/2025, 1/12/2026, 2/3/2026, 3/121/2026, 4/16/2026, 6/2/2026 and 7/7/2026 have been identified and the documents considered. The corresponding signed and initialed PTO Form 1449 has been mailed with this action. Initials indicate that the document has been considered even if the reference is lined through. In the case that only an English abstract was identified, this is indicated.
The IDS filed 5/14/2025 was filed with 900 plus documents. The actual IDS form could not be found in the filing. If applicants can provide a replacement, those references will be considered.
Drawings
Figures 1, 2A, 3A, 17 and 20B are objected to under 37 CFR 1.83(a) because they fail to show any details as described in the specification. Specifically, figure 1 has text that is illegible. Figure 2A, 3A, 17 and 20B are photos but it is not clear what the image is as each of them are actually just monotone in structure and color. Any structural detail that is essential for a proper understanding of the disclosed invention should be shown in the drawing. MPEP § 608.02(d). A proposed drawing correction or corrected drawings are required in reply to the Office action to avoid abandonment of the application. The objection to the drawings will not be held in abeyance.
Claim Objections
Claim 19 is objected to because of the following informalities: a verb is missing between “ligand” and “selective” in line 3. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 3, 5, 7, 10-13, 16, 17, 19-21, 25, 276, 29, 30, 35, 37, 29, 30, 53-55, 57 and 68 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 1, 3, 5, 7, 10-13, 16, 17, 19-21, 25, 276, 29, 30, 35, 37, 29, 30, 53-55, 57 and 68 are vague and indefinite in that the metes and bounds of the term “derived from” or “derivative of” are unclear. It is unclear the nature and number of steps required to obtained a “derivative” of. The term implies a number of different steps that may or may not result in a change in the functional characteristics of from the source that it is “derived from”.
Claim Rejections - 35 USC § 112, first paragraph
The following is a quotation of the first paragraph of 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 3, 5, 7, 10-13, 16, 17, 19-21, 25, 27, 29, 30, 35, 37, 29, 30, 53-55, 57 and 68 are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for preparing a platelet comprising exogenous mRNA or a megakaryocyte comprising exogenous mRNA or exogenous DNA, the method comprising transfecting in vitro the platelet or the megakaryocyte with lipid nanoparticles (LNP) comprising the mRNA or the DNA wherein platelets can be desialyated or modified to express heterologous target ligands, does not reasonably provide enablement for any other embodiment. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
The test of enablement is whether one skilled in the art could make and use the claimed invention from the disclosures in the patent coupled with information known in the art without undue experimentation (United States v. Telectronics, Inc., 8 USPQ2d 1217 (Fed. Cir. 1988)). Whether undue experimentation is required is not based on a single factor but is rather a conclusion reached by weighing many factors (See Ex parte Forman, 230 USPQ 546 (Bd. Pat. App. & Inter, 1986) and In re Wands, 8USPQ2d 1400 (Fed. Cir. 1988); these factors include the following:
1) Nature of invention. The instant claims are drawn to platelets comprising “exogenous material and/or a derivative thereof”, methods of making and methods of using to deliver the material to a recipient cell.
2) Scope of the invention. The scope of the invention is extremely broad in that the material is any and even derivatives, the platelet cell is any and the target recipient cell any as well as methods of delivering. Delivering only requires “contacting” the platelet to the recipient cell.
3) Number of working examples and guidance. The specification teaches methods of producing platelets comprising mRNA (example 1). In this method, isolated platelets were transfected with mRNA. These platelets were used to transduce human cells in vitro (example 2). To develop protein carrying platelets, megakaryocytes were transfected with lentivirus and then cultured to produce the platelets comprising expressed protein (example 3). In vivo delivery was performed with the mRNA containing platelets into mice by injection (example 4 and 5). The platelets localized in the liver. “Luminescent imaging revealed preferential luciferase mRNA transfer and expression in the liver of FRG mice (FIG. 8C).”
Platelets were loaded with DNA encoding Cre and GFP and platelets added to HEK293T cells with expression of GFP in the cells (example 6). Example 7 and 8 are directed to transduction of mRNA into isolated human and mouse platelets respectively. The platelets were subsequently incubated with human cells and transferred the contents. The disclosure teaches that “genes” were transferred from platelets to co-incubated cells (see ¶0109). While it is mRNA, the transfer appears to be of nucleic acids. Example 9 and 11 teach modifications of platelet to improve cell selectivity wherein the sialic acid was removed and modified surface glycans RCA-1 and MAL-1 were adhered. In example 14, anchoring ligands were linked with Biotin-WGA to render biotin conjugated ligands or transducing of megakaryocytes with ligand coding sequences.
Applicants propose in example 10 use of the platelets loaded with CRISPR-Cas9 to be used to treat disorders such as Tyrosinemia type 1 and Ornithine transcarbamylase (OTC). As proof of principle, platelets were transfected with RNA encoding the RNP complex comprising Cas9, gRNA, crRNA and tracrRNA was introduced into the platelets and incubated with cultured iPSC cells and fluorescence confirmed the expression. The transfer was dose dependent based upon the mount of RNP. However, no confirmation of the results in vivo were shown or knockout of genes. Example 12 identifies “possible” anchoring proteins” and identified CD61 by detection of an HA epitope. Analysis (example 15) demonstrated that the molecules move from platelets by exocytosis. Example 16 follows platelet mitochondria transport to co-incubated cells. Example 17 determines the ability to use CD34+ cells as a source for platelets and megakaryocytes.
4) State of the art. The method of the claims is drawn to 1) preparing platelets with exogenous material, 2) the platelets and 3) methods of delivering exogenous material with the platelets. Using cells for therapies has provided an ideal delivery sources to protect cargo. Platelets are especially attractive, (it is noted that this publication is post-filing Islam et al, 2025, pages 1-11).
The type of cell used for developing cell therapies depends on the disease being treated and the desired function of the therapeutic cell17. Platelets possess many unique characteristics that make them attractive candidates for the in vivo delivery of natural and synthetic payloads. They have an extensive circulation range in the body, accumulate at sites of injury, and naturally release biomolecules into the extracellular fluid upon activation18–21. In addition, platelets are anucleate cells, making them ideal therapeutic cells because they present no concerns about unwanted integration of foreign DNAs into the host genome. Therefore, platelets are well equipped for mRNA and protein delivery.
As to means of transforming the cells, LNP have become the method that transforms without altering the differentiation state of the cells (see Leung et al, J Thromb Haemost.2025;23:306–313, especially page 306).
5) Unpredictability of the art. Novakowski et al teach motivation to use platelets (Scientific Reports, 2019, pages 1-11, see page 1).
Platelets are natural delivery vehicles within the blood, carrying and releasing their contents at sites of vasculature damage. Investigating the biology of platelets, and modifying them for new therapeutic uses, is limited by a lack of methods for efficiently transfecting these cells.
However, at that time, Novakowski et al page 8.
Since translation of the delivered mRNA was not observed, additional characterization of the RNA following uptake into the platelets is needed. It is unclear whether the absence of translation was due to degradation of the mRNA, differences in how translation is regulated in platelets compared to other mammalian cells, or whether the mRNA was not delivered to the appropriate location in the platelet.
There is no known methods of contacting a fluid, a salt, a nutrient, a sugar, a small molecule, a lipid, an organelle, an endosome, a vesicle, a protein, a polypeptide, a peptide or an antibody or combinations including these into a platelet. The art and the disclosure teach transfection the art of developing platelets as carriers of exogenous material or derivatives was limited to transfection of the cells with mRNA,
(Novakowski et al, page 1)Since platelets are anucleate, modifying protein expression within the mature platelet requires delivery of RNA-based agents.
Because platelets are anucleate (lack a nucleus) they cannot be transfected with DNA as there is no machinery to transcribe the DNA. However, megakaryocytes can be transfected with DNA (Islam et al, Communications Biology, 2025, pages 1-11, see page 5).
Platelets are anucleate blood cells that circulate throughout the body with diverse roles in hemostasis, wound healing, angiogenesis ,inflammation, and clot formation. They are naturally filled with secretory granules that store large amounts of bioactive proteins and are released upon activation.
But, this is not the same as contacting platelets with a fluid, a salt, a nutrient, a sugar, a small molecule, a lipid, an organelle, a mitochondrion, an endosome, a vesicle, a protein, a polypeptide, a peptide, an antibody, a nucleic acid, or any combination thereof. The ability to contact the platelet is limited to an RNA. Applicants have expanded upon this and shown that platelet mitochondria transfer into cells co-incubated with the platelets- however this is not exogenous material. Hence, to the first goal, there is no evidence that the large genus of exogenous materials and derivatives can be contacted to platelets (a).
As to contacting megakaryocytes (b), megakaryocytes have been shown in the instant disclosure and the art to be transfected with usually DNA that upon differentiation into platelets leads to expression wherein the expressed product appears in the platelet (Islam, page 5, disclosure ¶0154). But, no evidence of the protein contacting either the platelet or the megakaryocyte has been shown in either the art or the platelet. Complicating this is that the use of megakaryocytes is not a starting cell that is predictable. Islam et al, page 2 teach,
Platelets are released from MKs, a rare cell population that accounts for less than 0.1% of nucleated cells in the bone marrow. Due to this low number and their inability to divide, harvesting and genetically modifying MKs is impractical.
Liu et al (Front. Cell Dev. Biol, 2021) detail the obstacles that have hindered the development of megakaryocytes and platelets
(page 1) limited success has been achieved in obtaining truly mature and functional platelets in vitro, indicating the studies of platelets fall behind those of other blood cell types. This is possibly because megakaryocytes, which produce platelets, are very rare in blood and marrow.
This is in part because of the limited success in developing functional platelets from in vitro culture (reviewed in Liu and see page 2),
However, only limited success has been achieved so far in producing truly mature and functional platelets from these in vitro cultures. With various differentiation methods, platelets could be generated, and they are phenotypically similar to plasma-derived platelets, however, the in vivo functions of these platelets were either not tested or not as good as plasma-derived platelets. More importantly, their lifespan is much shorter than that of primary platelets. Therefore, platelet differentiation protocols require further optimization.
At the heart is the lack of characterization of the biology and development of megakaryocytes (Liu, page 8-9),
In summary, although significant progress has been made toward the in vitro generation of platelets from HSCs, hPSCs, fibroblasts, and adipose-derived cells, with various stem cells as the most promising starting materials, the current issues of scalability, cost, duration of differentiation, and cell functionality are all hurdles to applying these in vitro generated platelets into clinical applications. A better understanding of the biology and development of megakaryocytes will hopefully address some of these issues and greatly facilitate in vitro platelet biogenesis on a large scale for transfusion medicine.
This lack of characterization also means that while megakaryocytes can be transfected to comprise the mRNA or DNA, the process is still so nascent a reliable clinical product is not predictable. Leung et al, post filing details a process to produce transfected cells that are not differentiation and function impaired (page 311).
A concern with transfection methods that rely on DNA or viral vectors is transgene protein expression early in the differentiation cycle, which can affect cellular maturation and other downstream processes, as well as low transduction efficiencies [27]. A potential benefit of transfecting with LNPs is the ability to transfect at later stages of differentiation, mitigating impaired differentiation or cell function.
Furthermore, the step of “allowing” is broad and undefined. The steps of allowing appear to be a consideration of the practitioner without guidance or steps to do so. Islam et al teach that this is not a step of allowing but a step of maturation of the megakaryocytes and then platelet activation (Islam page 4).
A characteristic of achieving functional platelets is their ability to activate when exposed to thrombin and ADP, which initiates platelets to express a large amount of P-selectin.
It is notable that the activation of in vitro-produced platelets takes longer than what is observed in vivo, likely because the in vitro conditions lack dynamic flow and other components that naturally trigger platelet activation following wounding in vivo.
Considering the method of delivering the exogenous material and/or derivative to a recipient cell (claim 29 and 30), applicants have only shown this in vitro and in mouse models. It is not clear that the method of transfer can happen in vivo. And to that end, the use of the delivery method in vivo to transfer or deliver the material to a recipient cell must meet a goal which appears elaborated on in claims 54, 55 and 57 to be to induce immune protection and editing genes. As to the latter, it is not described what exogenous material can be presented in order to induce immune protection against virus, bacteria or protozoan in a subject. As to gene editing, the description of this method is limited to platelets comprising CRISPR/Cas9 (figure 13) . A variety of disorders are listed as potential targets.
In some embodiments, the disease is tyrosinemia type 1 and the modification to the genome comprises a modification to the fumarylacetoacetate hydrolase (Fah) gene. In some embodiments, the disease is ornithine transcarbamylase deficiency and the modification to the genome comprises a modification to the ornithine transcarbamylase (OTC) gene. In some embodiments, the disease is citrullinemia type 1 (CTLN1) and the modification to the genome comprises a modification to the argininosuccinate synthetase (ASS1). In some embodiments, the disease is adult-onset type II citrullinemia (CTLN2) and the modification to the genome comprises a modification to the citrin (solute carrier family 25, member 13; SLC25A13) gene.
The assertions are prophetic. The issues above highlight the nascent state of the art with which the ability to use these cells for use in immune protection and gene editing and to transfer such a large genus of exogenous material and derivatives face. But, reviewing what is known in the art for in vivo use, it is clear the art is nascent. While the opportunities with platelets are promising, the practical use has not been explored (see Wang, Nano Today, 2021, pages 1-9, see page 6 and page 8)
Although a number of treatment strategies have been put forward, tumor immunotherapy in the clinic is only achieving limited progress in recent years. It is generally recognized that platelets participate widely in immune responses and interact with other bio- particulates [68]. However, treatment approaches leveraging the interaction between platelets and other cells such as neutrophils, DCs and CTCs have seldom been explored.
Like any other newborn treatment modalities, several factors from the perspectives of platelets’ physiological properties and manufacturing processes should be taken into account to expedite the clinical translation of engineered platelets. Firstly, although platelets transfusion has been proved safe in the clinic, it sometimes brings about risks of adverse reactions such as thrombosis, especially in patients with underlying conditions [75]. In this regard, deeper understanding of the roles of platelets in different diseases is essential for the clinical translation of the engineered platelets. Be sides, personalized therapy that allow adjusting and tailoring the dose and dose regimen of the engineered platelets according to the individual patient’s needs will help avoid severe adverse reactions.
Like any other newborn treatment modalities, several factors from the perspectives of platelets’ physiological properties and manufacturing processes should be taken into account to expedite the clinical translation of engineered platelets. Firstly, although platelets transfusion has been proved safe in the clinic, it sometimes brings about risks of adverse reactions such as thrombosis, especially in patients with underlying conditions [75]. In this regard, deeper understanding of the roles of platelets in different diseases is essential for the clinical translation of the engineered platelets. Be sides, personalized therapy that allow adjusting and tailoring the dose and dose regimen of the engineered platelets according to the individual patient’s needs will help avoid severe adverse reactions.
“It is the specification, not the knowledge of one skilled in the art, that must supply the novel aspects of an invention in order to constitute adequate enablement.” (quoting Genentech, Inc. v. Novo Nordisk A/S, 108 F.3d 1361, 1366 (Fed. Cir. 1997))).
While the results presented in the art do not necessarily preclude Applicant's hypothesis, they certainly fail to support it. This is exacerbated by the art which teaches, Consequently, the prior art (and post-filing art) when combined with the lack of any disclosed direct experimental test of Applicant's hypothesis, shows that one of skill in the art at the time the invention was made would have had no basis to reasonably predict or conclude the claimed invention would succeed. There is no evidence that the specification offers a solution to the problem set forth in the specification. Though not controlling, the lack of working examples, is, nevertheless, a factor to be considered in a case involving both physiological activity and an undeveloped art. When a patent applicant chooses to forego exemplification and bases utility on broad terminology and general allegations, he runs the risk that unless one with ordinary skill in the art would accept the allegations as obviously valid and correct, the PTO may, properly, ask for evidence to substantiate them. Ex parte Sudilovsky, 21 USPQ2d 1702, 1705 (BPAI 1991); In re Novak, 134 USPA 335 (CCPA 1962); In re Fouche, 169 USPQ 429 (CCPA 1971).
6) Undue experimentation. The claims have been evaluated in light of the art at the time of filing and found not to be commensurate in scope with the specification. MPEP 2164.05 teaches, “However, the examiner should carefully compare the steps, materials, and conditions used in the experiments of the declaration with those disclosed in the application to make sure that they are commensurate in scope; i.e., that the experiments used the guidance in the specification as filed and what was well known to one of skill in the art. Such a showing also must be commensurate with the scope of the claimed invention, i.e., must bear a reasonable correlation to the scope of the claimed invention. The invention recites use of a broad group of sequence. Given the unpredictability of the art, the poorly developed state of the art with regard to predicting the structural/ functional characteristics of engineered platelets and megakaryocytes, the lack of adequate working examples and the lack of guidance provided by applicants, the skilled artisan would have to have conducted undue, unpredictable experimentation to practice the claimed invention.”
Consequently, the prior art (and post-filing art) when combined with the lack of any disclosed direct experimental test of Applicant's hypothesis, shows that one of skill in the art at the time the invention was made would have had no basis to reasonably predict or conclude the claimed sequences could be identified given the lack of details necessary to identify those meeting the necessary functions. Though not controlling, the lack of working examples, is, nevertheless, a factor to be considered in a case involving both physiological activity and an undeveloped art. When a patent applicant chooses to forego exemplification and bases utility on broad terminology and general allegations, he runs the risk that unless one with ordinary skill in the art would accept the allegations as obviously valid and correct, the PTO may, properly, ask for evidence to substantiate them. Ex parte Sudilovsky, 21 USPQ2d 1702, 1705 (BPAI 1991); In re Novak, 134 USPA 335 (CCPA 1962); In re Fouche, 169 USPQ 429 (CCPA 1971).
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1, 3, 5, 11, 12, 13, 25, 29, 30, 53 and 68 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Risitano (Blood, 2012, pages 6288-6295).
Risitano et al teach transfection of megakaryocytes (see page 6289, col 1) with GFP and BrUTP using lipofectin thus meeting claims 1, 3, 5, 11, 12. The megakaryocytes were stimulated and platelets comprising the protein produced (see page 6289, col 1). The platelets transfer the contents to recipient cells thus meeting claims 13, 25, 29, 30, 53 and 68.
Claims 1, 2, 3, 5, 10 and 53 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Novakowski et al (Scientific Reports, 2019, pages 1-11).
Novakowski et al teach platelets comprising mRNA wherein the platelets are prepared by contacting the platelets with mRNA (page 2). This meets the limitations of claims 1, 2, 3, 5, 10.
Claims 1, 3, 5, 10-13, 16, 25, 27, 53, 54 and 68 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Woods et al (Molecular Therapy: Nucleic Acids, 8 March 2022, pages 774-786) as evidenced by Kaur et al (Antiviral Res, 2026, pages 1-6).
Woods et al teach transfection of megakaryocytes with lentivirus (DNA) encoding cell surface ligands (see figure 1). Platelets were derived from the transfected cells and protein expressed (see page 778, col 1). Similarly, IFN which is used to treat measles (this is designed to modulate immune activity as evidenced by Kaur et al page 4) is transfected into the megakaryocytes and then detected in the platelets (see e.g. page 782, col 2 and page 784, col 2).
The megakaryocytes are treated with stimulator hTHPO (thrombopoietin) and platelets activated with thrombin (see page 784, col 2)
Claims 1, 3, 5, 7, 10-13, 16, 19, 21, 27, 29, 30, 35, 37, 29, 30, 53-55 and 68 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Patterson et al (US 20220251165).
Patterson et al teach engineered platelets with receptors for desired target specificity wherein the platelets comprise cargo (see abstract). The cargo can be DNA or RNA encoding the receptor and a second sequence (see page 3, col 2, ¶0015). The sequence can encode CRISPR (see e.g. ¶0017). Platelets were obtained from megakaryocytes engineered to comprise the cargo by viral transduction (see e.g. ¶0018,0044 and 0321) and the platelets released following activation (see abstract). This includes contact with ADP or collagen (see e.g. ¶0320)
The receptor comprises a transmembrane domain and a heterologous targeting domain (see e.g. ¶0013). The Tm can be from GPVI (see e.g. ¶0077).
The cargo is in vitro delivered to a recipient target cell (see e.g. ¶0018). The compounds are part of pharmaceutical compositions (see e.g. ¶0226).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1, 3, 5, 7, 10-13, 16, 17, 19-21, 25, 27, 29, 30, 35, 37, 29, 30, 53-55, 57 and 68 are rejected under 35 U.S.C. 103 as being unpatentable over Patterson et al (US 20220251165) or Novakowski et al (Scientific Reports, 2019, pages 1-11) or Woods et al (Molecular Therapy: Nucleic Acids, 8 March 2022, pages 774-786) or Risitano (Blood, 2012, pages 6288-6295) in view of Tao et al (Journal of Hematology & Oncology 2017 pages 1-4) and de Bruin et al (Transfusion, 2019, pages 2964-2973) and Zhang et al (US 20200190487).
Tao et al teach improvement of therapies following desialyation and use of sialidase inhibitors as beneficial in therapeutics associated with platelets (see e.g. page 3).
De Bruin teaches monitoring platelets therapeutically have involved biotin labeling with streptavidin (page 2964 and 2969).
This method is used to evaluate the effects of donor, recipient, and PLT storage factors on PLT survival after transfusion in the recipient. Also, radiolabeling is required by the Food and Drug Administration (FDA) to analyze the effect of altered PLT storage protocols, such as new additive solutions (ASs) and pathogen reduction technologies. However, radiolabeling exposes the recipient to potential harmful ionization.
BioPLT can be used to evaluate the in vivo effect of new ASs, donor variability, and the effect of transfusion in various patient categories.
The major advantage of biotin is that it enables in vivo tracing of transfused PLTs without exposing the recipient to radiation.
Finally, CRISPR/Cas9 treatment of disorders such as tyrosinemia was well known at the time of filing. Zhang teaches methods and means to treat tyrosinemia with CRISPR (see Table 9 and ¶0943).
Based on such teachings, it would have prima facie been obvious to one of ordinary skill in the art at the time the invention was made to incorporate the improvements taught by Tao et al, de Bruin et al and Zhang et al. Such a modification would have resulted in methods encompassed by claims 17, 20 and 57. As noted above: 1) each of Patterson, Novakowski, Risitano and Woods teach engineering of platelets by introducing DNA into megakaryocytes or mRNA into platelets; 2) Tao improves platelets engineering by desialyation 3) de Bruin teaches labeling methods will benefit developing clinical use and 4) Zhang teaches targets and means of treating other disorders such as tyrosinemia. Thus, a person of ordinary skill in the art, absent evidence to the contrary, would have reasonably expected that the additional modifications would bring platelets closer to clinical use.
Conclusion
No claims allowed.
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/MARIA MARVICH/Primary Examiner, Art Unit 1634
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