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 .
Applicant’s response to restriction requirement filed on December 23, 2025 have been received and entered. Claims 1-41 are pending in the instant application.
Election/Restrictions
Applicant’s election without traverse of claims 1-27 (group I) in the reply filed on December 23, 2025 is acknowledged.
Claims 28-41 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention there being no allowable generic or linking claim. Election was made without traverse in the reply filed on December 23, 2025.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 12/29/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Claims 1-27 are under consideration.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-27 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
In determining whether Applicant’s claims are enabled, it must be found that one of skill in the art at the time of invention by applicant would not have had to perform “undue experimentation” to make and/or use the invention claimed. Such a determination is not a simple factual consideration, but is a conclusion reached by weighing at least eight factors as set forth in In re Wands, 858 F.2d at 737, 8 USPQ 1400, 2d at 1404. Such factors are: (1) The breadth of the claims; (2) The nature of the invention; (3) The state of the art; (4) The level of one of ordinary skill in the art; (5) The level of predictability in the art; (6) The amount of direction and guidance provided by Applicant; (7) The existence of working examples; and (8) The quantity of experimentation needed to make and/or use the invention.
The office has analyzed the specification in direct accordance to the factors outlines in In re Wands. MPEP 2164.04 states: “[W]hile the analysis and conclusion of a lack of enablement are based on factors discussed in MPEP 2164.01(a) and the evidence as whole, it is not necessary to discuss each factor in written enablement rejection.” These factors will be analyzed, in turn, to demonstrate that one of ordinary skill in the art would have had to perform “undue experimentation” to make and/or use the invention and therefore, applicant’s claims are not enabled.
Nature of the Invention:
The claims are directed to a method of producing and using genetically modified (GM) pig organs for xenotransplantation that are personalized to a specific organ recipient and that do not require chronic immunosuppression following xenotransplantation, the method comprising:
transferring cells and factors of the organ recipient into a GM donor pig fetus in utero, wherein, prior to transferring, the cells and factors of the organ recipient (i) are collected from blood and bone marrow of the organ recipient and (ii) are partially depleted of CD4+ and CD8+ T cells,
wherein the transferring is accomplished by injecting the partially depleted cells and factors of the organ recipient into the abdominal cavity of the GM donor pig fetus, wherein the donor pig fetus is a genetically modified donor pig fetus being gestated in a genetically modified parent pig, wherein the genetic modifications of the donor pig fetus are the same as the genetic modifications of the parent pig, wherein the genetic modifications are limited to three gene knockouts and, optionally, three human transgenes, and wherein the GM donor pig fetus is the same sex and compatible blood group as the organ recipient;
transferring, after completion of gestation of the GM donor pig fetus and delivery and some development of the resultant GM donor pig, the organ recipient's cells and factors from the GM donor pig back into the organ recipient,
wherein, prior to transferring, the cells and factors of the GM donor pig
are collected from one or more of blood, bone marrow, spleen, cord blood and lymph nodes of the GM donor pig,
are depleted of donor pig cells, and
are subject to enrichment, expansion, and/or purification for the organ recipient’s cells selected from the group consisting of foxP3+CD4+CD3+CD25+ natural T regulatory cells, adaptive CD4+CD49b+LAG3+CD226+ regulatory Tr1 cells, CD4+CD25-CD69+foxP3-LAP+ (TGFβ-producing type 3 helper T cells), and organ recipient PD-L1 human dendritic cells,
wherein, 5 to 9 days prior to transferring, the organ recipient is administered Cyclophosphamide +/- Fludarabine and
(c) transplanting, 5 to 9 days following the transferring of the organ recipient’s cells and factors from the GM donor pig back into the organ recipient, an organ from the same GM donor pig into the organ recipient.
Dependent claim limits the organ recipient is a subject having been diagnosed as having a disease or disorder selected from the group consisting of heart diseases, kidney diseases, liver diseases, lung diseases, eye diseases, pancreatic diseases, and congenital diseases of one or more organs and wherein the organ from the GM donor pig comprises all or part of a heart, bone, liver, lung, kidney, pancreas, eye, or intestine. Dependent claims further limit the method of claim 1, wherein the pig organ after transplanting in the recipient grows less than 5%, 10%, 15%, or 15% in volume.
Claims 16 and 17 further limits the genetic modifications to the donor pigs are limited to fewer that seven genetic modifications and genetic modifications are made using somatic Cell Nuclear Transfer (SCNT).
Breadth of the claims:
The breadth of the claimed invention encompasses
using donor pig fetus that is a genetically modified donor pig fetus being gestated in a genetically modified parent pig, wherein the genetic modifications are limited to any of the three known or yet to identified gene knockouts and, optionally, any of the three known or yet to identified human transgenes ;
transferring any cells and any factors that are collected from blood and bone marrow of the organ recipient that are partially depleted of CD4+ and CD8+ T cells into a GM donor pig fetus in utero;
after completion of gestation and some unknown extent, type or stage development of the resultant GM donor pig, the organ recipient's cells are selected from the group consisting of foxP3+CD4+CD3+CD25+ natural T regulatory cells, adaptive CD4+CD49b+LAG3+CD226+ regulatory Tr1 cells, CD4+CD25-CD69+foxP3-LAP+ (TGFß-producing type 3 helper T cells), and organ recipient PD-L1 human dendritic cells and known or unknow factors from the GM donor pig back into the organ recipient; and
transplanting, 5 to 9 days following the transferring of the organ recipient's cells and know or yet to be identified factors from the GM donor pig back into the organ recipient, an organ from the same GM donor pig into the organ recipient for xenotransplantation that are personalized to the specific organ recipient of any species that do not require chronic immunosuppression.
The specification fails to provide any evidence that such a xenotransplantation method would overcome the art recognized unpredictability. The disclosure provided by the applicant, in view of prior art, must encompass a wide area of knowledge to a reasonably comprehensive extent. In other word each of these, aspect must be shown to a reasonable extent so that one of the ordinary skills in the art would be able to practice the invention without any undue burden being on such Artisan.
Guidance of the Specification and The Existence of Working Examples:
The specification as filed provides a general description of conditions GM pig fetuses with specific cells and factors collected from the future organ recipient to make the pigs resulting from the treated fetuses more matched to the organ recipient, appearing more like self-tissue to the organ recipient. The specification contemplates this would greatly reduce the anti-transplant reaction of the recipient and paves the way for xenotransplantation without the need for chronic immunosuppression (para. 8 of the specification). The specification prophetically contemplates the method also conditions the future organ recipient with specific recipient's cells and factors conditioned and collected back from the recipient-matched pig (the future organ donor) to prepare the organ recipient's immune system prior to organ transplantation. This completes the reduction of the anti-transplant reaction of the recipient allowing xenotransplantation without the need for chronic immunosuppression (see para. 8 of the specification). Figure 1 of the specification teaches schematic of Yucatan weight-age chart showing the pig weight varies no more than one standard deviation away from the average over time. Figure 2 is a schematic diagram showing the exemplary method of generating genetically modified pigs including GGTA−/−, CMAH−/−, B4GALNT2−/−, Xeno 3 pigs and GGTA−/−, CMAH−/−, B4GALNT2−/−, hTBM/hCD46/hCD55 Xeno 6 pigs. Figure 3 depicts a schematic diagram showing the transfer of cells and factors from an organ recipient to a fetal donor pig, where the fetal donor pig later serves as a source of both tolerance-inducing immunosuppressive cells and factors and a transplant organ. The specification prophetically contemplates using the cell therapy between human recipients and pig donors (transferring lymphocytes, stem cells and factors from the organ recipient and having those cells populate the GM donor fetus organs and then after delivery of the GM donor piglet and expansion and purification of these recipient's lymphocytes and stem cells, these cells are transferred back to the organ recipient prior to organ transplantation) allows a more humanized pig organ to be transplanted, as the pig organ has been repopulated with the recipient cells, such that the organ recipient develops tolerance and avoids the need for chronic immunosuppression (see para. 132). . Remaining specification discloses definition of terms, general description of biological method, method of xenotransplant. Furthermore, it is noted that application states recipient subjects are typically, the subject is a human, such a human patient in need of treatment for a disease or disorder and organ failure. In some forms, the recipient has been identified as having, or as being at risk of having a disease. The disease can be chronic or acute. Exemplary diseases include congenital diseases of one or more organs or tissues. For example, in some forms, the recipient is a subject having a disease that causes end-stage failure of an organ, necessitating transplantation (see para. 188). In summary, the specification does not provide any specific guidance for the claimed invention because the specification as filed does not teach how human immune cells would respond to pig signal, how human cells would interact with the pig tissue following gene edit in the pig, how the microenvironment in gene edit pig would affect the human cells. Given this lack of reasonable predictability in specification and the art, the Artisan would require a large amount of information from Applicant’s examples to provide the guidance to provide reasonable predictability. An artisan would have to carry out extensive experimentation to make use the invention, without reasonable expectation of success.
State of the Art and Predictability of the Art and the Amount of Experimentation Necessary:
The claimed method encompasses transfer of a human recipient's cells that can further differentiate into regulatory lymphocytes, into a genetically modified pig fetus in which those human cells will eventually differentiate and mature into one or more of the following cells: foxP3+CD4+CD3+CO25+ natural T regulatory cells, adaptive CD4+CD49b+LAG3+CD226+ regulatory Tri cells, CD4+CD25-CD69+foxP3-LAP+ (TGFl3-producing type 3 helper T cells), and PO-L 1 human dendritic cells. Those cells are then isolated/purified/expanded postnatally and transferred back to the human recipient, in order to elicit immuno-tolerance against a pig organ that is later transplanted from the pig formerly used in the fetal stage, into the human recipient. In the instant case, neither specification nor prior art provides and evidence and/or example that such a transplantation method would work.
The claimed method encompasses use of three gene knock-outs and optionally three human transgenes, without specifying any of those genetic modifications, resulting in a myriad of possibilities. The art teaches substantial knowledge gaps in understanding of adaptive pig-to-human immunity (see page 207, col. 1, para. 3, Schmauch et al Nature, 2026, 650, 205-217). The multi omics data from a genetically modified pig (GGTA KO) shows a complex immune response prior to tissue rejection. The results concludes that a complex network of interactions among diverse infiltrating human immune populations from both the innate and adaptive compartments, interact not only with each other but also with resident pig immune cells and injured tubular cells. This multifaceted immune and inflammatory response, evident in both human and pig cells, was detected before histological sign of antibody mediated response (AMR) (See page 214, col. 1, para. 2). This study provides an extensive resource for understanding the dynamics and importance of inflammatory and tissue-repair archetypes, interactions with resident pig immune cells and infiltrating human immune cells comprising both the innate and adaptive immune systems of the recipient (See page 216, col. 1, para. 2). This study is further supported by the teaching of Pan (Med, 2024, 5, 1016-1029) who performed single-cell RNA sequencing and longitudinal RNA-seq analyses of the xenotransplantation using porcine of aGAL-KO kidney to dissect xenotransplantation-associated cellular dynamics and xenograft-recipient interactions (abstract). It is noted that while no hyperacute rejection signal was observed through standard histological analyses, results provide strong evidence that both kidney xenografts presented early signs of an AbMR phenotype at 54 h pXTx. The evidence obtained in this study includes (1) the infiltration and the activation of human macrophage and NK cells in the xenografts (Figures 2 and 3), (2) the detection of AbMR-associated marker gene expression through time-resolved RNA-seq of xenograft biopsies (Figure 3), (3) activation of endothelial cells in xenografts (Figure 3), and (4) the holistic xenograft tissue damage signals (Figure 4). Notably, these expression changes were not observed in the contralateral untransplanted kidneys that also experienced ischemia, indicating that the observed evidence reflects xeno transplantation-induced responses but not ischemic injury-induced effects. (See Med page 1025, para. 2). The breadth of instant claim recites using cells and factors of the organ recipient of any species (human) from blood and bone marrow for transplanting into a genetically modified donor pig fetus of any species, wherein the genetic modifications are limited to three known or yet to identified gene knockouts and, optionally, any three human transgenes. The claims as presented is not enabled because transgenic knock out of gene does not eliminate the immune response. In the instant specification provide prophetic guidance with respect to gene knock out of GGTA1, CMAH and B4GALNT2 in a Yucatan miniature pig (see pages 12-14 of the specification). However, Wang (J Biomed Res, 2018 Jul 11;33(4):235-243) reported “Human serum IgG and IgM binding decreased in some triple knock out (TKO) porcine tissues of heart, lung, and kidney, show that eliminating the reactivity of preformed human antibodies with those tissues can be achieved by gene targeting. However, comparable levels of IgG and IgM binding were observed in the liver, spleen, and pancreas of TKO and WT pig, suggesting that other immunoreactive xenoantigens such as swine leukocyte antigens (SLA) maybe the dominant xenoantigens in those organs (see page 242, col. 1, last para.). In fact, Shim (Transgenic Res 2021;30(5):619–634 ) teaches genetic modification of donor pigs for xenotransplantation should be tailored to the target organ and silencing of additional genes such s CMAH or A3GALT2 based on GTKO might not be essential in Yucatan miniature pigs (see abstract). These results clearly show even a specific GGTA1, CMAH and B4GALNT2 in a Yucatan miniature pig reduces antigen induced rejection but does not fully eliminate immune reactivity (emphasis added). The specification has not provided any specific guidance to use any genetically modified pig that removes all known or yet to be determined immune target and may require additional gene knockout. There is no evidence on record that the triple knockout pig model that is necessary to reduce immune response is sufficient and predictable for xenograft survival. An artisan would have to perform undue experimentation to first identify genes that need to be edited and then determine resulting knockout pig would fully eliminate immune reactivity for xenograft survival, without reasonable expectation of success.
Claims embrace delivering cells and factors of the organ recipient that are collected from blood and bone marrow of the organ recipient into a genetically modified donor pig to collect resulting from GM donor pig the organ recipient cells and factor from the DM donor pig back into the organ recipient (eg human). The specification prophetically contemplates transfer of a human recipient's cells (such as hematopoietic stem cells or mesenchymal stem cells) and know or yet to be identified factors, that can further differentiate into regulatory lymphocytes, into a genetically modified pig fetus in which those human cells would eventually differentiate and mature into one or more of the following cells: foxP3+CD4+CD3+CD25+ natural T regulatory cells, adaptive CD4+CD49b+LAG3+CD226+ regulatory Tri cells, CD4+CD25-CD69+foxP3-LAP+ (TGFj3-producing type 3 helper T cells), and PD-L 1 human dendritic cells. These cells are then isolated/purified/expanded postnatally and transferred back to the human recipient, in order to exert immuno-tolerance against a pig organ that is later transplanted from the pig formerly used in the fetal stage, into the human recipient. The specification provides prophetic guidance of factors and cells of the organ recipient that could be repopulate mature T regulatory cells for eliciting immune tolerance as embraced by the breadth of the claim. Prior to instant invention, Shim (Xenotransplantation 2016: 23: 300-309) states “a well expanded regulatory T cells did not attain long term tolerance and was rejected by activated immune cells, particularly T cells following withdrawal of immunosuppressive drug” (see abstract, page 307, col. 1, last para.). The teaching of Shim clearly shows unpredictability in transplanting T reg cells to develop tolerance in xenotransplantation. Kalscheuer et al (The Journal of Immunology, 2014, 192: 3442–3450) reported suboptimal maintenance and homeostasis of human T cells generated in a porcine thymus graft (see fig. 6). The study shows human T cells generated in porcine thymus grafts are functional, self-tolerant, and specifically tolerant toward the porcine donor. Functional Tregs develop normally in the porcine thymus contribute to tolerance. However, human T cells generated in porcine thymus grafts demonstrate immune defects might be attributable to suboptimal post thymic interactions with human APCs following positive selection on porcine MHC (See page 3450, col. 2, last para.) .Porret ((2025) Front. Immunol. 16:1685682. 1-8) reported Treg therapy involve significant challenge as it is a complex area that is still under evaluation in allotransplantation. This the unique immunological context of xenotransplantation presents an opportunity to study Tregs ability to home to the graft ultimately reducing the burden of immunosuppression. Their efficacy should be confirmed in NHP xenotransplantation models, including the use of repeated infusions, ideally from allogeneic sources (see page 7, col. 1, last para). In the instant case, the specification fails to address art recognized unpredictability in proliferating and/or enriching organ recipient cells into foxP3+CD4+CD3+CD25+ natural T regulatory cells, adaptive CD4+CD49b+LAG3+CD226+ regulatory Tri cells, CD4+CD25-CD69+foxP3-LAP+ (TGFj3-producing type 3 helper T cells), and PD-L 1 human dendritic cells to make and use to develop immune tolerance to organ from donor pig. One of skill in the art would have to perform undue experimentation to make and use the invention, without reasonable expectation of success.
In conclusion, in view of breadth of the claims and absence of a strong showing by Applicant, in the way of specific guidance and direction, and/or working examples demonstrating the same, such invention as claimed by Applicant is not enabled for the claimed inventions. An artisan of skill would have required undue experimentation to practice the invention, without reasonable expectation of success as supported by the observations in the art record.
Claim Rejections - 35 USC § 112-written description
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-27 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claim embraces a genus of cell cells and factors of the organ recipient of any species that are collected from blood and bone marrow of the organ recipient and are partially depleted of CD4+ and CD8+ T cells transplanted to triple KO pig to produce GM donor pig to isolate blood, bone marrow, spleen. Cord blood and lymph node to enrich, expand and/or purify for the cells selected from the group consisting of foxP3+CD4+CD3+CD25+ natural T regulatory cells, adaptive CD4+CD49b+LAG3+CD226+ regulatory Tr1 cells, CD4+CD25-CD69+foxP3-LAP+ (TGFβ-producing type 3 helper T cells), and organ recipient PD-L1 human dendritic cells.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111 (Fed. Cir. 1991), clearly states that ''applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed.'' Vas-cath Inc. v. Mahurkar, 19USPQ2d at 1 117. The specification does not ''clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.'' Vas-cath Inc. v. Mahurkar, 19USPQ2d at 1116.
The cells and factors of the organ recipient of any species encompassed within the genus of cells and factor eventually resulting in one or more cells selected from the group consisting of foxP3+CD4+CD3+CD25+ natural T regulatory cells, adaptive CD4+CD49b+LAG3+CD226+ regulatory Tr1 cells, CD4+CD25-CD69+foxP3-LAP+ (TGFβ-producing type 3 helper T cells), and organ recipient PD-L1 human dendritic cells have not been disclosed. Based upon the prior art there is expected to be sequence variation among the different species of cell type and factors from the blood and bone marrow.
The specification prophetically contemplates inducing tolerance is when the GM organ graft is populated by recipient's lymphocytes, stem cells, and factors, which are introduced within a donor animal when it is in a form of a developing pig fetus. During this time the lymphocytes and stem cells differentiate and mature into regulatory cells, suppressor cells, select B cells, and antibodies which after delivery of the pig fetus, are enriched and expanded ex-vivo (see page 26 of the specification). the cells could be incubated with recombinant human GM-CSF, IL1, IL3, IL6, IL7, growth hormone, or insulin-like growth factors, etc. or a combination of factors (see page 29 of the specification). The art teaches BM-Treg and splenic Treg are phenotypically and functionally distinct and influenced by niche-specific mediators that selectively support their respective Treg populations (see abstract, Nicholls et al Frontiers in Cell and Developmental Biology , 2021, 1-20) . The specification does not disclose a specific combination of cell and factor that introduced within a donor animal in order to differentiate stem cell into regulatory cells embraced by the breadth of the claim.
It is apparent that on the basis of applicant’s disclosure, an adequate written description of the invention defined by the claims require more than mere statement that it is part of invention and reference to potential cell and factors are essential for stem cells to differentiate and mature into regulatory cells, suppressor cells, select B cells, and antibodies as claimed. The specification does not provide any disclosure as to what would have been the structure of the representative number of the species of the claimed broad genus of cells and factors encompassed by the claims for contemplated biological activity.
The claimed invention as a whole is not adequately described if the claims require essential or critical elements which are not adequately described in the specification and which is not conventional in the art as of applicants effective filing date. Possession may be shown by actual reduction to practice, clear depiction of the invention in a detailed drawing or by describing the invention with sufficient relevant identifying characteristics such that a person skilled in the art would recognize that the inventor had possession of the claimed invention. Pfaff v. Wells Electronics. Inc., 48 USPQ2d 1641, 1646 (1998).
. The specification does not teach the structure and identifying characteristics of a sufficient number of representative species of different cells and factors that would facilitate differentiation and maturation into regulatory cells. The skilled artisan cannot envision the detailed structure of a genus of factors and cell that must show the contemplated biological activity, and therefore, conception is not achieved until reduction to practice has occurred, regardless of the complexity/simplicity of the structure and/or methods disclosed in specification.
In conclusion, this limited information is not deemed sufficient to reasonably convey one skilled in art that Applicant was in possession of the claimed broad genus at the time the application was filed. Thus, it is concluded that the written description requirement is not satisfied for the claimed broad inventions.
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 1-27 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.
Claim 1 recite phrase “a pig organ that are personalized to a specific organ recipient” in a “method of producing an organ” and “using the organ” is unclear as neither instant specification nor the claim defines any characteristics necessary to obtain a personalized to a specific organ recipient. Further, claim 1 recite phrase “some development of the resultant GM donor pig” is indefinite and unclear because the phrase does not disclose extent, type or stage of development and therefore metes and bounds of the phrase some development of the resultant GM donor pig could not be ascertained. Additionally, claim as written encompasses method of making and using the organ without establishing clear nexus between two distinct inventive concepts. It is unclear if the invention pertains to making, using or both. One of ordinary skill in the art could not determine the scope of the claim. A direct recitation of all the steps to be performed in a clear order establishing relationship with the preceding step would be remedial. Further, the metes and bounds of term “factor of organ recipient are collected from blood and bone marrow” is unclear. It is unclear if the factor pertains to (a) inducing tolerance to the organ, (b) increase expansion of cells from blood and bone marrow or something else. A direct recitation of enhancing proliferation, maturation, and differentiation of the organ recipient’s cells in presence of growth factor isolated from blood and bone marrow would obviate remedial. Appropriate correction is required.
Regarding claim 6, the phrase "e.g. for example" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 17 recite the phrase “genetic modification is made using SCNT” however, SCNT is a cloning process that involves nucleus of a somatic cell that is transferred into a egg cells whose nucleus has been removed . SCNT by itself does not modify gene. Therefore, metes and bounds of the statement of genetic modification is made using SCNT is unclear. Appropriate correction is required.
Likewise, claim 21 recite a phase “more personally matched” is vague and indefinite to the extent neither instant specification nor the claim describes how much match qualifies the phrase to more personally matched. Likewise, recitation of pig organ "is repopulated with the recipient's cells" without specifying how, at which step and with which cell the organ is repopulated. The metes and bounds of the term could not be ascertained.
Claims 22-25 recites the limitation “the removal of the recipient’s lymphocytes " in line 1. There is insufficient antecedent basis for this limitation in the claim. It is noted that independent claim 1 does not recite recipient’s lymphocytes. Appropriate correction is required.
Conclusion
No claims allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Rothblatt (US2022211018) teaches a transgenic pig comprising at least six transgenes, wherein the at least six transgenes are incorporated and expressed at a single locus under the control of at least two promoters, and the at least six transgenes are selected from: (i) CD46, DAF, EPCR, HO-1, TBM, and CD47; (ii) EPCR, HO1, TBM, CD46, DAF and TFPI; (iii) EPCR, CD55, CD46, TFPI, HO-1 and CD47; (iv) EPCR, DAF, CD46, TFPI, CD59, and CD47; or (v) EPCR, CD55, CD46, TBM, HO-1, and CD39; and wherein the transgenic pig lacks expression of alpha 1, 3-galactosyltransferase (GGTA1) gene, growth hormone receptor (GHR) gene, β-1,4-N-acetyl-galactosaminyltransferase 2 (βGalNT2) gene, and cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH) gene.
Hearing (US20180092338) teaches genetically modified pig comprising an exogenous polynucleotide encoding a human leukocyte antigen G (HLA-G) polypeptide, wherein the HLA-G is HLA-G1, HLA-G2, HLA-G3, HLA-G4, HLA-G5, HLA-G6, or HLA-G7.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ANOOP K. SINGH whose telephone number is (571)272-3306. The examiner can normally be reached Monday-Friday, 8AM-5PM.
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/ANOOP K SINGH/Primary Examiner, Art Unit 1632
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