DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Specification
The use of the term “Transwell”, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
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.
Claim 3 contains the trademark/trade name Transwell™. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe a membrane based culture vessel and, accordingly, the identification/description is indefinite.
Claim Interpretation
Claim 2 states requirements A-E which read as if all steps are required for the method of claim 1, from which claim 2 depends. However, requirement F states “combinations thereof”, implying that only one or more of A-E is required for claim 2 to be satisfied. As such, prior art reading on one or more of requirements A-E will be considered as fully satisfying the requirement of claim 2. Applicant is encouraged to amend claim 2 by denoting if each step is required (i.e., removing step F and amending claim 2 from “tight junction formation comprises” to “tight junction formation comprises the following”) or amending claim 2 by adding wording such as “comprises one or more of the following” or by making use of phrases such as “and/or” at the end of steps A-E, respectively.
As claims 3, 7, 8, and 9 all depend from claim 2 and further specify the components of claim 2, claims 3, 7, 8, and 9 will be examined on the merits if they relate to the letter of claim 2 which is identified in the prior art. For example, if there is prior art found detailing letter A of claim 2, claim 3 will be examined as it further specifies the requirements of the subject matter of letter A of claim 2. In that instance, as claim 2 is interpreted to need one or more of letters A-E to be considered fully anticipated by the prior art, claims 7-9 would not be examined as they relate to components of claim 2 other than letter A.
Claim Rejections - 35 USC § 102
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 (i.e., changing from AIA to pre-AIA ) 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 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.
Claim(s) 1, 16, 19, and 22 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lanza et al. (US 10584313 B2)
Regarding claim 1: Lanza discloses a method of cloning animals and cells (57) which, in an embodiment of the invention, comprises supplementing the media in order to disrupt the formation of tight junctions. (Col 28, ln 29-32) In addition, Lanza discloses a table of culture variables detailing differentiation inducing factors, including use of BMP. (Col 35, Table 1) Lanza further discloses the use of pluripotent stem cells, which may include human embryonic stem cells. (Col 9, ln 39-47)
Regarding claim 16: Lanza discloses that the pluripotent stem cells of the claimed invention may be genetically modified. (Col 9, ln 44-45)
Regarding claim 19: Lanza discloses the addition of multiple BMP variants as culture variables, including BMP2 and BMP4 as shown in Table 1 below:
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Regarding claim 22: The method of claim 1 describes contacting a modified cell population with BMP. As evidenced by the Specification provided by the Applicant, primed PSCs may be manipulated via stimulation with BMP to produce primordial germ cells. (Specification, Summary, ln 19-23) As such, it is inherent that the culture method of claim 1, from which claim 22 depends, would result in primordial germ cells due to use of BMP on a population of pluripotent stem cells. The method taught by Lanza also comprises contacting a population of pluripotent stem cells (col 2, ln 31-37) and, in an embodiment, exposing the cells to BMP as described in table 1 (above), which would inherently result in the generation of primordial germ cells as is the result of the method of claim 1. Furthermore, Example 11 as taught by Lanza (col 73-75) details the generation of ES lines from embryos and blastomeres, and describes multiple culture stages, all which require the harvesting of the cell from culture. This reads on the harvest of at least one primordial germ cell from the culture medium which, in certain embodiments, comprises BMP.
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 (i.e., changing from AIA to pre-AIA ) 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 2 and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Lanza et al. (US 10584313 B2) in view of Wang et al. (Exploring tight junction alteration using double fluorescent probe combination of lanthanide complex with gold nanoclusters, 2016)
The teachings of Lanza are discussed above. Lanza fails to teach a method of inhibiting tight junction formation comprising any of steps A-F as listed in claim 2.
Regarding claim 2: Wang et al. teaches a method of quantifying the changes in tight junction formation using a double fluorescent probe to examine the structure of the impact of EDTA and vanadyl complexes on tight junction formation. (Pg 1, Abstract) Wang teaches that EDTA causes reversible tight junction (hereafter “TJ”) opening via the calcium and magnesium ion channels and use of EDTA to disrupt TJ formation resulted in TJ pore size to increase and the TJ retention capacity to decrease. (Pg 3, Results and Discussion) Lastly, Wang teaches that the TJ plays a key role in the regulation of the passage of liquids, ions, and large solutes through the paracellular pathway. (Pg 1, Abstract)
Regarding claim 9: As discussed above, Wang teaches use of EDTA as an inhibitor in TJ formation.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Wang with the culture method taught by Lanza to use EDTA as an inhibitor in TJ formation. One skilled in the art would have had motivation and a reasonable expectation of success at doing so based on the teachings of Wang who, when the teachings of EDTA acting on TJ pore size and retention capacity are combined with the teachings that the TJ regulates the passage of liquids, ions, and large solutes, teaches that manipulation of the TJ with EDTA as an inhibitor can lead to the ability to manipulate the passage of liquids, ions, and large solutes through the paracellular pathway.
Claim(s) 10 is rejected under 35 U.S.C. 103 as being unpatentable over Lanza et al. (US 10584313 B2) in view of Cui et al. (US 7696343 B2)
The teachings of Lanza are discussed above. Lanza fails to teach inhibition of at least one of ZO1, ZO2, ZO3, OCLN, CLDN2, CLDN5, CLDN6, or CLDN7.
Regarding claim 10: Cui teaches knockdown of occludin (hereafter OCLN) to open tight junctions by way of binding to proteins and small interfacing nucleic acids which downregulate the mRNA encoding the proteins. (57). Specifically, Cui teaches that OCLN inhibition can be used to downregulate RNA interference and open tight junctions. (Col 3, ln 56-59)
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teaching of Cui with the culture method of Lanza to inhibit OCLN. One skilled in the art would have had motivation and a reasonable expectation of success based on the teachings of Cui, who state that downregulation of OCLN leads to the opening of the tight junctions.
Claim(s) 12 is rejected under 35 U.S.C. 103 as being unpatentable over Lanza et al. (US 10584313 B2) in view of Walsh et al. (Rho Kinase Regulates Tight Junction Function and Is Necessary for Tight Junction Assembly in Polarized Intestinal Epithelia, 2001)
The teachings of Lanza are discussed above. Lanza fails to teach use of a ROCK inhibitor in the culture medium.
Regarding claim 12: Walsh teaches that tight junctions are crucial determinants of barrier function and are regulated by ROCK. (Abstract) Importantly, Walsh teaches that use of a ROCK inhibitor does not impact the solubility of tight junction proteins nor does it redistribute the localization of tight junction proteins. (Pg 6, Results) Importantly, Walsh teaches that ROCK is directly involved in determining assembly of the tight junction proteins, and inhibition of ROCK was associated with disorganization and poor forming of the tight junctions of cells in culture. (Pg 12, Discussion)
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Walsh with the culture method taught by Lanza. One skilled in the art would have had motivation and a reasonable expectation of success based on the teachings of Walsh, who state that ROCK plays a central role in the formation of tight junctions and inhibition of ROCK led to disorganization of the tight junctions.
Claim(s) 18 is rejected under 35 U.S.C. 103 as being unpatentable over Lanza et al. (US 10584313 B2) in view of Otani et al. (Claudins and JAM-A coordinately regulate tight junction formation and epithelial polarity, 2019)
Regarding claim 18: Lanza fails to teach the genetic modification of the cells themselves to impact tight junction formation. Otani et al. teaches a systematic knock out of tight junction components by genome editing and discovered that upon the removal of claudin and JAM-A, cells lacked tight unction strands, electrolyte permeability barrier, and membrane appositions. (Pg 1, Abstract) This demonstrates that claudins and JAM-A coordinate to regulate tight junction formation.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Otani with the culture method taught by Lanza to create a culture method with primordial germ cells which have been genetically modified to disrupt tight junction formation. One skilled in the art would have had motivation and a reasonable expectation of success based on the teachings of Otani, who demonstrate that the knockout of both claudin and JAM-A result in the malformation of tight junctions via loss of strands, electrolyte permeability barriers, and membrane appositions.
Claim(s) 23 is rejected under 35 U.S.C. 103 as being unpatentable over Lanza et al. (US 10584313 B2) in view of Obata et al. (US 2018/0251729 A1)
The teachings of Lanza are discussed above. Lanza fails to teach the differentiation of one or more primordial germ cells into mature germ cells or the implantation of said germ cell into a subject.
Regarding claim 23: Obata teaches a two-step culture method for the maturation of primordial germ cells which results in a functionally mature oocyte. (0055) Obata further specifies that “functionally mature oocyte” is defined as having the capability to mature into an egg by in vitro maturation and having the capability to develop into a normal offspring via fertilization. (0121)
Claim(s) 25 is rejected under 35 U.S.C. 103 as being unpatentable over Lanza et al. (US 10584313 B2) in view of Obata et al. (US 2018/0251729 A1) and Tilly et al (US 2019-0300852A1)
The teachings of Lanza and Obata are described above. Both fail to teach the implantation of the primordial germ cell into a subject.
Regarding claim 25: Tilly teaches a method for in vitro fertilization of a female subject comprising the production of an oocyte by the culture of a peripheral blood derived female germline stem cell, the fertilization of said oocyte in vitro, and the implantation of said fertilized embryo in the uterus of a female subject. Tilly further teaches that the cells of the claimed invention may be genetically modified (0199) prior to administration or implantation. This allows for the production of viable offspring from genetically altered stem cells.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Tilly with the teachings of Obata and the culture method taught by Lanza. One skilled in the art would have had motivation and a reasonable expectation of success based on the teachings of Tilly, who teach a method for producing viable offspring from genetically modified cells by the implantation of said oocyte into a female subject.
Claim(s) 26, 27, 29, 31, and 33 are rejected under 35 U.S.C. 103 as being unpatentable over Lanza et al. (US 10584313 B2) in view of Ingber et al. (US 10655098 B2)
The teachings of Lanza are discussed above. Lanza fails to teach the culture of pluripotent stem cells on a porous membrane wherein the cells are genetically modified to reduce the function of a tight junction gene which is cultured in BMP.
Regarding claims 26 and 27: As discussed in the 35 U.S.C. 102 (a)(1) rejection of claims 1, 16, 18, 19, and 22, Lanza teaches a method of culturing pluripotent stem cells in a culture medium comprising BMP. Lanza fails to teach use of a porous surface or use of a membrane as said porous surface.
Ingber teaches a method of culturing and maintaining intestinal cells, tissues, and organoids in an environment which can mimic a natural environment. (57) In Example 1 of the claimed invention, Ingber teaches use of a porous flexible membrane coated with ECM which is designed to mimic in vivo tissue-tissue interfaces. (Col 33-37, Example 1)
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Ingber with the teachings of Lanza. One skilled in the art would have been motivated based on the teachings of Ingber, who state that use of a porous membrane more closely mimics in vivo cell-cell interactions and interfaces.
Regarding claim 29: Lanza teaches that the cells of the claimed invention may be genetically engineered. (Col 9, ln 44-45)
Regarding claim 31: Lanza discloses that in certain embodiments of the invention, culture conditions are modified in a way that reduces embryonic vesicle formation (col 7, ln 8-10) which one skilled in the art would understand would result in a reduction of the formation of tight junctions.
Regarding claim 33: Lanza discloses the addition of multiple BMP variants as culture variables, including BMP2 and BMP4 as shown in Table 1 pictured above (in the rejection of claim 19).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HANNA M THUESON whose telephone number is (571) 272-3680. The examiner can normally be reached M-F 7:30-5 EST. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Tracy Vivlemore, can be reached on (571) 272-2914. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/HANNA MARIE THUESON/ Examiner, Art Unit 1638
/Tracy Vivlemore/ Supervisory Primary Examiner, Art Unit 1638
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