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 .
Election/Restrictions
Applicant’s election of Group I, claims 1, 3-7 and 17-20 in the reply filed on 08/03/26 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)). Currently, claims 1, 3-7, 12-14 and 17-20 are pending. Claims 12-14 are withdrawn as being directed to non-elected inventions. Accordingly, claims 1, 3-7 and 17-20 are under examination.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Abstract
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
The instant abstract utilized implied phrases see “The invention relates to”. This language should be avoided.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (e.g. page 1, paragraph 0002. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
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.
Written Description
Claims 1, 3-7 and 17-20 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims are directed a method of preventing a non-HLA antibody mediated rejection against a renal allograft.
The specification on page 11, paragraph 0088 discloses administering to said individual a treatment for preventing a non-HLA antibody mediated rejection against a renal allograft. The specification on page 20, paragraph 0160, discloses to prevent or delay the onset of the symptoms, complication, or otherwise arrest or inhibit further development of the disorder. Thus, the specification is showing that preventing and delaying are two separate entities. The specification on page 42, para 0344 discloses that the invitro methods and kits described herein may also be implemented as “companion tests” to improve diagnostic methods and to improve methods of treatment regularly used to cure to prevent acute organ rejections in an individual before or after a renal allograft. However, the specification does not provide any data, graphs, examples, experiments to show the prevention of a non-HLA antibody mediated rejection against a renal allograft. Although the specification in paragraph 0159 discloses that the term “prevent” does not require 100% elimination the term does allow for 100% elimination. Thus, The term “preventing” (recited in claims 1 and 20) as currently recited may include complete prevention which implies an absolute and complete prevention of the appearance/onset of a non-HLA antibody mediated rejection against a renal allograft, i.e., not any overt symptom or pre-symptomatic marker or damage may be present at any level. However, the specification has not provided data, graphs , examples or experiments which shows they treatment provides a complete prevention of renal allograft but rather appears to only provide support for a delay or reduction of a non-HLA antibody mediated rejection against a renal allograft. It is recommended to delete the term from the claims.
Written Description
Claims 1, 3-7 and 17-20 are rejected under 35 U.S.C. 112, 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(s), at the time the application was filed, had possession of the claimed invention.
The claims are drawn to engineered human glomerular endothelial cells wherein the human glomerular endothelial cel is engineered to suppress the expression of HLA I and HLA II and wherein the cells bind toa non-HLA antibody, that is an engineered human glomerular endothelial cell that present a unique reduction in HLA I and HLA II and binds to non-HLA antibodies. Although drawn to DNA arts, the findings in University of California v. Eli Lilly and Co., 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997) and Enzo Biochem, Inc. V. Gen-Probe Inc. are relevant to the instant claims. The Federal Circuit addressed the application of the written description requirement to DNA-related inventions in University of California v. Eli Lilly and Co.,119 F. 3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997). The court stated that “[a] written description of an invention involving a chemical genus, like a description of a chemical species, ‘requires a precise definition, such as by structure, formula, [or] chemical name,’ of the claimed subject matter sufficient to distinguish it from other materials.” Id. At 1567, 43 USPQ2d at 1405. The court also stated that
a generic statement such as “vertebrate insulin cDNA” or “mammalian insulin
cDNA” without more, is not an adequate written description of the genus because
it does not distinguish the genus from others, except by function. It does not
specifically define any of the genes that fall within its definition. It does not define
any structural features commonly possessed by members of the genus that
distinguish them from others. One skilled in the art therefore, cannot, as one can
do with a fully described genus, visualize or recognize the identity of the
members of the genus. A definition by function, as we have previously indicated,
does not suffice to define the genus because it is only an indication of what the
gene does, rather than what it is.
.Id. At 1568, 43 USPq2d at 1406. The court concluded that “naming a type of material generally known to exist, in the absence of knowledge as to what that material consists of, is not a description of that material.” Id.
Finally, the court addressed the manner by which a genus of cDNAs might be described. “ A description of a genus of cDNAs may be achieved by means of a recitation of a representative number of cDNAs, defined by nucleotide sequence, falling within the scope of the genus or of a recitation of structural features common to the members of the genus, which features constitute a substantial protion of the genus.” Id.
The Federal Circuit has recently clarified that a DNA molecule can be adequately described without disclosing its complete structure. See Enzo Biochem, Inc. V. Gen-Probe Inc., 296 F.3d 1316, 63 USPQ2d 1609 (FED. Cir. 2002). The Enzo court adopted the standard that “the written description requirement can be met by ‘show[ing] that an invention is compete by disclosure of sufficiently detailed, relevant identifying characteristics….i.e., complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics.” Id. At 1324, 63 USPQ2d at 1613 (emphasis omitted, bracketed material in original).
The inventions at issue in Lilly and Enzo were DNA constructs per se, the holdings
of those cases are also applicable to claims such as those at issue here. A disclosure that does not adequately describe a product itself logically cannot adequately describe a method of using that product.
Thus, the instant specification may provide an adequate written description of the engineered human glomerular endothelial cell, per Lilly by structurally describing a representative number of engineered human glomerular endothelial cells or by describing “structural features common to the members of the genus, which features constitute a substantial portion of the genus.” Alternatively, per Enzo, the specification can show that the claimed invention is complete “by disclosure of sufficiently detailed, relevant identifying characteristics, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics.”
In this case, the specification does not describe the engineered glomerular endothelial cells in a manner that satisfies either the Lilly or Enzo standards. The specification does not provide the complete structure or any human glomerular endothelial cell other than that of a genetically engineered human glomerular endothelial cell mediated by CRISPR/Cas9 gene disruption of a gene encoding B2M and/or a gene encoding CIITA wherein the disruption is in exon 1 and/or exon 2 of the gene encoding B2M, and/or the disruption is in exon 2 and/or in exon 3 of a gene encoding CIITA. Although the specification discloses genetically engineered human glomerular endothelial cell mediated by CRISPR/Cas9 gene disruption of a gene encoding B2M and/or a gene encoding CIITA wherein the disruption is in exon 1 and/or exon 2 of the gene encoding B2M, and/or the disruption is in exon 2 and/or in exon 3 of a gene encoding CIITA, this does not provide a description of any and all engineered human glomerular endothelial cells that binds to non-HLA antibodies and possesses the unique characteristic of suppressed HLA 1 and HLA II that would satisfy the standard set out in Enzo.
The specification on pages 28-29 discloses genetically human engineered glomerular endothelial cells in which the genes encoding for B2M and/or CIITA have been disrupted by a crisper/Cas9 gene wherein the disruption is in exon 1 and/or exon 2 of the gene encoding B2M, and/or the disruption is in exon 2 and/or in exon 3 of a gene encoding CIITA.
The specification also fails to describe the engineered human glomerular endothelial cells that present the unique capability of suppress HLA I and HLA II and still presents an epitope for binding to a non-HLA antibody by the test set out in Lilly. The specification describes only genetically engineered human glomerular endothelial cell mediated by CRISPR/Cas9 gene disruption of a gene encoding B2M and/or a gene encoding CIITA wherein the disruption is in exon 1 and/or exon 2 of the gene encoding B2M, and/or the disruption is in exon 2 and/or in exon 3 of a gene encoding CIITA. Therefore, it necessarily fails to describe a “representative number” of such species. In addition the specification also does not describe “structural features common to the members of the genus, which features constitute a substantial portion of the genus.”. Thus, the specification does not provide an adequate written description of the engineered human glomerular endothelial cells that present the unique capability of suppress HLA I and HLA II and still presents an epitope for binding to a non-HLA antibody that is required to practice the claimed invention. Therefore, since it fails to describe the engineered human glomerular endothelial cells that present the unique capability of suppress HLA I and HLA II and still presents an epitope for binding to a non-HLA antibody, it also fails to adequately describe the claimed methods.
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 5 and 17 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 5, the phrase "in particular" 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, line 1 is indefinite in reciting improper Markush language in reciting “ said treatment is selected among…” because it appears to intend to limit the scope of the treatment recited in the claims but improperly defines it as such. Perhaps, Applicant intends “said treatment is selected from the group consisting of”.
Allowable Subject Matter
Claims 1, 3-7 and 17-20 would be allowable if rewritten or amended to overcome the rejection(s) under 35 U.S.C. 112(a), and 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, set forth in this Office action.
Nakagawa et al (Clin Exp Nephrol, 2002, 6 pages 111-117) is considered to be the closest prior art of record. Nakagawa et al discloses a method to indicate the likelihood of occurrence of acute rejection in renal transplantation (e.g. abstract). Nakagawa et al discloses the method comprises incubating human glomerular endothelial cells with a serum or plasma sample from an individual and measuring a level of seroreactivity (e.g. abstract, page 113). Nakagawa et al discloses measuring a level of seroreactivity and comparing to that of recipients without rejection (reference value) (e.g. Fig. 1A) . Nakagawa et al also discloses that IgG-AECA against human glomerular endothelial cells in the AECA-positive sera was significantly higher than that in normal human serum (another reference value) (e.g. Table 2). Nakagawa et al discloses that the determined levels can be correlated with acute rejection in renal transplantation (e.g. page 116, col 2-conclusion). However, Nakagawa et al does not teach nor fairly suggest incubating at least one engineered human glomerular endothelial cell with a blood sample of said individual, said blood sample being presumed to contain non-HLA antibodies, said human glomerular endothelial cell being engineered to suppress the expression of HLA I and HLA II.
Conclusion
No claims are allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Nickerson (Am J Transplant 2020; 20, pages 1222) discloses antibody-mediated rejection in kidney transplantation and treatment of ABMR.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GARY W COUNTS whose telephone number is (571)272-0817. The examiner can normally be reached M-F 7:00-4:00.
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, Gregory Emch can be reached at 571-272-8149. 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.
/GARY COUNTS/ Primary Examiner, Art Unit 1678
Prosecution Insights