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 .
Application Status
Claims 1-13 are pending and examined on the merits herein.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - Sequences appearing in the specification are not identified by sequence identifiers (i.e., “SEQ ID NO:X” or the like) in accordance with 37 CFR 1.831(c). Specifically on page 37, line 11 and in table 2, page 37.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required sequence identifiers, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
Specification
The disclosure is objected to because of the following informalities:
The reference to the sequence listing is disclosed in kilobytes but is required to be disclosed in bytes under ST.26.
Appropriate correction is required.
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code on page 10. 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 use of the term FACScanto™ on pages 7, 35-36, and 38, xCelligence™ on pages 8-9 and 40, and Biacore™ on pages 35-36 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.
Drawings
The drawings are not of sufficient quality to permit examination, specifically Figure 4 is illegible. Accordingly, replacement drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to this Office action. The replacement sheet(s) should be labeled “Replacement Sheet” in the page header (as per 37 CFR 1.84(c)) so as not to obstruct any portion of the drawing figures. If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action.
Applicant is given a shortened statutory period of TWO (2) MONTHS to submit new drawings in compliance with 37 CFR 1.81. Extensions of time may be obtained under the provisions of 37 CFR 1.136(a) but in no case can any extension carry the date for reply to this letter beyond the maximum period of SIX MONTHS set by statute (35 U.S.C. 133). Failure to timely submit replacement drawing sheets will result in ABANDONMENT of the application.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 2 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 2 is drawn to the PRAME binding molecule according to claim 1, comprising the heavy chain variable region and the light chain variable region. Claim 1 recites a PRAME binding molecule comprising a heavy chain variable region containing the HCDRs and a light chain variable region containing the LCDRs. Therefore claim 2 is not further limiting to claim 1 from which it depends as claim 1 already comprises the heavy and light chain variable regions.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 112(b)
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 4 is 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 4 recites “wherein the binding capability of the PRAME binding molecule to a peptide consisting of the amino acid sequence represented by SEQ ID NO: 19, a peptide consisting of the amino acid represented by SEQ ID NO: 20, a peptide consisting of the amino acid sequence represented by SEQ ID NO: 21, a peptide consisting of the amino acid sequence represented by SEQ ID NO: 23, a peptide consisting of the amino acid sequence represented by SEQ ID NO: 24, a peptide consisting of the amino acid sequence represented by SEQ ID NO: 25, a peptide consisting of the amino acid sequence represented by SEQ ID NO: 26 is equal to or less than ½ of the binding capability of the PRAME binding molecule to a peptide consisting of the amino acid sequence represented by SEQ ID NO: 17.” This claim is indefinite as it is unclear if the PRAME binding molecule will bind to all of the peptide sequences recited, and if so the coordinating conjunction “and” should be added between options SEQ ID NO: 25 and 26; or if the claim should be in the alternative by adding the preamble “selected from”, “at least one member of”, or the coordinating conjunction “or” between the options of SEQ ID NO: 25 and 26.
The instant specification discloses in para 0034; The PRAME-binding molecule of the present invention can specifically recognize PRAMEp301-309 (SEQ ID NO: 17). From this viewpoint, the binding capability of the PRAME-binding molecule of the present invention to at least one member selected from the group consisting of peptides in which part of PRAMEp301-309 is mutated (a peptide consisting of the amino acid sequence represented by SEQ ID NO: 19, a peptide consisting of the amino acid sequence represented by SEQ ID NO: 20, a peptide consisting of the amino acid sequence represented by SEQ ID NO: 21, a peptide consisting of the amino acid sequence represented by SEQ ID NO: 23, a peptide consisting of the amino acid sequence represented by SEQ ID NO: 24, a peptide consisting of the amino acid sequence represented by SEQ ID NO: 25, and a peptide consisting of the amino acid sequence represented by SEQ ID NO: 26) (preferably, two members or more, three members or more, four members or more, five members or more, six members or more, or seven members (all)), is preferably 1/2 or less (preferably, 1/5 or less, 1/10 or less, 1/20 or less, 1/100 or less, 1/500 or less, 1/2000 or less, or 1/10000 or less) of the binding capability of the PRAME-binding molecule of the present invention to PRAMEp301-309 (SEQ ID NO: 17).
Claim Rejections - 35 USC § 112(a)
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.
Claim 13 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for methods of treating cancer, does not reasonably provide enablement for methods of preventing cancer. 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. This is a scope of enablement rejection.
Nature of the invention/ Breadth of the claims. The claims are drawn to a method of treating or preventing cancer in a subject in need thereof comprising administering to the subject pharmaceutical composition comprising the lymphocyte cell that comprises a polynucleotide encoding the PRAME binding molecule.
State of the prior art/ Predictability of the art. There is prior art demonstrating the effectiveness of administering PRAME specific T cells to treat cancer. Pankov (Oncotarget. 2017 Jul 26;8(39):65917-65931; PTO-892) teaches generation of a polyclonal antibody (Membrane associated PRAME Antibody 1, MPA1) against an extracellular peptide sequence of PRAME with validated in vitro binding through ELISA, flow cytometry and confocal microscopy as well as in vivo binding through radiolabeling (abstract). Pankov further teaches that PRAME can be exploited for multiple clinical applications, including targeted therapy, diagnostic imaging and treatment guidance in a wide-range of malignancies, with minimal off-target toxicity (abstract). Orlando (Cancer Res, 2018, 78 (12): 3337–3349; PTO-892) teaches that T cells genetically modified with a high-affinity, PRAME-specific TCR and iC9 may represent a promising innovative approach for treating patients with HLA-A*02+ medulloblastoma (abstract). Quintarelli (Blood, 2011 Mar 24,117(12):3353-62; IDS entered 06/09/2023) teaches generation of polyclonal, PRAME-specific CTL lines, with a high proportion of cells recognizing a previously uninvestigated HLA-A*02–restricted epitope, P435-9mer (NLTHVLYPV) (abstract). Quintarelli further teaches that the cytotoxic activity of our PRAME-specific CTLs was directed not only against leukemic blasts as well as against leukemic progenitor cells, but did not affect normal hematopoietic progenitors, indicating that this approach may be of value for immunotherapy of PRAME+ hematologic malignancies (abstract). The state of the art does not recognize that administering a lymphocyte comprising a PRAME binding molecule for immunotherapy would prevent cancer.
Working examples. There are no working examples provided in the instant disclosure for prevention of cancer in the instant disclosure.
Guidance in the specification. The specification provides guidance towards the meaning of the term “prevent”.
The instant specification discloses that “Such lymphocyte cells or the like are useful for treatment or prevention of cancer or the like because they specifically recognize cancer tissue (tumor tissue)” (paragraph 0078).
The instant specification further discloses: The type of disease diagnosed, treated, or prevented using the pharmaceutical composition is not particularly limited as long as the diagnosis, treatment, or prevention can be achieved (para 0086).
The specification lacks the critical steps necessary in presenting some type of predictable response in a population of hosts deemed necessary to prevent cancer. Reasonable guidance with respect to preventing any disease relies on quantitative analysis from defined populations which have been successfully pre-screened and are predisposed to particular types of cancer. The essential element towards the validation of a preventive therapeutic is the ability to test the drug on subjects monitored in advance of cancer and link those results with subsequent histological confirmation of the presence or absence of disease. This irrefutable link between antecedent drug and subsequent knowledge of the prevention of the disease is the essence of a valid preventive agent.
Amount of experimentation necessary. An extensive amount of additional research is required in order to determine how effective administering to the subject a pharmaceutical composition comprising the lymphocyte cell that comprises a polynucleotide encoding the PRAME binding molecule at preventing cancer and to determine to which population of subjects to administer the pharmaceutical composition that could predictably prevent cancer as claimed in the instant claim 13.
For the reasons discussed above, it would require undue experimentation for one skilled in the art to use the claimed methods as recited.
Allowable Subject Matter
Claims 1, 3, and 5-12 allowed.
The following is an examiner’s statement of reasons for allowance:
The CDRS comprising the PRAME binding molecule containing SEQ ID NO: 1-3 and 9-11 have been found free of the prior art.
Claims 3 and 5-12 depend from claim 1 and are therefore also allowable.
The state of the prior art teaches antibodies with specific binding to PRAME as seen in Pankov (Oncotarget. 2017 Jul 26;8(39):65917-65931; PTO-892). Pankov teaches generation of a polyclonal antibody (Membrane associated PRAME Antibody 1, MPA1) against an extracellular peptide sequence of PRAME with validated in vitro binding through ELISA, flow cytometry and confocal microscopy as well as in vivo binding through radiolabeling (abstract). Pankov further teaches that PRAME can be exploited for multiple clinical applications, including targeted therapy, diagnostic imaging and treatment guidance in a wide-range of malignancies, with minimal off-target toxicity (abstract). However the antibody of Pankov is not the same as the instant claimed anti-PRAME antibody. Although methods of generating new antibodies are known in the art, the exact CDR sequences of any antibody produced is unpredictable and would not be expected to comprise the instant CDRs, therefore, the instantly claims antibody is not obvious over the antibody of Pankov.
Any comments considered necessary by applicant must be submitted no later than the payment of the issue fee and, to avoid processing delays, should preferably accompany the issue fee. Such submissions should be clearly labeled “Comments on Statement of Reasons for Allowance.”
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMBER K FAUST whose telephone number is (703)756-1661. The examiner can normally be reached Monday - Thursday 9:00am-6:00pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Julie Wu can be reached at 571-272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/AMBER K FAUST/Examiner, Art Unit 1643
/JULIE WU/Supervisory Patent Examiner, Art Unit 1643