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 without traverse of invention I in the reply filed on 6/1/26 is acknowledged.
Claims 19, 20, 26, 28-31, 35, 36, 38 and 39 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 6/18/26.
Claims 1-4, 10 and 14-16 and 18 are examined on the merits.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12/30/24; 5/29/25; 9/29/25 and 6/1/26 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
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 3, 10 and 16 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 3 recites the limitation "CDV-H" in line 1. There is insufficient antecedent basis for this limitation in the claim.
Claim 10 recites the limitation "CDV-F" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim 16 recites the limitation "CDV-H" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim 4 recites, “The pseudotyped virus of claim 3, wherein the CDV-H polypeptide comprises…a truncated N-terminal cytoplasmic domain, as compared to the sequence set forth in SEQ ID NO: 17.” However, it is unclear if the limitation “a truncated N-terminal cytoplasmic domain” is requiring that the CDV-H is only this truncated domain or the H protein is lacking the N-terminal cytoplasmic domain.
Claim 10 recites, “wherein said CDV-F polypeptide comprises:…a signal peptide sequence that is less than 75 amino acid residues in length.” However, the recitation of “a signal peptide that is less than 75 amino acid residues in length” is unclear since the source of the signal peptide and amino acids are not recited in the claim. Is the signal peptide from CDV-F or a heterologous protein.
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 4 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. Presently, claim 4 recites, “The pseudotyped virus of claim 3, wherein the CDV-H polypeptide comprises…a truncated N-terminal cytoplasmic domain, as compared to the sequence set forth in SEQ ID NO: 17.” Claim 3 requires that the CDV-H polypeptide comprises amino acid mutations at residues outside the N-terminal cytoplasmic domain, but claim 4 appears to require that the CDV-H only comprises this cytoplasmic domain. Therefore, claim 4 would not require the amino acid residues of claim 3, from which it depends. 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 § 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.
Claim(s) 1, 3, 10 and 18 are rejected under 35 U.S.C. 102a1 as being anticipated by Logan et al. Vaccine, 2016, Vol. 34, pages 814-822).
The claimed invention is drawn to a pseudotyped virus comprising a canine distemper virus (CDV) hemagglutinin (H) polypeptide and a CDV fusion (F) polypeptide, wherein said virus lacks nucleic acid encoding said H polypeptide and lacks nucleic acid encoding said F polypeptide. The pseudotype virus can also be part of a composition.
The CDV-H polypeptide comprises an amino acid substitution at one or more positions 194, 195, 478, 479, 540, 544 and 548 according to the amino acid number of SEQ ID NO: 17. How, without specific amino acid residues being identified for each position, if the prior art teaches a CDV-H protein with amino acid residues at positions 194, 195, 478, 479, 540, 544 and 548, it will meet the limitations of claim 3 as written.
The CDV-F polypeptide comprises a signal peptide sequence that is less than 75 amino acids in length.
Logan et al. teach generating a recombinant vesicular stomatitis virus (VSV) that is pseudotyped to that possesses the H and F proteins of Canine distemper virus. [see abstract] Logan et al. teach the generation of this virus by transfecting HEK 293T cells with expression vectors encoding the CDV H and F proteins followed by super-infection by VSV, which expresses luciferase proteins in place of the endogenous G protein. [see left column of page 816]
Logan et al. do not teach that the CDV H and F encoding sequences are integrated into the pseudotyped virus, therefore, Logan et al. generated a pseudotyped virus that lacks the nucleic acids encoding the H and F.
Therefore, Logan et al. anticipate the instant invention.
Claim Rejections - 35 USC § 103
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 14 are rejected under 35 U.S.C. 103 as being unpatentable over Logan et al. as applied to claims 1, 3, 10 and 18 above, and further in view of Kines et al. (Experimental Parasitology, 2006, Vol. 112, pages 209-220).
The claimed invention also requires that the virus is a lentivirus and the nucleic acid within is disarmed. The specification (page 20, line 5) states that a disarmed virus is replication incompetent virus.
The teachings of Logan et al. are summarized above, however, they do not teach the use of a pseudotype lentivirus that is disarmed (replication incompetent).
Kines et al. teach the generation of a replication incompetent lentivirus (Moloney murine leukemia retrovirus which is psuedotyped by the presence of the VSV Glycoprotein (G). [see abstract and section 2.3]
It would have been obvious to one of ordinary skill in the art to modify the compositions taught by Logan et al. in order to employ a disarmed lentivirus as the pseudotyped virus. One would have been motivated to do so, given the suggestion by Logan et al. that a pseudotyped virus can be achieved by addition of plasmids encoding the CDV-H and F proteins to a cell followed by a infecting that cell with an enveloped virus to be pseudotyped. There would have been a reasonable expectation of success, given the knowledge that another enveloped virus, such as a disarmed lentivirus, can be pseudotyped to by the presence of VSV G protein, as taught by Kines et al. Thus the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art at the time the invention was made.
Claims 4 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Logan et al. as applied to claims 1, 3, 10 and 18 above, and further in view of Frost et al. (US PGPub 20170296678).
The claimed invention also requires that the lentivirus encodes an exogenous nucleic acid sequence encoding a CAR polypeptide. The claimed invention also requires the CDV-H comprises a truncated N-terminal cytoplasmic domain, as compared to the sequence set forth in SEQ ID NO: 17.
The teachings of Logan et al. are summarized above, while the teaching recombinant pseudotyped viruses, they do not teach that the pseudotyped viruses are lentiviruses and that they encode an CAR as well as CDV-H and CDV-F proteins.
Frost et al. teach at paragraph [0004] Lymphocytes isolated from a subject (e.g. patient) can be activated in vitro and genetically modified to express synthetic proteins that enable redirected engagement with other cells and environments based upon the genetic programs incorporated. An example of such a synthetic protein is a chimeric antigen receptor (CAR). One CAR that is currently used is a fusion of an extracellular recognition domain (e.g., an antigen-binding domain), a transmembrane domain, and one or more intracellular signaling domains encoded by a replication incompetent retrovirus. Frost et al. also teach at paragraph [0427] In some embodiments, including those directed to transducing T cells and/or NK cells, the recombinant retroviruses of the methods and compositions disclosed herein are pseudotyped with mutated or variant versions of the measles virus fusion (F) and hemagglutinin (H) polypeptides, in illustrative examples, cytoplasmic domain deletion variants of measles virus F and H polypeptides. In some embodiments, the mutated F and H polypeptides are “truncated H” or “truncated F” polypeptides, whose cytoplasmic portion has been truncated, i e amino acid residues (or coding nucleic acids of the corresponding nucleic acid molecule encoding the protein) have been deleted. “HΔY” and “FΔX” designate such truncated H and F polypeptide, respectively, wherein “Y” refers to 1-34 residues that have been deleted from the amino termini and “X” refers to 1-35 residues that have been deleted from the carboxy termini of the cytoplasmic domains. In a further embodiment, the “truncated F polypeptide” is FΔ24 or FΔ30 and/or the “truncated H protein” is selected from the group consisting of HΔ14, HΔ15, HΔ16, HΔ17, HΔ18, HΔ19, HΔ20, HΔ21+A, HΔ24 and HΔ24+4A, more preferably HΔ18 or HΔ24. In an illustrative embodiment, the truncated F polypeptide is MV(Ed)-FΔ30 and the truncated H polypeptide is MV(Ed)-HΔ18.
It would have been obvious to one of ordinary skill in the art to modify the compositions taught by Logan et al. in order to employ a lentivirus as the pseudotyped virus and it also encodes a CAR and the CDV-H can comprise a truncated N-terminal cytoplasmid domain, compared to SEQ ID NO: 17. One would have been motivated to do so, given the suggestion by Logan et al. that a pseudotyped virus can be achieved by addition of plasmids encoding the CDV-H and F proteins to a cell followed by an infecting that cell with an enveloped virus to be pseudotyped. There would have been a reasonable expectation of success, given the knowledge that another enveloped virus, such as a lentivirus, can be pseudotyped to by the presence of measles H and F proteins and that disarmed lentivirus can encode a CAR and that truncated H proteins can also be used in pseudotyping the retrovirus/lentivirus, which have a truncated cytoplasmic domain can also be employed, as taught by Frost et al. Thus the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art at the time the invention was made.
Claim(s) 16 is rejected under 35 U.S.C. 103 as being unpatentable over Logan et al. as applied to claims 1, 3, 10 and 18 above, and further in view of Ungerechts et al. (Cancer Research, 2007, Vol. 67, pages 10939-10947).
The claimed invention also requires that the CDV-H polypeptide comprises an amino acid sequence of a single chain antibody.
The teachings of Logan et al. are summarized above, however, they do not teach adding a single chain antibody sequence to their CDV-H polypeptide.
Ungerechts et al. teach the generation of a mutated measles virus with a chimeric H protein possessing a single chain antibody specific for CD20. The chimeric H protein facilitates entry of the measles virus into cells by binding to CD20 on the cell surface. [left column of page 10940 and Figure 1]
It would have been obvious to one of ordinary skill in the art to modify the compositions taught by Logan et al. in order to generate a pseudotyped virus that encodes a CDV-H which also comprises an amino acid sequence of a single chain antibody. One would have been motivated to do so, given the suggestion by Logan et al. that a pseudotyped virus can be achieved by addition of plasmids encoding recombiannt CDV-H and F proteins to a cell followed by a infecting that cell with an enveloped virus to be pseudotyped. There would have been a reasonable expectation of success, given the knowledge that recombinant measles virus (a morbillivirus) H proteins can be modified to also express a single chain antibody, which facilities cell targeting for viral infection, as taught by Ungerechts et al. Thus the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art at the time the invention was made.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BENJAMIN P BLUMEL whose telephone number is (571)272-4960. The examiner can normally be reached M-F 8-5 EST.
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/BENJAMIN P BLUMEL/Primary Examiner, Art Unit 1671
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