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 .
Claims 1-39, 49-61 have been canceled. Claims 64-73 have been added. Claims 40-48, 62-73 are pending.
Applicant's arguments filed 11-3-25 have been fully considered but they are not persuasive.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim interpretation
The phrase “wherein the human FcγRIα chain extracellular portion comprises an EC1 [EC2, EC3] domain encoded by nucleotides 103-357 [358-569, 570-894] of SEQ ID NO: 3” in claim 42-45 and 53-56 is clear. The specification defines where exon 3 lies within SEQ ID NO: 3 on pg 23. Pg 22, para 101 says the sequences are cDNA with consecutive exons that are separated by alternating underlined text, i.e. exon 1 of SEQ ID NO: 3 (nt 1-81) is not underlined, exon 2 of SEQ ID NO: 3 (nt 82-102) is underlined, exon 3 of SEQ ID NO: 3 (nt 103-357) is not underlined, exon 4 of SEQ ID NO: 3 (nt 358-569) is underlined, exon 5 of SEQ ID NO: 3 (nt 570-894) is not underlined, exon 6 of SEQ ID NO: 3 (nt 895-2176) is underlined.
Claim objections
Claim 47 should clearly refer to the amino acid sequence of SEQ ID NO: 5, i.e. ---an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 5---.
Reference to “an amino acid sequence of SEQ ID NO: 5” makes claim 48 unclear because it may refer to any two or more amino acids SEQ ID NO: 5. Claim 48 should clearly refer to the amino acid sequence of SEQ ID NO: 5, i.e. ---comprises the amino acid sequence of SEQ ID NO: 5---.
The preamble of claim 63 can be written more clearly as ---measuring a pharmacokinetic property of a human antibody in vivo---.
Claim Rejections - 35 USC § 112
Written Description
The rejection of claims 62 and 63 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or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement has been withdrawn. The rejection regarding modifying an endogenous FcγRI “locus” encoding a humanized FcγRI protein in claim 62 and 63 has been withdrawn because the term “locus” has been replaced with “gene”.
Enablement
The rejection of claims 62 and 63 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, enablement, has been withdrawn. The rejection regarding modifying an endogenous FcγRI “locus” encoding a humanized FcγRI protein in claim 62 and 63 has been withdrawn because the term “locus” has been replaced with “gene”.
Indefiniteness
The rejection regarding modifying an endogenous FcγRI “locus” encoding a humanized FcγRI protein in claim 62 and 63 has been withdrawn because the term “locus” has been replaced with “gene”.
The rejection regarding the phrase “immune effector response” and the method steps in claim 62 has been withdrawn in view of the amendment.
The rejection regarding the phrase “pharmacokinetic properties and/or FcγR-mediated ADCC of a human antibody” and the method steps in claim 63 has been withdrawn in view of the amendment.
Claims 62, 64-68 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 Rejections - 35 USC § 103
Withdrawn rejections
The rejection of claims 40, 41, 46, 49-52, 57, 60-63 under 35 U.S.C. 103 as being unpatentable over Heijnen (J Clin Invest 1996, Vol. 97, pg 331-338) in view of Meagher (8912385) and Harrison (Protein Engineer 1998;11:225-32) has been withdrawn in view of the amendment which requires a mouse cell whose genome has a replacement of an endogenous sequence encoding an FcRI extracellular domain with a sequence encoding a human FcRI extracellular domain. Heijnen, Meagher, and Harrison did not teach making any such replacement.
The rejection of claims 42, 45, 53, 56 under 35 U.S.C. 103 as being unpatentable over Heijnen (J Clin Invest 1996, Vol. 97, pg 331-338) in view of Meagher (8912385) and Harrison (Protein Engineer 1998;11:225-32) as applied to claims 40, 41, 46, 49-52, 57, 60-63 and further in view of DC428565 (2007) has been withdrawn for reasons set forth above.
The rejection of claims 43, 45, 54, 56 under 35 U.S.C. 103 as being unpatentable over Heijnen (J Clin Invest 1996, Vol. 97, pg 331-338) in view of Meagher (8912385) and Harrison (Protein Engineer 1998;11:225-32) as applied to claims 40, 41, 46, 49-52, 57, 60-63 and further in view of HY055736 (2006) has been withdrawn for reasons set forth above.
The rejection of claims 44, 45, 55, 56 under 35 U.S.C. 103 as being unpatentable over Heijnen (J Clin Invest 1996, Vol. 97, pg 331-338) in view of Meagher (8912385) and Harrison (Protein Engineer 1998;11:225-32) as applied to claims 40, 41, 46, 49-52, 57, 60-63 and further in view of BG011316 (2000) has been withdrawn for reasons set forth above.
New rejections
A) Claims 40, 41, 46, 62, 63, 64, 66, 69, 71 as newly amended are rejected under 35 U.S.C. 103 as being unpatentable over Heijnen (J Clin Invest 1996, Vol. 97, pg 331-338) in view of Voronina (10314296) and NM_010186 (1990).
Heijnen taught a transgenic mouse whose genome comprises an exogenous nucleic acid sequence comprising a human FcRI gene (Fig. 1), which encodes an entire FcγRI comprising the chain, EC1, EC2 and EC3 domain, transmembrane domain and cytoplasmic tail domain (see the Specification and Harrison, e.g. Fig. 1). The hFcRI was expressed on myeloid lineage cells including macrophages, monocytes, neutrophils (abstract and Results). The mouse was made by microinjecting oocytes that developed into a mouse embryo comprising embryonic stem cells whose genome comprising the hFcRI transgene.
Heijnen did not teach the FcRI gene contained a replacement of a nucleic acid sequence encoding an endogenous FcRI α chain extracellular portion with a nucleic acid sequence encoding a human FcRI α chain extracellular portion, wherein the FcRI gene encodes a chimeric FcRI comprising the human FcRI extracellular portion and mouse FcRI intracellular portion as required in claim 40.
However, the sequence of mouse FcRI was well-known (NM_010186) and it was well known to make a Voronina made a transgenic mouse with a chimeric gene that had a replacement of a nucleic acid sequence encoding an endogenous extracellular portion with a nucleic acid sequence encoding a human extracellular portion, wherein the gene encodes a chimeric protein comprising the human extracellular portion and mouse intracellular portion. This is evidenced by Voronina who made a transgenic mouse with an MHC gene that had a replacement of a nucleic acid sequence encoding an endogenous MHC chain extracellular portion with a nucleic acid sequence encoding a human MHC chain extracellular portion, wherein the MHC gene encodes a chimeric MHC comprising the human MHC extracellular portion and mouse MHC intracellular portion (claim 1).
Thus, it would have been obvious to those of ordinary skill in the art at the time of filing to make a genetically modified mouse expressing a humanized FcγRIα protein as described by Heijnen by replacing only the endogenous sequence encoding the extracellular domain of the gene of interest with that of the human protein as described by Voronina using NM_010186. Those of ordinary skill in the art at the time of filing would have been motivated to humanize only the extracellular domain for protein-protein interaction assays while leaving the endogenous intracellular protein machinery intact for improved intracellular function. This is equivalent to the mouse cell whose genome comprises the humanized FcγRIα gene in claim 40.
Heijnen taught the extracellular domain of human FcγRIα contained an EC1, EC2, or EC3 domain as required in claim 41.
Voronina taught leaving the transmembrane portion of the protein intact in the mouse which is equivalent to claim 46, 66, 71.
The combined teachings of Heijnen, NM_010186 and Voronina taught a mouse or mouse cell comprising the protein as required in claims 49, 50 for reasons set forth above.
The nucleic acid encoding the humanized FcγRIα in claim 40 encodes the humanized FcγRIα protein in claim 51.
Heijnen taught the extracellular domain of human FcγRIα contained an EC1, EC2, or EC3 domain as required in claim 52.
Voronina taught leaving the transmembrane portion of the protein intact in the mouse which is equivalent to claim 57.
The combined teachings of Heijnen, NM_010186 and Voronina taught a mouse or mouse cell comprising the protein as required in claims 60, 61 for reasons set forth above.
Claims 62 and 63 have been included because Heijnen administered human antibodies to the mouse to determine the immune response and pharmacokinetics of the antibody.
B) Claim 42 is rejected under 35 U.S.C. 103 as being unpatentable over Heijnen (J Clin Invest 1996, Vol. 97, pg 331-338) in view of Voronina (10314296) and NM_010186 (1990) as applied to claims 40, 41, 46, 62, 63, 64, 66, 69, 71 and further in view of DC428565 (2007).
The combined teachings of Heijnen, NM_010186 and Voronina taught the mouse cell having a chimeric FcγRIα gene as required in claim 40. They did not teach the protein contained an EC1 domain encoded by nucleotides 103-357 of SEQ ID NO: 3 as required in claims 42.
However, an EC1 domain encoded by nucleotides 103-357 of SEQ ID NO: 3 was well-known in the art as described by DC428565 in 2007.
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Thus, it would have been obvious to those of ordinary skill in the art at the time of filing to make a nucleic acid sequence or amino acid sequence of claim 40 or 51 as described by the combined teachings of Heijnen, Voronina (10314296) and NM_010186 (1990) using an EC1 domain encoded by nucleotides 103-357 of SEQ ID NO: 3 as described by DC428565. Those of ordinary skill in the art at the time of filing would have been motivated to use DC428565 as a matter of design choice.
Thus, Applicants' claimed invention as a whole is prima facie obvious in the absence of evidence to the contrary.
C) Claims 43 is rejected under 35 U.S.C. 103 as being unpatentable over Heijnen (J Clin Invest 1996, Vol. 97, pg 331-338) in view of Voronina (10314296) and NM_010186 (1990) as applied to claims 40, 41, 46, 62, 63, 64, 66, 69, 71 and further in view of HY055736 (2006).
The combined teachings of Heijnen, NM_010186 and Voronina taught the mouse cell having a chimeric FcγRIα gene as required in claim 40.
They did not teach the protein contained an EC2 domain encoded by nucleotides 358-569 of SEQ ID NO: 3 as required in claim 43.
However, an EC2 domain encoded by nucleotides 358-569 of SEQ ID NO: 3 was well-known in the art as described by HY055736 (2006).
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Thus, it would have been obvious to those of ordinary skill in the art at the time of filing to make a nucleic acid sequence or amino acid sequence of claim 40 or 51 as described by the combined teachings of Heijnen and Meagher using an EC2 domain encoded by nucleotides 358-569 of SEQ ID NO: 3 as described by HY055736. Those of ordinary skill in the art at the time of filing would have been motivated to use HY055736 as a matter of design choice.
Thus, Applicants' claimed invention as a whole is prima facie obvious in the absence of evidence to the contrary.
D) Claims 45, 65, 70 are rejected under 35 U.S.C. 103 as being unpatentable over Heijnen (J Clin Invest 1996, Vol. 97, pg 331-338) in view of Voronina (10314296) and NM_010186 (1990) as applied to claims 40, 41, 46, 62, 63, 64, 66, 69, 71 and further in view of BG011316 (2000).
The combined teachings of Heijnen, NM_010186 and Voronina taught the mouse cell having a chimeric FcγRIα gene as required in claim 40.
They did not teach the protein contained an EC3 domain encoded by nucleotides 570-894 of SEQ ID NO: 3 as required in claims 44.
However, an EC3 domain encoded by nucleotides 570-894 of SEQ ID NO: 3 was well-known in the art as described by BG011316 (2000).
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Thus, it would have been obvious to those of ordinary skill in the art at the time of filing to make a nucleic acid sequence or amino acid sequence of claim 40 or 51 as described by the combined teachings of Heijnen and Meagher using an EC3 domain encoded by nucleotides 570-894 of SEQ ID NO: 3 as described by BG011316. Those of ordinary skill in the art at the time of filing would have been motivated to use BG011316 as a matter of design choice.
Thus, Applicants' claimed invention as a whole is prima facie obvious in the absence of evidence to the contrary.
E) Claims 42-45, 65, 70 are rejected under 35 U.S.C. 103 as being unpatentable over Heijnen (J Clin Invest 1996, Vol. 97, pg 331-338) in view of Voronina (10314296) and NM_010186 (1990) as applied to claims 40, 41, 46, 62, 63, 64, 66, 69, 71 and further in view of DC428565 (2007), HY055736 (2006), and BG011316 (2000).
The combined teachings of Heijnen, NM_010186 and Voronina taught the mouse cell having a chimeric FcγRIα gene as required in claim 40. They did not teach the protein contained an EC1 domain encoded by nucleotides 103-357 of SEQ ID NO: 3, an EC2 domain encoded by nucleotides 358-569 of SEQ ID NO: 3, and an EC3 domain encoded by nucleotides 570-894 of SEQ ID NO: 3 as required in claims 45, 65, 70.
However, an EC1 domain encoded by nucleotides 103-357 of SEQ ID NO: 3 was well-known in the art as described by DC428565 in 2007; an EC2 domain encoded by nucleotides 358-569 of SEQ ID NO: 3 was well-known in the art as described by HY055736 (2006), and an EC3 domain encoded by nucleotides 570-894 of SEQ ID NO: 3 was well-known in the art as described by BG011316 (2000).
Thus, it would have been obvious to those of ordinary skill in the art at the time of filing to make a nucleic acid sequence or amino acid sequence of claim 40 or 51 as described by the combined teachings of Heijnen and Meagher using an EC1 domain encoded by nucleotides 103-357 of SEQ ID NO: 3 as described by DC428565; an EC2 domain encoded by nucleotides 358-569 of SEQ ID NO: 3 as described by HY055736, and an EC3 domain encoded by nucleotides 570-894 of SEQ ID NO: 3 as described by BG011316. Those of ordinary skill in the art at the time of filing would have been motivated to use DC428565, HY055736, and BG011316 as a matter of design choice..
Thus, Applicants' claimed invention as a whole is prima facie obvious in the absence of evidence to the contrary.
Double Patenting
The rejection of claims 40-63 on the ground of nonstatutory double patenting as being unpatentable over the claims of U.S. Patent No. 11503812, 10555507, and 9474255 has been withdrawn in view of the terminal disclaimer filed 11-3-25.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Inquiry concerning this communication or earlier communications from the examiner should be directed to Michael C. Wilson who can normally be reached at the office on Monday through Friday from 9:30 am to 6:00 pm at 571-272-0738.
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Michael C. Wilson
/MICHAEL C WILSON/
Primary Examiner, Art Unit 1638