DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 2-25-26 has been entered.
Claims 1-34, 36, 37, 39-45 have been canceled. Claims 35, 38, 46, 47 remain pending and under consideration.
Applicant's arguments filed 2-25-26 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 objections
The last line of item a) in claim 35 should be “rat and/or human Ig light chain constant (CL) gene segments”.
Claim 38 is objected to because it is dependent upon claim 35.
Claim interpretation
It is assumed the last line of item a) in claim 35 should be “rat and/or human Ig light chain constant (CL) gene segments”.
Claim Rejections - 35 USC § 112
Written Description
Claims 46, 47 remain 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.
Withdrawn rejections
The rejection regarding a rat with human Ig VH, DH, and JH gene segments operably linked to any Ig CH gene segments, a rat with human Ig VL, DL, and JL gene segments operably linked to any Ig CL gene segments, or a rat capable of making an antibody comprising a human Ig variable domain operably linked to any CH or CL domains as broadly encompassed by claim 35 other than a rat with human Ig VH, DH, and JH gene segments operably linked to rat and human Ig CH gene segments, a rat with human Ig VL, DL, and JL gene segments operably linked to rat and human Ig CL gene segments, and a rat capable of making an antibody comprising a human Ig variable domain operably linked to rat or human CH and CL domains has been withdrawn in view of the amendment (assuming the last line of item a) in claim 35 is “rat and/or human Ig light chain constant (CL) gene segments”.
The rejection regarding “further comprising a replacement of an endogenous Ig heavy chain constant (CH) gene segment with a human Ig CH gene segment, wherein the chimeric heavy chain comprises an Ig CH region comprising a human IgCH doman and rat Ig CH domains” in claim 38 has been withdrawn in view of the amendment and Figure 1 which describes a modified rat heavy chain gene containing exons encoding a human CH1 domain and rat CH2,3 and 4 domains (pg 16, para 114).
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Pg 25, para 173, teaches “an exemplary artificial C constant region gene is a constant region gene encoding a human IgG CH1 domain and rat IgG CH2 and CH3 domain.” and pg 27, para 186, teaches: “constant region genes encode a human CH1 domain and rat CH2 CH3 domains, or a human CH1 and rat CH2, CH3 and CH4 domains.”
Pending rejections
A) The specification lacks written description for an antibody “wherein the Ig CH region of the chimeric immunoglobulin comprises a human CH1 domain and rat CH2, CH3” and optionally rat CH4 domains as broadly encompassed by claims 46 and 47.
First, claim 35 does not require the chimeric Ig contains an Ig CH region, so the phrase “the Ig CH region” lacks antecedent basis.
Second, Figure 1 describes a modified rat heavy chain gene containing exons encoding a human CH1 domain and rat CH2,3 and 4 domains (pg 16, para 114).
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Pg 25, para 173, teaches “an exemplary artificial C constant region gene is a constant region gene encoding a human IgG CH1 domain and rat IgG CH2 and CH3 domain.” and pg 27, para 186, teaches: “constant region genes encode a human CH1 domain and rat CH2 CH3 domains, or a human CH1 and rat CH2, CH3 and CH4 domains.”
However, an immunoglobulin only has one CH domain, so the Ig cannot comprise a human CH1 domain, a rat CH2 domain, a rat CH3 domain, and a rat CH4 domain.
Accordingly, the specification lacks written description for an antibody “wherein the Ig CH region of the chimeric Ig comprises a human CH1 domain and rat CH2, CH3” and optionally rat CH4 domains as broadly encompassed by claims 46 and 47.
Response to arguments
Applicants argue the amendment overcomes the rejection. Applicants’ argument is not persuasive for reasons set forth above.
Enablement
Claims 46, 47 remain 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 a chimeric immunoglobulin (Ig) comprising a human Ig VH region operably linked to a rat Ig CH region obtained from a transgenic rat whose genome comprises a replacement of all endogenous Ig VH gene segments replaced with a plurality of human Ig VH gene segments operably linked to a plurality of Ig CH gene segments (Fig. 1), does not reasonably provide enablement for any chimeric antibody or rat as broadly encompassed by claim 35. 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/or use the invention commensurate in scope with these claims.
Withdrawn rejections
The rejection regarding a rat with human Ig VH, DH, and JH gene segments operably linked to any Ig CH gene segments, a rat with human Ig VL, DL, and JL gene segments operably linked to any Ig CL gene segments, or a rat capable of making an antibody comprising a human Ig variable domain operably linked to any CH or CL domains as broadly encompassed by claim 35 other than a rat with human Ig VH, DH, and JH gene segments operably linked to rat and human Ig CH gene segments, a rat with human Ig VL, DL, and JL gene segments operably linked to rat and human Ig CL gene segments, and a rat capable of making an antibody comprising a human Ig variable domain operably linked to rat or human CH and CL domains has been withdrawn in view of the amendment (assuming the last line of item a) in claim 35 is “rat and/or human Ig light chain constant (CL) gene segments”.
The rejection regarding “further comprising a replacement of an endogenous Ig heavy chain constant (CH) gene segment with a human Ig CH gene segment, wherein the chimeric heavy chain comprises an Ig CH region comprising a human IgCH doman and rat Ig CH domains” in claim 38 has been withdrawn in view of the amendment and Figure 1 which describes a modified rat heavy chain gene containing exons encoding a human CH1 domain and rat CH2,3 and 4 domains (pg 16, para 114).
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Pg 25, para 173, teaches “an exemplary artificial C constant region gene is a constant region gene encoding a human IgG CH1 domain and rat IgG CH2 and CH3 domain.” and pg 27, para 186, teaches: “constant region genes encode a human CH1 domain and rat CH2 CH3 domains, or a human CH1 and rat CH2, CH3 and CH4 domains.”
Pending rejections
A) The specification does not enable making an antibody “wherein the Ig CH region of the chimeric immunoglobulin comprises a human CH1 domain and rat CH2, CH3” and optionally rat CH4 domains as broadly encompassed by claims 46 and 47.
First, claim 35 does not require the chimeric Ig contains an Ig CH region, so the phrase “the Ig CH region” lacks antecedent basis.
Second, Figure 1 describes a modified rat heavy chain gene containing exons encoding a human CH1 domain and rat CH2,3 and 4 domains (pg 16, para 114).
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Pg 25, para 173, teaches “an exemplary artificial C constant region gene is a constant region gene encoding a human IgG CH1 domain and rat IgG CH2 and CH3 domain.” and pg 27, para 186, teaches: “constant region genes encode a human CH1 domain and rat CH2 CH3 domains, or a human CH1 and rat CH2, CH3 and CH4 domains.”
However, an immunoglobulin only has one CH domain, so the Ig cannot comprise a human CH1 domain, a rat CH2 domain, a rat CH3 domain, and a rat CH4 domain.
Given the lack of guidance in the specification taken with the art at the time of filing, it would have required those of skill undue experimentation to determine how to make an antibody “wherein the Ig CH region of the chimeric Ig comprises a human CH1 domain and rat CH2, CH3” and optionally rat CH4 domains as broadly encompassed by claims 46 and 47.
Response to arguments
Applicants argue the amendment overcomes the rejection. Applicants’ argument is not persuasive for reasons set forth above.
Indefiniteness
Claims 46 and 47 remain 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 pre-AIA the applicant regards as the invention.
The rejection regarding a chimeric Ig “further comprising a replacement of an endogenous Ig heavy chain constant (CH) gene segment with a human Ig CH gene segment, wherein the chimeric heavy chain comprises an Ig CH region comprising a human IgCH doman and rat Ig CH domains” in claim 38 has been withdrawn in view of the amendment.
Pending rejections
A) The concept of an antibody “wherein the Ig CH region of the chimeric immunoglobulin comprises a human CH1 domain and rat CH2, CH3” and optionally rat CH4 domains as broadly encompassed by claims 46 and 47 is indefinite.
First, claim 35 does not require the chimeric Ig contains an Ig CH region, so the phrase “the Ig CH region” lacks antecedent basis.
Second, Figure 1 describes a modified rat heavy chain gene containing exons encoding a human CH1 domain and rat CH2,3 and 4 domains (pg 16, para 114).
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Pg 25, para 173, teaches “an exemplary artificial C constant region gene is a constant region gene encoding a human IgG CH1 domain and rat IgG CH2 and CH3 domain.” and pg 27, para 186, teaches: “constant region genes encode a human CH1 domain and rat CH2 CH3 domains, or a human CH1 and rat CH2, CH3 and CH4 domains.”
However, an immunoglobulin only has one CH domain, so the Ig cannot comprise a human CH1 domain, a rat CH2 domain, a rat CH3 domain, and a rat CH4 domain as required in claim 46 or a human CH1 domain, a rat CH2 domain, and a rat CH3 as required in claim 47. Therefore, the claims do not make logical, legal, or scientific sense.
Response to arguments
Applicants argue the amendment overcomes the rejection. Applicants’ argument is not persuasive for reasons set forth above.
Claim Rejections - 35 USC § 102
The rejection of claims 35-39 under pre-AIA 35 U.S.C. 102b as being anticipated by McWhirter (9204624) was withdrawn. McWhirter is limited to a transgenic rat whose genome comprises a randomly integrated transgene encoding a rearranged human Ig VH gene segment operably linked to an endogenous Ig CH gene segment (claim 1; description of Fig. 1 and Example 2 (col. 92) and Example 3 (col. 96)). The antibody produced by the rat comprises a human Ig VH region and a rat Ig CH region. McWhirter did not teach this randomly integrated transgene allowed VH or VL gene segments to undergo rearrangement or produce “a repertoire of variable regions” as required in claim 35.
The art at the time of filing did not teach or suggest a genetically modified rat having the structures/functions of those required to perform the “process” portion of the of the “product-by-process” in claim 35.
Double Patenting
The chimeric antibody claimed is patentably distinct from the rodent germ cell with an endogenous Ig gene inactivated by meganuclease in 8703485 (12130818) and the rat with an ablated endogenous Ig heavy chain gene and/or ablated endogenous Ig light chain gene in 9388233 (13192407).
The rejection of claims 35-39 on the ground of nonstatutory double patenting as being unpatentable over the claims of U.S. Patent No. 10072069 (15206063) was withdrawn in view of the terminal disclaimer filed 8-28-23.
Conclusion
Claims 35 and 38 are allowable, but there is an objection to claim 35.
Claims 46 and 47 remain rejected.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Green (6833268) taught transgenic mice in which the entire endogenous IgG gene is inactivated and replaced with the entire human IgG gene which contains the Ch1 gene segment (col. 11, lines 24-43; col. 12, line 51; col. 14, line 29; col. 25, line 53).
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Michael C. Wilson
/MICHAEL C WILSON/
Primary Examiner, Art Unit 1638
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