DETAILED ACTION
Claims 1-14 are currently pending in this application. The present application is being examined under the pre-AIA first to invent provisions. An action on the merits follows.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 4/25/24, 4/29/25, 5/2/25, and 7/1/25 are in compliance with the provisions of 37 CFR 1.97 and 1.98. Accordingly, the information disclosure statements have been considered by the examiner, and initialed and signed copies of the 1449s are attached to this action.
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 6-14 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 pre-AIA the applicant regards as the invention.
Independent claim 6 recites in (1)(i) that , “the transgene comprises an immunoglobulin constant region”, and in (1)(ii) that, “said rearranged human immunoglobulin variable region is linked to an endogenous immunoglobulin constant region”. Claim 6 also recites, “wherein the transgenic animal has produced a repertoire of antibodies that bind said antigen having the rearranged human immunoglobulin variable region encoded by the rearranged human immunoglobulin variable region comprised in said transgene..”. The claim is confusing as the rearranged human immunoglobulin variable region refers to polypeptide encoded by the transgene- see (1) which recites, “a transgene encoding a rearranged human immunoglobulin variable region”. The sequence which encodes the variable region and which is present in the transgene is a rearranged human immunoglobulin variable region nucleotide sequence. In the portions of the claim cited above, it is therefore confusing whether applicant is referring to a polypeptide or to an nucleotide sequence or is attempting to use the same term to refer to both an amino acid sequence and a nucleotide sequence. As such, the metes and bounds of the claim cannot be determined. Claims 7-14 all depend either directly or indirectly on claim 6 and thus are included in this rejection.
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.
Claims 1-14 are 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 an antibody producing B cell isolated from a transgenic mouse whose genome comprises a transgene encoding a single rearranged human immunoglobulin light chain variable region or a single rearranged human immunoglobulin heavy chain variable region, where sequence encoding the rearranged human variable region is operatively linked to an endogenous constant region gene segment, does not reasonably provide enablement for an antibody producing B cell isolated from any transgenic non-human animal whose genome comprises the claimed transgene operatively linked to an endogenous constant region gene segment. 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 or use the invention commensurate in scope with these claims.
Claims 1-5 read on B cells isolated from a transgenic murine animal, whereas claims 6-12 read on B cells isolated from any transgenic non-human animal, or nucleic acid sequences obtained from those B cells. The term “murine” refers to the subfamily Murinae, which includes rats and mice, of which there are hundreds of individual species. The genus of non-human animals includes millions of species including insects, amphibians, invertebrates both aquatic and land based, avians, and mammals. The specification, however, only provides specific guidance for generating transgenic mice, and further provides specific guidance for transgenes comprising a single human V gene segment fused to a single J gene segment and encoding a single rearranged human light chain variable region and wherein the rearranged V-J genes are operably linked either to a constant region present in the transgene, or are site-specifically inserted into the mouse genome into the kappa light chain locus such that the V-J sequence present in the transgene is operably linked to the endogenous kappa light chain constant region gene. The specification clearly teaches that the purpose of the transgenic non-human animals, specifically mice, is the generation of human/humanized antibodies. The specification discloses that other non-human mammals may be generated, including rats, but provides no specific guidance for preparing a transgenic rat or any other non-human animal of any species. The working examples are limited to the generation and use of transgenic mice whose genome comprises a transgene encoding a single rearranged human kappa V gene segment where the transgene comprises a human IGVK1-39 gene sequence fused to a human JK gene segment and operably linked to a murine constant region gene, where the transgene lacks the MoEki enhancer and/or contains a truncated mouse 3’ kappa enhancer, where the transgene has been inserted into a mouse ES cell which is then implanted into a surrogate female mouse. Thus, the specification, while broadly teaching the generation of non-human animals with a targeted insertion into an immunoglobulin locus, provides no specific guidance for generating a targeted insertion into the genome of any other non-human animal. The specification does not disclose ES cells from any species of animal other than the mouse, or provide alternative methods to generate a knockin genotype in the genome of a non-huma animal which do not rely on the use of ES cells which are manipulated in vitro and are capable of contributing to the germline of an animal.
At the time of filing, circa 2008, the technology to produce animals with a gene-targeted knockout or knockin was considered limited to transgenic mice because the available technology used homologous recombination in embryonic stem (ES) cells, and at the time of invention only mouse ES cells were available for the production of transgenic mice by homologous recombination. This is because only mouse ES cells were known to be able to colonize the germ line. Clark et al., states "despite intensive efforts, knockout technology is limited to mouse as germline competent ES cells have not been developed for other species of mammals" (Clark et al. (2003) Nature Reviews: Genetics. Vol. 4, 825-833, page 828, col. 1, para. 1, lines 18-21). This is further supported by Niemann et al. who assert that the "true ES cells, those able to contribute to the germ line, are only available from inbred mouse strains" (Niemann et al (2005) Rev. Sci, Tech. Off. Int. Spiz. Vol. (24), 285-298, pages 290 last para. bridging to page 291, para.1). Niemann further emphasizes that ES-like cells and primordial germ cells have been reported for several farm animal species without germ line contribution (page 291, col. 1, lines 5-9). Likewise, Wheeler states ES cells have been isolated from several species including Syrian golden hamster, rat, rabbit, mink, pig, cow, sheep and primate, but the totipotency, the ability to colonize the germ line, awaits validate in the form of transgenic offspring (Wheeler (2001) Theriogenology. Vol. 56, 1345-1369, page 1351, para. 1). Prelle et al. states many attempts have been made to establish ES and EG cell lines from species other than mouse; however, there is no data that these cells can colonize the germ line of chimeric animals (Prelle et al. (2002) Anat. Histol. Embryol., Vol. 31, 169-186, see page 172, col. 1, lines 1-11). Finally, Munoz et al. teaches that even as of 2009, months after the effective filing date of this application, and despite extensive investigation, ES cells lines from animals other than mouse and human had yet to be established due to difficulties in the isolation and maintenance of ESC lines from other species (Munoz et al. (2009) Stem Cell Rev. and Rep., Vol. 5, 6-9, pages 6 and 9). Thus, the art of record clearly establishes that at the time of filing, of non-human animal species, only mouse ES cells were known to colonize the germ line, and therefore, the prior art at the time of filing only provides support for the production of knockin mice using mouse ES cells.
In addition, at the time of filing it was well known that not all animal species share the same or equivalent immunoglobulin loci structure or functions. Flajnik et al., for example, teaches that there are substantial differences in antibody loci structure, the classes and structure of antibody generated, and the mechanism of producing antibody diversity between placental mammals, avians, amphibians, and various fish (Flajnik et al. (2002) Nat. Rev., Vol. 2, 688-698). Flajnik further teaches that while certain vertebrates including several mammals utilize gene conversion for generating diversity- referred to as GALT species by Flajnik, which include chickens, rabbits, and cows, many other mammals, including mice and humans, utilize rearrangement and somatic hypermutation for generating antibody diversity (see Flajnik, Table I). Thus, the art at the time of filing establishes that there are substantial differences in antibody loci structure, the classes and structure of antibody generated, and the mechanism of producing antibody diversity not only between disparate animal such as mammals, avians, amphibians, and various fish, but that such structural and mechanistic divergence is observed even between various mammalian species. As such, the skilled artisan would not have been able to predict without undue experimentation whether a rearranged human variable region sequence would be able to functionally join with any constant region sequence and be further able to pair with any endogenous cognate variable region sequence.
Thus, due to the art recognized substantial differences in Ig loci and diversity generation between humans and mice and other animals, including other mammals, the lack of specific guidance in the specification for inserting transgenes into the genomes of animals other than mice, the lack of availability at the time of filing for ES cells capable of contributing to the germ line of any non-human animal other the mouse, the limitation of the working examples to the generation of knock-in transgenic mice using mouse ES cells, and the breadth of the claims, it would have required undue experimentation to make and use the scope of B cells isolated from transgenic animals as claimed.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of pre-AIA 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 –
(b) the invention was patented or described in a printed publication in this or a foreign country or in public use or on sale in this country, more than one year prior to the date of application for patent in the United States.
Claims 6-14 are rejected under pre-AIA 35 U.S.C. 102(b) as being anticipated by U.S. Patent Application Publication 2006/0015957 (2006), hereafter referred to as Lonberg '957.
It is noted that the claims 6-11 as written read on B cells derived from two alternative transgenic mouse, one in which the transgene comprising the rearranged variable region sequence also comprises a constant region gene sequence, and the second in which the transgene comprising the rearranged variable region sequence is linked to an endogenous immunoglobulin constant region sequence. This 102 rejection is based on the first alternative where the transgene further comprises a constant region gene sequence.
Lonberg et al. teaches transgenic mice with disrupted endogenous immunoglobulin loci whose genome comprises human unrearranged or rearranged human immunoglobulin heavy and light chain transcripts useful for producing human or humanized antibodies (Lonberg et al., paragraphs 16-17, 25, Figure 33, 196-197, 201, 222, 232-233, and 265). Lonberg et al. teaches that preferred embodiments include a transgenic mouse comprising a rearranged human light chain transgene and an unrearranged human heavy chain transgene (Lonberg et al., paragraphs 48, 175, 197-198, 201, 232-233, 481-482, and 562, and Figure 33). Lonberg et al. further teaches that the rearranged light chain is a kappa light chain and that the transgene encoding the rearranged light chain comprises a human Vk sequence joined to a Jk sequence and further comprising a Ck sequence (Lonberg et al. paragraphs 481-482 and Figure 33). In particular, Lonberg et al. teaches that transgenic mice generated from a transgene construct comprising a rearranged human light chain variable region can be bred with human unrearranged heavy chain transgenic mice to produce a mouse which expresses a spectrum of antibodies in which the diversity of the primary repertoire is contributed by the unrearranged heavy chain transgene (Lonberg et al., paragraph 482). Lonberg et al. further teaches that, “The advantage of this scheme, as opposed to the use of unrearranged light chain miniloci, is the increased light chain allelic and isotypic exclusion that comes from having the light chain ready to pair with a heavy chain as soon as heavy chain VDJ joining occurs” (Lonberg et al., paragraph 482). In an alternative embodiment, Lonberg et al. teaches that the rearranged huma variable region sequence is a rearranged huma heavy chain variable region sequence, where a functional human rearranged VDJ sequence is inserted into a transgene construct in operable linkage to one or more heavy chain constant region sequence(s), which is then microinjected into the pronuclei of mouse embryos to generate transgenic animals (Lonberg et al., paragraph 544). Lonberg et al. further teaches isolating B cells from immunized transgenic mice, immortalizing the B cells, culturing the immortalized B cells and collecting antibody produced by the immortalized B cells (Lonberg et al., paragraph 331). In addition, Lonberg et al. teaches the use of B cells as a source of nucleic acid encoding the rearranged light chain variable region and cognate heavy chain variable region, or vice versa, which can then be cloned into one or more expression vectors and introduced into a recombinant host cell capable of expressing the encoded antibody (Lonberg et al., paragraphs 332, 335, 374-378, 382-383, and 562-565). Thus, by teaching all the limitations of the claims as written, Lonberg et al. anticipates the instant invention as claimed.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 6-14 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over U.S. Patent Application Publication 2006/0015957 (2006), hereafter referred to as Lonberg '957, in view of WO 02/066,630 (2002), hereafter referred to as Murphy et al..
As noted above, claims 6-11 read on two alternative transgenes present in the genome of the transgenic mouse from which the B cells are derived. This rejection is directed to the second alternative in which the transgene comprising the rearranged variable region sequence is linked to an endogenous immunoglobulin constant region sequence.
Lonberg et al. teaches transgenic mice with disrupted endogenous immunoglobulin loci whose genome comprises human unrearranged or rearranged human immunoglobulin heavy and light chain transcripts useful for producing human or humanized antibodies (Lonberg et al., paragraphs 16-17, 25, Figure 33, 196-197, 201, 222, 232-233, and 265). Lonberg et al. teaches that preferred embodiments include a transgenic mouse comprising a rearranged human light chain transgene and an unrearranged human heavy chain transgene (Lonberg et al., paragraphs 48, 175, 197-198, 201, 232-233, 481-482, and 562, and Figure 33). Lonberg et al. further teaches that the rearranged light chain is a kappa light chain and that the transgene encoding the rearranged light chain comprises a human Vk sequence joined to a Jk sequence and further comprising a Ck sequence (Lonberg et al. paragraphs 481-482 and Figure 33). In particular, Lonberg et al. teaches that transgenic mice generated from a transgene construct comprising a rearranged human light chain variable region can be bred with human unrearranged heavy chain transgenic mice to produce a mouse which expresses a spectrum of antibodies in which the diversity of the primary repertoire is contributed by the unrearranged heavy chain transgene (Lonberg et al., paragraph 482). Lonberg et al. further teaches that, “The advantage of this scheme, as opposed to the use of unrearranged light chain miniloci, is the increased light chain allelic and isotypic exclusion that comes from having the light chain ready to pair with a heavy chain as soon as heavy chain VDJ joining occurs” (Lonberg et al., paragraph 482). In an alternative embodiment, Lonberg et al. teaches that the rearranged huma variable region sequence is a rearranged huma heavy chain variable region sequence, where a functional human rearranged VDJ sequence is inserted into a transgene construct in operable linkage to one or more heavy chain constant region sequence(s), which is then microinjected into the pronuclei of mouse embryos to generate transgenic animals (Lonberg et al., paragraph 544). Lonberg et al. further teaches isolating B cells from immunized transgenic mice, immortalizing the B cells, culturing the immortalized B cells and collecting antibody produced by the immortalized B cells (Lonberg et al., paragraph 331). In addition, Lonberg et al. teaches the use of B cells as a source of nucleic acid encoding the rearranged light chain variable region and cognate heavy chain variable region, or vice versa, which can then be cloned into one or more expression vectors and introduced into a recombinant host cell capable of expressing the encoded antibody (Lonberg et al., paragraphs 332, 335, 374-378, 382-383, and 562-565).
While Lonberg et al. clearly teaches transgenic mice comprising unrearranged human light chain or heavy chain transgenes which express chimeric immunoglobulin light or heavy chains comprising a human variable region and a mouse constant region, Lonberg et al. does not specifically teach a transgenic mouse comprising a rearranged human light or heavy chain transgene linked to an endogenous mouse constant region gene and which expresses chimeric immunoglobulin light chains comprising a human variable region and a mouse constant region. However, as discussed in detail above, Lonberg et al. does specifically teach that transgenic mice expressing human light or heavy chain variable regions can be made using either an unrearranged or rearranged human immunoglobulin light chain or heavy chain transgene. Lonberg et al. further provides specific motivation for using a rearranged rather than an unrearranged light chain transgene by teaching that the advantage of using a rearranged light chain transgene, as opposed to the use of unrearranged light chain miniloci, is the increased light chain allelic and isotypic exclusion that comes from having the light chain ready to pair with a heavy chain as soon as heavy chain VDJ joining occurs (Lonberg et al., paragraph 482). Furthermore, at the time of filing, Murphy et al. teaches that mice producing fully human antibodies have reduced affinity to mouse receptors which affects B cell maturation and survival and that this can be avoided by producing mice which express chimeric antibodies comprising human variable regions and mouse constant regions (Murphy et al., pages 42-43). According to Murphy et al., the mouse Fc regions in the chimeric antibodies are more specific than human Fc regions in their interactions with Fc receptors and other receptors important for strong and specific immune response, proliferation and maturation of B cells, and affinity maturation of antibodies (Murphy et al., pages 43-44). Murphy et al. teaches the replacement of all mouse light chain variable region V and J genes with human V and J genes and the replacement of all mouse heavy chain variable region V, D, and J genes with human V, D, and J genes such that the introduced VJ or VDJ genes are operatively linked to mouse light chain constant region genes or mouse heavy chain constant regions genes respectively (Murphy et al., page 43). Thus, based on the teachings and motivation provided by Lonberg et al. to make a transgenic mouse whose genome comprises a human immunoglobulin light chain transgene or human heavy chain transgene and which expresses a chimeric immunoglobulin light or heavy chain comprising a human light chain variable region and a mouse light chain constant region, the motivation provided by Lonberg et al. to use a rearranged human immunoglobulin light chain transgene over an unrearranged light chain transgene, the detailed guidance provided by Lonberg et al. for making immunoglobulin transgenes comprising a rearranged human light chain variable region sequence or a rearranged human heavy chain variable region sequence, and the motivation to use mouse constant region genes over human constant region genes in transgenic mice taught by Murphy et al., it would have been prima facie obvious to the skilled artisan at the time of filing to make a transgenic mouse whose genome comprises a transgene comprising a human rearranged light chain variable region sequence operably linked to a mouse light chain constant region sequence, or transgene comprising a human rearranged heavy chain variable region sequence operably linked to a mouse heavy chain constant region sequence, and in particular where the human rearranged variable region sequence is operably linked to an endogenous mouse constant region sequence, and which expresses a chimeric light chain or heavy chain comprising a human variable region and a mouse constant region with a reasonable expectation of success.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP §§ 706.02(l)(1) - 706.02(l)(3) for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-7 and 9-14 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of U.S. Patent No. 9,944,695, hereafter referred to as the ‘695 patent claims. Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons.
The ‘695 patent claims recite a species of the methods of instant claims 1-5, 10, 11, and 13 where the ‘695 patent claims recite methods of using a transgenic mouse to obtain an antibody comprising immunizing a transgenic mouse whose genome comprises a transgene comprising a rearranged human light chain variable region sequence comprising a human germline light chain V gene segment joined to a human germline light chain J gene segment such that there is no mutation due to said joining, where the transgene comprises a murine immunoglobulin light chain constant region gene segment or said rearranged human immunoglobulin variable region sequence is operatively liked to an endogenous immunoglobulin light chain constant region, with an antigen, obtaining B cells from the immunized transgenic mouse, isolating nucleic acids encoding at least the rearranged heavy chain, expressing the nucleic acid encoding the rearranged heavy chain with a nucleic acid encoding the rearranged light chain in a host cell, an obtaining the antibody. It is well established that a species of a claimed invention renders the genus obvious. In re Schaumann , 572 F.2d 312, 197 USPQ 5 (CCPA 1978). Thus, as the ‘695 patent claims recite a species of the instant broader claims, claims 1-3 of the ‘695 patent render the instant methods of claims 1-5, 10, 11, and 13 obvious.
In addition, the ‘695 claims render obvious the products used and made in the methods, including the B cells obtained from the transgenic mouse, the host cell comprising expressible nucleic acid encoding the claimed rearranged light chains and heavy chains, and expression systems for the isolated nucleic acid encoding the rearranged heavy and/or light chains. As such claims 1-3 render obvious instant product claims 6-7, 9, 12, and 14.
Claims 1-7, and 9-14 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 9,951,124, hereafter referred to as the ‘124 patent claims. Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons.
The ‘124 patent claims, particularly patent claims 2-4, represent a species of the instant method claims. The ‘124 patent claims recite methods of using a species of the genus of transgenic animals recited in the instant claims to prepare an antibody, where the species is limited to a transgenic mouse whose genome comprises a transgene comprises a rearranged human light chain variable region sequence comprising a human germline light chain gene segment joined to a human germline J gene segment such that there is no mutation due to said joining, where the transgene comprises a murine immunoglobulin light chain constant region gene segment or said rearranged human immunoglobulin variable region sequence is operatively liked to an endogenous immunoglobulin light chain constant region, and wherein the methods include isolating B cells from the transgenic mouse and either 1) culturing the cells and obtaining the antibody (claim 2 of the ‘124 patent) or 2) isolating nucleic acid encoding the antibodies from the isolated B cells, inserting the nucleic acids into an expression cassette and expressing the antibodies in a host cell (claim 3 of the ‘124 patent). The method steps recited in claims 2 and 3 of the ‘124 patent are the same as those recited in instant method claims 1-5, 10, 11, and 13. It is well established that a species of a claimed invention renders the genus obvious. In re Schaumann, 572 F.2d 312, 197 USPQ 5 (CCPA 1978). Thus, as a species of the instant broader claims, claims 1-4 of the ‘124 patent render obvious instant method claims 1-5, 10, 11, and 13.
In addition, the ‘124 claims render obvious the products used and made in the methods, including the B cells obtained from the transgenic mouse, the host cell comprising expressible nucleic acid encoding the claimed rearranged light chains and heavy chains, and expression systems for the isolated nucleic acid encoding the rearranged heavy and/or light chains. As such claims 1-4 of the ‘124 patent render obvious instant product claims 6-7, 9, 12, and 14.
Claims 1-7 and 9-14 are rejected on the ground of nonstatutory double patenting as being unpatentable over 1) claims 1-14 of U.S. Patent No. 10,966,411, hereafter referred to as the ‘411 patent, OR 2) claims 1-7 of U.S. Patent No. 11,559,049, hereafter referred to as the ‘049 patent, OR 3) claims 1-5 of U.S. Patent No. 9,765,133, hereafter referred to as the ‘133 patent, OR 4) claims 1-6 of U.S. Patent No. 11,925,174, hereafter referred to as the ‘174 patent, in view of U.S. Patent Application Publication 2006/0015957 (2006), hereafter referred to as Lonberg '957.
The ‘411 patent claims OR the ‘049 patent claims OR the ‘133 patent claims OR the ‘174 patent claims are product claims drawn to a species of the transgenic animals recited in the method claims of instant claims 1-5, 10, 11, and 13. The ‘411 patent claims OR the ‘049 patent claims OR the ‘133 patent claims OR the ‘174 patent claims are drawn to a transgenic mouse whose genome comprises a transgene comprises a rearranged human kappa light chain variable region sequence, where the transgene comprises a murine immunoglobulin light chain constant region gene segment or said rearranged human immunoglobulin variable region sequence is operatively liked to an endogenous immunoglobulin light chain constant region.
While the ‘411 patent claims OR the ‘049 patent claims OR the ‘133 patent claims OR the ‘174 patent claims do not recite methods of using B cells derived from said transgenic mouse, or the B cells products, or host cells expressing nucleic acids obtained from said B cells, such is disclosed in the specification of the ‘411 patent OR the ‘049 patent OR the ‘133 patent OR the ‘174 patent as a particular use for the transgenic mouse claimed in the ‘411 patent claims OR the ‘049 patent claims OR the ‘133 patent claims OR the ‘174 patent claims, and more specifically for B cells obtained from said mouse. Note that MPEP 804(II)(2)(a) sets forth instances where it is acceptable to utilize the disclosure of a U.S. patent document in conjunction with its claims for obvious-type double patenting rejections. In particular, the MPEP notes that the portion of the specification that supports the patent claims may be considered. The court in AbbVie Inc. v. Kennedy Institute of Rheumatology Trust pointed out that “this use of the disclosure is not in contravention of the cases forbidding its use as prior art, nor is it applying the patent as a reference under 35 U.S.C. 103, since only the disclosure of the invention claimed in the patent may be examined.” In AbbVie Inc. v. Kennedy Institute of Rheumatology Trust, 764 F.3d 1366, 112 USPQ2d 1001 (Fed. Cir. 2014). In particular, the court explained that it is also proper to look at the disclosed utility in the reference disclosure to determine the overall question of obviousness in a nonstatutory double patenting context. See Pfizer, Inc. v. Teva Pharm. USA, Inc., 518 F.3d 1353, 86 USPQ2d 1001 (Fed. Cir. 2008); Geneva Pharmaceuticals Inc. v. GlaxoSmithKline PLC, 349 F3d 1373, 1385-86, 68 USPQ2d 1865, 1875 (Fed. Cir. 2003). Thus, the methods and products obtained or made by the methods as instant claimed are in fact disclosed utilities of the mice recited in the ‘411 claims OR the ‘049 patent claims OR the ‘133 patent claims OR the ‘174 patent claims and thus are relevant to the obviousness of the instant methods and products.
Further, the prior art teaches uses of transgenic mice as claimed including isolation of B cell products, production of host cells expressing antibodies and expression systems encoding rearranged heavy and/or light chain variable regions derived from said B cells. Specifically, Lonberg et al. teaches a transgenic mouse whose genome comprises a rearranged human light chain transgene and an unrearranged human heavy chain transgene (Lonberg et al., paragraphs 48, 175, 197-198, 201, 232-233, 481-482, and 562, and Figure 33). Lonberg et al. teaches B cells isolated from said mouse, and the use of immortalized B cells to obtain antibodies or as a source of nucleic acid encoding the rearranged light chain variable region and cognate rearranged heavy chain variable region which can then be cloned into one or more expression vectors and introduced into a recombinant cell capable of expressing the encoded antibody (Lonberg et al., paragraphs 332, 335, 374-378, 382-383, and 562-565). Lonberg et al. further specifically teaches isolating B cells from immunized transgenic mice, immortalizing the B cells, culturing the immortalized B cells and collecting antibody produced by the immortalized B cells (Lonberg et al., paragraph 331). Lonberg et al. therefore teaches methods comprising the same method steps as set forth in the instant methods of claims 1-5, 10, 11, and 13. Thus, in view of the art-recognized methods of using transgenic mice as claimed in methods of producing B cells and antibodies as taught by the Lonberg, it would have been obvious to the skilled artisan at the time of filing to practice the methods of Lonberg using the transgenic mice recited in the ‘411 patent claims OR the ‘049 patent claims OR the ‘133 patent claims OR the ‘174 patent claims, and in the practice of those methods to produce the isolated B cells products, host cells, and expression systems as claimed in the instant claims 6-7, 9, 12, and 14 with a reasonable expectation of success.
No claims are allowed.
Any inquiry concerning this communication from the examiner should be directed to Anne Marie S. Wehbé, Ph.D., whose telephone number is (571) 272-0737. If the examiner is not available, the examiner’s supervisor, Maria Leavitt, can be reached at (571) 272-1085. For all official communications, the technology center fax number is (571) 273-8300. Please note that all official communications and responses sent by fax must be directed to the technology center fax number. For informal, non-official communications only, the examiner’s direct fax number is (571) 273-0737. For any inquiry of a general nature, please call (571) 272-0547.
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Dr. A.M.S. Wehbé
/ANNE MARIE S WEHBE/Primary Examiner, Art Unit 1634