DETAILED ACTION
Applicant’s amendment and response received on 4/13/26 has been entered. Claims 1-21 and 23-25 are now canceled, and new claims 26-35 have been added. Claims 22 and 26-35 are currently pending and under examination in this application. The present application is being examined under the pre-AIA first to invent provisions. An action on the merits follows.
Those sections of Title 35, US code, not included in this action can be found in a previous office action.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 1/14/26 and 8/18/26 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.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) and 35 U.S.C. 120 as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
As noted in the previous office action, the disclosure of the prior-filed application, provisional Application No. 61/133,274, filed on 6/27/08, hereafter referred to as the provisional ‘274 application, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. Applicant does not dispute the lack of disclosure in the provisional application.
The previous office action further stated that in addition, the disclosures of the prior-filed applications, Application No. 12/589,181, filed on 10/19/09, hereafter referred to as the ‘181 application, and Application No. 12/459,285, filed on 6/29/09, hereafter referred to as the ‘285 application, fail to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. Specifically, neither the ‘181 application nor the ‘285 application provide support for a library of cells as claimed wherein the at least two nucleic acids sequences encoding heavy chain variable regions present in each cell are under the control of different regulatory elements, and/or are expressed at different levels in the cell as recited in previously pending and now canceled claims 4 or 13, and claims 5 or 14 respectively, and which is now recited in new claims 28-29. Furthermore, it was stated that neither the ‘181 application or the ‘285 application disclose screening a library comprising performing a bioassay measuring “antagonistic activating activity” as recited in previously pending claims 22-23. It was stated in the previous office action that the first disclosure of the subject matter indicated above appears in the claims filed in Application No. 15/863,787, which was filed on 1/5/18.
The applicant argues that amended and new claims, claims 22 and 26-35, are all entitled to benefit of priority to the ‘285 application, filed on 6/29/09. According to applicant, claim 22 as amended now recites the limitation of screening the library by performing a bioassay measuring antagonistic or activating activity. The applicant argues that paragraphs 44-45 describes a library of “oligoclonic” host cells that express mixtures of antibodies, but also incorporates by reference both WO/04106375 and WO/05068622. The applicant states that what it already known in the art need not taught and may preferably be omitted from the specification. The applicant argues that the disclosure of the WO/05068622 publication is incorporated by reference and includes extensive disclosure of bioassays for screening libraries by measuring antagonistic or activating activity, and further provides express disclosures related to limitations of new claims 28 and 29. In response, regarding the amended limitation in claim 22 for screening the library by performing a bioassay measuring antagonistic or activating activity, it is noted that while the ‘285 application does not recite “bioassay”, the specification does disclose several assays for screening the activity, including inhibitory activity and immune complex formation, of for example IL-6 antibodies- see paragraphs 208-210. As amended claim 22 now recites “antagonistic or activating activity” and not “antagonistic activating activity”, it is acknowledged that the ‘286 application specification supports the limitations of claim 22. Note that applicant’s argument concerning the incorporation by reference of two WO publications as providing support for claim 22 was not found persuasive nor was it the basis for the determination that claim 22 finds support in the ‘286 application.
In regards to applicant’s argument that the elements of claims 28-29 can be found in WO/05068622 whose teachings have been incorporated by reference, the applicant is reminded that as set forth in 37 CFR 1.57 (d):
d) "Essential material" may be incorporated by reference, but only by way of an incorporation by reference to a U.S. patent or U.S. patent application publication, which patent or patent application publication does not itself incorporate such essential material by reference.
The limitations in claims 28 and 29 respectively, where in the library of cells the at least two nucleic acids sequences encoding heavy chain variable regions present in each cell are under the control of different regulatory elements, and/or are expressed at different levels in the cell are material essential to the written description and enablement of these claims. Applicant may not rely on the incorporation of teachings from a WO publication to provide the missing teachings. Furthermore, it is not agreed that the library of cells and its particular elements regarding regulatory elements and expression levels are well known in the prior art. As such, it is maintained that the subject matter recited in claims 28 and 29 is not entitled to the benefit of priority to either the ‘285 or ‘181 applications.
Based on the above analysis, the effective filing date for the claim is as follows: claims 1-2, 7, 10, 12, 16, 19, 21, and 24-25 are entitled by benefit of priority under 35 U.S.C. 120 to an earliest effective filing date of 6/29/09 based on the filing date of Application No. 12/459,285; and claims 28-29 are entitled by benefit of priority under 35 U.S.C. 120 to an earliest effective filing date of 1/5/18 based on the filing date of Application No. 15/863,787.
Claim Rejections - 35 USC § 112
The rejection of previously pending claims 8-9, 17-18, and 22-25 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, is withdrawn over canceled claims 8-9, 17-18, and 23-25, and further withdrawn over claim 22 based on applicant’s amendments to claim 22.
The rejection of previously pending claims 1-2, 4-5, 7-10, 12-14, 16-19, and 21-25 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, for scope of enablement is withdrawn over canceled claims 1-2, 4-5, 7-10, 12-14, 16-19, 21, and 23-25 and maintained in modified form over amended and new claims 22 and 26-35. Applicant’s amendments to the claims and arguments have been fully considered but have not been found persuasive in overcoming the modified grounds of rejection set forth below.
Based on the claims as currently amended, the following scope of enablement has been identified: the specification, while being enabling for a method for identifying a cell producing antibodies having at least two separate heavy chain variable regions having different target epitopes that antagonize or activate a function of a molecule comprising at least one of said target epitopes, comprising: producing a library of cells, wherein essentially each cell comprises nucleic acid that encode at least two different heavy chain variable regions each having specificity for different targets or for different target epitopes, such production comprising: isolating nucleic acid encoding heavy chain variable regions from B cells of transgenic murine animals that have been immunized to generate an immune response against different targets or targets containing different target epitopes, wherein the genomes of the transgenic murine animals comprise a transgene comprising a single human immunoglobulin light chain V gene segment fused to a single human immunoglobulin light chain J gene segment, wherein the fused V/J gene segments encode a rearranged immunoglobulin light chain variable region, wherein the transgene lacks a regulatory element that contributes to somatic hypermutation of the rearranged immunoglobulin light chain variable region, and wherein the transgene comprises a light chain constant region gene segment; wherein at least one of the endogenous light chain loci in said transgenic murine animal is functionally silenced; and wherein said transgenic murine animals produce populations of B cells producing repertoires of target- or target epitope-specific antibodies, wherein said repertoires of antibodies comprise the rearranged light chain immunoglobulin variable region encoded by the fused V/J gene segments paired with a diversity of heavy chain variable regions; and transfecting nucleic acid encoding said heavy chain variable regions and nucleic acid encoding said rearranged immunoglobulin light chain variable region into host cells, and allowing for integrating of said nucleic acid into the genome of said host cells, thereby producing a library of cells that produces antibodies comprising said heavy chain variable regions and said rearranged light chain variable region, and contacting the library with said different target epitopes and screening for and selecting a cell expressing heavy chain variable regions recognizing said target epitopes and performing a bioassay measuring said antagonistic or activating activity, does not reasonably provide enablement for said process using a transgenic avian animal wherein the transgene lacks a regulatory element that contributes to somatic hypermutation of the light chain variable region in the transgenic avian. 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.
The claims were previously limited to isolating nucleic acid encoding heavy chain variable regions from B cells isolated from any transgenic non-human animal. Independent claim 22 has been amended to recite that the transgenic animal is a murine animal or an avian animal. It is noted that applicant’s amendments and arguments have overcome previously raised issues related to genomic modification in murine animals other than mice, such as rats. However, the rejection of record is maintained in modified form over generating and using transgenic avian animals whose genome comprises the claimed transgene, particularly at the endogenous avian light chain locus, and where the at least one of the endogenous light chain loci is functionally silenced, wherein the transgene is expressed and the avian produces antibodies comprising a light chain comprising the transgene encoded human light chain variable region and a diversity of endogenous heavy chains. The claims as amended further raise the issue of the lack of enabling disclosure regarding regulatory elements that contributes to somatic hypermutation of the light chain variable region in an avian.
In regards to the enablement for making transgenic avians and particularly avians with site-specific insertions of a transgene into a particular locus, or site-specific deletions of one of the endogenous avian light chain loci, the applicant argues that it was recognized in the prior art that transgenic avians were possible including germ line transmission of transgenes, citing Scott and Lois. The applicant also argues that ES cells that can colonize the germ line of animals other than mice were reported by a number of groups, citing abstracts by Li et al., Buehr et al., and Ueda et al. In response, none of references cited- Scott and Lois, Li et al., Buehr et al., or Ueda et al.- were provided with the instant response or cited in an IDS. As such, the teachings of these references could not be evaluated, and applicant’s arguments based on these references have not been found persuasive.
In regards to the generation of B cells expressing antibody specific antibodies comprising a light chain comprising the human rearranged light chain variable region encoded by the transgene and an endogenous heavy chain in transgenic immunized avians as currently claimed, the applicant argues that Flajnik et al., cited in the rejection of record, recognized fundamental structural and functional similarities of the claimed transgenic and avian animals. According to applicant, Flajnik et al. states that birds, humans, and mice all have immunoglobulin loci comprising V, D, and J gene segments, even if they differ in the number of individual segments and relative utilization of VDJ rearrangement and somatic mutation. The applicant states that the rejection of record does not identify why the skilled artisan would not reasonable conclude that the human and avian sequences would pair.
In response, the rejection of record stated that the specification 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. Further, the specification only provides guidance for inactivating an endogenous mouse kappa or lambda light chain locus by deleting a portion of each locus in the mouse genome using targeted homologous recombination. 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 avines, but provides no specific guidance for preparing a transgenic avine. The word avine only appears once in the specification in paragraph 17. The specification provides no guidance for manipulating the avian genome, and in particular no guidance for targeted knockin or knockout at an endogenous avian light chain locus. 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. Regarding regulatory elements that contribute to somatic hypermutation, the specification only discloses the mouse MoEki enhancer and a mouse 3’ kappa enhancer, and further only teaches and demonstrates that lack of the mouse intronic enhance (MoEki enhancer) and/or the present of a truncated mouse 3’ kappa enhancer can affect somatic hypermutation. The specification does not teach that these same regulatory elements are present in the avine light chain immunoglobulin locus, or that any such sequences present in avines have the same function in regards to somatic hypermutation as they have in mice. Thus, the specification, while broadly teaching the generation of non-human animals, including an avine, provides no specific guidance for generating a targeted insertion into the genome of an avine, and further does not disclose regulatory elements that contribute to somatic hypermutation in avians (avines).
In addition, the rejection of record pointed out that 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). While applicant is correct that Flajnik does teach that many animals including chickens (avians), mice, and humans have V, (D),and J gene segments, Flajnik further teaches that in contrast to humans and mice which utilize gene rearrangement of light chain locus comprising multiple V gene segments and multiple J gene segments followed by somatic hypermutation to diversify the light chain loci, the avian light chain locus comprises only a single functional V gene segments and a single functional J gene segment and utilizes a completely different mechanism for generating antibody diversity which involves gene conversion between multiple V pseudogenes and the single functional V gene segment (see Flajnik, Box 1, Table I). Flajnik et al. teaches:
[s]o, in contrast to the human and mouse models, in which B cells are generated throughout life in the bone marrow, chicken B cells (and most probably B cells in all GALT species) seed secondary lymphoid tissues early in life, after which time the primary lymphoid tissue degenerates (FIG. 2 and TABLE 1).There is only a single functional V gene that rearranges at chicken heavy- and light-chain loci (chickens have only one light chain of the λ type) in developing B cells, which is modified by gene conversion by upstream V pseudogenes (Flajnik et al., page 690)
Flajnik et al. also states: “[t]he V(D)J-recombination events that occur in chicken B cells do not create diversity as in mouse and human B cells but, instead, provide the substrate for subsequent gene-conversion events that create the antibody repertoire” (Flajnik et l., page 690). Thus, contrary to applicant’s argument, Flajnik et al. identifies substantial differences between the immunoglobulin loci in mice and humans, versus avians such as chickens, and the methods in which antibody diversity is generated in these animals. Furthermore, in regards to regulatory elements associated with somatic hypermutation, Flajnik et al. teaches that the mechanism and components required for gene conversion and/or hypermutation were still being elucidated (Flajnik et al., page 694). Blagodatski et al. states in 2009, several months after the effective filing date, that they were searching for the elusive cis-acting hypermutation control sequence in the chicken IgL locus (Blagodatski et al. (2009) PloS Genet., Vol. 5(1): e100332 doi:10.1371/journal.pgen.1000332, pages 1-11). Thus, at the time of filing, not only were the substantial mechanistic differences between antibody production in avians versus mice and humans well known, but the regulatory elements required and associated with somatic hypermutation in chickens were yet to be identified.
Therefore, it is maintained that due to the art recognized substantial differences in Ig loci and diversity generation between humans and mice, and avians, the lack of specific guidance in the specification for inserting transgenes into the genomes of animals other than mice, the lack of guidance in the specification and in the art at the time of filing regarding regulatory elements associated with somatic hypermutation in chickens, 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 the methods of producing an antigen specific antibody expressing B cell as claimed where the transgenic animal is a transgenic avian.
Claim Rejections - 35 USC § 102
The rejection of claims 1 and 7-10 under pre-AIA 35 U.S.C. 102(b) as being anticipated by U.S. Patent Application Publication 2005/0170398 (2005), hereafter referred to as Van Berkel et al., is withdrawn in view of the cancellation of claims 1 and 7-10.
Claim Rejections - 35 USC § 103
The rejection of claims 4-5 under pre-AIA 35 U.S.C. 103(a) as being unpatentable over U.S. Patent Application Publication 2005/0170398 (2005), hereafter referred to as Van Berkel et al., in view of U.S. Patent Application Publication 2012/0101000 (2012), hereafter referred to as Zhou, with an effective filing date of 11/20/2009, is withdrawn in view of the cancellation of these claims.
The rejection of previously pending claims 1-2, 7-10, 12, 16-19, 21, and 24-25 under pre-AIA 35 U.S.C. 103(a) as being unpatentable over U.S. Patent Application Publication 2005/0170398 (2005), hereafter referred to as Van Berkel et al., in view of U.S. Patent Application Publication 2006/0015957 (2006), hereafter referred to as Lonberg '957, de Wildt et al. (1999) J. Mol. Biol., Vol. 285, 895-901, and the V-BASE sequence directory (1997) www2.mrc-lmb.cam.ac.uk., is withdrawn in view of the cancellation of these claims.
The rejection of previously pending claims 4-5 and 13-14 under pre-AIA 35 U.S.C. 103(a) as being unpatentable over U.S. Patent Application Publication 2005/0170398 (2005), hereafter referred to as Van Berkel et al., in view of U.S. Patent Application Publication 2006/0015957 (2006), hereafter referred to as Lonberg '957, de Wildt et al. (1999) J. Mol. Biol., Vol. 285, 895-901, and the V-BASE sequence directory (1997) www2.mrc-lmb.cam.ac.uk, as applied to claims 1-2, 7-10, 12, 16-19, 21, and 24-25 above, and further in view of U.S. Patent Application Publication 2012/0101000 (2012), hereafter referred to as Zhou, with an effective filing date of 11/20/2009, is withdrawn in view of the cancellation of these claims.
The rejection of claims 22-23 under pre-AIA 35 U.S.C. 103(a) as being unpatentable over U.S. Patent Application Publication 2014/0314755 (2014), hereafter referred to as Logtenberg et al., in view of U.S. Patent Application Publication 2007/0059766 (2007), hereafter referred to as Logtenberg 2007, is withdrawn over canceled claim 23, and further withdrawn over claim 22 in view of applicant’s amendments to the claims which now recite that the transgene comprises a light chain constant region gene segment and lacks a regulatory element that contributes to somatic hypermutation of the rearranged immunoglobulin light chain variable region.
Applicant’s amendments to the claims has necessitated the following new grounds of rejection.
New claims 28-29 are newly rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over U.S. Patent Application Publication 2014/0314755 (2014), hereafter referred to as Logtenberg et al., in view of U.S. Patent Application Publication 2007/0059766 (2007), hereafter referred to as Logtenberg 2007, U.S. Patent Application Publication 2005/0170398 (2005), hereafter referred to as Van Berkel et al., and U.S. Patent Application Publication 2012/0101000 (2012), hereafter referred to as Zhou.
Note that claims 28-29 are only entitled by benefit of priority under 35 U.S.C. 120 to an earliest effective filing date of 1/5/18 based on the filing date of Application No. 15/863,787. See the discussion of priority set forth in detail above. As such U.S. Patent Application Publication 2014/0314755 qualifies as prior art under pre-AIA 35 U.S.C. 102(b).
Logtenberg et al. teaches methods of making a library of cells encoding rearranged heavy chain variable region sequences obtained from B cells of an immunized transgenic mouse whose genome comprises a transgene comprising a rearranged human V-K sequence which comprises a human immunoglobulin light chain germline V gene segment sequence fused to a human immunoglobulin light chain germline J gene segment without mutation, and where (Logtenberg et al., claims 31-41, paragraphs 92, and Table 12). Note that Table 12 give the sequence of germline human Vk gene segment sequence fused directly to a germline human Jk gene segment sequence with no mutation from the fusion. Logtenberg teaches to obtain nucleic acids encoding the heavy chain variable region from transgenic whose genome comprises the single rearranged human V-J sequence which have been immunized with an antigen and generating a bacterial cell phage display library where cells in the library comprise nucleic acid encoding the heavy chain variable region sequence and the single rearranged V-J variable region sequence present in the transgenic mouse (Logtenberg et al., paragraphs 196-197). Logtenberg et al. then teaches to screen and select for clones expressing an antibody which bind to the immunizing antigen, and to generate expression vectors comprising the sequence encoding the selected heavy chain sequences (Logtenberg et al., paragraphs 205-206). Logtenberg et al. further teaches to transfect mammalian cells, particularly PER.C6 cells, with at least two to five expression vectors encoding different selected heavy chain sequences and an expression vector encoding the single rearranged V-J light chain sequence, thus providing a library of such cells, and to select stable clones (Logtenberg et al., paragraphs 196, and 214).
Logtenberg et al. differs from the methods of instant claims 28-29 by not teaching to screen the cell library of stable cells comprising nucleic acids encoding at least two to five different selected heavy chain sequences and a single rearranged V-J light chain sequence, using a bioassay to measure either an antagonistic or activating activity of the expressed antibodies against a target molecule comprising the target epitope. Logtenberg 2007 supplements Logtenberg et al. by teaching methods of screening a library of cells for antagonistic or activating activity using a bioassay for antagonism or for activation of a target molecule comprising a target epitope comprising contacting a library of cells with different target epitopes and screening for and selecting a cell expressing binding proteins recognizing the target epitopes and having either an antagonistic or activating function based o the bioassay (Logtenberg 2007, paragraphs 19-21). Logtenberg 2007 further teaches where the library of cells comprises cells comprising at least two separate single polypeptide chain binding proteins having different target epitopes, and more specifically where the cells express at least two different antibodies (Logtenberg 2007, paragraphs 30-32). Logtenberg 2007, also teaches that the method comprises transferring the nucleic acids encoding at least two separate single antigen binding chains selected in the bioassay into a production cell (Logtenberg 2007, paragraph 19).
Therefore, in view of the motivation provided by Logtenberg 2007 to screen a library of cells expressing more than one antibody using a bioassay for antagonistic or activating activity in regards to a target molecule comprising a target epitope, it would have been prima facie obvious to the skilled artisan at the time of filing to practice the screening methods taught by Logtenberg 2007 using the library of cells taught by Logtenberg et al. with a reasonable expectation of success.
Logtenberg et al. and Logtenberg 2007 further differ from the invention of claims 28 and 29 by not teaching to use different promoters to express the two or more heavy chain variable region sequences in the host cell, and/or that the two or more heavy chain variable regions are expressed at different levels in the host cell. Van Berkel et al. supplements Logtenberg et al. and Logtenberg 2007 by teaching a similar host cell stably transformed with nucleic acid sequences encoding a single common light chain variable region and at least 2, including 3, 4 ,5 ,6 ,7 ,8 , 9, and 10 or more, different nucleic acids encoding different heavy chain variable region sequences, where the 2 or more heavy chain variable regions sequence have specificity for different target antigens, or different epitopes within the same target antigen, where the heavy chain variable regions are expressed and secreted as IgG, IgA, or IgM, and where the heavy chains are fully human or chimeric (Van Berkel et al., paragraphs 18-19, 55-63, 95, and 97). Van Berkel et al. further teaches that the at least two different heavy chain may be expressed at different levels (Van Berkel et al., paragraph 22, 62, and 83). Van Berkel et al. also teaches that host cell can be cloned and that the population of clones, i.e. a library of clones, can be screened for the production of a mixture of antibodies having a desired effect (Van Berkel et al., paragraph 22, 62, and 81). Van Berkel et al. teaches to transform the host cells with vector(s) encoding the 2 or more heavy chain variable regions, where each heavy chain is encoded by a different vector or by the same vector, and where each vector comprises a promoter and other regulatory elements for driving expression of the encoded variable regions (Van Berkel et al., paragraphs 63-66). Van Berkel et al. also teaches a particular expression vector for expression of the heavy chain where the vector comprises the HAVT20 leader sequence which comprises a secretion signal peptide (Van Berkel et al., paragraph 115). Van Berkel et al. further teaches that the host cells are eukaryotic cells, or mammalian cells such as human cells (Van Berkel et al., paragraph 68). In particular, Van Berkel et al., like Logtenberg, teaches the use of the immortalized PER.C6.TM cell as the host cell (Van Berkel al., paragraphs 68 and 70).
While Van Berkel et al. teaches that various promoters can be used to express the heavy and light chain sequences in the host cell, and further teaches that heavy chains may be expressed at different levels, Van Berkel et al. does not specifically teach the use of at least two different regulatory elements to express the heavy chains. Zhou supplements Van Berkel et al. by teaching that different promoters can be used in the same or in separate vectors to express immunoglobulin chains in a mammalian cell, including a number of promoters taught by Van Berkel et al. (Zhou et al., paragraph 108). Thus, in view of the teachings of Zhou et al. that more than one immunoglobulin chain can be expressed in a mammalian cell using different promoters, and the teachings of Van Berkel al. that various promoters can be used to express the heavy and light chain sequences in the host cell and that the two or more heavy chains may be expressed at different levels, it would have been prima facie obvious to the skilled artisan at the time of filing to construct a single vector or multiple vectors encoding the two or more heavy chain variable regions and the common light chain variable region for use in the methods of screening taught by Logtenberg et al. in view of Logtenberg 2007, where each immunoglobulin chain is operably linked to its own promoter element and where the promoter element for each heavy chain variable region sequence is different, thus resulting in different levels of expression of each immunoglobulin heavy chain variable region in the library of cloned host cells, with a reasonable expectation of success.
Double Patenting
The rejection of previously pending claims 1-2, 4-5, 7-10, 12-14, and 16-19 on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 11,785,924, hereafter referred to as the ‘924 patent, is withdrawn in view of applicant’s cancellation of these claims.
The provisional rejection of previously pending claims 1-2, 4-5, 7-10, 12-14, 16-19, 21, and 24-25 on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-4, 22, 25-27, and 30-35 of copending Application No.15/866,374, hereafter referred to as the ‘374 application in view of U.S. Patent Application Publication 2005/0170398 (2005), hereafter referred to as Van Berkel et al., is withdraw in view of the cancellation of these claims.
No claims are 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.
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.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
Dr. A.M.S. Wehbé
/ANNE MARIE S WEHBE/Primary Examiner, Art Unit 1634
Prosecution Insights