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 .
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. The present application is drawn from PCT/US21/39389, filed 6/28/2021; and claims benefit under 35 U.S.C. 119(e) to U.S. Provisional application 63/045687, filed 6/29/2020.
Status of Claims
Claims 1-17 are pending and are being examined on the merits.
Claim Objections
Claim 17 is objected to because of the following informalities: Claim 17 recites “A method of treating EMAPII mediated disease.” As “EMAPII mediated disease” is not a specific disease defined in the art, rather it is a group of diseases whereby the anti-EMAPII antibody disclosed may bind to and reduce the levels of EMAPII available to interact with target cells (see specifications, pg. 22, last paragraph). Therefore, the particular “EMAPII mediated disease” to be treated is a singular disease selected from the group, and there should be an indefinite article (i.e., a or an) before the reference to EMAPII mediated diseases. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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.
Claims 1-7 and 13-17 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 1 recites an antibody comprising a heavy chain variable domain having an amino acid sequence with 90% or greater sequence identity to SEQ ID NO: 1 and a light chain variable domain having an amino acid sequence with 90% or greater sequence identity to SEQ ID NO: 6. However, SEQ ID NO: 1 is 471 amino acids in length, and comprises a constant domain of human IgG1. Therefore, SEQ ID NO: 1 is consistent with a full heavy chain, which comprises a VH domain. However, it is unclear if the claimed antibody is limited to only a “heavy chain variable domain” or to the full heavy chain of “SEQ ID NO: 1.” The same issue is present in SEQ ID NO: 2. As the metes and bounds of the claimed antibody are unclear, the claim is rendered indefinite. Similarly, SEQ ID NO: 6 is 239 amino acids in length, and comprises a kappa constant domain. Therefore, SEQ ID NO: 6 is consistent with a full light chain, which comprises a VL domain. However, it is unclear if the claimed antibody is limited to only a “light chain variable domain” or to the full light chain of “SEQ ID NO: 6.” The same issue is present in SEQ ID NO: 9. As the metes and bounds of the claimed antibody are unclear, claim 1 is rendered indefinite. As claims 2-3 and 13-17 depend from claim 1 but fail to rectify the indefiniteness issues, they are also rejected. Further, as claims 4-7 recite SEQ ID NOs: 1-2, 6 or 9, and use the same indefinite language, directed to a “variable domain having an amino acid sequence of SEQ ID NO:”, claims 4-7 are also rejected for indefiniteness.
Claims 1-7 and 13-17 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 1 recites an antibody comprising a heavy chain variable domain having an amino acid sequence with 90% or greater sequence identity to SEQ ID NO: 1 and a light chain variable domain having an amino acid sequence with 90% or greater sequence identity to SEQ ID NO: 6. However, as described above, SEQ ID NO: 1 is 471 amino acids in length, and comprises a constant domain of human IgG1. SEQ ID NO: 1 also comprises a VH domain; however, the VH domain is not explicitly defined in the specifications. If, for example, the VH domain comprises an amino acid sequence that is comparable to the VH of instant SEQ ID NO: 10 (see specifications, pg. 17, para. 3), that amino acid sequence is 118 amino acids in length. Therefore, it is unclear how many residues may be mutated to result in a VH that is “90%” or greater than SEQ ID NO: 1. That is, allowing for 10% variability, in a sequence that is 471 residues allows up to 47 individual amino acids substitutions; whereas, in a sequence that is 118 residues in length, only 11 individual amino acid substitutions. This is also true for SEQ ID NO: 2; or for the VL of SEQ ID NOs: 6 or 9. SEQ ID NO: 6 is 239 amino acids in length, whereas the VL of SEQ ID NO: 11 (specs., pg. 17) is only 112 amino acids in length. Therefore it is unclear if up to 23 or 11 amino acid substitutions may be made and still encompass an amino acids sequence that is 90% or greater in sequence identity to SEQ ID NO: 6. This is also true for the VL of SEQ ID NO: 9. As the metes and bounds of the claim are unclear, claim 1 is rendered indefinite. As claims 2-3 and 13-17 depend from claim 1 but fail to rectify the indefiniteness issues (i.e., they also recite % sequence identity as a claim limitation), they are also rejected. Further, as claims 4-7 recite SEQ ID NOs: 1-2, 6 or 9, and use the same indefinite language, directed to a “% sequence identity of an undefined sequence length”, claims 4-7 are also rejected for indefiniteness.
Claim Rejections - 35 USC § 112(a)
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.
Claims 1-9 and 13-17 are 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The following quotation from section 2163 of the Manual of Patent Examination
Procedure is a brief discussion of what is required in a specification to satisfy the 35 U.S.C. 112 written description requirements for a generic claim covering several distinct inventions:
The written description requirement for a claimed genus may be satisfied through
sufficient description of a representative number of species by actual reduction to practice... reduction to drawings...or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus... See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation
within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
Thus, when a claim covers a genus of inventions, the specification must provide written description support for the entire scope of the genus. Support for a genus is generally found where the applicant has provided a number of examples sufficient so that one in the art would
recognize from the specification the scope of what is being claimed.
Regarding claims 1-3 and 8-9; claims 1 and 8 recite an anti-EMAPII antibody comprising a heavy chain variable region having an amino acid sequence with 90% or greater sequence identity to any of SEQ ID NOs: 1-5, and a light chain variable region having an amino acid sequence with 90% or greater sequence identity to any of SEQ ID NOs: 6-9. While applicants do not identify the residues that constitute the VH of SEQ ID NOs: 1-5 (which clearly also encode constant domains, as described above), an analysis of SEQ ID NO: 1 suggests the VH is a minimum of 118 amino acids, comprising residues 25-142; and comprising 3 HCDRs: CDR1 (residues 50-57), CDR2 (residues 75-85), and CDR3 (residues 123-131), according to IMGT numbering. Thus, the claim allows for up to 11 amino acid differences within the 118 amino acid VH regions, and whereby the substitutions may occur within the CDR regions. There are 20 alternative amino acids that may be substituted at up to 11 residues, in any combination, at any location in the VH; thus the 220 alternative amino acid substitutions may be made in any combination of residues throughout the 118 amino acid VH domain. It is clear that the claim encompasses a vast number of alternative embodiments. For example, substituting any one of 20 amino acids, across 10 consecutive residues, in any order, allows for 184,756 different combinations; in this case there are 118 residues from any 10 non-consecutive residues may be selected which to apply the various combinations, thus there are millions of combinations of amino acids substitutions encompassed. Further, allowing 11 mutations encompasses mutating an entire CDR region of any one of CDRs 1-3, as each CDR is less than 11 residues. Similarly, the VL region of SEQ ID NO: 6 comprises a minimum of 112 amino acids residues, with 3 CDRs: CDR1 (residues 46-57), CDR2 (residues 75-77) and CDR3 (residues 114-122). Thus, the VL regions may have up to 11 amino acid differences within the 112 amino acid VL regions, and whereby the substitutions may occur within the CDRs. The broadest reasonable interpretation of claim 1 is a sub-genus of anti-EMAPII variant antibodies comprising unidentified HCDRs 1-3 and LCDRs 1-3. Claims 2 and 9 recite 95% or greater sequence identity, and further limit the number of amino acid substitutions to 5 residues. Nonetheless, any 5 residues within the 118 residue VH or the 112 residue VL may be mutated; any 5 consecutive residues chosen results in 15,504 amino acid combinations, and selecting any 5 residues selected from a group of 100 residues results in >75,000,000 possible combinations of 5 selected residues for mutation. Claims 2 and 9 also allow the residues selected for mutation to occur in the CDR domains. Claim 3 further limits the number of amino acid substitutions to only 1 out of the 118 residue VH or the 112 residue VL domains; encompassing at least 2,360 variant VHs and 2,240 variant VLs. Any chosen residue can be substituted with any chosen amino acid, and may occur in any of the CDR regions. Thus, the claims are interpreted to encompass a vast number of variant peptides, comprising a sub-genus of any one of the variable domains of instant SEQ ID NOs: 1-9, with no guidance as to which residues may be substituted, or with which amino acids, and wherein the substitutions may occur anywhere within any of the CDRs of each variable domain, such that the sub-genus of variant embodiments comprise unidentified CDR sequences.
In support of the claimed genus of variants, the specifications disclose 6 anti-MAPII VH domains (SEQ ID NOs: 1-5, pgs. 14-16; and SEQ ID NO: 10, pg. 17) and 5 anti-MAPII VL domains (SEQ ID NOs: 6-9, pg. 16; and SEQ ID NO: 11, pg. 17). The VHs of SEQ ID NOs: 1-5 differ by no more than 6 amino acids at specifically defined residues (i.e. all >94% similar); the VLs of SEQ ID NOs: 6-9 differ by no more than 4 amino acids at specifically defined residues (i.e. all >96% similar). The VHs of SEQ ID NOs: 1-5 differ from the VH of SEQ ID NO: 10 by no less than 13 amino acids (i.e. all < 90% similar), and the VLs of SEQ ID NOs: 6-9 differ from the VL of SEQ ID NO: 11 by no less than 15 amino acids (i.e. all < 90% similar); whereby some mutations may occur in the CDRs. The representative VHs and VLs are derived from the VH and VL of SEQ ID NOs: 10 and 11, whereby they are humanized (specs. pg. 27, lines 11-17; pg. 28, Table 1). However, no information is provided as to what the donor framework regions were, or which residues of the parental variable domains are subject to mutation in the process of humanizing. Thus, no guidance is provided as to which residues may be substituted, or with which alternative amino acids; only the specific embodiments of SEQ ID NOs: 1-9 are provided as guidance as to the claimed genus of > 1,000,000 variant embodiments. Further, no CDRs are described within the variable domains, and no guidance is provided as to which of the CDR residues may be mutated with alternative amino acid residues. When determining the representative examples and the art, it is important to consider whether there is evidence of a singular shared structural feature which imparts the defining property of the claimed genus, and which would necessarily be present in every species of the claimed genus. In this case, only 5 VHs and only 4 VLs are disclosed which are humanized and which bind EMAPII, and no variants which are 90% or greater in sequence identity to any of the claimed variable domains are disclosed. Further, there is no teaching of where the substitutions may be made in variant embodiments, or what the defining structural feature of all claimed species are required to have, in order to impart the required properties of functionally binding EMAPII and to be humanized.
Regarding the state of the art; it is known in the art that the antigen binding domain of an antibody requires the 6 complementarity determining regions (CDR) of the heavy and light chains, whereby the 3 CDRs of the heavy chain and the 3 CDRs of the light chain are structurally inter-dependent in forming the unique binding pocket of the antibody paratope region; and thus the CDRs constitute critical aspects of the antibody paratope and ultimately impart the paratope-epitope binding functionality with regard to specificity and affinity (for review see MacCallum et al., 1996). However, the structure-to-function correlation continues to be highly unpredictable. For example, Chen et al., (1992) teaches that a single amino acid substitution in the VH CDR2 of PC-specific T15 antibody could increase, decrease or ablate binding the target antigen (abstract, Fig. 3), and this occurred in an unpredictable manner based on which residue was mutated. Similarly, a single point mutation in the heavy chain CDR3 region of the high affinity anti-VEGF antibody G6.31, could in some cases enhance, or otherwise completely ablate binding to the target antigen, and this also occurred in an unpredictable manner (Koenig et al., PNAS, 2017). That is, only screening each mutation individually provided insight as to the resulting changes in functionality. In some cases this extends even beyond the CDRs. Within the framework regions, Koenig et al. (PNAS, 2017) teaches that various amino acid point mutations can increase or decrease binding or neutralization capacity. Some amino acid residues are more tolerant to substitution, while other “conserved” residues are less tolerant, such that a single amino acid substitution may defunctionalize the antibody (pg. E487, Fig. 1). Thus, while antibodies share certain characteristics such as Fc regions or hinge regions, these regions are not correlated with the binding function of the antibody. Conversely, the hyper-variable regions, comprising the complementary set of 6 CDRs, are well established in the art as the portion of the binding regions which impart the specificity of the antibody; and yet, there is no way to look at an amino acid sequence and envision, a priori, whether the combination of six CDRs will bind a particular epitope, even when the CDRs are highly related, without teachings of the basic shared amino acid residues that are sufficient to impart functional binding across all variants. Further, even when provided with several related antibodies that bind the desired target, this does not represent the astronomical and potentially unknowable breadth of all possible amino acid sequences which will result in the desired binding properties. This is exemplified by the Court decision in Abbvie (Abbvie v Janssen 759 F.3d 1285 (Fed. Cir. 2014)), where Abbvie developed over 200 antibodies that shared 99.5% identity in the variable regions (pg. 7) and which bound the target, but in no way allowed one to envisage the unique structure of Centocor’s antibodies which bound the same target but shared only 50% sequence similarity (see table on pg. 11). Thus, when claiming a genus of antibodies based on their binding to a common target, the representative examples must cover the full scope of structural variabilities which encompass all species variants that would bind the target.
Section 2163(II)(A)(3)(a)(ii) of the MPEP states that the written description for a claimed genus may be satisfied through either a) a representative number of species, or b) disclosed correlation between function and structure. Here the applicants do not provide any variants of the claimed embodiments, in which alternative mutations were made, which were reduced to practice; nor do they identify the shared structural properties of the variants, such as the CDR residues or humanized framework regions, that would define the genus beyond the desired functionality. Currently the essential property of binding EMAPII is imparted by the specific humanized variable domain embodiments, with unidentified CDR sequences, that have been reduced to practice; and that accounts for only 9 examples out of millions of potential embodiments as claimed. Specifically, the physical features (or amino acid residues encoding said features) which impart the property of humanized variable domains binding the same epitope of EMAPII should be disclosed. Further, a description of the type and number of amino acid residue substitutions that may be made at such identified positions within the sequence, that result in “at least 90%, at least 95%, or at least 99%” sequence identity to a selected sequence, would be essential in determining the degree of variability that may be allotted in total sequence identity. This lack of definition complicates the determination of the boundaries of the claimed genus with regard to which, as of yet unidentified, species variants (variable domains with 90%, 95% or 99% identical sequences) would be anticipated, a priori, by one skilled in the art, to fall within the scope of the claims. Without the identification of the necessary shared structural properties of all species variants that fall within the scope of the genus, it may be that an embodiment species comprising the CDRs of SEQ ID NOs: 10 and 11, with entirely different “humanized” framework regions, would be < 90% in shared sequence identity to any of claimed SEQ ID NOs: 1-11, and would still bind EMAPII; or conversely, that antibodies with > 99% sequence identity, but comprising a deleterious mutation in a CDR region would lose functional binding to EMAPII.
In view of this uncertainty and the lack of a representative number of examples of the claimed genus, claims 1-3 and 8-9 are rejected for lack of adequate written description support. Claims 13-17 are also rejected as they are dependent on rejected claim 1.
Regarding claims 4-7; claims 4 and 5 recite a humanized anti-EMAPII antibody comprising only a heavy chain variable region, with 90% or greater sequence identity to SEQ ID NOs: 1-5, or greater than 95% sequence identity to SEQ ID NOs: 2 or 3. Claims 6-7 recite humanized anti-EMAPII antibodies comprising only a light chain variable region, with 90% or greater sequence identity to SEQ ID NOs: 6-9, or greater than 95% sequence identity to SEQ ID NOs: 6 or 9. The reasons why the % sequence identity of the claims are rejected for lack of written description applies to claims 4-7 for the same reasons it applies to claims 1-3 and 8-9, as described above. However, claims 4-7 also fail the written description requirement because they claim the variant antibodies by only a single variable region; only a VH in claim 4-5 and only a VL in claim 6-7. As described above, it is known in the art that in traditional antibody formats, all 6 CDRs are required to impart the binding specificity and affinity to the antibody. In some instances, a single domain antibody (i.e. VHH), can be derived from a unique host animal, such as a camel, which provides antigen binding with only a single variable domain comprising only 3 CDRs. However, neither the claims nor the specifications describe the instant variable domains of SEQ ID NOs: 1-9 as being single domain antibodies. The specifications do demonstrate, by way of example, that any of the VHs of SEQ ID NOs: 1-5 can be alternatively paired with any of the VLs of SEQ ID NOs: 6-9 (see figures 1-8). However, in each case, both a VH and a VL, which together would provide a set of 6 CDRs, are required. There are no examples of antigen binding by only a single variable domain, and there are no examples provided whereby a single variable domain can be paired with any other variable domain in the art, and maintain binding specificity to MAPII. Applicants have not provided an adequate number of representative examples, nor have applicants identified the shared structural features of the necessary complementary variable domain, with which to pair to any one variable domain of SEQ ID NOs: 1-9, which would maintain the required functionality of total antibody binding to MAPII.
“The purpose of the written description requirement is to ‘ensure that the scope of the
right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s
contribution to the field of art as described in the patent specification.’” Ariad Pharm., Inc. v. Eli
Lilly & Co., 598 F.3d 1336, 1353-54 (Fed. Cir. 2010) (en banc) (quoting Univ. of Rochester v. G.D.
Searle & Co., 358 F.3d 916, 920 (Fed. Cir. 2004)). To satisfy the written description
requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed
invention. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir.
1991). See also MPEP 2163.04. Otherwise, the “claims merely recite a description of the
problem to be solved while claiming all solutions to it and … cover any compound later actually
invented and determined to fall within the claim’s functional boundaries- leaving it to the
pharmaceutical industry to complete an unfinished invention.” Ariad Pharmaceuticals, Inc. v. Eli
Lilly and Co., 598 F.3d 1336, 1353 (Fed. Cir. 2010).
Applicants have not described the claimed invention of a genus of alternative antibodies which comprise only a single variable domain, of any of SEQ ID NOs: 1-9, combined with any alternative variable domain in the art, which maintain binding to MAPII, and thus fail to show they had possession of the claimed genus. Thus, claims 4-7 are rejected for lack of adequate written description.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 8-12 are rejected under 35 U.S.C. 103 as being unpatentable over Clauss et al., (from IDS of 8/12/2025; US 20140221607; published 8/7/2014) and Wadehra et al., (WO 2017096397; published 6/8/2017).
Clauss et al. teaches monoclonal antibodies and antigens for diagnosing and treating lung disease and injury (title). Clauss teaches the monoclonal antibodies bind to a form of EMAPII; and that the epitope serves as the basis for a humanized antibody that can be used to treat patients that suffer from pathologies that exhibit elevated levels of EMPAII expression (abstract). Specifically, Clauss claims an antibody comprising a heavy chain variable region of SEQ ID NO: 2 and a light chain variable region of SEQ ID NO: 3, wherein the antibody is humanized and wherein the antibody binds to EMAPII (pg. 20, claims 1-5). The heavy chain variable region amino acid sequence of Clauss SEQ ID NO: 2 is 100% identical in sequence identity to the instant heavy chain variable region of instant SEQ ID NO: 10; and the light chain variable region amino acid sequence of Clauss SEQ ID NO: 3 is 100% identical in sequence identity to the light chain variable regions of instant SEQ ID NO: 11. Clauss teaches that the VH of SEQ ID NO: 2 and VL of SEQ ID NO: 3 are derived from rat antibody clone M7/1 (pg. 2, Sequence Listing table). Clauss teaches methods for treating a patient having emphysema or COPD comprising the step of administering a therapeutically effective amount of at least one EMAPII neutralizing compound, which may be an anti-EMAPII antibody (pg. 6, para. 0075). Clauss teaches the anti-EMAPII antibody may be chimeric (pg. 6, para. 0075). Thus Clauss teaches an anti-EMAPII antibody comprising the VH and VL of instant SEQ ID NOs: 10 and 11, respectively, and the use of the antibody in a method for treating emphysema or COPD. However, Clauss does not teach a specific embodiment comprising a chimeric anti-EMAPII antibody.
Wadehra et al. teaches the art of making antibodies useful for the treatment of cancers that overexpress EMP2 (abstract). Wadehra teaches the antibody comprises a VH and a VL domain which, in this case, are specific for EMP2. However, Wadehra teaches antibodies can be a variety of structures including chimeric antibodies (pg. 14, para. 0070), and that chimeric antibodies traditionally comprise variable regions from a mouse or rat and the constant regions from a human (pg. 15, para. 0073). For example, Wadehra teaches species PG-101 which has a heavy chain comprising the VH domain and a human IgG1 constant domain; and a light chain comprising the VL domain and a human Kappa constant domain (pg. 51, paras. 00233-00236; SEQ ID NOs: 17-18). The IgG1 constant domain of the PG-101 antibody of Wadehra (SEQ ID NO: 17) has 100% amino acid sequence identity to the non-VH residues 143-471 of instant SEQ ID NO: 1; and the kappa constant domain of the PG-101 antibody of Wadehra (SEQ ID NO: 18) has 100% amino acid sequence identity to the non-VL residues 133-239 of instant SEQ ID NO: 6. Thus, Wadehra teaches that it is common knowledge in the art to combine a human IgG1 constant domain with a murine antibody VH to form a chimeric heavy chain, and to combine a human kappa constant domain with a murine antibody VL to form a chimeric light chain; thereby making an antibody with an antigen binding domain derived from a rodent, into a chimeric antibody with human constant domains.
Wadehra also teaches the art making antibodies, whereby nucleic acids encoding the antibody (pg. 30, para. 00148) are incorporated into expression vectors (pg. 30, para. 00150), which are incorporated into suitable host cells to create a recombinant host cell (pg. 30, para. 00151), and whereby the host cell is maintained under conditions suitable for expression, including in suitable culture media, whereby the encoded polypeptides are produced (pg. 31, para. 00151).
It would have been obvious to one of skill in the art to make the anti-EMAPII antibody of Clauss et al. into a chimeric antibody comprising a human IgG1 constant domain and/or a human kappa constant domain. One would have been motivated to do so given that adding human constant domains to murine antibody variable domains are methods of reducing the immunogenicity of nonhuman antibodies, as described by Wadehra et al. There would have been a reasonable expectation for success given that antibody variable domains were successfully combined with human IgG1 and kappa constant regions, as taught by Wadehra et al. Thus, the invention was prima facie obvious to one of skill in the art at the time of the invention.
Regarding claims 8-9 and 10-12, the combination chimeric antibody of Clauss and Wadehra is described above, wherein the antibody comprises the VH and VL of Clauss SEQ ID NOs: 2 and 3. As the VH and VL of Clauss SEQ ID NOs: 2 and 3 are 100% identical in amino acid sequence to instant SEQ ID NOs: 10 and 11, the chimeric antibody of Clauss and Wadehra makes obvious instant claims 8 and 9. As Wadehra teaches that antibodies can be produced by incorporating the nucleic acid encoding the antibody into a vector (re. claim 10), incorporating the vector into a suitable host cell (re. claim 11) and culturing the host cells to produce the encoded polypeptides (re. claim 12); the combination of the antibodies of Clauss, which comprise the VH or VL of instant SEQ ID NOs: 10 or 11, and the methods of making the antibodies of Wadehra, make obvious instant claims 10-12.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAMES R. MELCHIOR whose telephone number is (703)756-4761. The examiner can normally be reached M-F 8:00-5:00 CST.
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/JAMES RYLAND MELCHIOR/ Examiner, Art Unit 1644
/DANIEL E KOLKER/ Supervisory Patent Examiner, Art Unit 1644