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 .
Claim Status
Claims 1, 9-10, 12-13, 15, 28-33, 35, and 37-41 are pending.
Claims 13 and 39-41 are withdrawn.
Claims 1, 9-10, 12, 15, 28-33, 35 and 37-38 are under examination.
New Claim Objections
Claims 1 and 9-10 are objected to because of the following informalities:
Claim 1 recites “L chain variable domain” which appears to refer to a light chain variable domain. Because the rest of the claim uses the term “light chain” and not “L chain” it is recommended that Applicant ament to “light chain” to be consistent with the remainder of the claim and to improve the clarity and readability of the claim.
Claims 1 and 10 each recite “rodent Cλ1, Cλ2, Cλ3 coding sequence, or a combination thereof” which is missing a conjunction between “Cλ2” and “Cλ3 coding sequence.”
Claim 9 recites “the engineered immunoglobulin variable region locus comprises one or more bovine Vλ gene segment coding sequences.” However, claim 1, upon which claim 9 depends, already recites “the engineered immunoglobulin locus comprises bovine Vλ and Jλ Gene segment coding sequences” and therefore it is unnecessarily redundant to include the limitation of “the engineered immunoglobulin variable region locus comprises one or more bovine Vλ gene segment coding sequences” in claim 9 because this is already required by claim 1.
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.
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 1, 9-10, 12, 15, 28-33, 35 and 37-38 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 the limitation of “constant region that is native to the rodent or rodent cell” which encompasses all possible rodent constant region sequences and is broader than the previously recited “C λ1, C λ2, C λ3” coding sequence in the engineered immunoglobulin locus and makes the scope of the claim indefinite because the claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c).
By nature of their ultimate dependency on claim 1, claims 9-10, 12, 15, 28-33, 35 and 37-38 are also rejected because they do not clarify the issue.
Claim 9 recites the broader “a rodent λ constant region coding sequence” while claim 1, upon which claim 9 depends, already recites the narrower “rodent Cλ1, Cλ2, Cλ3 coding sequence,” and makes the scope of the claim indefinite because the claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). Furthermore, this recitation of “a rodent λ constant region coding sequence” also makes the scope of the claim indefinite because it is unclear whether it intends to refer back to the previously recited “rodent Cλ1, Cλ2, Cλ3 coding sequence,” or whether it is intended to encompass an additional limitation.
By nature of its dependency on claim 9, claim 10 is also rejected because it does not clarify the issue.
Regarding claims 1 and 9, a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) is considered indefinite, since the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). Note the explanation given by the Board of Patent Appeals and Interferences in Ex parte Wu, 10 USPQ2d 2031, 2033 (Bd. Pat. App. & Inter. 1989), as to where broad language is followed by "such as" and then narrow language. The Board stated that this can render a claim indefinite by raising a question or doubt as to whether the feature introduced by such language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. Note also, for example, the decisions of Ex parte Steigewald, 131 USPQ 74 (Bd. App. 1961); Ex parte Hall, 83 USPQ 38 (Bd. App. 1948); and Ex parte Hasche, 86 USPQ 481 (Bd. App. 1949).
Moot Claim Rejections - 35 USC § 112(b)
The rejection of claims 8 and 14 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite as set forth in the previous office action is moot in view of the cancellation of these claims.
Withdrawn Claim Rejections - 35 USC § 102
The rejection of claims 1, 12, 28-33, 35 and 37-38 under 35 U.S.C. 102(a)(1) as being anticipated by Wabl et al. (US-20170303517-A1; henceforth “Wabl”) as evidenced by Inlay et al. (Nat Immunol. 2002 May;3(5):463-8. Epub 2002 Apr 22.; henceforth “Inlay”) as set forth in the previous office action is withdrawn in view of Applicant’s amendments.
Moot Claim Rejections - 35 USC § 102
The rejection of claims 8 and 14 under 35 U.S.C. 102(a)(1) as being anticipated by Wabl et al. (US-20170303517-A1; henceforth “Wabl”) as evidenced by Inlay et al. (Nat Immunol. 2002 May;3(5):463-8. Epub 2002 Apr 22.; henceforth “Inlay”) as set forth in the previous office action is moot in view of the cancellation of these claims.
Moot Claim Rejections - 35 USC § 103
The rejection of claim 14 under 35 U.S.C. 103 as being unpatentable over Wabl et al. (US-20170303517-A1; henceforth “Wabl”) in view of MacDonald et al. (WO-2013096142-A1; henceforth “MacDonald”) and Reilly et al. (Proc Natl Acad Sci U S A. 1984 Apr;81(8):2484-8.; henceforth “Reilly”) as set forth in the previous office action is moot in view of the cancellation of this claim.
New 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 1, 9-10, 12, 15, 28-33, 35 and 37-38 are rejected under 35 U.S.C. 103 as being unpatentable over Wabl et al. (US-20170303517-A1; henceforth “Wabl”) in view of MacDonald et al. (WO-2013096142-A1; henceforth “MacDonald”) and Reilly et al. (Proc Natl Acad Sci U S A. 1984 Apr;81(8):2484-8.; henceforth “Reilly”) as evidenced by Inlay et al. (Nat Immunol. 2002 May;3(5):463-8. Epub 2002 Apr 22.; henceforth “Inlay”).
Regarding claim 1, Wabl discloses a transgenic rodent (mouse) or rodent cell (ES cell clones) comprising a genome comprising an engineered partly bovine (“transgenic mammals that express bovine-based immunoglobulins, including transgenic rodents that express bovine-based immunoglobulins” abstract) immunoglobulin light chain locus comprising bovine immunoglobulin λ light chain variable region gene segments (“an array of 25 bovine lambda variable region gene segments” para. [0135]); Examples 4-6; Figures 2-11; see also claims 1-2), wherein the engineered immunoglobulin locus comprises bovine Vλ (“an array of 25 bovine lambda variable region gene segments (951), each comprised of bovine coding sequences embedded in mouse noncoding regulatory or scaffold sequences” para. [0135]; see also Examples 5-6) and Jλ gene segment coding sequences (“a 2 Kb piece of DNA containing the bovine Jλ, region gene segments embedded in mouse noncoding DNA (955)” para. [0135]; see also Examples 5-6) embedded in rodent non-coding regulatory or scaffold sequences of a rodent immunoglobulin K light chain variable region gene locus (“used in place of the K-K DNA” para. [0135] see also para. [0133] “carrying the deletion of sequence in one of the two homologous copies of their immunoglobulin kappa chain locus”).
Regarding claim 1, the transgenic moue disclosed by Wabl comprises rodent (mouse) cells that comprise the engineered partly bovine immunoglobulin light chain locus comprising bovine immunoglobulin λ light chain variable region gene segments (see also claim 3).
Additionally, regarding claim 1, Wabl discloses mouse or rat embryonic stem (ES) cells with the claimed features (“Mouse embryonic stem (ES) cells derived from C57B1/6NTac mice” para. [0126]; see also para. [0025-0027, 0031, 0056, 0061, 0090, 0094, 0096-0097, 0110-0111, 0113, 0115, 0117, 0119-0120, 0127, 0129-0130, 0133, 0137-0138, 0143-0148, 0151-0152]; claims 23-24).
Regarding claim 1, concerning the limitation that “the engineered immunoglobulin locus is capable of expressing immunoglobulin comprising bovine variable domains,” the mouse disclosed by Wabl comprises the bovine variable domains in its genome and is therefore capable of expressing the domains. Additionally, Wabl discloses that “Monoclonal antibodies recovered from these mice are comprised of bovine heavy chain variable domains paired in some cases with bovine kappa variable domains and in other cases with bovine lambda variable domains” (para. [0153]) and Wabl discloses the mice are “capable of producing an antibody with bovine V regions” (para. [0010]) which means that the bovine lambda variable domains are expressed and are therefore capable of being expressed as claimed.
Regarding claims 1 and 9-10, although Wabl discloses the engineered immunoglobulin locus comprises a rodent immunoglobulin K locus in which one or more rodent VK gene segment coding sequences and one or more rodent JK gene segment coding sequences have been deleted (“the deletion of sequence in one of the two homologous copies of their immunoglobulin kappa chain locus” para. [0133, 0135]: Figures 2-11) and replaced by one or more bovine Vλ gene segment coding sequences (“an array of 25 bovine lambda variable region gene segments (951), each comprised of bovine coding sequences embedded in mouse noncoding regulatory or scaffold sequences” para. [0135]) and one or more Jλ gene segment coding sequences (“a 2 Kb piece of DNA containing the bovine JA, region gene segments embedded in mouse noncoding DNA” (para. [0135]), respectively (see “L-K” para. [0135]; See also Example 4) and Wabl teaches rodent CK coding sequences with rodent C λ1, C λ2, C λ3 coding sequence (“the mouse lambda constant domain gene segments are C1 and/or C2 and/or C3” para. [0148]), Wabl is silent to a rodent λ constant region coding sequence in the K locus (instant claim 9) and Wabl is silent to replacing rodent CK coding sequences in the locus with rodent C λ2 coding sequence (instant claims 1 and 10).
Nevertheless, regarding claims 1 and 9-10, MacDonald teaches a transgenic rodent (mouse) or rodent cell comprising an engineered immunoglobulin light chain locus comprising a non-rodent (human) λ light chain variable region gene segments and a mouse Cλ2 domain (Cλ2 gene; para. ;0246]) in a kappa light chain locus (“a genetically modified mouse is provided that expresses a Vλ region on a CL that is a CK” para. [00246-00247]; “a genetically modified mouse is provided that expresses a hVλ region on a mouse CK” para. [00247]; see also para. [00101, 00246, 00288, 00293, 00305, 00309-00310, 00358, 00545-00546, 00565, 00691]; claims 42-44 and 28).
Additionally, regarding claims 1 and 9-10, Reilly teaches rearrangement of λ light chain sequences is more restricted that K chains (abstract), and that each of the Cλ gene segments is paired with a unique Jλ segment (pg. 2484 col. 1; see also pg. 2487 col. 1 last para. and col. 2 1st para.).
Therefore, regarding claims 1 and 9-10, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to prepare the mouse of Wabl, and simply substitute the known prior art element of the mouse Cλ2 constant domain of MacDonald for the endogenous mouse kappa constant domain of Wabl to obtain the predictable result of a mouse with a mouse Cλ2 constant domain in the kappa locus. One of ordinary skill would have been motivated to do so as taught by Reilly because recombination is more restricted for λ light chain sequences and substituting the Cλ2 constant domain of MacDonald would allow λ light chain variable sequences to recombine with Jλ segments. Regarding the reasonable expectation of success, Wabl evidences preparation of a transgenic mouse with λ sequences in the mouse λ chain locus (para. [0135]); Examples 4-6; Figures 10-11; see also claims 1-2).
Regarding claim 1, concerning the limitation that “immunoglobulin comprises a fully bovine L chain variable domain and a constant region that is native to the rodent or rodent cell” it is first noted that this immunoglobulin refers to previously recited clause of “the engineered immunoglobulin locus is capable of expressing immunoglobulin comprising bovine variable domains,” and therefore the structure of the suggested mouse need only be capable of expressing this immunoglobulin. As set forth above, Wabl teaches the locus comprises bovine light chain variable segments (“an array of 25 bovine lambda variable region gene segments” para. [0135]); Examples 4-6; Figures 2-11; see also claims 1-2), and MacDonald and Reily suggest and make obvious rodent Cλ gene segment coding sequence constant segments of C1 and/or C2 and/or C3” (which meet the structural requirements of “native” to the rodent as claimed). Therefore, the cell or rodent as suggested above comprises the structure requirements to encode an “immunoglobulin comprises a fully bovine L chain variable domain and a constant region that is native to the rodent or rodent cell” and is capable of making this immunoglobulin and meets instant claims.
Regarding claim 1, concerning the limitation of “produces more ” immunoglobulin comprising λ light chain than immunoglobulin comprising K light chain, this refers to all amounts of “more” production and includes natural variability in expression that would result in a slight increase in immunoglobulin comprising λ light chain than immunoglobulin comprising K light chain and is therefore met by the mouse or cell of Wabl above.
Furthermore, regarding claim 1, concerning the limitation of “produces more ” immunoglobulin comprising λ light chain than immunoglobulin comprising K light chain, as set forth above, Wabl teaches the deletion of sequence in one of the two homologous copies of their immunoglobulin kappa chain locus in rodents and replacement of those sequences with bovine Vλ gene segment coding sequences. Therefore, because the suggested rodent or rodent cell has a reduction in rodent JK gene segment coding sequences and an increase in bovine Vλ gene segment coding sequences, it would be an obvious and expected result to have an increase in immunoglobulin comprising λ light chain because there would be more λ light chain sequences during encoding since an entire copy of the immunoglobulin kappa chain locus would now be unavailable to use and instead would be replaced with bovine Vλ gene segment coding sequences.
Regarding claim 12, further to the discussion of claim 1 above, Wabl teaches the transgenic mouse (which comprises transgenic mouse cells as discussed above) comprises one or more bovine Vλ gene segment coding sequences (“an array of 25 bovine lambda variable region gene segments, each comprised of bovine lambda coding sequences” para. [0148]) located upstream of one or more J-C units ((“an array of J-C units where each unit is comprised of a bovine J λ, gene segment and a mouse lambda constant domain gene segment”; para. [0148]; see Figure 10) wherein each J-C unit comprises a bovine Jλ gene segment coding sequence (“the bovine Jλ gene segments are those encoding J1, J2, J6 and 17” para. [0148]) and a rodent Cλ gene segment coding sequence (“the mouse lambda constant
domain gene segments are C1 and/or C2 and/or C3” para. [0148]) and rodent Cλ non-coding sequences (this disclosed embodiment is in the rodent λ locus and therefore comprises the remaining rodent Cλ non-coding sequences in addition to the coding sequences).
Regarding claim 28, further to the discussion of claim 1 above, although Wabl is silent to whether the engineered bovine immunoglobulin light chain locus comprises a rodent intronic K enhancer (iEK) and 3 'EK regulatory sequences, Wabl teaches the engineered bovine immunoglobulin light chain locus is the mouse K chain locus (para. [0133, 0135]: Figures 2-11; Example 4).
Regarding claim 28, Inlay evidences the mouse K chain locus comprises intronic K enhancer (iEK) and 3 'EK regulatory sequences (“Two enhancers have been identified within the κ loci: one within the Jκ-Cκ intron (iEκ) and the other ∼9-kb downstream of Cκ (3′Eκ)” pg. 463 col. 1 2nd para.).
Therefore, regarding claim 28, the mouse K chain locus taught by Wabl comprises the intronic K enhancer (iEK) and 3 'EK regulatory sequences.
Regarding claim 15, further to the discussion of claims 1 above, as stated above (see claims 9-10 and 14 rejection above), Wabl in view of MacDonald and Reilly make obvious substituting the mouse Cλ2 constant domain of MacDonald for the endogenous mouse kappa constant domain of Wabl which would result in the claimed configuration of the bovine Vλ gene segment coding sequences upstream of one or more bovine Vλ gene segment coding sequences which are upstream of one or more rodent Cλ coding sequences.
Regarding claim 29, further to the discussion of claim 1 above, Wabl teaches the transgenic rodent or rodent cell comprises an engineered partly bovine immunoglobulin heavy chain locus comprising bovine immunoglobulin heavy chain variable region gene coding sequences and rodent non-coding regulatory or scaffold sequences of the rodent immunoglobulin heavy chain locus (“Upon introduction of the appropriate recombinase (604), the partly bovine immunoglobulin locus (629) is integrated into the genome upstream of the endogenous non-bovine constant region genes (627), resulting in the genomic structure illustrated at 631” para. [0099]; Figure 6; see in particular Example 3 and Figure 8) (“10 DH and 4 JH bovine coding sequences” Example 6; para [0155]).
Regarding claim 30, further to the discussion of claims 1 and 29 above, Wabl teaches the engineered bovine immunoglobulin heavy chain locus comprises bovine VH (1-20 bovine VH coding regions), D and JH gene segments (“10 DH and 4 JH bovine coding sequences” Example 6; para [0155]).
Regarding claim 31, further to the discussion of claims 1 and 29-30 above, Wabl teaches each bovine VH, D or JH coding gene segment comprises VH, D or JH coding sequence embedded in rodent noncoding regulatory or scaffold sequences of the rodent immunoglobulin heavy chain locus (“is integrated into the genome upstream of the constant gene region (1127) as shown at 1129” Example 6; Figure 11).
Regarding claim 32, further to the discussion of claims 1 and 29-31 above, Wabl teaches the heavy chain rodent non-coding regulatory or scaffold sequences are interspersed by functional ADAM6A (“upstream sequences may contain non-immunoglobulin genes, such as ADAM6 (FIG. 1)” para. [0019]; “the engineered partly bovine immunoglobulin locus further comprises one or more of an ADAM6 gene” para. [0024]; see also para. [0069]; Table 4; claims 19 and 30).
Regarding claim 33, further to the discussion of claim 1 above, Wabl teaches the rodent regulatory or scaffold sequences are part of the rodent locus which comprises intervening sequences including introns and enhancers) (para. [0051]; see also para . [0069] and “mouse intergenic and intronic sequences” para. [0073], “intervening sequences based on the endogenous non-bovine genome” para. [0099] and para. [0103, 0117, 0133, 0135, 0142, 0148]).
Regarding claim 35, further to the discussion of claim 1 above, Wabl teaches the rodent is a mouse or rat (“rodent, e.g., a mouse or a rat” para. [0032]; see also para. [0005, 0007-0008, 0016, 0024, 0027, 0039, 0046-0048, 0067, 0069, 0072-0073, 0083, 0094, 0095-0096, 0103, 0105-0111, 0113, 0117, 0120-0127, 0129, 0133, 0135, 0138-0144, 0147-0148, 0152-0155]; claim 17).
Regarding claim 37, further to the discussion of claim 1 above, Wabl teaches the rodent cell is a mouse or rat embryonic stem (ES) cell (“Mouse embryonic stem (ES) cells derived from C57B1/6NTac mice” para. [0126]; see also para. [0025-0027, 0031, 0056, 0061, 0090, 0094, 0096-0097, 0110-0111, 0113, 0115, 0117, 0119-0120, 0127, 0129-0130, 0133, 0137-0138, 0143-0148, 0151-0152]; claims 23-24).
Regarding claim 38, further to the discussion of claim 1 above, Wabl teaches a cell of B lymphocyte lineage obtained from the transgenic rodent (“cell of B lymphocyte lineage from the transgenic rodent” para. [0024]) wherein the engineered immunoglobulin locus expresses a chimeric immunoglobulin heavy chain or light chain comprising a bovine variable region and a rodent immunoglobulin constant region (“expresses immunoglobulin chains comprised of bovine variable domains and rodent constant domains” para. [0024]).
Hence, the claimed invention as a whole was prima facie obvious.
Response to Arguments
Applicant’s arguments, filed 7th, July, 2026, have been fully considered but are not found persuasive.
Applicant argues “The Examiner is using impermissible hindsight of the prior art to arrive at the
present claims (pg. 8).
In response, Applicant is directed to MPEP 2145 (X)(A) which states that "[a]ny judgment on obviousness is in a sense necessarily a reconstruction based on hindsight reasoning, but so long as it takes into account only knowledge which was within the level of ordinary skill in the art at the time the claimed invention was made and does not include knowledge gleaned only from applicant’s disclosure, such a reconstruction is proper." In re McLaughlin, 443 F.2d 1392, 1395, 170 USPQ 209, 212 (CCPA 1971). In the instant case, because the each of the claimed elements is made obvious by the combination as set forth above, which takes into account only knowledge which was within the level of ordinary skill in the art at the time the claimed invention was made, the reconstruction is proper. Motivation is discussed further below and is set forth in the grounds of rejection above.
Applicant argues “a skilled person would not have been motivated to use the disclosures of MacDonald and Reilly to modify the teachings of Wabl to arrive at the currently pending claims” (pg. 7).
In response, the motivation to combine is set forth in the grounds of rejection above. In brief, the prior arts of MacDonald and Reily together provide the motivation because Reily teaches rearrangement of λ light chain sequences is more restricted that K chains (abstract), and that each of the Cλ gene segments is paired with a unique Jλ segment and substituting the Cλ2 constant domain of MacDonald would allow λ light chain variable sequences to recombine with Jλ segments.
Applicant is reminded that a 35 U.S.C. § 103(a) based test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). In the instant case for the reasons set forth above, the combined teachings of the references of MacDonald and Reily together suggest substituting Cλ gene segments for the reasons set forth above.
Furthermore, Applicant is directed to MPEP 2143 which states that the key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious and the Supreme Court in KSR noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit. In Ball Aerosol v. Ltd. Brands, 555 F.3d 984, 89 USPQ2d 1870 (Fed. Cir. 2009), the Federal Circuit offered additional instruction as to the need for an explicit analysis. The Federal Circuit explained that the Supreme Court’s requirement for an explicit analysis does not require record evidence of an explicit teaching of a motivation to combine in the prior art (see MPEP 2143). "[T]he analysis that "should be made explicit" refers not to the teachings in the prior art of a motivation to combine, but to the court’s analysis. . . . Under the flexible inquiry set forth by the Supreme Court, the district court therefore erred by failing to take account of ‘the inferences and creative steps,’ or even routine steps, that an inventor would employ and by failing to find a motivation to combine related pieces from the prior art." Ball Aerosol, 555 F.3d at 993, 89 USPQ2d at 1877 (see MPEP 2143).
Applicant argues “while MacDonald and Reilly disclose using human VA and JA gene segments in combination with a rodent CA, neither reference provides any information on any improvement in expression compared to a rodent Ck, and certainly provide no guidance on improving expression of partly bovine immunoglobulins.
Applicant argues “Without the present disclosure, a skilled person would not have been motivated to replace the endogenous rodent Ck region with a rodent CA in the K light chain locus in order obtain high levels of expression of bovine VA and JA gene segments. Wabl discloses transgenic rodents that were considered functional for expression of partly bovine immunoglobulins.” (pg. 8)
In response, as set forth above, the combination of art provides a motivation, but as noted by Applicant, this motivation is not “in order obtain high levels of expression of bovine VA and JA gene segments” (pg. 8) and also is not based on “improving expression of partly bovine immunoglobulins.” In response to Applicant's arguments against the reason to combine the prior art references, MPEP 2144 (IV) states that the reason or motivation to modify a reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by Applicant. See, e.g., In re Kahn, 441 F.3d 977, 987, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006). The fact that Applicant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
Applicant argues “Cell surface lgM expression surprisingly and significantly reduced when bovine Vλ gene segments are linked to mouse CK gene segments” (pg. 7).
In response, Applicant appears to allege that “Cell surface lgM expression surprisingly and significantly reduced when bovine Vλ gene segments are linked to mouse CK gene segments” (pg. 7), is an unexpected result.
In response to Applicant’s arguments, arguments of counsel cannot take the place of
factually supported objective evidence in the record. See In re Schulze, 346 F.2d 500, 602, 145
USPQ 716, 718 (CCPA 1965), In re Huang, 100 F.3d 135, 139-40, 40 USPQ2d 1685, 1689 (Fed.
Cir. 1996); In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984). Thus,
Attorney statements regarding the unexpected result are not evidence without a supporting declaration. Specifically, Applicant has not provided objective scientific evidence on the record that the Cell surface lgM expression is significantly reduced when bovine Vλ gene segments are linked to mouse CK gene segments when compared to prior art products.
Concerning the alleged unexpected results, the burden is on the Applicant to establish results are unexpected and significant (MPEP 716.02(b)(I)), Applicants have the burden of explaining the proferred data (and MPEP 716.02(b)(II)), and the objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support (MPEP 716.02(d)(I)).
The evidence relied upon should establish "that the differences in results are in fact unexpected and unobvious and of both statistical and practical significance." Ex parte Gelles, 22 USPQ2d 1318, 1319 (Bd. Pat. App. & Inter. 1992) (Mere conclusions in appellants’ brief that the claimed polymer had an unexpectedly increased impact strength "are not entitled to the weight of conclusions accompanying the evidence, either in the specification or in a declaration."); Ex parte C, 27 USPQ2d 1492 (Bd. Pat. App. & Inter. 1992) (Applicant alleged unexpected results with regard to the claimed soybean plant, however there was no basis for judging the practical significance of data with regard to maturity date, flowering date, flower color, or height of the plant.). See also In re Nolan, 553 F.2d 1261, 1267, 193 USPQ 641, 645 (CCPA 1977) and In re Eli Lilly, 902 F.2d 943, 14 USPQ2d 1741 (Fed. Cir. 1990) as discussed in MPEP § 716.02(c) (MPEP 716.02(b)(I)). Evidence of unexpected properties may be in the form of a direct or indirect comparison of the claimed invention with the closest prior art which is commensurate in scope with the claims. See In re Boesch, 617 F.2d 272, 205 USPQ 215 (CCPA 1980) and MPEP § 716.02(d) - § 716.02(e). See In re Blondel, 499 F.2d 1311, 1317, 182 USPQ 294, 298 (CCPA 1974) and In re Fouche, 439 F.2d 1237, 1241-42, 169 USPQ 429, 433 (CCPA 1971) for examples of cases where indirect comparative testing was found sufficient to rebut a prima facie case of obviousness. (MPEP 716.02(b)(II)).
In the instant case, Applicant’s alleged unexpected results are insufficient to overcome the rejection of record under 35 U.S.C. 103 because the alleged unexpected results do not appear to be in scope with the claimed invention, as the cited Example 9 appears to also require an IGM backbone while instant claims include all immunoglobulin backbone types.
Moot Non-Statutory Double Patenting
U.S. Patent No. 10793829
The rejection of claim 8 on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4 and 7-8 of US patent No. 10793829 (Henceforth “Wabl2”) as evidenced by Inlay et al. (Nat Immunol. 2002 May;3(5):463-8. Epub 2002 Apr 22.; henceforth “Inlay”) as set forth in the previous office action is moot in view of the cancellation of this claim.
The rejection of claim 14 on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4 and 7-8 of US patent No. 10793829 (Henceforth “Wabl2”) in view of MacDonald et al. (WO-2013096142-A1; henceforth “MacDonald”) and Reilly et al. (Proc Natl Acad Sci U S A. 1984 Apr;81(8):2484-8.; henceforth “Reilly”) as set forth in the previous office action is moot in view of the cancellation of this claim.
Withdrawn Non-Statutory Double Patenting
U.S. Patent No. 10793829
The rejection of claims 1, 12, 28-33, 35 and 38 on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4 and 7-8 of US patent No. 10793829 (Henceforth “Wabl2”) as evidenced by Inlay et al. (Nat Immunol. 2002 May;3(5):463-8. Epub 2002 Apr 22.; henceforth “Inlay”) as set forth in the previous office action is withdrawn in view of Applicant’s filing of a terminal disclaimer.
The rejection of claims 9-10 and 15 on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4 and 7-8 of US patent No. 10793829 (Henceforth “Wabl2”) in view of MacDonald et al. (WO-2013096142-A1; henceforth “MacDonald”) and Reilly et al. (Proc Natl Acad Sci U S A. 1984 Apr;81(8):2484-8.; henceforth “Reilly”) as set forth in the previous office action is withdrawn in view of Applicant’s filing of a terminal disclaimer.
Conclusion
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.
No claim is allowable.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRIANA N EBBINGHAUS whose telephone number is (703)756-4548. The examiner can normally be reached M-F 9:30 AM to 5:30 PM ET.
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/BRIANA N EBBINGHAUS/Examiner, Art Unit 1632
/PETER PARAS JR/Supervisory Patent Examiner, Art Unit 1632
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