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Timestamp: 2019-04-19 15:03:52+00:00

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Application for Patent filed April 27, 1987, Serial No. 043,119; which is a continuation-in-part of application Serial No. 828,388, filed February 11, 1986, now abandoned; which is a continuation-in-part of application Serial No. 944,905, filed January 5, 1987, now abandoned. Recombinant Human B-Cell Growth Factor.
This is an appeal from the examiner's final rejection of claims 1, 3 through 8, 12, 14 and 18, which are all the claims remaining in the application.
1. A recombinant DNA vector comprising a DNA sequence which encodes a protein exhibiting a molecular weight between about 8 and about 14 kilodaltons upon gel exclusion chromatography, said protein having an amino acid sequence which includes the non-B-galactosidase-derived sequence of amino acids displayed in Figure 4, or a biologically functional equivalent thereof, and having a BCGF biological activity characterized by an ability to stimulate the incorporation of thymidine into DNA of BCGF-dependent B-cells, or an ability to stimulate the comitogenesis of anti-u activated B-cells, when said protein is cocultured in effective concentrations with said respective B-cells in vitro.
Maizel et al. (Maizel), Proc. Natl. Acad. Sci. USA, "Long-term growth of human B cells and their use in a microassay for B-cell growth factor," Vol. 80, August 1983, pages 5047-5051.
Beaucage et al. (Beaucage), Tetrahedron Letters, "Deoxynucleoside Phosphoramidites--A New Class Of Key Intermediates For Deoxypolynucleotide Synthesis," Vol. 22, No. 20, 1981, pages 1859-1862.
Freeman et al. (Freeman), Proc. Natl. Acad. Sci. USA, "Sequential expression of new gene programs in inducer T-cell clones," Vol. 80, July 1983, pages 4094-4098.
Clark et al. (Clark), Proc. Natl. Acad. Sci. USA, "Human T-cell growth factor: Partial amino acid sequence, cDNA cloning and organization and expression in normal and leukemic cells," Vol. 81, April 1984, pages 2543- 2547.
Mehta et al. (Mehta), Federation Proceedings, "Expression Of Human B Cell Growth Factor In Escherichia Coli, Vol. 44, No. 4, S5123, March 5, 1985, page 1287.
Appellants' invention concerns a protein molecule or "factor" which has the ability to maintain the growth of B-cells in a culture medium. Appellants do not claim the protein as such but, rather, claim recombinant vectors [FN1] containing a DNA sequence which encodes the protein or an equivalent thereof and causes a recombinant cell containing said DNA sequence to produce said protein or its equivalent. Claims 1 and 3 are directed to recombinant DNA vectors containing the requisite DNA sequence. Claims 4 and 8 are directed to recombinant cells bearing the recombinant DNA vector. Claim 5 is directed to a cell which produces the desired protein but is not limited with regard to the DNA encoding the protein. Claims 12 and 14 claim the recombinant DNA sequence itself and claim 18 is directed to a method of utilizing recombinant cells to produce the B-cell growth factor (BCGF) protein.
*2 Appellants do not argue the separate patentability of the various independent and dependent claims. Accordingly all claims stand or fall together. In re Nielson, 816 F.2d 1567, 2 U.S.P.Q.2d 1525 (Fed.Cir.1987); In re Kroekel, 803 F.2d 705, 231 USPQ 640 (Fed.Cir.1986).
(a) Claims 1, 3 through 8, 12, 14 and 18 stand rejected under 35 U.S.C. § 112, first paragraph, as being directed to subject matter not described in the specification as filed. This is a "new matter" rejection.
(b) Claims 1, 4, 5, 7, 12, 14 and 18 stand rejected under 35 U.S.C. § 112, first paragraph, as being broader than the enabling disclosure.
(c) Claim 1, 3 through 8, 12, 14 and 18 stand rejected under 35 U.S.C. § 102(a) or, alternatively, under 35 U.S.C. § 103 over Okano.
(d) Claims 1, 3 through 8, 12, 14 and 18 stand rejected under 35 U.S.C. § 103 as being unpatentable over Clark or Freeman, each in view of Beaucage and Maizel.
Before considering the propriety of the examiner's rejections, it is helpful to consider the scope of appellants' claims. To do so, every limitation positively recited in a claim must be given effect in order to determine what subject matter that claim defines. In re Wilder, 429 F.2d 447, 166 USPQ 545 (CCPA1970). We are mindful that during prosecution the claims are given their broadest reasonable interpretation in light of the specification. In re Yamamoto, 740 F.2d 1569, 1571, 222 USPQ 934, 936 (Fed.Cir.1984).
Claim 1 herein describes a recombinant DNA vector which comprises any DNA sequence which encodes a protein characterized as (a) exhibiting a molecular weight within a defined range, (b) having an amino acid sequence [FN2] which includes the sequence of amino acids displayed in Figure 4, and (c) having BCGF biological activity as measured by two specific and alternative tests set forth in the claims. Importantly, appellants' claims are not limited to a DNA which encodes solely the protein described by the amino acid sequence set forth in Figure 4 but, rather, include language such as "or a biologically functional equivalent thereof" or "corresponds biologically to" which broadens the claims such that the claims encompass any recombinant DNA, vector or cell which encodes any protein having sufficient BCGF biological activity such that it may properly be considered a "biologically functional equivalent" of the protein having the amino acid sequence displayed in Figure 4.
Appellants have attempted to relate, and thereby limit, the phrase "biologically functional equivalent" to proteins having amino acid substitutions wherein the substituted acids have similar hydrophobicity and charge characteristics such that the substitutions are "conservative" and do not modify the basic functional characteristics of the BCGF protein. However, as defined in appellants' specification at page 26, lines 24 through 28, the phrase "biological functional equivalent" is so broad as to encompass any protein regardless of structure that is "functionally equivalent to BCGF in terms of biological activity." Such a protein may be a highly truncated protein comprising mainly the active site of the BCGF protein. Other cells or DNA's encoding proteins having dissimilar structural configurations but similar biological functionality would fall within the scope of appellants' claims. Appellants' Brief, pages 18 through 20, describes several proteins including TCGF which exhibit B cell activity quite similar to the BCGF activity exhibited by the presently claimed factor. Such materials would reasonably be considered to fall within the scope of appellants' "biologically functional equivalent" language.
If this claim can be maintained, it matters not by what process or machinery the result is accomplished. For aught that we now know some future inventor, in the onward march of science, may discover a mode of writing or printing at a distance by means of the electric or galvanic current, without using any part of the process or combination set forth in a plaintiff's specification. His invention may be less complicated--less liable to get out of order--less expensive in construction, and in its operation. But yet if it is covered by this patent the inventor could not use it, nor the public have the benefit of it without the permission of this patentee.
It is well established that there must be a reasonable correlation between the scope of the exclusive right granted to a patent applicant and the scope of enablement set forth in the patent application. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA1970). On the facts before us, we are in full agreement with the examiner that the scope of the exclusive right sought by appellants is far in excess of that warranted by the scope of enablement set forth in the specification.
We consider next the examiner's rejection of claims 1, 3 through 8, 12, 14 and 18 under 35 U.S.C. § 112, first paragraph, on the ground that the subject matter now claimed is not described in the specification as filed. This is a "new matter" rejection.
*4 We have carefully considered the declaration of Surendra Sharma identified as Exhibit H and all of the arguments set forth in appellants' Brief and Reply Brief. Nevertheless, we are unpersuaded of error in the examiner's rejection and, accordingly, we affirm the rejection.
The examiner has criticized the Sharma declaration for a number of reasons specifically set forth on pages 8 and 9 of the Answer. As best we understand the examiner's position, the declaration is considered deficient because it (1) does not indicate that the plasmid newly sequenced is from the cells actually deposited in the ATCC, (2) does not indicate the protocols used in the original and re-sequencing experiments, and (3) does not adequately explain the changes in the protein sequence, especially the start position for the protein. [FN5] Appellants' Brief and Reply Brief do not explain the lack of specific information.
We recognize that errors may well arise in the sequencing of DNA and that a mechanism for correcting such errors in the Patent and Trademark Office is highly desirable. Appellants have urged this Board to establish general rules and guidelines to be followed. Unfortunately, no general rule can be established because the question of whether or not a change in the chemical structure of a DNA sequence set forth in the specification is permitted depends on the facts of each case and the significance of the modification to both the subject matter claimed, i.e., the invention, and the subject matter described in the specification.
We are cognizant of the position of this Board in Ex parte Marsili, supra. Nevertheless, we are of the opinion that the Marsili case may be distinguished on its facts. In Marsili, the invention involved a chemical compound and its method of preparation. Claims to the method of preparation had been allowed but claims to the compound were on appeal because Marsili had advised the PTO of an error in the structural formula of a single ring moiety of a complex compound and had modified the ring structure of the claims to eliminate the error. (The error was minor in nature reflecting the difference in an aromatic vs. non aromatic heterocyclic ring structure.) Marsili provided analytical data and literature references to support the propriety and scientific desirability of the changes. Indeed, the Marsili board noted that the original description of the compound in the specification included "sufficient characteristics to distinguish" the claimed compound. There was no question of Marsili's adding characteristics not previously mentioned but only a question of error in a structural formula.
*5 The issue that must be broached in this and any other case is whether the description of the claimed compound in the original disclosure is adequate to identify and distinguish the claimed subject matter. In re Nathan, 328 F.2d 1005, 140 USPQ 601 (CCPA1964).
Appellants' change, unlike Marsili's, is major in nature and of the type recognized by the art as having potentially drastic consequences on the properties of the DNA and protein deduced therefrom. Appellants have provided no evidence that the description of the invention set forth in the specification includes sufficient characteristics to distinguish the invention set forth in the claims.
A review of appellants' specification reveals that there is little or no description of the DNA sequence of the claims other than the biological activity of the protein it codes for, its presence in the plasmids pARJ43 and pARJ45, the former being on deposit in the ATCC in the form of E. coli cells, and a rough estimate of the molecular weights of the active DNAs spliced into pARJ43 and pARJ45. Appellants' specification admits that the DNA of the pARJ43 and pARJ45 differed considerably and that each produced truncated proteins as compared to mature BCGF. Importantly, appellants did not purify and sequence the protein produced by the cloned plasmids and have described the protein only by its capability of being produced by E. coli containing the plasmid and by its biological activity. Appellants' Reply Brief, page 7, admits that "there are numerous molecules known to have BCGF activity (even TCGF)." Appellants' claims do not describe the DNA directly but, rather, in terms of the protein and/or its amino acid sequence. As we view it, appellants' description of the protein solely in terms of its biological function, and approximate molecular weight, is insufficient to describe the protein and, thereby, place appellants in "possession" thereof.
Appellants' deposit in the ATCC was limited to a single cell line containing only one of the two plasmids (vectors) said to contain DNA coding for a protein exhibiting BCGF activity. At best, appellants' specification may be said to "describe" the deposited 67099 cell line and the plasmid pARJ43 which was incorporated in the deposited cells. The specification can not be said to "describe" the protein or the broad subject matter set forth in claims 1 and 5 because the amino acid sequence set forth as a descriptive parameter in the original specification was erroneously deduced and the protein was not purified and/or isolated. In other words, the specification does not "convey with reasonable clarity to those skilled in the art that, as of the filing date ... [appellants were] ... in possession of the invention," i.e., "whatever is now claimed." See Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 19 U.S.P.Q.2d 1111, 1117 (Fed.Cir.1991).
We consider next the examiner's rejection of claims 1, 3 through 8, 12, 14 and 18 under 35 U.S.C. § 102(a) or, alternatively, under 35 U.S.C. § 103 over Okano. We affirm the rejection.
*6 Appellants strongly urge that Okano's work was directed to a different BCGF molecule than that claimed herein. We are unpersuaded by this argument for two reasons. First, appellants do not claim a BCGF molecule of any sort. Rather, appellants claim a DNA which produces a protein which exhibits a certain molecular weight, and has certain biological activity. Moreover, appellants' claims extend to "biologically functional equivalents thereof." We have carefully reviewed the Okano reference and find nothing therein which reveals that the BCGF gene developed by Okano differs at all from that claimed herein even if one were to exclude the "biological equivalents" language of the claims. Okano's process of producing the DNA is virtually the same as that utilized by appellants. Okano isolated a mRNA fraction and utilizing reverse transcriptase produced a cDNA library that corresponds to BCGF mRNA. Okano teaches that the preferred mRNA fraction is that which corresponds to a molecular weight between the precipitation constants 15s and 21s in sucrose density gradient centrifugation. Appellants utilized a fraction having a molecular weight corresponding to 16s-18s which is approximately the same fraction preferred by Okano. Okano prepared a recombinant DNA and inserted the DNA into vector host microorganisms. The mRNA utilized tested positively by the same assay utilized by appellants (see page 9 of the translation). There is no reason to believe that the cDNA synthesized from the mRNA would not correspond to the claimed DNA and produce the necessary protein when inserted into an appropriate vector. We are in complete agreement with the examiner that the DNA produced by Okano either anticipates or makes obvious the subject matter claimed herein.
When an examiner obtains a product which reasonably appears to fall within the scope of that which is claimed by a patent applicant, it is reasonable to shift the burden to the applicant to provide evidence showing that the product of the prior art does not fall within the scope of applicants' claims. See In re Swinehart, 439 F.2d 210, 169 USPQ 226 (CCPA1971); In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA1977) and In re Fitzgerald, 619 F.2d 67, 205 USPQ 594 (CCPA1980).
We consider next the examiner's rejection of claims 1, 3 through 8, 12, 14 and 18 under 35 U.S.C. § 103 over each of Clark and Freeman, each in view of Beaucage and Maizel.
It is the examiner's position that BCGF is described as a protein useful in bolstering the immune response and the knowledge of the existence of this protein would have motivated one of skill in the art to utilize recombinant DNA protocols to (1) isolate the protein, (2) sequence the protein, (3) construct synthetic DNA probes from the proteins, (4) utilize the probes to isolate messenger RNA, (5) synthesize a cDNA, and (6) produce additional protein. We reverse the rejection.
*7 The examiner's position reflects the "obviousness to try" approach of the "armchair" chemist. As noted by appellants there is nothing in the references which indicates that BCGF is a protein ordinarily produced in such great amounts that one skilled in the art would have no trouble isolating and sequencing the protein. In the absence of being able to isolate substantial quantities of the protein to purity, it would be virtually impossible to produce probes insofar as sequencing the proteins would be disrupted by the presence of significant portions of other proteins. Appellants' specification indicates that the BCGF protein had not been isolated to sufficient purity and sufficient quantity for confirmation of its identity as of the time the application was filed. The examiner has not taken issue with this position and none of the references cited by the examiner reveals the sequence of the protein. Appellants' specification also reveals (pages 12 through 14) that the kinetics of accumulation of BCGF activity is such that a maximum yield occurs from 48 to 72 hours of culture and that a special procedure had to be developed to separate BCGF from TCGF. We are in complete agreement with appellants that the protocol set forth by the examiner would not have been enabling to one of skill in the art and, accordingly, we reverse the rejection.
The examiner's rejections of the claims under 35 U.S.C. § 112, first paragraph, for new matter and lack of enablement are affirmed. The examiner's rejection of the claims under 35 U.S.C. §§ 102/103 over Okano is also affirmed. The examiner's rejection of the claims under 35 U.S.C. § 103 over Clark et al. is reversed.
Our review of this specification reveals that there is no statement of utility for the BCFG protein and no indication in the specification of "how to use" the BCGF protein which is produced by the recombinant DNA vectors and cell lines of the claims. Appellants' specification clearly states that as of its filing date, the actual function of BCGF protein was unknown (specification, page 3, lines 19 through 28). Should this application be prosecuted further we urge the examiner to specifically consider whether or not the application complies with the utility requirements of 35 U.S.C. § 112 and to note his or her consideration on the record. In this regard, In re Hafner, 410 F.2d 1403, 161 USPQ 783 (CCPA1969), may be of interest insofar as some later dated publications of appellants and others may constitute prior art if the examiner were to hold the application originally filed by the appellants did not comply with the utility requirements of 35 U.S.C. § 112.
FN1. A vector is a carrier molecule to which a desired segment of DNA is linked. The vector serves to incorporate foreign DNA into host cells. The vector exemplified by appellants is a plasmid. Viruses may also serve as vectors.
FN2. The protein itself is not claimed; the claims are directed to the DNA sequence which encodes the protein.
FN3. The broad scope of appellants' claims is evidenced by certain statements made in the response submitted January 9, 1990 (Paper No. 9). At page 10 thereof it is stated that applicants' cloning procedure is directed toward identifying clones expressing proteins having a "particular biological activity" and that the claims are phrased in terms of such biological activity rather than a particular DNA sequence per se. AT page 9 of the same response, it is stated that one skilled in the art would be enabled to isolate a DNA sequence which encodes a protein exhibiting a molecular weight of between about 8 and about 14 kilodaltons wherein the protein exhibits a BCGF biological activity. The scope of such proteins is intended to encompass any of the "multiple BCGF species" which had not been isolated at that time.
FN4. The relationship between the sequencing errors and the change in the N-terminus from the ATG MET codon at position +76 to position +88 has not been explained.
FN5. With regard to the start position for the protein, appellants' specification, page 25, lines 27 through 31, indicates the start sequence for the protein is at the zero point. The Sharma declaration, without explanation, places the N-terminal (start sequence) at position 82.
FN6. Copies of the Watson et al. pages are attached hereto.
FN7. Appellants are not specific regarding whether the specification or the deposit of the cell line constitutes the "description" of the claimed invention.
*8 Appellants request reconsideration of our decision mailed May 27, 1992, in particular that portion of our decision in which we affirmed the examiner's rejection of claims 1, 3 through 8, 12, 14 and 18 under 35 U.S.C. § 112 as being directed to subject matter not described in the specification as filed, i.e., the "new matter" rejection.
We have carefully considered all the arguments set forth in appellants' request but are unpersuaded of error in our decision and decline to modify the decision.
Appellants assert that because the specification (including the ATCC deposit) is enabling for pARJ43, the specification inherently enables the sequence contained on pARJ43 and, accordingly, satisfies the description requirement for the claimed subject matter.
... we hereby reaffirm, that 35 U.S.C. 112, first paragraph, requires a 'written description of the invention' which is separate and distinct from the enablement requirement. The purpose of the 'written description' requirement is broader than to merely explain how to 'make and use'; the applicant must also convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed (citations omitted).
Second, the invention claimed herein is not the specific plasmid pARJ43 but, rather, a generic invention directed to DNA which produces either a protein molecule of specified amino acid sequence or, importantly, a biological equivalent of that protein.
We discuss first the effect of appellants' ATC deposit on the description requirement.
Appellants assert that they have satisfied the description requirement of 35 U.S.C. § 112 by depositing the pARJ43 plasmid in the American Type Culture Collection. This is not necessarily the case.
We recognize that a patent applicant's deposit of a biological material in a public depository effectively incorporates the deposited material, by reference, into the patent application. It is analogous to a cross-reference to an earlier filed patent application for a description of the preparation of a starting material. See Ex parte Schmidt-Kastner, 153 USPQ 473 (Bd.App.1963). In this case, however, the deposit does not satisfy the description requirement for either the BCFG type DNA being claimed or the protein produced thereby because there is no evidence of record that those skilled in the art having the deposited material would have been aware of the BCGF DNA structure and the protein encoded thereby or would have been able to accurately determine said DNA structure and protein sequence without undue experimentation. Indeed, in this case the evidence is to the contrary because appellants who are skilled in the art were unable to accurately sequence the DNA and protein until subsequent to the filing date of the application.
*9 As noted in our decision, the structures of DNA now claimed [FN1] and the protein produced thereby are not effectively described in the specification itself. Indeed, they are badly misdescribed. Stripped of accurate DNA and protein sequences, the description of DNA which remains in the specification is limited to molecular weight, biological activity and method of preparation. In this case it is insufficient.
A gene is a chemical compound, albeit a complex one, and it is well established in our law that conception of a chemical compound requires that the inventor be able to define it so as to distinguish it from other materials, and to describe how to obtain it.... Conception does not occur unless one has a mental picture of the structure of the chemical, or is able to define it by its method of preparation, its physical or chemical properties, or whatever characteristics sufficiently distinguish it. It is not sufficient to define it solely by its principal biological property, e.g., encoding human erythropoietin, because an alleged conception having no more specificity than that is simply a wish to know the identity of any material with that biological property. (Emphasis added). 927 F.2d at 1206, 18 U.S.P.Q.2d at 1021.
We note that in this case the molecular biological property of interest is not peculiar to BCGF proteins but is also possessed by TCGF proteins (specification, page 3). Moreover many proteins would have the same molecular weight. There remains only the method of making the plasmid as a mechanism for describing the DNA.
Appellants' specification does set forth a procedure for preparing plasmids containing cDNA capable of translating an active protein. However, the plasmids described by appellants did not contain full length inserts of the BCGF gene. Moreover, out of 700 clones which contained cDNA inserts only two, pARJ43 and pARJ45, included inserts which coded for a biologically active protein. These cDNA inserts differed considerably in molecular size. Were one to reproduce the experiments set forth in the specification by appellants, there is no guarantee that plasmid pARJ43 would be reproduced. Accordingly, from a description viewpoint, appellants' specification with its misstated DNA sequence does not of itself include enough information to otherwise satisfy the description requirement.
We discuss next the scope of appellants' claims vis-a-vis the scope of the description in the specification.
As noted in our decision of May 27, 1992, all of appellants' claims are generic claims directed to recombinant vectors or cells comprising DNA sequences encoding for a specific protein as set forth in the figures or a "biologically functional equivalent thereof." Appellants' claims do not describe [FN2] the DNA by what it is (an assemblage of nucleotides) but by the protein it encodes for. Appellants did not directly sequence the protein encoded by the BCGF DNA but, rather, deduced the protein sequence from the structure of the missequenced DNA. The deduced sequence misidentified the protein. Importantly, absent an accurate description of the protein sequence, one cannot describe or envisage the "biological equivalents thereof." On this point we note that appellants' theory of conservative replacement of amino acids based on hydropathic index (specification, pages 26 and 27) is in this case mere verbiage because the basic amino acid sequence was misdescribed at the time this application was filed.
[I]t is essential that there be no question that, at the time an application for patent is filed, the invention claimed therein is fully capable of being reduced to practice (i.e., that no technological problems, the resolution of which would require more than ordinary skill and reasonable time, remain in order to obtain an operative, useful embodiment).
Surely at the time of filing the instant application one of skill in the art, lacking a description of the amino acid structure of the protein, would have been unable to envisage and/or reduce to practice any "biologically functional" equivalent of the protein or the DNA coding for the equivalent. Accordingly, from a "scope of claim" viewpoint, appellants' description of the invention at the time of filing the instant application, fell far short of what is now claimed.
It would appear that appellants did not comply with the patent statutes and filed the instant application prematurely, without adequate descriptive support. The patent laws do not permit insertion of additional descriptive matter subsequent to an applicant's filing date in order to complete its disclosure so as to conform the specification's description of the invention to the statutory standard.
Appellants urge that the examiner and this board have accused the Sharma declaration of being "untruthful." This is not the case. We have again reviewed the examiner's discussion of the Sharma declaration, which discussion appears on pages 8 through 10 of the Answer. We are in agreement with the examiner's positions and comments as set forth therein. The examiner's questions regarding how the error was discovered and how the resequencing was accomplished appear to reflect a desire to know whether the error would have been readily and easily detected by one skilled in the art. With regard to the source of the sample of pARJ43 which was resequenced, the examiner rightly appears to be taking the position that a chain of evidence has been broken. Appellants' only description of the DNA set forth in Figure 4 is the material on deposit in the ATCC depository. Accordingly, proof of the accurate DNA sequence should include resequencing of either the material on deposit or a laboratory colony of pARJ43 material proven to be identical to that which was deposited in the ATCC.
We remain somewhat confused by appellants' explanation of the zero point and the discussion of the errors in DNA sequencing and their effect on the protein structure as set forth in paragraph 5 of the Sharma Declaration. As we read appellants' specification, everything after the zero point of Figure 4 constitutes BCGF DNA sequences whereas everything which precedes the zero point constitutes the B-galactosidase structural gene. There is nothing in appellants' original specification which describes the first amino acid of BCGF as being encoded by the codon starting at position +79 or at +82. Additionally, there is nothing in the specification which describes the amino acid sequence from +1 to +79 as corresponding to a "quite apparent" leader sequence of the BCGF molecule as now alleged by appellants (Request, page 8). Indeed, appellants' specification, page 24, unequivocally states that "there is no leader sequence" in the vectors pARJ43 and pARJ45. Moreover, because it is known that proteins are synthesized in the amino-to-carboxyl direction (left to right in Fig. 4), we are unable to understand Sharma's comments that deletion "frame shifting" at codons +185 and +196 caused the BCGF N-terminus codon (which is "left" of the 185 codon) to shift from +76 to +86.
*11 Appellants' request for reconsideration is granted to the extent we have reconsidered and clarified our decision but is denied to the extent it seeks modification thereof.
FN1. Both appellants and the examiner have treated the claims as if appellants' proposed amendments to Figure 4 have been entered. The examiner's Final Rejection and Examiner's Answer both indicate the amendments have not been entered. In the interest of efficiency, we have treated the claims as if the amendment to the figures had been entered.
FN2. We recognize that appellants take issue with our indicating that the claims define the DNA by "describing" the DNA in terms of the protein it codes for. Similar language was apparently considered appropriate and utilized by the court in In re Johnson, 558 F.2d 1008, 194 USPQ 187, 194 (CCPA1977). We consider it appropriate here.

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