DETAILED CORRESPONDENCE
Application Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Applicants’ amendment to the claims filed on 05/13/2026 is acknowledged. This listing of claims replaces all prior listings of claims in the application.
3. Claims 21-40 are pending.
Election/Restrictions
4. Applicant’s election without traverse of Group I, claims 21-39, in the reply filed on 05/13/2026 is acknowledged.
5. Claim 40 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 05/13/2026.
Claims 21-39 are pending and examined on the merits.
Priority
6. Acknowledgement is made of this divisional application of U.S. Non-provisional Application 16/311,561, filed on 12/19/2018, which is a national stage entry of PCT/EP2017/065010, filed on 06/20/2017, which claims foreign priority under 35 U.S.C. 119(a)-(d) to Luxembourg patent application 93251, filing date 12/19/2018, and European Patent Application EP160013850, filing date 06/20/2016. The certified copies has been filed in the parent ‘561 application, filed on 12/19/2018.
Information Disclosure Statement
7. The IDS filed on 06/05/2023 has been considered by the examiner and a copy of the Form PTO/SB/08 is attached to the office action.
Drawings
8. The Drawings filed on 06/05/2023 are acknowledged and accepted by the examiner.
Specification
9. The specification is objected to for the following informalities. . The incorporation of essential material in the specification by reference to an unpublished U.S. application, foreign application or patent, or to a publication is improper. Applicant is required to amend the disclosure to include the material incorporated by reference, if the material is relied upon to overcome any objection, rejection, or other requirement imposed by the Office. The amendment must be accompanied by a statement executed by the applicant, or a practitioner representing the applicant, stating that the material being inserted is the material previously incorporated by reference and that the amendment contains no new matter. 37 CFR 1.57(g). In the instant case, NCBI accession numbers set forth in the specification appears to be an attempt to incorporated essential subject matter by reference without a proper sequence listing.
The attempt to incorporate subject matter into this application by reference to NCBI accession numbers is ineffective because it is unclear whether the versions of the accession numbers that have been submitted to the database have been uniquely identified.
If applicants plan to file a sequence listing to uniquely identify the essential subject matter incorporated by reference, it is noted that the application must comply with the requirements of 37 CFR 1.821 through 1.825; applicants’ attention is directed to the final rulemaking notice published at 55 FR 18230 (May 1, 1990), and 1114 OG 29 (May 15, 1990). To be in compliance, applicants should identify nucleotide sequences of at least 10 nucleotides and amino acid sequences of at least 4 amino acids in the specification by a proper sequence identifier, i.e., “SEQ ID NO:” (see MPEP 2422.01). If these sequences have not been listed in the computer readable form and paper copy of the sequence listing, applicant must provide an initial computer readable form (CRF) copy of the “Sequence Listing”, an initial paper copy of the “Sequence Listing”, as well as an amendment directing its entry into the specification, and a statement that the content of the paper and CRF copies are the same and, where applicable, include no new matter as required by 37 C.F.R. 1.821(e) or 1.821(f) or 1.821(g) or 1.821(b) or 1.825(d).
10. Claim 33 is objected to for making a direct reference to a non-U.S. patent document publication that contains “essential material” needed to determine the metes and bounds of claim 3 within the meaning of 35 U.S.C. 112(b) that is improper and does not comply with the requirements of 37 CFR 1.57 as elucidated above.
It is noted that 37 CFR 1.57(h)(1) provides the following:
A correction to comply with paragraph (c)(1) of this section is permitted only if the application as filed clearly conveys an intent to incorporate that material by reference. A mere reference to material does not convey in an intent to incorporate the material by reference.
Claim Rejections - 35 USC § 112(b)
11. 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.
12. Claims 21-39 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.
Regarding claims 21-39, the term "reduced” is a relative term which renders the claim indefinite. The term "reduced" is a term of degree and the examiner has reviewed the specification and can find no examples or teachings that can be used for ascertaining the variance intended by the recited term of degree. Moreover, there is nothing in the specification or prior art of record to indicate what the recited term is being compared relative to. It is suggested that applicant clarify the meaning of the claims. See Supplementary Examination Guidelines for Determining Compliance with 35 U.S.C. §112 and for Treatment of Related Issues in Patent Applications, 76 FR 7162 (Feb. 9, 2011), page 7165.
Further regarding claim 31, the term “decreased” is a relative term which renders the claim indefinite. The term "decreased" is a term of degree and the examiner has reviewed the specification and can find no examples or teachings that can be used for ascertaining the variance intended by the recited term of degree. Moreover, there is nothing in the specification or prior art of record to indicate what the recited term is being compared relative to. It is suggested that applicant clarify the meaning of the claims. See Supplementary Examination Guidelines for Determining Compliance with 35 U.S.C. §112 and for Treatment of Related Issues in Patent Applications, 76 FR 7162 (Feb. 9, 2011), page 7165.
Claim Rejections - 35 USC § 112(a)
13. The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
A. Essential Subject Matter
14. Claim 33 is 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.
Claim 33 recites essential subject matter, i.e. the sequence database accession numbers for the B4GALNT3 and B4GALNT4 genes without any corresponding sequence identifiers, which fails to satisfy the written description requirement because the claims attempt to incorporate essential subject matter by reference, which is improper. See MPEP § 608.01(p). The complete sequence within the accession numbers recited in the claims is needed for one of skill in the art to practice the invention. While database accession numbers are provided, its contents are an improper incorporation by reference, as the sequence within the database is essential to the claimed subject matter. Furthermore, the sequence within the database can change at any time, including after the time of filing of the instant application. Any version of the sequence within the database after the time of filing of the instant application cannot support the instant claims. Accordingly, claim 33, fails to satisfy the written description requirement.
B. Written Description
15. Claims 21-39 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.
MPEP 2163.II.A.2.(a).i) states, “Whether the specification shows that applicant was in possession of the claimed invention is not a single, simple determination, but rather is a factual determination reached by considering a number of factors. Factors to be considered in determining whether there is sufficient evidence of possession include the level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention”.
For claims drawn to a genus, MPEP § 2163 states 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.
MPEP § 2163 further states that “[s]atisfactory disclosure of a ‘representative number’ depends on whether one of skill in the art would recognize that the applicant was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus…Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are ‘representative of the full variety or scope of the genus,’ or by the establishment of ‘a reasonable structure-function correlation.’ Such correlations may be established ‘by the inventor as described in the specification,’ or they may be ‘known in the art at the time of the filing date.’"
The factors considered in the Written Description requirement are (1) level of skill and knowledge in the art, (2) partial structure, (3) physical and/or chemical properties, (4) functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the (5) method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient." MPEP § 2163.
Claims 21-29 and 33-39 are drawn to an engineered eukaryotic cell comprising: (i) a first beta-1,4-N-acetylgalactosaminyltransferase gene comprising at least a first and a second allele; (ii) a second beta-1,4-N-acetylgalactosaminyltransferase gene that is different from the first beta-1,4-N-acetylgalactosaminyltransferase gene and wherein the second beta-1,4-N-acetylgalactosaminyltransferase gene comprises at least a first allele and a second allele; and the engineered eukaryotic cell comprising: (a) one or more genetic modifications in the first allele of the first beta-1,4-N-acetylgalactosaminyltransferase gene resulting in its reduced or eliminated expression, and one or more genetic modifications in the second allele of the first beta-1,4-N-acetylgalactosaminyltransferase gene resulting in its reduced or eliminated expression, (b) one or more genetic modifications in the first allele of the second beta-1,4-N-acetylgalactosaminyltransferase gene resulting in its reduced or eliminated expression, and one or more genetic modifications in the second allele of the second beta-1,4-N-acetylgalactosaminyltransferase gene resulting in its reduced or eliminated expression or active; or (c) both (a) and (b).
Claim 30 is drawn to the engineered cell of claim 21, wherein the one or more genetic modification(s) in the first allele of the first beta-1,4-N-acetylgalactosaminyltransferase gene, the second allele of the first beta-1,4-N-acetylgalactosaminyltransferase gene, the first allele of the second beta-1,4-N-acetylgalactosaminyltransferase gene and/or the second allele of the second beta-1,4-N-acetylgalactosaminyltransferase gene result(s) in introduction of one or more insertion(s), deletion(s) and/or substitution(s) of one or more nucleotides or a combination thereof in a coding and/or regulatory region of the first allele of the first beta-1,4-N-acetylgalactosaminyltransferase gene, the second allele of the first beta-1,4-N-acetylgalactosaminyltransferase gene, the first allele of the second beta-1,4-N-acetylgalactosaminyltransferase gene and/or the second allele of the second beta-1,4-N-acetylgalactosaminyltransferase gene.
Claim 31 is drawn to the engineered cell of claim 21, wherein the one or more genetic modifications in the first allele of the first beta-1,4-N-acetylgalactosaminyltransferase gene, the second allele of the first beta-1,4-N-acetylgalactosaminyltransferase gene, the first allele of the second beta-1,4-N-acetylgalactosaminyltransferase gene and/or the second allele of the second beta-1,4-N-acetylgalactosaminyltransferase gene result(s) in decreased transcription and/or expression of the first allele of the first allele of the first beta-1,4-N-acetylgalactosaminyltransferase gene, the second allele of the first beta-1,4-N-acetylgalactosaminyltransferase gene, the first allele of the second beta-1,4-N-acetylgalactosaminyltransferase gene and/or the second allele of the second beta-1,4-N-acetylgalactosaminyltransferase gene and/or result(s) in production of variants of the beta-1,4-N-acetylgalactosaminyltransferases, wherein said variants are truncated and/or have altered enzymatic activity.
In this case, the specification discloses an actual reduction to practice of the following representative species of the genus of engineered eukaryotic cell comprising one or more genetic modification to a first and second allele of a first beta-1,4-N-acetylgalactosaminyltransferase gene and first and second allele of a second beta-1,4-N-acetylgalactosaminyltransferase gene as encompassed by the claims (i.e. deletion of the B4GALNT3 and B4GALNT4 alleles in H9D8 cell). Other than the above disclosed species there are no other drawings or structural formulas of the infinite modifications to any eukaryotic cell and any allele of a beta-1,4-N-acetylgalactosaminyltransferase gene that results in reduced expression or decreased activity of a beta-1,4-N-acetylgalactosaminyltransferase as encompassed by the claims.
Ryan et al. (WO 2015/138855 A1; cited in IDS filed on 06/05/2013) teach that because industrial yeast strains tend to be polyploidy, and standard genetic tools based on the integration of linear DNA by homologous recombination are not efficient enough for the creation of loss-of-function alleles in polyploids or modifying multiple loci simultaneously for synthetic biology applications. Further, current technologies allow for only a limited number of genome integrations because each integration must be linked to a dominant selectable marker, so creating homozygous mutants requires the use of two or more markers for any single locus [see paragraph 0005].
Cigan et al. (WO 2016/100309 A1; cited on IDS filed on 06/05/2013) teach that hexaploidy has been considered a significant obstacle in researching and developing useful variants of wheat. In fact, very little is known regarding how homeologous genes of wheat interact, how their expression is regulated, and how different proteins produced by homeologous genes function separately or in concert [see p. 2].
The reference of Singh et al. (Current Protein and Peptide Science, 2017; examiner cited) reviews various protein engineering methods and discloses that despite the availability of an ever-growing database of protein structures and highly sophisticated computational algorithms, protein engineering is still limited by the incomplete understanding of protein functions, folding, flexibility, and conformational changes [see p. 7, column 1, top].
The reference of Zhang et al. (Structure, 2018; examiner cited) discloses that a mutation of a residue that was predicted to be benign caused significant structural changes and unexpected effects on the function of a polypeptide [p. 1475, column 1].
In the Federal Circuit decision, Juno Therapeutics, Inc. v. Kite Pharma, Inc., 10 F.4th 1330, 1337 (Fed. Cir. 2021), the courts found that for broad claims to a nucleic acid encoding a chimeric T cell receptor with a functional requirement to bind a target, “the written description must demonstrate that the applicant made a generic invention that achieves the claimed result and do so by showing that the applicant has invented species sufficient to support a claim to the functionally-defined genus”. In the instant case, the claims are drawn to fragments of 2A peptides of unlimited structure and function, and the specification does not disclose sufficient structural features of the claimed peptide that can be effective in methods of treating a cancer. While a person skilled in the art might be able to embark on their own research program to find suitable multiple fragments of 2A peptides, the four corners of the written description do not demonstrate possession of such. This analysis is consistent with AbbVie Deutschland GmbH v. Janssen Biotech, Inc., 759 F.3d 1285, 1300 (Fed. Cir. 2014) which required an inventor to show “that one has truly invented the genus, i.e. that one has conceived and described sufficient representative species encompassing the breadth of the genus. Otherwise, one has only a research plan, leaving it to others to explore the unknown contours of the claimed genus”.
Given that the specification discloses only a relative few representative species of engineered eukaryotic cell comprising one or more genetic modification to a first and second allele of a first beta-1,4-N-acetylgalactosaminyltransferase gene and first and second allele of a second beta-1,4-N-acetylgalactosaminyltransferase gene as encompassed by the claims, the specification is considered to be insufficient to describe the claimed genus of engineered eukaryotic cell comprising one or more genetic modification to a first and second allele of a first beta-1,4-N-acetylgalactosaminyltransferase gene and first and second allele of a second beta-1,4-N-acetylgalactosaminyltransferase gene as encompassed by the claims. In this case, the specification at best describes a research plan for making, testing, and identifying those species that are encompassed by the claimed genus of engineered eukaryotic cells, however, a plan for making the claimed invention is not sufficient to show possession at the time of filing. One of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genus, and thus, that the applicant was not in possession of the recited genus.
For these reasons, it is the examiner’s position that the specification fails to adequately describe the claimed invention.
C. Scope of Enablement
16. Claims 21-39 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for deletion of the B4GALNT3 and B4GALNT4 alleles in H9D8 cell, does not reasonably provided enablement for all engineered eukaryotic cells comprising one or more genetic modification to a first and second allele of a first beta-1,4-N-acetylgalactosaminyltransferase gene and first and second allele of a second beta-1,4-N-acetylgalactosaminyltransferase gene resulting in reduced expression as encompassed by the claims. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
“The test of enablement is not whether any experimentation is necessary, but whether, if experimentation is necessary, it is undue.” In re Angstadt, 537 F.2d 498, 504, 190 USPQ 214, 219 (CCPA 1976). Factors to be considered in determining whether undue experimentation is required are summarized in In re Wands (858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)) as follows: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. See MPEP § 2164.01(a). The Factors considered to be most relevant to the instant rejection are addressed in detail below.
The breadth of the claims: Claims 21-29 and 33-39 are drawn to an engineered eukaryotic cell comprising: (i) a first beta-1,4-N-acetylgalactosaminyltransferase gene comprising at least a first and a second allele; (ii) a second beta-1,4-N-acetylgalactosaminyltransferase gene that is different from the first beta-1,4-N-acetylgalactosaminyltransferase gene and wherein the second beta-1,4-N-acetylgalactosaminyltransferase gene comprises at least a first allele and a second allele; and the engineered eukaryotic cell comprising: (a) one or more genetic modifications in the first allele of the first beta-1,4-N-acetylgalactosaminyltransferase gene resulting in its reduced or eliminated expression, and one or more genetic modifications in the second allele of the first beta-1,4-N-acetylgalactosaminyltransferase gene resulting in its reduced or eliminated expression, (b) one or more genetic modifications in the first allele of the second beta-1,4-N-acetylgalactosaminyltransferase gene resulting in its reduced or eliminated expression, and one or more genetic modifications in the second allele of the second beta-1,4-N-acetylgalactosaminyltransferase gene resulting in its reduced or eliminated expression or active; or (c) both (a) and (b). The modifications to any cell that result in reduced expression of beta-1,4-N-acetylgalactosaminyltransferase genes is unlimited.
Claim 30 is drawn to the engineered cell of claim 21, wherein the one or more genetic modification(s) in the first allele of the first beta-1,4-N-acetylgalactosaminyltransferase gene, the second allele of the first beta-1,4-N-acetylgalactosaminyltransferase gene, the first allele of the second beta-1,4-N-acetylgalactosaminyltransferase gene and/or the second allele of the second beta-1,4-N-acetylgalactosaminyltransferase gene result(s) in introduction of one or more insertion(s), deletion(s) and/or substitution(s) of one or more nucleotides or a combination thereof in a coding and/or regulatory region of the first allele of the first beta-1,4-N-acetylgalactosaminyltransferase gene, the second allele of the first beta-1,4-N-acetylgalactosaminyltransferase gene, the first allele of the second beta-1,4-N-acetylgalactosaminyltransferase gene and/or the second allele of the second beta-1,4-N-acetylgalactosaminyltransferase gene. The modifications to any cell that result in reduced expression of beta-1,4-N-acetylgalactosaminyltransferase genes is unlimited.
Claim 31 is drawn to the engineered cell of claim 21, wherein the one or more genetic modifications in the first allele of the first beta-1,4-N-acetylgalactosaminyltransferase gene, the second allele of the first beta-1,4-N-acetylgalactosaminyltransferase gene, the first allele of the second beta-1,4-N-acetylgalactosaminyltransferase gene and/or the second allele of the second beta-1,4-N-acetylgalactosaminyltransferase gene result(s) in decreased transcription and/or expression of the first allele of the first allele of the first beta-1,4-N-acetylgalactosaminyltransferase gene, the second allele of the first beta-1,4-N-acetylgalactosaminyltransferase gene, the first allele of the second beta-1,4-N-acetylgalactosaminyltransferase gene and/or the second allele of the second beta-1,4-N-acetylgalactosaminyltransferase gene and/or result(s) in production of variants of the beta-1,4-N-acetylgalactosaminyltransferases, wherein said variants are truncated and/or have altered enzymatic activity. The modifications to any cell that result in reduced expression of beta-1,4-N-acetylgalactosaminyltransferase genes is unlimited.
The state of the prior art; The level of one of ordinary skill; and The level of predictability in the art: As noted above, the structure and function of the claimed modifications to any eukaryotic cell is unlimited.
Regarding the level of skill and knowledge in the art of amino acid modification, MPEP 2144.08.II.A.4.(c) states, "[i]n the area of biotechnology, an exemplified species may differ from a claimed species by a conservative substitution ("the replacement in a protein of one amino acid by another, chemically similar, amino acid... [which] is generally expected to lead to either no change or only a small change in the properties of the protein." Dictionary of Biochemistry and Molecular Biology 97 (John Wiley & Sons, 2d ed. 1989)). The effect of a conservative substitution on protein function depends on the nature of the substitution and its location in the chain. Although at some locations a conservative substitution may be benign, in some proteins only one amino acid is allowed at a given position. For example, the gain or loss of even one methyl group can destabilize the structure if close packing is required in the interior of domains. James Darnell et al., Molecular Cell Biology 51 (2d ed. 1990)."
Ryan et al. (WO 2015/138855 A1; cited in IDS filed on 06/05/2013) teach that because industrial yeast strains tend to be polyploidy, and standard genetic tools based on the integration of linear DNA by homologous recombination are not efficient enough for the creation of loss-of-function alleles in polyploids or modifying multiple loci simultaneously for synthetic biology applications. Further, current technologies allow for only a limited number of genome integrations because each integration must be linked to a dominant selectable marker, so creating homozygous mutants requires the use of two or more markers for any single locus [see paragraph 0005].
Cigan et al. (WO 2016/100309 A1; cited on IDS filed on 06/05/2013) teach that hexaploidy has been considered a significant obstacle in researching and developing useful variants of wheat. In fact, very little is known regarding how homeologous genes of wheat interact, how their expression is regulated, and how different proteins produced by homeologous genes function separately or in concert [see p. 2].
The reference of Singh et al. (Current Protein and Peptide Science, 2017; examiner cited) reviews various protein engineering methods and discloses that despite the availability of an ever-growing database of protein structures and highly sophisticated computational algorithms, protein engineering is still limited by the incomplete understanding of protein functions, folding, flexibility, and conformational changes [see p. 7, column 1, top].
The reference of Zhang et al. (Structure, 2018; examiner cited) discloses that a mutation of a residue that was predicted to be benign caused significant structural changes and unexpected effects on the function of a polypeptide [p. 1475, column 1].
The evidence of record demonstrates that identifying which of the numerous 2A peptide fragments was not known in the art, and one of skill in the art would recognize a high level of unpredictability in the art of amino acid modification.
The amount of direction provided by the inventor and The existence of working examples: The specification discloses the following working examples of engineered eukaryotic cell comprising one or more genetic modification to a first and second allele of a first beta-1,4-N-acetylgalactosaminyltransferase gene and first and second allele of a second beta-1,4-N-acetylgalactosaminyltransferase gene, i.e. deletion of the B4GALNT3 and B4GALNT4 alleles in H9D8 cell. Other than these working examples, the specification fails to disclose any other working examples of engineered eukaryotic cells with genetic modifications as encompassed by the claims.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure: In the Federal Circuit decision of Idenix Pharmaceuticals LLC v. Gilead Sciences Inc., 941 F.3d 1149, 1156 (Fed. Cir. 2019), the court stated that “the key enablement question is whether a person of ordinary skill in the art would know, without undue experimentation, which [species] would be effective….because of the many thousands of [species] which need to be screened for…efficacy, the quantity of experimentation needed is large and weighs in favor of non-enablement.” In the instant case, the number is not thousands but an infinite number of fragments, and as such, the quantity of experimentation would be many orders of magnitude more than that in Idenix.
While methods for modifying the amino acid sequence of a polypeptide were known before the effective filing date, it was not routine in the art to screen by a trial and error process for all genetic modifications as broadly encompassed by the claims.
In view of the overly broad scope of the claims, the lack of guidance and working examples provided in the specification, the high level of unpredictability, and the state of the prior art, undue experimentation would be necessary for a skilled artisan to make and use the entire scope of the claimed invention. Applicants have not provided sufficient guidance to enable one of ordinary skill in the art to make and use the claimed invention in a manner reasonably correlated with the scope of the claims. The scope of the claims must bear a reasonable correlation with the scope of enablement (In re Fisher, 166 USPQ 19 24 (CCPA 1970)). Without sufficient guidance, determination of having the desired biological characteristics is unpredictable and the experimentation left to those skilled in the art is unnecessarily, and improperly, extensive and undue. See In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988).
Conclusion
17. Status of the claims:
Claims 21-40 are pending.
Claim 40 stands withdrawn pursuant to 37 CFR 1.142(b).
Claims 21-39 are rejected.
No claims are in condition for an allowance.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PAUL J HOLLAND whose telephone number is (571)270-3537. The examiner can normally be reached Monday to Friday from 8AM to 5PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath Rao can be reached at 571-272-0939. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PAUL J HOLLAND/Primary Examiner, Art Unit 1656
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