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 .
Detailed Action
This action is in response to the papers filed August 25, 2025.
Amendments
Applicant's response and amendments, filed August 25, 2025, to the prior Office Action is acknowledged. Applicant has cancelled Claims 1-11, 13-14, and 17-19, amended Claims 12, 15-16, and 20, and added new claims, Claims 20-35.
Claims 12, 15-16, and 20-35 are pending and under examination.
Priority
This application is a continuation of application 16/995,572 filed on August 17, 2020, now U.S. Patent 11,732,246, which is a continuation of application 16/191,709 filed on November 15, 2018, now U.S. Patent 10,781,430, which is a continuation of application 15/122,853 filed on August 31, 2016, now U.S. Patent 10,167,454, which is a 371 of PCT/US2015/19513 filed on March 9, 2015. Applicant’s claim for the benefit of a prior-filed application provisional application 61/950,157, filed on March 9, 2014 under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged.
Terminal Disclaimer
1. The terminal disclaimer filed on August 25, 2025 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of U.S. Patents 9,890,365, 10,167,454, 10,781430, and 11,732,246 has been reviewed and is accepted. The terminal disclaimer has been recorded.
Allowable Subject Matter
2. Claims 34-35 allowed.
The following is a statement of reasons for the indication of allowable subject matter: Applicant has filed the Terminal Disclaimers.
3. Claims 22 and 31 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claim Objections
4. Claim 12 is objected to because of the following informalities: Where a claim sets forth a plurality of elements or steps, each element or step of the claim should be separated by a line indentation, 37 CFR 1.75(i). See MPEP §608.01(m).
Appropriate correction is required. See Claims 27 and 34, for example.
Claim Rejections - 35 USC § 112
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.
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.
5. Claims 12, 15-16, and 20-33 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.
Claims 12, 21, 27, and 30 recite the phrase “at least about”. The metes and bounds of the term “at least about" are unclear because there are two limitations in this phrase: "at least" and "about". The limitation "about" is broad, but not indefinite. Similarly, the limitation "at least" is broad, but not indefinite. However, "at least about" is indefinite because the metes and bounds of limitation "at least about" can not be determined. “About” indicates values below the referenced number, which necessarily fails to meet the "at least" requirement.
Dependent claims are included in the basis of the rejection because they do not correct the primary deficiencies of the independent claim(s).
The Examiner suggests amending the claim to recite either “at least” or “about”, but not both. Choose one.
See also, for example, Office Action mailed September 8, 2017 in parent application 15/122,853.
6. Claims 20, 33, and 35 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.
The claims recite a pharmaceutical composition comprising “an effective amount” of the rAAV.
An effective amount to do what??
The recitation implies a genus of undisclosed phenotypes by which “an effective amount” is to be determined and/or identified, thereby rendering the claim indefinite. A claim may be rendered indefinite by reference to an object that is variable. (MPEP §2173.05(b)).
The claims denote that there is an amount of the rAAV vectors that is/are not “an effective amount”.
The claims are considered indefinite because that which does/does not constitute “an effective amount” is considered an arbitrary and subjective determination.
7. Claims 12, 15-16, 20-21, 23-30, and 32-33 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 12 previously recited “ornithine transcarbamylase (OTC)”, and has been amended to recite “a transcarbamylase (OTC)”. A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, Claim 12 recites the broad recitation “a transcarbamylase”, and the claim also recites (OTC), which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
The art recognizes a genus of transcarbamylase enzymes, each of which act on different substrates, e.g. aspartate, ornithine, N-acetyl-L-ornithine, N-succinyl-L-ornithine, putrescine, oxamate, uredioglycine, L-2,3-diaminopropionate, and L-2,4,-diamnobutyrate (Google search notes).
Dependent claims are included in the basis of the rejection because they do not correct the primary deficiencies of the independent claim(s).
8. Claim(s) 12, 15-16, 20-21, 23-30, and 32-33 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.
Claim 12 previously recited “ornithine transcarbamylase (OTC)”, and has been amended to recite “a transcarbamylase (OTC)”.
Clear support for the new limitation(s) cannot be found in the instant application or priority documents. Accordingly, the amendment(s) to Claim 12 is considered to constitute new matter.
MPEP 2163.06 notes “If new matter is added to the claims, the examiner should reject the claims under 35 U.S.C. 112, first paragraph - written description requirement. In re Rasmussen, 650 F.2d 1212, 211 USPQ 323 (CCPA 1981).” MPEP 2163.02 teaches that “Whenever the issue arises, the fundamental factual inquiry is whether a claim defines an invention that is clearly conveyed to those skilled in the art at the time the application was filed...If a claim is amended to include subject matter, limitations, or terminology not present in the application as filed, involving a departure from, addition to, or deletion from the disclosure of the application as filed, the examiner should conclude that the claimed subject matter is not described in that application”. MPEP 2163.06 further notes “When an amendment is filed in reply to an objection or rejection based on 35 U.S.C. 112, first paragraph, a study of the entire application is often necessary to determine whether or not “new matter” is involved. Applicant should therefore specifically point out the support for any amendments made to the disclosure” (emphasis added).
The art recognizes a genus of transcarbamylase enzymes, each of which act on different substrates, e.g. aspartate, ornithine, N-acetyl-L-ornithine, N-succinyl-L-ornithine, putrescine, oxamate, uredioglycine, L-2,3-diaminopropionate, and L-2,4,-diamnobutyrate (Google search notes).
Applicant’s amendment to Claim 12 is an attempt to change the definition of the OTC acronym, broadening the scope of “OTC”. Rather, as disclosed in [0004], OTC is the acronym for ornithine transcarbamylase.
Alternatively, if Applicant believes that support for the broadening amendment is present and clearly envisaged in the instant application or earlier filed priority documents, applicant must, in responding to this Office Action, point out with particularity, where such support may be found.
Declarations and new references cannot demonstrate possession of a concept after the fact.
Applicant does not indicate where these limitations are supported by the original specification, or how, as is Applicant's burden. See MPEP §714.02, last sentence of the third paragraph from the end and MPEP §2163.06 (I) last sentence.
Dependent claims are included in the basis of the rejection because they do not correct the primary deficiencies of the independent claim(s).
Claims 27 and 34 recite OTC, and do not correct the deficiencies of Claim 12.
9. Claims 12, 15-16, 20-21, 23-30, and 32-33 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.
Claims 12 and 27 recite a nucleic acid sequence that is at least about 96% identical to SEQ ID NO:5 that encodes a functional OTC protein.
Claims 21 and 30 recite a nucleic acid sequence that is at least about 99% identical to SEQ ID NO:5 that encodes a functional OTC protein.
As discussed above, Applicant’s amendment to Claim 12 is a broadening amendment to the genus of transcarbamylases, for which art recognizes a genus of transcarbamylase enzymes that act on different substrates, e.g. aspartate, ornithine, N-acetyl-L-ornithine, N-succinyl-L-ornithine, putrescine, oxamate, uredioglycine, L-2,3-diaminopropionate, and L-2,4,-diamnobutyrate
As discussed above, Applicant’s amendment to Claim 12 is a broadening amendment to the genus of transcarbamylases, for which art recognizes a genus of transcarbamylase enzymes that act on different substrates, e.g. aspartate, ornithine, N-acetyl-L-ornithine, N-succinyl-L-ornithine, putrescine, oxamate, uredioglycine, L-2,3-diaminopropionate, and L-2,4,-diamnobutyrate
A claim may be rendered indefinite by reference to an object that is variable. (MPEP §2173.05(b)).
If there are multiple ways to measure “functional protein”, to wit, different enzymatic substrates, yet each yields a different result, then the claim may be indefinite because it is unclear which method is to be performed to determine infringement.
Dependent claims are included in the basis of the rejection because they do not correct the primary deficiencies of the independent claim(s).
10. Claim(s) 12, 15-16, 20-21, 23-30, and 32-33 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.
Claims 12 and 27 recite a nucleic acid sequence that is at least about 96% identical to SEQ ID NO:5 that encodes a functional OTC protein.
Claims 21 and 30 recite a nucleic acid sequence that is at least about 99% identical to SEQ ID NO:5 that encodes a functional OTC protein.
As discussed above, Applicant’s amendment to Claim 12 is a broadening amendment to the genus of transcarbamylases, for which art recognizes a genus of transcarbamylase enzymes that act on different substrates, e.g. aspartate, ornithine, N-acetyl-L-ornithine, N-succinyl-L-ornithine, putrescine, oxamate, uredioglycine, L-2,3-diaminopropionate, and L-2,4,-diamnobutyrate
Without a correlation between structure and function, the claim does little more than define the claimed invention by function. That is not sufficient to satisfy the written description requirement. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406 (“definition by function ... does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is’).
In analyzing whether the written description requirement is met for genus claims, it is first determined whether a representative number of species have been described by their complete structure. To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof. The disclosure of a single species is rarely, if ever, sufficient to describe a broad genus, particularly when the specification fails to describe the features of that genus, even in passing. (see In re Shokal 113USPQ283(CCPA1957); Purdue Pharma L.P. vs Faulding Inc. 56 USPQ2nd 1481 (CAFC 2000).
The court explained that “reading a claim in light of the specification, to thereby interpret limitations explicitly recited in the claim, is a quite different thing from ‘reading limitations of the specification into a claim,’ to thereby narrow the scope of the claim by implicitly adding disclosed limitations which have no express basis in the claim.” The court found that applicant was advocating the latter, i.e., the impermissible importation of subject matter from the specification into the claim.). See also In re Morris, 127 F.3d 1048, 1054-55, 44 USPQ2d 1023, 1027-28 (Fed. Cir. 1997).
The specification discloses “about” to mean +/- 10% of the referenced value (e.g. [00083]).
SEQ ID NO:5 is 1068 nucleotides in length.
Thus, Claims 12 and 27 encompass a genus of nucleic acid molecules having as little as 86% identity to SEQ ID NO:5, and Claims 21 and 30 encompass a genus of nucleic acid molecules having as little as 89% identity to SEQ ID NO:5
86% identity to SEQ ID NO:5 allows for 150 nucleotide substitutions, insertions, and/or deletions dispersed throughout the referenced SEQ ID NO:5.
89% identity to SEQ ID NO:5 allows for 118 nucleotide substitutions, insertions, and/or deletions dispersed throughout the referenced SEQ ID NO:5.
96% identity to SEQ ID NO:5 allows for 43 nucleotide substitutions, insertions, and/or deletions dispersed throughout the referenced SEQ ID NO:5.
99% identity to SEQ ID NO:5 allows for 11 nucleotide substitutions, insertions, and/or deletions dispersed throughout the referenced SEQ ID NO:5.
4^150 = about 2x10^90 structurally and functionally undisclosed variants of SEQ ID NO:5.
4^118 = about 1x10^71 structurally and functionally undisclosed variants of SEQ ID NO:5.
4^43 = about 8x10^25 structurally and functionally undisclosed variants of SEQ ID NO:5.
4^11 = about 4x10^6 structurally and functionally undisclosed variants of SEQ ID NO:5.
(www.calculator.net/exponent-calculator; last visited August 25, 2025).
Claims 12, 21, 27, and 30 also allow for as many as 150, 118, 43, and 11 amino acid variants of the OTC polypeptide encoded by SEQ ID NO:5 (356 amino acids) when each nucleotide change affects a different codon, and thus a different amino acid.
20^150 = about 1x10^195 structurally and functionally undisclosed amino acid variants of the OTC encoded by SEQ ID NO:5.
20^118 = about 3x10^153 structurally and functionally undisclosed amino acid variants of the OTC encoded by SEQ ID NO:5.
20^43 = about 9x10^55 structurally and functionally undisclosed amino acid variants of the OTC encoded by SEQ ID NO:5.
20^11 = about 2x10^14 structurally and functionally undisclosed amino acid variants of the OTC encoded by SEQ ID NO:5.
Thus, the claims reasonably encompass an enormously vast genus of about 2x10^90, 1x10^71, 8x10^25, and/or 4x10^6 structurally and functionally undisclosed variants of SEQ ID NO:5.
Thus, the claims reasonably encompass an enormously vast genus of about 1x10^195, 3x10^153, 9x10^55, and/or 2x10^14 structurally and functionally undisclosed variants of the OTC polypeptide encoded by SEQ ID NO:5.
The specification discloses “functional” encompasses embodiments whereby the polypeptide has as little as 40% biological activity as a wildtype human OTC polypeptide (e.g. [00078]).
The art recognizes that ornithine transcarbamylase has different functional domains, e.g. carbamoyl phosphate binding domain, L-ornithine binding domain, and catalytic domain.
Thus, the claims encompass OTC polypeptide variants having a broad genus of:
i) reduced or eliminated carbamoyl phosphate binding functional properties;
ii) reduced or eliminated L-ornithine binding functional properties; and/or
iii) reduced or eliminated catalytic functional properties.
Moreira et al (Hot spots—A review of the protein–protein interface determinant amino-acid residues, Proteins 68: 803-812, 2007) is considered relevant prior art for having taught Protein–protein interactions are very complex and can be characterized by their size,
shape, and surface complementarity (e.g. pg 803, Protein-Protein). The hydrophobic and electrostatic interactions they establish, as well as the flexibility of the molecules involved, are very significant.
Moreira et al taught that in a protein–protein interface, a small subset of the buried amino acids typically contribute to the majority of binding affinity as determined by the change in the free energy of binding. Although there is no purely geometric reason, these energetic determinants are compact, centralized regions of residues crucial for protein association (e.g. pg 804, col. 2).
Moreira et al taught that most interfaces are optimal tight-fitting regions characterized by complementary pockets scattered through the central region of the interface, and enriched in structurally conserved residues. These pockets are classified as ‘‘complementary’’ because there is a large complementarity both in shape and in the juxtaposition of hydrophobic and hydrophilic hot spots, with buried charged residues forming salt bridges and hydrophobic residues from one surface fitting into small nooks on the opposite face. Usually, the hot spot of one face packs against the hot spot of the other face establishing a region determinant for complex binding (e.g. pg 806, col. 1). Complementarity is basically affected by the size of the buried surface, alignment of polar and nonpolar residues, number of buried waters, and the packing densities of atoms involved in the protein–protein interface. Packing defects at the protein–protein interface result in these gaps or pockets, and it is unclear whether unfilled pockets contain water molecules or how the dynamics of water molecules entering and escaping these pockets may affect binding stability (e.g. pg 807, col. 2). Moreira et al taught that common methodology to determine hot spot locations on the artisan’s protein of interest, alanine-scanning mutagenesis is slow and labor-intensive (e.g. pg 804, col. 1). Similarly, systematic mutagenesis is very laborious and time-consuming to perform, as individual mutant proteins must be purified and analyzed separately (e.g. pg 808, col. 2).
Ng et al (Predicting the Effects of Amino Acid Substitutions on Protein Function, Annual Review Genomics Human Genetics 7: 61-80, 2006) is considered relevant prior art for having taught that non-synonymous nucleotide changes which introduce amino acid changes in the corresponding protein have the largest impact on human health. Most algorithms to predict amino acid substation consequences of protein function indicate about 25% to 30% of amino acid changes negatively affect protein function (Abstract). Existing prediction tools primarily focus on studying the deleterious effects of single amino acid substitutions through examining amino acid conservation at the position of interest among related sequences, an approach that is not directly applicable to multiple amino acid changes, including insertions or deletions. Ng et al taught that 83% of disease-causing mutations affect protein stability (e.g. pg 63, col. 1), which in this case, would affect the ability of t he enormously vast genus of about 2x10^90, 1x10^71, 8x10^25, and/or 4x10^6 structurally and functionally undisclosed variants of SEQ ID NO:5 and the enormously vast genus of about 1x10^195, 3x10^153, 9x10^55, and/or 2x10^14 structurally and functionally undisclosed variants of the OTC polypeptide encoded by SEQ ID NO:5 that are to have the property of being “functional”.
Ng et al taught that while multiple sequence alignment of the homologous sequences reveals what positions have been conserved throughout evolutionary time, and these positions are inferred to be important for function (e.g. pg 63, col. 1), Users should be cautious even with proteins that are judged to be orthologous based on phylogeny. Orthologous genes in different species are derived from a common ancestor, but they may not necessarily have the same function. If function has changed, then amino acids that are important for the function of one protein may not necessarily be important for the function of the ortholog. 2% of disease-causing mutations in human genes are identical to the sequences of their respective mouse orthologs, suggesting that even though these positions have huge phenotypic effects on human health, they have different roles or are no longer important in mice. If the orthologs in alignment have slightly different functions, then the positions that differentiate function among orthologs may be incorrectly predicted. (e.g. pg 68, col. 1). When there are many missense mutations in the gene(s) of interest, assaying all missense mutations, which introduce amino acid changes, can be expensive and time-consuming (e.g. pg 74, col. 1). Prediction accuracy has gradually improved, but few head-to-head comparisons exist. Moreover, as the number of servers providing AAS prediction increases, it will become increasingly difficult for investigators to interpret the predictions. (e.g. pg 74, col. 2). Ng et al taught that the error rate of functional annotations in the sequence database is considerable, making it even more difficult to infer correct function from a structural comparison of a new sequence with a sequence database (e.g. Table 1, error rates of about 40% to 60%).
The claims fail to recite, and the specification fails to disclose, a structure/function nexus for the he enormously vast genus of about 2x10^90, 1x10^71, 8x10^25, and/or 4x10^6 structurally and functionally undisclosed variants of SEQ ID NO:5 and the enormously vast genus of about 1x10^195, 3x10^153, 9x10^55, and/or 2x10^14 structurally and functionally undisclosed variants of the OTC polypeptide encoded by SEQ ID NO:5 that are to have the property of being “functional”, e.g. having:
i) as little as 0.1%, 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99% carbamoyl phosphate binding functional properties, alone and/or in combination with;
ii) as little as 0.1%, 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99% L-ornithine binding functional properties, alone and/or in combination with;
iii) as little as 0.1%, 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99% catalytic functional properties, as compared to wildtype human OTC.
In Amgen, Inc., v. Sanofi (872 F.3d 1367 (2017)
At 1375, [T]he use of post-priority-date evidence to show that a patent does not disclose a representative number of species of a claimed genus is proper.
At 1377, [W]e questioned the propriety of the "newly characterized antigen" test and concluded that instead of "analogizing the antibody-antigen relationship to a `key in a lock,'" it was more apt to analogize it to a lock and "a ring with a million keys on it." Id. at 1352.
An adequate written description must contain enough information about the actual makeup of the claimed products — "a precise definition, such as by structure, formula, chemical name, physical properties, or other properties, of species falling within the genus sufficient to distinguish the genus from other materials," which may be present in "functional" terminology "when the art has established a correlation between structure and function." Ariad, 598 F.3d at 1350. But both in this case and in our previous cases, it has been, at the least, hotly disputed that knowledge of the chemical structure of an antigen gives the required kind of structure-identifying information about the corresponding antibodies. See, e.g., J.A. 1241 (549:5-
16) (Appellants' expert Dr. Eck testifying that knowing "that an antibody binds to a particular amino acid on PCSK9 ... does not tell you anything at all about the structure of the antibody"); J.A. 1314 (836:9-11) (Appellees' expert Dr. Petsko being informed of Dr. Eck's testimony and responding that "[m]y opinion is that [he's] right"); Centocor, 636 F.3d at 1352 (analogizing the antibody-antigen relationship as searching for a key "on a ring with a million keys on it") (internal citations and quotation marks omitted).
In the instant case, knowing that the initial nucleic acid sequence of SEQ ID NO:5 does not tell you anything at all about the structure/function nexus for the enormously vast genus of about 2x10^90, 1x10^71, 8x10^25, and/or 4x10^6 structurally and functionally undisclosed variants of SEQ ID NO:5 and the enormously vast genus of about 1x10^195, 3x10^153, 9x10^55, and/or 2x10^14 structurally and functionally undisclosed variants of the OTC polypeptide encoded by SEQ ID NO:5 that are to have the property of being “functional”, e.g. having:
i) as little as 0.1%, 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99% carbamoyl phosphate binding functional properties, alone and/or in combination with;
ii) as little as 0.1%, 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99% L-ornithine binding functional properties, alone and/or in combination with;
iii) as little as 0.1%, 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99% catalytic functional properties, as compared to wildtype human OTC, encompassed by the claims.
In Amgen, Inc., v. Sanofi (U.S. Supreme Court, No. 21-757 (2023))
“Amgen seeks to monopolize an entire class of things defined by their function”.
“The record reflects that this class of antibodies does not include just the 26 that Amgen has described by their amino acid sequence, but a “vast” number of additional antibodies that it has not.”
“It freely admits that it seeks to claim for itself an entire universe of antibodies.”
In the instant case, the record reflects that the claimed class of OTC variants encompasses the enormously vast genus of about 2x10^90, 1x10^71, 8x10^25, and/or 4x10^6 structurally and functionally undisclosed variants of SEQ ID NO:5 and the enormously vast genus of about 1x10^195, 3x10^153, 9x10^55, and/or 2x10^14 structurally and functionally undisclosed variants of the OTC polypeptide encoded by SEQ ID NO:5 that are to have the property of being “functional”, e.g. having:
i) as little as 0.1%, 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99% carbamoyl phosphate binding functional properties, alone and/or in combination with;
ii) as little as 0.1%, 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99% L-ornithine binding functional properties, alone and/or in combination with;
iii) as little as 0.1%, 1%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99% catalytic functional properties, as compared to wildtype human OTC.
“They leave a scientist forced to engage in painstaking experimentation to see what works. 159 U.S., at 475.
This is not enablement. More nearly, it is “a hunting license”. Brenner v. Manson, 383 U.S. 519, 536 (1966).
“Amgen has failed to enable all that it has claimed, even allowing for a reasonable degree of experimentation”.
While the “roadmap” would produce functional combinations, it would not enable others to make and use the functional combinations; it would instead leave them to “random trial-and-error discovery”.
“Amgen offers persons skilled in the art little more than advice to engage in “trial and error”.
“The more a party claims for itself the more it must enable.”
“Section 112 of the Patent Act reflects Congress’s judg-ment that if an inventor claims a lot, but enables only a lit-tle, the public does not receive its benefit of the bargain. For more than 150 years, this Court has enforced the stat-utory enablement requirement according to its terms. If the Court had not done so in Incandescent Lamp, it might have been writing decisions like Holland Furniture in the dark. Today’s case may involve a new technology, but the legal principle is the same.
Applicant’s working example(s) is/are directed to SEQ ID NO:5.
Thus, for the reasons outlined above, it is concluded that the claims do not meet the requirements for written description under 35 U.S.C. 112, first paragraph.
MPEP 2163 - 35 U.S.C. 112(a) and the first paragraph of pre-AIA 35 U.S.C. 112 require that the “specification shall contain a written description of the invention ....” This requirement is separate and distinct from the enablement requirement. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1340, 94 USPQ2d 1161, 1167 (Fed. Cir. 2010) (en banc)
Dependent claims are included in the basis of the rejection because they do not correct the primary deficiencies of the independent claim(s).
Conclusion
11. Claims 12, 15-16, 20-21, 23-30, and 32-33 are rejected.
Claims 22 and 31 are objected to for reciting allowable subject matter, but being dependent upon rejected claims.
Claims 34-35 are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KEVIN K. HILL whose telephone number is (571)272-8036. The examiner can normally be reached 12pm-8pm EST.
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KEVIN K. HILL
Examiner
Art Unit 1638
/KEVIN K HILL/Primary Examiner, Art Unit 1638