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 .
Election/Restrictions
Applicant’s election without traverse of Group II in the reply filed on 11/18/25 is acknowledged.
Claims 19-26 and 37-38 are withdrawn as being drawn to a non-elected invention.
Applicant has also elected the species of a polypeptide formed of an amino acid sequence set forth in SEQ ID NO: 3. However, during prosecution, all identified species have been examined and are hereby rejoined.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 28-36 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 28 and 33 are indefinite for the reasons set forth below.
Claim 28, in line 3, recites “an altered biotinylation enzyme reduced in substrate specificity”.
Claim 33, in lines 2-3, recites “an altered biotinylation enzyme reduced in substrate specificity”.
As to claims 28 and 33, the limitation “an altered biotinylation enzyme reduced in substrate specificity” is indefinite since it is a limitation that is defined by reference to an object, and the relationship between the limitation and the object is not sufficiently defined.
For further explanation, see MPEP 2173.05(b), under the subheading “II. REFERENCE TO AN OBJECT THAT IS VARIABLE MAY RENDER A CLAIM INDEFINITE”, a portion of which is provided hereby below.
A claim may be rendered indefinite when a limitation of the claim is defined by reference to an object and the relationship between the limitation and the object is not sufficiently defined. That is, where the elements of a claim have two or more plausible constructions such that the examiner cannot readily ascertain positional relationship of the elements, the claim may be rendered indefinite. See, e.g., Ex parte Miyazaki, 89 USPQ2d 1207 (Bd. Pat. App. & Inter. 2008) (precedential) and Ex parte Brummer, 12 USPQ2d 1653 (Bd. Pat. App. & Inter. 1989). In Miyazaki, the Board held that claims to a large printer were not sufficiently definite because:
The language of claim 1 attempts to claim the height of the paper feeding unit in relation to a user of a specific height who is performing operations on the printer.... Claim 1 fails to specify, however, a positional relationship of the user and the printer to each other.
Miyazaki, 89 USPQ2d at 1212. In Brummer, the Board held that a limitation in a claim to a bicycle that recited “said front and rear wheels so spaced as to give a wheelbase that is between 58 percent and 75 percent of the height of the rider that the bicycle was designed for” was indefinite because the relationship of parts was not based on any known standard for sizing a bicycle to a rider, but on a rider of unspecified build. Brummer, 12 USPQ2d at 1655.
In the present case, the limitation “reduced in substrate specificity” is indefinite since it is a limitation that is defined by reference to an object [i.e., the particular substrate and the particular specificity, and the particular standard for comparison to determine whether there is a reduction is substrate specificity], and the relationship between the limitation and the object is not sufficiently defined.
The limitation “an altered biotinylation enzyme reduced in substrate specificity” depends on a particular type of substrate and a particular specificity, neither of which is specified in the claim 28 nor claim 33. Also what is considered “reduced” depends on what standard is used, which is not specified in claim 28 nor claim 33.
Additionally, what particular biotinylation enzyme substrate or specificity, among multiples, is also not defined in Applicant’s specification. Also, what standard determines whether a substrate specificity is reduced is not defined in Applicant’s specification.
In short, what is considered “reduced in substrate specificity” depends on a determination or predetermination based on an unspecified object (i.e., a particular substrate and a particular specificity and what is considered “reduced”), rather than any known standard, and the relationship between the limitation and the object is not sufficiently defined in the claims nor specification.
Therefore the present limitation is indefinite for reasons analogous to that set forth in Miyazaki, where the limitation is indefinite because the claim recites the height of the paper feeding unit in relation to a user of a specific height who is performing operations on the printer though fails to specify a positional relationship of the user and the printer to each other. The present limitation is also analogous to Brummer, where the limitation is indefinite because the relationship of parts was not based on any known standard for sizing a bicycle to a rider, but on a rider of unspecified build.
Moreover, Applicant’s specification does not provide clarity to the limitation “reduced in substrate specificity”. The specification gives some examples but does not provide a definition. While the claims are read in light of the specification, the disclosures in the specification are not read into the claims unless they provide a clear definition to a limitation in the claim.
Applicant’s specification in the Pre-Grant Publication US 20230251254, for instance, in paragraph 0049-0057 gives examples of an altered biotinylation enzyme reduced in substrate specificity, as follows.
“16. The evaluation method according to any one of the above-mentioned items 10 to 15, wherein the altered biotinylation enzyme is any one or more of the following polypeptides:
(1) a polypeptide formed of an amino acid sequence set forth in SEQ ID NO: 1;
(2) a polypeptide formed of an amino acid sequence set forth in SEQ ID NO: 2;
(3) a polypeptide formed of an amino acid sequence set forth in SEQ ID NO: 3;
(4) a polypeptide formed of an amino acid sequence set forth in SEQ ID NO: 12;
(5) a polypeptide formed of an amino acid sequence set forth in SEQ ID NO: 13;
(6) a polypeptide formed of an amino acid sequence set forth in SEQ ID NO: 14;
(7) a polypeptide formed of an amino acid sequence set forth in SEQ ID NO: 15;
(8) a polypeptide formed of an amino acid sequence set forth in SEQ ID NO: 16;…” Paras. 0049-0057.
The above are examples, but do not provide a definition. While the claims are read in light of the specification, the disclosures in the specification are not read into the claims unless they provide a clear definition to a limitation in the claim.
In summary, the meaning of “altered biotinylation enzyme activity reduced in substrate specificity” depend on factors that can vary in a way that renders the limitation indefinite in a claim. What is considered “reduced in substrate specificity” depends on a determination or predetermination based on an unspecified object (i.e., a particular substrate and a particular specificity and what is considered “reduced”), rather than any known standard, and the relationship between the limitation and the object is not sufficiently defined in the claims nor specification.
Moreover, claim 34 is indefinite for the reasons set forth below.
Claim 34, in lines 11-14, recites “(9) a polypeptide that has 1 to 10 amino acids substituted, deleted, inserted, and/or added in any one of the amino acid sequences set forth in SEQ ID NOS: 1 to 3 and 12 to 16, and that has substantially equivalent biotinylation enzyme activity to that of a polypeptide formed of any one of the amino acid sequences set forth in SEQ ID NOS: 1 to 3 and 12 to 16”.
Claim 34, in lines 15-18, recites “(10) a polypeptide that has 90% or more identity to any one of the amino acid sequences set forth in SEQ ID NOS: 1 to 3 and 12 to 16, and that has substantially equivalent biotinylation enzyme activity to that of a polypeptide formed of any one of the amino acid sequences set forth in SEQ ID NOS: 1 to 3 and 12 to 16”.
Claim 34, both in subsection (9) in lines 11-14 and subsection (10) in lines 15-18, recites a polypeptide that has substantially equivalent biotinylation enzyme activity to that of a polypeptide formed of any one of the amino acid sequences set forth in SEQ ID NOS: 1 to 3 and 12 to 16.
A claim may be rendered indefinite when a limitation of the claim is defined by reference to an object and the relationship between the limitation and the object is not sufficiently defined. That is, where the elements of a claim have two or more plausible constructions such that the examiner cannot readily ascertain positional relationship of the elements, the claim may be rendered indefinite. See, e.g., Ex parte Miyazaki, 89 USPQ2d 1207 (Bd. Pat. App. & Inter. 2008) (precedential) and Ex parte Brummer, 12 USPQ2d 1653 (Bd. Pat. App. & Inter. 1989).
The limitation of “equivalent biotinylation enzyme activity” to that of a polypeptide formed of any one of the amino acid sequences set forth in SEQ ID NOS: 1 to 3 and 12 to 16 is defined by reference to an object [i.e., the amino acid sequences set forth in SEQ ID NOS: 1 to 3 and 12 to 16], and the relationship [i.e., what particular biotinylation activity and what is considered “equivalent” biotinylation enzyme activity] between the limitation and the object is not sufficiently defined. What particular biotinylation enzyme activity is not defined, and what standard is used to determine equivalent biotinylation enzyme activity is not defined.
The remaining rejected claims are rejected since they depend from claim 28, which is rejected above, without clarifying the indefiniteness mentioned above.
Examiner notes that the alternatives in claim 34 in subsections (1) through (8) does meet the requirement under 35 U.S.C. 112(b) in particularly pointing out and distinctly claiming the subject matter which the inventor regards as the invention. However, since claim 34 includes the alternatives in subsections (9) and (10), which is rejected under 35 U.S.C. 112(b) for failing to particularly point out and distinctly claim the subject matter which the inventor regards as the invention, as mentioned above, claim 34 as a whole is rejected under 35 U.S.C. 112(b).
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.
Claims 28-36 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 claims contain 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 pre-AIA the inventors, at the time the application was filed, had possession of the claimed invention. This is a written description rejection.
Claim 28, in line 3, and claim 33, each requires “an altered biotinylation enzyme reduced in substrate specificity”. The specification does not describe which amino acid residues or other molecular components are responsible for the functions claimed. Rather, the specification indicates or implies that these potential agents must first be screened in an assay to ascertain if the agents have the functions required by the instant claims. Although the specification provides a few examples of potential agents, it fails to disclose the structures common to all members of the genus of peptides encompassed by the broad limitation provided by applicant. The specification does not disclose the structure of all of the claimed variant agents and fails to disclose which regions of the agents are responsible for the functions claimed. In the absence of a known or disclosed correlation between structure and function, claims which encompass variants defined by their function are generally not considered described.
Applicant is directed to MPEP § 2163 for guidelines on compliance with the written description requirement. Here, applicant has not described a reasonable number of members of the genus of altered biotinylate enzyme reduced in substrate specificity, i.e. the required starting materials for the claims, but rather has presented the public with an idea of how to perform an assay that might identify some peptides that fall within the scope of the claim. Of course, depending on what agents are used in the screening assay, it may well identify none. The Court of Appeals for the Federal Circuit addressed claims of this sort in great detail in University of Rochester v. G.D. Searle and Co. (69 USPQ 2nd 1886, CAFC 2004). In Rochester, the Federal Circuit upheld the district court's ruling that patent claims which recited administration of compounds not disclosed, but rather to be identified in a screening assay, were invalid on their face.
The specification does provides some examples of altered biotinylation enzyme reduced in substrate specificity (see specification in paragraphs 0049-0057, which is also provided further above, under the heading “Claim Rejections - 35 USC § 112”). However, the specification does not describe the structure of the full genus of altered biotinylation enzyme reduced in substrate specificity responsible for the functions claimed. Applicant has not identified in the claim a particular substrate, and even if a particular substrate is identified in the claim, adequate written description of the substrate alone is not considered adequate written description of a claimed “altered biotinylation enzyme reduced in substrate specificity”, even when preparation of such biotinylation enzyme is routine and conventional.
While generically the structure of biotinylation enzyme is known, and the amino acid sequences are identified as SEQ ID NOS: 1 to 3 and 12 to 16, the structure of the presently recited “altered biotinylation enzyme reduced in substrate specificity” can vary substantially within the above given claimed recitations.
Analogous to the decision in Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017), in which the Court noted that knowledge that an antibody binds to a particular epitope on an antigen tells one nothing at all about the structure of the antibody, knowledge that a biotinylation enzyme binds to a particular substrate tells us nothing at all about the structure of the biotinylation enzyme that has reduced substrate specificity.
Therefore, those of skill in the art would not accept that the inventor had been in possession of the full genus of altered biotinylation enzyme reduced in substrate specificity presently claimed.
Functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description support, especially in technology fields that are highly unpredictable, where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus. Abbvie Deutschland GMBH & Co. v. Janssen Biotech, Inc. (759 F.3d 1285 (Fed. Cir. 2014). “When a patent claims a genus using functional language to define a desired result, the specification must demonstrate that the applicant has 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." Capon v. Eshhar, 418 F.3d 1349 (Fed. Cir. 2005).
Consequently, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus nor guidance as to which of the myriad of molecules encompassed by the genus would meet the limitations of the claims.
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111 (Fed. Cir. 1991), clearly states that “applicant must 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.” (See page 1117). The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116).
The skilled artisan cannot envision the detailed chemical structure of the genus of “altered biotinylation enzyme reduced in substrate specificity”, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of identification. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016 (Fed. Cir. 1991). Therefore, the instant claims do not meet the written description provision of 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph.
Similarly, claim 34, both in subsection (9) in lines 11-14 and subsection (10) in lines 15-18 recites a polypeptide that has substantially equivalent biotinylation enzyme activity to that of a polypeptide formed of any one of the amino acid sequences set forth in SEQ ID NOS: 1 to 3 and 12 to 16.
More specifically, claim 34, in lines 11-14, recites “(9) a polypeptide that has 1 to 10 amino acids substituted, deleted, inserted, and/or added in any one of the amino acid sequences set forth in SEQ ID NOS: 1 to 3 and 12 to 16, and that has substantially equivalent biotinylation enzyme activity to that of a polypeptide formed of any one of the amino acid sequences set forth in SEQ ID NOS: 1 to 3 and 12 to 16”.
Claim 34, in lines 15-18, recites “(10) a polypeptide that has 90% or more identity to any one of the amino acid sequences set forth in SEQ ID NOS: 1 to 3 and 12 to 16, and that has substantially equivalent biotinylation enzyme activity to that of a polypeptide formed of any one of the amino acid sequences set forth in SEQ ID NOS: 1 to 3 and 12 to 16”.
Thus both subsection (9) and subsection (10) of claim 34 recites a polypeptide that has substantially equivalent biotinylation enzyme activity to that of a polypeptide formed of any one of the amino acid sequences set forth in SEQ ID NOS: 1 to 3 and 12 to 16.
The specification does not describe which amino acid residues or other molecular components are responsible for the functions claimed. Rather, the specification states that these potential agents must first be screened in an assay to ascertain if the agents have the functions required by the instant claims. The specification fails to disclose the structures common to all members of the genus of peptides encompassed by the broad definition provided by applicant. The specification does not disclose the structure of all of the claimed variant agents and fails to disclose which regions of the agents are responsible for the functions claimed. In the absence of a known or disclosed correlation between structure and function, claims which encompass variants defined by their function are generally not considered described.
Therefore, those of skill in the art would not accept that the inventor had been in possession of the full genus of a polypeptide that has substantially equivalent biotinylation enzyme activity to that of a polypeptide formed of any one of the amino acid sequences set forth in SEQ ID NOS: 1 to 3 and 12 to 16 presently claimed.
Functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description support, especially in technology fields that are highly unpredictable, where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus. Abbvie Deutschland GMBH & Co. v. Janssen Biotech, Inc. (759 F.3d 1285 (Fed. Cir. 2014). “When a patent claims a genus using functional language to define a desired result, the specification must demonstrate that the applicant has 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." Capon v. Eshhar, 418 F.3d 1349 (Fed. Cir. 2005).
Consequently, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus nor guidance as to which of the myriad of molecules encompassed by the genus would meet the limitations of the claims.
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111 (Fed. Cir. 1991), clearly states that “applicant must 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.” (See page 1117). The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116).
The skilled artisan cannot envision the detailed chemical structure of the genus of “a polypeptide that has substantially equivalent biotinylation enzyme activity to that of a polypeptide formed of any one of the amino acid sequences set forth in SEQ ID NOS: 1 to 3 and 12 to 16”, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of identification. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016 (Fed. Cir. 1991). Therefore, the instant claims do not meet the written description provision of 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph.
The remaining claims are rejected since they depend from claim 28, which is rejected for the above reasons, without rectifying the failure to meet the written description requirement.
Examiner notes that the alternatives in claim 34 in subsections (1) through (8) do meet the written description requirement. However, since claim 34 includes the alternatives in subsections (9) and (10), which fail to meet the written description requirement as mentioned above, claim 34 as a whole is rejected for failure to meet the written description requirement.
Conclusion
No claims are allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Fernandez-Suarez et al., “Protein-Protein Interaction Detection in Vitro and in Cells by Proximity Biotinylation”, J. AM. CHEM. SOC. 2008, 130, 9251-9253. (Cited in IDS of 1/9/23). This reference discloses a protein of interest is fused to enzyme biotin ligase (BirA), while another protein is fused to BirA’s “acceptor peptide” (AP) substrate. Detection occurs on lysed or fixed cells, and the labeling of the PPI of interest occurs within live cells. (Page 9251, left col., second full para.) To reduce the affinity of AP for BirA, truncated AP sequences were used. (Page 9252, left column, first para.) [Examiner notes that this reference does not use altered biotinylation enzyme.]
Remnant et al., “In vitro BioID: mapping the CENP-A microenvironment with high temporal and spatial resolution”, Molecular Biology of the Cell, 2019, Vol. 30, p. 1314-1325. (Cited in IDS of 1/9/23). This reference teaches use of biotin ligase (BirA11BR or BirA*) to identify proteins within close proximity to a fusion protein of interest. Cells expression BirA* fusions were exposed to high biotin concentrations for 24 h during which the ligase transferred activated biotin (BioAmp) to other proteins within the immediate vicinity. The protein neighborhood could then be characterized by streptavidin-based purification and mass spectrometry. (See abstract.) [Examiner notes that this reference does not use altered biotinylation enzyme that is reduced in substrate specificity.]
Kulyyassov et al. “PUB-MS: A Mass Spectrometry-based Method to Monitor Protein-Protein Proximity in vivo”, Journal of Proteome Research, August 15, 2011, Vol. 10, pp. 4416-4427. (Cited in IDS of 1/9/23). This reference discloses monitoring protein-protein proximity, based on biotinylation of a protein fused to a biotin acceptor peptide (BAP) by a biotin-ligase, BirA, fused to its interaction partner. The biotinylation status of the BAP can be further detected by either Western analysis or mass spectrometry. The advantage of mass spectrometry is demonstrated by using BAPs with different sequences in a single experiment (allowing multiplex analysis) and the use of stable isotopes. (See abstract.) (See also page 4418, right column under “RESULTS”, disclosing modified sequence of the BAP.) [Examiner notes that this reference does not use altered biotinylation enzyme that is reduced in substrate specificity.]
Kido et al., “AirID, a novel proximity biotinylation enzyme, for analysis of protein-protein interactions”, eLife, May 11, 2020, Vol. 9, e54982 (24 pages). (Cited in IDS of 1/9/23). This reference teaches proximity biotinylation based on BirA enzymes such as BioID (BirA*) and TurboID for identifying proteins that interact with a target protein in a cell or organism. See abstract. A proximity labeling detects proteins that are very close together (page 1, under “Introduction”.) A single BirA mutation at R118G (BirA*) is known in 2004 for being the main improvement in proximity-dependent biotin identification (see page 2 of 24). [Examiner notes that there is no disclosure regarding altered biotinylation enzyme reduced in substrate specificity].
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/Ann Montgomery/Primary Examiner, Art Unit 1678