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
Election/Restrictions
Applicant's election without traverse of Group I, claims 1, 4, 5, 9, 10, 15, 47, 48, new claims 158-163 and SEQ ID No. 4 in the reply filed on 10/22/2025 is acknowledged.
Status of the Application
Claims 1, 4, 5, 9, 10, 15, 16, 19, 23, 27, 31, 32, 47, 48, 66, 67, 70, 77 and 158-163 are pending. Claims 1, 4, 5, 9, 10, 15, 47, 48 and new claims 158-163 are currently under examination. Claims 16, 19, 23, 27, 31, 32, 66, 67, 70 and 77 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Specification – Sequence Listing
The following guidelines illustrate the preferred layout for the specification of a utility application. These guidelines are suggested for the applicant’s use.
Arrangement of the Specification
As provided in 37 CFR 1.77(b), the specification of a utility application should include the following sections in order. Each of the lettered items should appear in upper case, without underlining or bold type, as a section heading. If no text follows the section heading, the phrase “Not Applicable” should follow the section heading:
(a) TITLE OF THE INVENTION.
(b) CROSS-REFERENCE TO RELATED APPLICATIONS.
(c) STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT.
(d) THE NAMES OF THE PARTIES TO A JOINT RESEARCH AGREEMENT.
(e) INCORPORATION-BY-REFERENCE OF MATERIAL SUBMITTED ON A READ-ONLY OPTICAL DISC, AS A TEXT FILE OR AN XML FILE VIA THE PATENT ELECTRONIC SYSTEM. (emphasis added).
(f) STATEMENT REGARDING PRIOR DISCLOSURES BY THE INVENTOR OR A JOINT INVENTOR.
(g) BACKGROUND OF THE INVENTION.
(1) Field of the Invention.
(2) Description of Related Art including information disclosed under 37 CFR 1.97 and 1.98.
(h) BRIEF SUMMARY OF THE INVENTION.
(i) BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING(S).
(j) DETAILED DESCRIPTION OF THE INVENTION.
(k) CLAIM OR CLAIMS (commencing on a separate sheet).
(l) ABSTRACT OF THE DISCLOSURE (commencing on a separate sheet).
(m) SEQUENCE LISTING. (See MPEP § 2422.03 and 37 CFR 1.821 - 1.825).
A “Sequence Listing” is required on paper if the application discloses a nucleotide or amino acid sequence as defined in 37 CFR 1.821(a) and if the required “Sequence Listing” is not submitted as an electronic document either on read-only optical disc or as a text file via the patent electronic system.
Specific deficiency - The incorporation by reference paragraph required by 37 CFR 1.834(c)(1), 1.835(a)(2), or 1.835(b)(2) is missing, defective or incomplete.
This requirement is necessary if the application has:
(i) One or more ASCII plain text files, submitted via the USPTO patent electronic filing system or on one or more read-only optical discs (see § 1.52(e)(8) ), identifying the names of each file, the date of creation of each file, and the size of each file in bytes, for the following document types:
(A) A "Computer Program Listing Appendix" (see § 1.96(c) );
(B) A “Sequence Listing" (see § 1.821(c) ); or
(C) "Large Tables" (see § 1.58(c) ).
(ii) An XML file for a " Sequence Listing XML" (see § 1.831(a) ), submitted via the USPTO patent electronic filing system or on one or more read-only optical discs (see § 1.52(e)(8) ), identifying the names of each file, the date of creation of each file, and the size of each file in bytes.
Required response - Applicant must:
• Provide a substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph, consisting of:
• A copy of the previously-submitted specification, with deletions
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1, 5, 9, 47, 48, 158 and 160-163 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a product of nature without significantly more.
Regarding claims 1, 9 and 158, the claims are drawn to “a CasVariPhi” polypeptide” and “a CasVariPhi guide RNA” and the specification defines the CasVariPhi polypeptide and the CasVariPhi guide RNA as naturally occurring in bacteriophage (0070-0073). Claims 1, 9 and 158 recite the polypeptide has at least 25% or 85% or more of sequence identity to the CasVariPhi polypeptide and encompasses the full polypeptide that naturally occurs in bacteriophage.
Regarding Step 1 in the analysis of Subject Matter Eligibility (MPEP 2106), the claims recite a composition of matter which is appropriate subject matter for a patent. Regarding Step 2A prong 1, claims 1, 9 and 158 recite a natural phenomenon because the CasVariPhi polypeptide and the CasVariPhi guide RNA naturally occur in bacteriophage and they do not have markedly different characteristics from those found in nature. Regarding Step 2A prong 2 and Step 2B, there are no additional elements recited in the claims which either integrate the judicial exception into a practical application or transform the claim into significantly more than the judicial exception. Thus the claims simply recites naturally occurring proteins and RNA found in bacteriophage without markedly different characteristics.
Regarding claim 5, the claim recites a composition of claim 1 comprising a lipid, a buffer or a combination thereof. The broadest reasonable interpretation of a lipid and a buffer would be lipids and cellular medium that are naturally found in bacteriophage, which do not integrate the judicial exception into a practical application. Further the claimed elements do not transform the claim into significantly more than the judicial exception.
Regarding claims 47, 48 and 161-163, the claims recite the CasVariPhi polypeptide and the CasVariPhi guide RNA are encoded by a DNA and comprises an inducible promoter and therefor is still drawn to a naturally occurring polypeptide and RNA and there are no additional elements that integrate the judicial exception into a practical application and further the DNA and inducible promoter do not transform the claim into significantly more than the judicial exception.
Regarding claim 160, the claim recites the CasVariPhi polypeptide and the CasVariPhi guide RNA is in a plasmid or viral vector and is still drawn to a naturally occurring polypeptide and RNA and there are no additional elements that integrate the judicial exception into a practical application and further the plasmid or viral vector do not transform the claim into significantly more than the judicial exception.
Therefore, the instant claims are directed to a natural product that is not markedly different from its natural protein and RNA in a bacteriophage, is not integrated into a practical applicant, does not include elements that amount to significantly more that the natural product itself and therefore do not qualify as patent eligible subject matter under 35 USC § 101.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 4, 5, 10, 15, 47, 48 and 159-163 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Doudna et al. (US Patent No. 11,685,909 with priority to Prov. 62,984,470 10/16/2019).
Claim 1(b) interpretation:
The claim is drawn to a CasVariPhi guide RNA without a particular SEQ ID No. The specification defines the guide RNA in [0065] The present disclosure provides guide RNAs (referred to herein as "CasVariPhi guide RNAs") that bind to and provide sequence specificity to the CasVariPhi proteins. Because Doudna et al. teach polypeptides meeting the limitations of a CasVariPhi polypeptide, any teaching of guide RNAs would meet the limitation of claim 1(b) based on the definition in the instant disclosure.
Regarding clam 1(a), Doudna et al. teach SEQ ID 10 corresponds to instant SEQ ID Nos. 2, 5 and SEQ ID No. 25 that corresponds to SEQ ID No. 6 with at least 36%, 39% and 53% sequence identity, respectively. SEQ ID Nos. 10 and 25 are identified in Doudna et al. as Cas12J polypeptides.
Regarding claim 1(b), Doudna et al. teach guide RNAs that bind a Cas12J polypeptide (col 14 lines 42-67 and col. 18 lines 10-12).
Regarding claim 4, Doudna et al. teach the polypeptide is fused to a NLS (col. 42 lines 60-67).
Regarding claim 5, Doudna et al. teach lipids and liposomes (col. 72 line 43-65).
Regarding claim 10, Doudna et al. teach the polypeptide is a nickase (col. 15 lines 5-25).
Regarding claim 15, Doudna et al. teach guide RNA modifications (col. 67).
Regarding claim 47-48, Doudna et al. teach DNA sequences encoding the guide RNA and polypeptide and linked promoters such as inducible promoters (col. 9).
Regarding claim 159, Doudna et al. teach the polypeptide can be catalytically inactive (col. 14, lines 42-60).
Regarding claim 160-163, Doudna et al. teach vectors for providing the nucleic acids encoding the guide and polypeptide (col. 63 lines 5-22).
Thus Doudna et al. anticipates the instant claims.
US-18-021-469-2.rai search result
Patent No. 11685909
GENERAL INFORMATION
APPLICANT: The Regents of the University of California
APPLICANT: Doudna, Jennifer
APPLICANT: Al-Shayeb, Basem
APPLICANT: Banfield, Jillian
APPLICANT: Pausch, Patrick
TITLE OF INVENTION: CRISPR-Cas Polypeptides and Methods of Use Thereof
SEQ ID NO 110
LENGTH: 757
Query Match 36.4%; Score 1472; Length 757;
Best Local Similarity 41.8%;
Matches 319; Conservative 140; Mismatches 261; Indels 44; Gaps 13;
US-18-021-469-5.rai search result
Patent No. 11685909
GENERAL INFORMATION
APPLICANT: The Regents of the University of California
APPLICANT: Doudna, Jennifer
APPLICANT: Al-Shayeb, Basem
APPLICANT: Banfield, Jillian
APPLICANT: Pausch, Patrick
TITLE OF INVENTION: CRISPR-Cas Polypeptides and Methods of Use Thereof
SEQ ID NO 110
LENGTH: 757
Query Match 39.8%; Score 1588; Length 757;
Best Local Similarity 44.8%;
Matches 345; Conservative 110; Mismatches 269; Indels 46; Gaps 14;
us-18-021-469-6.rai search result
Patent No. 11685909
GENERAL INFORMATION
APPLICANT: The Regents of the University of California
APPLICANT: Doudna, Jennifer
APPLICANT: Al-Shayeb, Basem
APPLICANT: Banfield, Jillian
APPLICANT: Pausch, Patrick
TITLE OF INVENTION: CRISPR-Cas Polypeptides and Methods of Use Thereof
SEQ ID NO 125
LENGTH: 765
Query Match 53.7%; Score 2130.5; Length 765;
Best Local Similarity 56.4%;
Matches 448; Conservative 103; Mismatches 180; Indels 63; Gaps 14;
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 1, 9 and 158 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 pre-AIA the applicant regards as the invention.
The claims refer to any one of CasVariPhi polypeptides as in Fig. 1A-1F This limitation is indefinite because MPEP 2173.05(s), which states:
“Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993).”
Thus the claims fail to particularly point out and distinctly claim the subject matter
in which applicant regards as the invention because the individual sequence identification number are not recited in the claims.
Claim Rejections - 35 USC § 112
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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.
Written Description
Claims 1, 4, 5, 9, 10, 15, 47, 48 and 158-163 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed by him. The courts have stated:
To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997); In re Gostelli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) ("[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious" and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966; Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The fundamental factual inquiry is whether the specification conveys with reasonable clarity to those skilled in the art that, as of the filing date sought, applicant was in possession of the invention as now claimed. See, e.g., Vas-Cath, Inc., 935 F.2d at 1563-64, 19 USPQ2d at 1117.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include: (1) Actual reduction to practice, (2) Disclosure of drawings or structural chemical formulas, (3) Sufficient relevant identifying characteristics (such as: i. Complete structure, ii. Partial Structure, iii. Physical and/or chemical properties, iv. Functional characteristics when coupled with a known or disclosed structure, and v. Correlation between function and structure), (4) Method of making the claimed invention, (5) Level of skill and knowledge in the art, and (6) Predictability in the art.
Moreover, the written description requirement for a genus may be satisfied through sufficient description of a representative number of species 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 functional and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus.” Thus when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
The claims are drawn to a genus of CasVariPhi polypeptides, 650-900 amino acid in length, having at least 25% or 85% sequence identity to the amino acid sequence depicted in any of Figures 1A-1F (which are SEQ ID Nos. 1-6) with the function of editing genes using a CRISPR-Cas system. Claim 158 is further drawn to CasVariPhi guide RNAs comprising at least 80% sequence identity to nucleic acid sequences depicted in any of Figures 1A-1F (which are SEQ ID Nos. 7-18).
The specification describes the CasVariPhi polypeptides of SEQ ID Nos. 1-6 having 718, 769, 754, 844, 762 and 763 amino acid sequences, respectively, and describes a CasVariPhi polypeptide of SEQ ID No. 4 (844 amino acids) and a gRNA having SEQ ID No. 123 (56 nucleotides in length) as being capable of editing the EGFP gene in cells in vitro. The Figures 1A-1F appear to have underlined regions of amino acid sequences but no explanation of this is found in the description of the drawings and it is unclear what this represents. Fig. 4 depicts the start and end points of certain domains of the CasVariPhi polypeptide and Fig. 7 provides a CasVariPhi structure showing the locations of the domains.
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. None of the figures or the specification indicates any actual CasVariPhi polypeptides that have at least 25% or 85% or more sequence identity to the sequence that have the function of editing genes using a CRISPR-Cas system. The claims encompass a vast number of unknown and uncharacterized proteins and the specification does not describe any functional tests to predict what functional domains are needed in polypeptides that have at least 25% or 85% or more sequence identity to the CasVariPhi sequence and still be capable of gene editing. Describing the start and end points of certain domains of the CasVariPhi polypeptide and illustrating the CasVariPhi structure showing the locations of the domains is not sufficient to identify distinguishing characteristics of the CasVariPhi polypeptide having at least 25% or 85% or more sequence identity to the CasVariPhi sequence that would be concisely shared by the members of the broad genus claimed.
Then next analysis is determining whether a representative number of species have been sufficiently described by other relevant identifying characteristics (i.e. other than amino acid sequence), specific features and functional attributes that would distinguish different members of the claimed genus. In the instant case, the only other identifying characteristics is editing of the EGFP gene in HEK293T cells using a CasVariPhi polypeptide having the full length of SEQ ID No. 4 and a gRNA having SEQ ID No. 123. This functional limitation cannot be the identifying characteristics that represents the entire genus because the CasVariPhi polypeptide having 25-85% or more sequence identify would not be expected to have the same function and ability to edit genes as taught by Spencer et al. ("Deep mutational scanning of S. pyogenes Cas9 reveals important functional domains." Scientific reports 7.1 (2017). Spencer et al. describes the importance of identifying functional regions of Cas proteins for use in the Crispr/Cas system for gene editing to identify which domains are needed for functionality (see intro para. page 1). Spencer et al. found that even with the well characterized SpCas9, certain deletions of amino acid had effects on the functionality of Cas proteins such as PAM recognition and gRNA specificity (see para 3 page 1). Spencer et al. discusses that identification of certain regions that are intolerant to mutations and structural analysis is needed to identify and find such regions (discussion).
A review of the specification shows that it provides no description or guidance that would allow one of skill to distinguish the functional species of the recited structural genus from the non-functional members without empirical determination. Since the disclosure and the prior art fail to describe the common attributes and characteristics concisely identifying members of the proposed genus, and because the claimed genus is highly variant comprising a vast number of different CasVariPhi polypeptides and CasVariPhi guide RNA, one of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genus claimed.
As explained above, "A sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can "visualize or recognize" the members of the genus" (AbbVie, 759 F.3d at 1297, reiterating Eli Lilly, 119 F.3d at 1568-69) (emphasis added). 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).
Lastly, the description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521,222 USPQ 369,372-372 (Fed. Cir. 1984) (affirming rejection because the specification does "little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate."). Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of the claims and does not reasonably convey to one skilled in the relevant art that the inventors, at the time the application was filed, had possession of the entire scope of the claimed invention.
Allowable Subject Matter
The CasVariPhi polypeptide sequence having SEQ ID Nos. 1, 3 and 4 or a sequence having at least 25% sequence identity is free of the prior searched. The prior art does not make it obvious to make the claimed sequence as the CasVariPhi polypeptide is not known in the prior art.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Kimberly Chong at (571)272-3111. The examiner can normally be reached Monday thru Friday between M-F 8:00am-4:30pm.
If attempts to reach the examiner by telephone are unsuccessful please contact the SPE for 1636 Neil Hammell at 571-272-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KIMBERLY CHONG/
Primary Examiner Art Unit 1636