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 SEQ ID Nos. 39, 7, 66 and substitution D89R in the reply filed on 05/18/2026 is acknowledged.
Status of the Application
Claims 1-5, 9, 10, 13, 14, 19, 21, 23, 24, 28, 29, 33, 39, 72, 75, 77 and 78 are pending and are currently under examination.
Claim Rejections – Improper Markush
Claims 1-5, 14, 75 and 77 are rejected on the judicially-created basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). The improper Markush grouping includes species of the claimed invention that do not share both a substantial structural feature and a common use that flows from the substantial structural feature. The members of the improper Markush grouping do not share a substantial feature and/or a common use that flows from the substantial structural feature for the following reasons: The claims are directed to a large multitude of variant polypeptides comprising amino acid sequences at least 95% identical to a vast number of sequences and comprising one or more of amino acid substitutions at varying positions and further comprising direct repeat sequences 90% sequence identity to different sequences. Thus the genus of variant polypeptides have vastly different structures.
When the Markush grouping is for alternatives of chemical compounds, they shall be regarded as being of a similar nature where the following criteria are fulfilled:
(A) All alternatives have a common property or activity; and
(B) (1) A common structure is present, i.e., a significant structural element is shared by all of the alternatives; or
(B) (2) In cases where the common structure cannot be the unifying criteria, all alternatives belong to a recognized class of chemical compounds in the art to which the invention pertains.
In paragraph (B)(1), above, the words “significant structural element is shared by all of the alternatives” refer to cases where the compounds share a common chemical structure which occupies a large portion of their structures, or in case the compounds have in common only a small portion of their structures, the commonly shared structure constitutes a structurally distinctive portion in view of existing prior art, and the common structure is essential to the common property or activity. The structural element may be a single component or a combination of individual components linked together.
In paragraph (B)(2), above, the words “recognized class of chemical compounds” mean that there is an expectation from the knowledge in the art that members of the class will behave in the same way in the context of the claimed invention. In other words, each member could be substituted one for the other, with the expectation that the same intended result would be achieved.
In order for the members of the Markush group to belong to “recognized class of chemical compounds” there must be an expectation that the members of the class will behave in the same way in the context of the claimed invention. In other words, each member of the class could be substituted one for the other with the expectation that the same intended result would be achieved. In the instant case, activity of any specific variant polypeptide is dependent on the amino acid structure comprising different positions of amino acid substitutions at different positions along with different direct repeat sequences 90% identical to several different sequences. 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).
There is no expectation that any one of the variant polypeptides as claimed can be substituted for any of the other with a completely different polypeptide structure with the expectation of the same activity.
In response to this rejection, Applicant should either amend the claim(s) to recite only individual species or grouping of species that share a substantial structural feature as well as a common use that flows from the substantial structural feature, or present a sufficient showing that the species recited in the alternative of the claims(s) in fact share a substantial structural feature as well as a common use that flows from the substantial structural feature. This is a rejection on the merits and may be appealed to the Board of Patent Appeals and Interferences in accordance with 35 U.S.C. 134 and 37 CFR 41.31(a)(1).
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 1-5, 9, 10, 13, 14, 19, 21, 23, 24, 28, 29, 33, 39, 72, 75, 77 and 78 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 variant polypeptides having at least 95% sequence identity to the amino acid sequence of SEQ ID No. 39 and having one or more substitutions as in claim 4 and one or more substitutions at positions in claim 5 with the function of editing genes using a CRISPR-Cas system.
The specification describes what appears to be prophetic examples of variant polypeptides (without identifying the sequences) that are capable of forming a ternary complex, and targeting mammalian genes (Examples 1-7). Further, the specification does not appear to describe the genus of variant polypeptides with the functions as listed in claims 10, 33 and 39.
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 variant polypeptides that have at least 95% or more sequence identity to SEQ ID No. 39 and comprising one or more substitutions 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 95% or more sequence identity to the claimed SEQ ID NO. 39 with amino acid substitutions at varying positions and still be capable of gene editing. Describing the different positions of substitutions in the variant polypeptide is not sufficient to identify distinguishing characteristics of the variant polypeptide 95% or more sequence identity to SEQ ID No. 39 that would be concisely shared by the members of the broad genus claimed.
Then the 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 specification further describes % indels induced in 3 different targets using variant polypeptides as set forth in SEQ ID No. 14-17 and 19-41. This functional limitation cannot be the identifying characteristics that represents the entire genus because the variant polypeptides having 95% 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).
Moreover, Al-Shayeb et al. (Cell. 2022 Nov 23;185(24):4574-4586) describes new Cas9-like proteins and 44 families related to type V CRISPR-Cas systems, including the Caslambda RNA guided nuclease family (with sequences having some identity to the claimed sequence) and states some mechanistic aspects of Caslambda remain to be defined, including the possible interchangeability of different variant guide RNAs to support catalytic activity. In addition, details of target binding, including the seed region within the target binding site as well as target recognition accuracy, remain to be established and states future research is needed to identify the functions of phage-encoded CRISPR systems that may extend beyond anti-phage defense and to further test the applications of Caslambda as a genome editing tool in plants, other organisms, and human cells. Thus it appears the functions of these variant polypeptides need to be further tested for their gene editing functions.
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 variant polypeptides comprising numerous different configurations of amino acid substitutions, 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.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the "right to exclude" granted by a patent and to prevent possible harassment by multiple assignees. See In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970);and, In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP §§ 706.02(l)(1) - 706.02(l)(3) for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/forms/. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-5, 9, 10, 13, 14, 19, 21, 23, 24, 28, 29, 33, 39, 72, 75, 77 and 78 are rejected under the judicially created doctrine of obviousness-type double patenting as being unpatentable over claims 1-23 of U.S. Patent No. 11,946,045. Although the conflicting claims are not identical, they are not patentably distinct from each other because the instant claims and the claims of the patent are drawn to patently indistinguishable subject matter
Patent ‘045 claims a variant polypeptide having SEQ ID No. 51 with is 99.5% identical to instant claim 1 having SEQ ID No. 39. Patent ‘045 claims the variant has direct repeat of SEQ ID Nos. 4, 5, 6, 7, claims PAM motifs, nanoparticles. Regarding instant claims 10 and 33 claiming enhanced enzymatic activity, for example, because the structure of Pat ‘045 is identical to the claimed sequence, these properties are inherent. Further regarding the methods in Patent ‘045, it would have been obvious to use the variant polypeptide in the methods. The Court of Appeals for the Federal Circuit in Pfizer Inc, v Teva pharmaceuticals USA Inc., 86 USPQ2d 1001 at page 1008 (March 2008), indicated that there is no patentable distinction between claims to a product and a method of using that product disclosed in the specification of the application. Thus, the co-pending product could be used in the method of the instant claims.
Patent No. 11946045
GENERAL INFORMATION
APPLICANT: ARBOR BIOTECHNOLOGIES, INC. (en)
SEQ ID NO 51
LENGTH: 756
Query Match 99.5%; Score 3932; Length 756;
Best Local Similarity 99.6%;
Matches 753; Conservative 0; Mismatches 3; Indels 0; Gaps 0;
Claims 1, 5, 9, 10, 13, 21, 23, 24, 28, 29, 33, 39, 72, 75, 77 and 78 are rejected under the judicially created doctrine of obviousness-type double patenting as being unpatentable over claims 1 and 4-7 of U.S. Patent No. 11,453,867. Although the conflicting claims are not identical, they are not patentably distinct from each other because the instant claims and the claims of the patent are drawn to patently indistinguishable subject matter
Patent ‘867 claims a variant polypeptide having SEQ ID No. 4 with is 99.3% identical to instant claims 1 having SEQ ID No. 39. Patent ‘045 claims the variant has direct repeat sequences, spacer and tracrRNA sequences. Regarding instant claims 10 and 33 claiming enhanced enzymatic activity, for example, because the structure of Pat ‘867 is identical to the claimed sequence, these properties are inherent.
Patent No. 11453867
GENERAL INFORMATION
APPLICANT: ARBOR BIOTECHNOLOGIES, INC.
SEQ ID NO 4
LENGTH: 756
Query Match 99.3%; Score 3923; Length 756;
Best Local Similarity 99.5%;
Matches 752; Conservative 0; Mismatches 4; Indels 0; Gaps 0
Claims 1-5, 9, 10, 13, 14, 19, 21, 23, 24, 28, 29, 33, 39, 72, 75, 77 and 78 are rejected under the judicially created doctrine of obviousness-type double patenting as being unpatentable over claims 1-23 of U.S. Patent No. 11,795,442. Although the conflicting claims are not identical, they are not patentably distinct from each other because the instant claims and the claims of the patent are drawn to patently indistinguishable subject matter
Patent ‘442 claims a CRISPR system comprising an amino acid sequence with at least 95% sequence identity to SEQ ID No. 4 comprising direct repeat sequences, NLS and PAM sequences. The instant claims are drawn to a variant polypeptide having SEQ ID No. 39 which is 99.3% identical to SEQ ID No. 4 having direct repeat sequences, NLS and PAM sequences. Regarding instant claims 10 and 33 claiming enhanced enzymatic activity, for example, because the structure of Pat ‘045 is identical to the claimed sequence, these properties are inherent. Further regarding the methods in Patent ‘442, it would have been obvious to use the variant polypeptide in the CRISPR system in the methods of biding to the target. The Court of Appeals for the Federal Circuit in Pfizer Inc, v Teva pharmaceuticals USA Inc., 86 USPQ2d 1001 at page 1008 (March 2008), indicated that there is no patentable distinction between claims to a product and a method of using that product disclosed in the specification of the application. Thus, the co-pending product could be used in the method of the instant claims.
Subject Matter Free of the Prior Art
A BLAST search on 07/20/2026 identified the closest sequence to SEQ ID No. 39 as taught by Al-Shayeb et al. (Cell. 2022 Nov 23;185(24):4574-4586) with the sequence name CasLambda as shown below. Query – SEQ ID No. 39:
PNG
media_image1.png
941
925
media_image1.png
Greyscale
Al-Shayeb et al. describes new Cas9-like proteins and 44 families related to type V CRISPR-Cas systems, including the Caslambda RNA guided nuclease family. Among the most divergent of the new enzymes identified, Caslambda recognizes double-stranded DNA using a uniquely structured CRISPR RNA (crRNA) (introduction page 4574). Some mechanistic aspects of Caslambda remain to be defined, including the possible interchangeability of different variant guide RNAs to support catalytic activity. In addition, details of target binding, including the seed region within the target binding site as well as target recognition accuracy, remain to be established and states future research is needed to identify the functions of phage-encoded CRISPR systems that may extend beyond anti-phage defense and to further test the applications of Caslambda as a genome editing tool in plants, other organisms, and human cells.
The prior art search and sequence search did not reveal or make obvious a variant polypeptide as set forth in SEQ ID Nos. 39 or 95% identical to SEQ ID No. 39 with the claimed substations at the varying positions.
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.
Patent applicants with problems or questions regarding electronic images that can be viewed in the Patent Application Information Retrieval system (PAIR) can now contact the USPTO’s Patent Electronic Business Center (Patent EBC) for assistance. Representatives are available to answer your questions daily from 6 am to midnight (EST). The toll free number is (866) 217-9197. When calling please have your application serial or patent number, the type of document you are having an image problem with, the number of pages and the specific nature of the problem. The Patent Electronic Business Center will notify applicants of the resolution of the problem within 5-7 business days. Applicants can also check PAIR to confirm that the problem has been corrected. The USPTO’s Patent Electronic Business Center is a complete service center supporting all patent business on the Internet. The USPTO’s PAIR system provides Internet-based access to patent application status and history information. It also enables applicants to view the scanned images of their own application file folder(s) as well as general patent information available to the public. For more information about the PAIR system, see http://pair-direct.uspto.gov.
For all other customer support, please call the USPTO Call Center (UCC) at 800-786-9199.
/KIMBERLY CHONG/
Primary Examiner Art Unit 1636
Prosecution Insights