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
2. The amendment filed 04/27/2026 is acknowledged and has been entered.
Claims 9, 11, and 13-15 are amended. Claims 1-8 and 16 have been canceled. New claims 17-31 have been added.
3. Claims 9-15 and 17-31 are pending in the application. Claims 17-22, 24-26 and 29-31 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 09/18/2025.
Claims 9-15, 23 and 27-28 are currently under prosecution.
Election/Restriction
5. Newly added claims 17-22, 24-26 and 29-31 are directed to an invention that is independent or distinct from the invention originally claimed for the following reasons:
Applicant elected Group III, claims 9-12 and 13-15, drawn to a binding moiety that binds SEQ ID NO: 170.
Thus, newly added claims 17-22, 24-26 and 29-31 are drawn to the subject matters of non-elected inventions.
Since applicant has received an action on the merits for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits. Accordingly, claims 17-22, 24-26 and 29-31 are withdrawn from consideration as being directed to non-elected inventions. See 37 CFR 1.142(b) and MPEP § 821.03.
Grounds of Objection and Rejection Withdrawn
6. Unless specifically reiterated below, Applicant’s amendment and/or arguments have obviated or rendered moot the grounds of objection and rejection set forth in the previous Office action mailed 10/28/2025.
New Grounds of Rejection
Claim Rejections - 35 USC § 112
7. 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.
8. 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.
9. Claims 9-15, 23 and 27-28 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.
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. A “representative number of species” means that the species which are adequately described are representative of the entire genus. See, e.g., AbbVie Deutschland GMBH v. Janssen Biotech, 759 F.3d 1285, 111 USPQ2d 1780 (Fed. Cir. 2014). Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number” of species. The “structural features common to the members of the genus” needed for one of skill in the art to ‘visualize or recognize’ the members of the genus takes into account the state of the art at the time of the invention. “Functional” terminology may be used “when the art has established a correlation between structure and function” but “merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing one has invented a genus and not just a species. Ariad Pharmaceuticals Inc. v. Eli Lilly & Co., 598 F3d 1336, 94 USPQ2d 1161, 1171 (Fed Cir. 2010).
On 22 February 2018, the USPTO provided a Memorandum clarifying the Written Description Guidelines for claims drawn to antibodies, which can be found at www.uspto.gov/sites/default/files/documents/amgen_22feb2018.pdf. That Memorandum indicates that, in compliance with recent legal decisions, the disclosure of a full characterized antigen no longer is sufficient written description of an antibody to that antigen. Accordingly, the instant claims have been re-evaluated in view of that guidance.
Scope of the claimed genus
Claims 9-15, 23 and 27-28 are drawn to a binding moiety that binds a polypeptide comprising the amino acid sequence of SEQ ID NO: 170 (SLSNRLYYL), wherein the binding moiety is a T cell receptor (TCR) or an antibody for use in treating cancer.
State of the Relevant Art
As summarized in the Specification, PIWIL1 (also known as piwi-like protein 1 or HIWI, the instant claimed SEQ ID NO: 170 is a fragment of PIWIL1) were known in the art; see [0057] of the published application.
As was well-known in the antibody art, antibodies as a class share an overall structure generally comprising two heavy chain polypeptides that each comprises a heavy chain variable region (VH) and a heavy chain constant region made up of several domain (CH1, hinge, CH2, CH3, and for some antibodies, a CH4). Each of the heavy chains pairs with a light chain polypeptide that comprises a light chain variable region (VL) and a constant region. But while this overall structure is shared amongst antibodies from a wide variety of sources (human, rat, mouse, rabbit), the structure each antibody uses to bind its particular epitope on an antigen is structurally distinct and is formed by a recombination event that results in high variability at the amino acid sequence level. By the time the invention was made, it is well established in the art that the formation of an intact antigen-binding site in an antibody usually required the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three “complementarity determining regions” (“CDRs”) which provide the majority of the contact residues for the binding of the antibody to its target epitope. E.g., Almagro & Fransson, Frontiers in Bioscience 2008; 13:1619-33 (see Section 3 “Antibody Structure and the Antigen Binding Site” and Figure 1). Chimeric antibodies comprise the heavy and light chain variable regions of a rodent antibody linked to human constant regions and preserve the entirety of the VH and VL of the parent antibody. Id. at 1619-20. Humanized antibodies comprise only the CDRs, or in some cases an abbreviated subset of residues within the CDRs, of a parental rodent antibody in the context of human framework sequences. Id. at Section 4. All of the CDRs of the heavy and light chain, in their proper order of CDR1, then 2, then 3, and in the context of framework sequences which maintain their required conformation are generally required to produce a humanized antibody in which the heavy and light chains associate to form an antigen-binding region that binds the same antigen as the parental rodent antibody. Id. at Section 4. Almagro provides a detailed discussion regarding various methods of humanization, including rationale design approaches and empirical approaches based on random screening. Almagro, Sections 4 and 5.
Examples of antigen binding domains comprising only a VH (or less commonly, a VL) that in turn comprise only three CDRs certainly do exist in the literature, but those antibodies generally comprise unique structures such as CDR1 and CDR3’s that are elongated in length and that are often disulfide linked. E.g., De Genst et al., Dev Comp Immunol 2006; 30:187-98. “Shuffling” of the VL (or less commonly the VH) had also been used to improve affinity of a parent antibody in certain instances. But the procedure generally required a "dominant" VH (i.e., a VH that is primarily responsible for antigen specificity). E.g., Yoshinaga et al., J. Biochem 2008; 143: 593-601.
Overall, at the time the invention was made, the level of skill for preparing antibodies and then selecting those antibodies with desired functional properties was high. However, even if a selection procedure was, at the time of the invention, sufficient to enable the skilled artisan to identify antibodies with the recited functional properties, the written description provision of 35 U.S.C § 112 is severable from its enablement provision. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336 (Fed. Cir. 2010); see also Centocor Ortho Biotech Inc. v. Abbott Labs., 97 USPQ2d 1870, 1876 (Fed. Cir. 2011) (“The fact that a fully-human antibody could be made does not suffice to show that the inventors of the '775 patent possessed such an antibody.”) Absent the conserved structure provided by all six CDRs of a parental antibody in the context of appropriate VH and VL framework sequences, the skilled artisan generally would not be able to visualize or otherwise predict, a priori, what an antibody with a particular set of functional properties would look like structurally.
Summary of Species disclosed in the original specification
Although the specification teaches the fragment of PIWIL1 set forth in SEQ ID NO: 170 (see Examples 1 and 3); however, the specification does not provide a representative number of species to which the claimed a genus of antibodies or TCRs that specifically binds to SEQ ID NO: 170 and can be used for treating cancer.
Are the disclosed species representative of the claimed genus?
MPEP § 2163 states that a “representative number of species” means that the species which are adequately described are representative of the entire 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.
However, the specification does not provide a representative number of species to which the claimed a genus of antibodies or TCRs that specifically binds to SEQ ID NO: 170 and can be used for treating cancer.
Identifying characteristics and structure/function correlation
In the absence of a representative number of species, the written description requirement for a claimed genus may be satisfied by disclosure of relevant, identifying characteristics; i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. To meet this requirement in the instant case, the specification must describe structural features that convey the claimed binding activity, a prerequisite for utility in the recited composition.
As noted above, the art generally accepted that the combination of the CDRs within the VH and VL pair of an antibody were essential for binding specificity. But the specification does not describe what residues within the CDRs confer the binding activity claimed. Accordingly, the skilled artisan would not be able to discern a structure/function correlation for antibodies other than those comprising either all six CDRs (in the context of VH and VL regions) of one parental antibody, or the VH and VL of one parental antibody.
Further, the specification does not show that either the VH or the VL is “dominant” and could be paired with other VH or VL to form a new antibody that still bound the same antigen. It is again acknowledged that the skilled artisan possessed the methodology needed to “shuffle” the VL and/or VH and screen for binders. But that methodology did not allow the skilled artisan to visualize the structure of the alternate VH/VL chains prior to the step of screening. Accordingly, absent supporting evidence of a “dominant” VH or VL, the recitation of only a VH or only a VL does not provide a structure that the skilled artisan would consider to correlate with binding function.
For all of the reasons presented above, one of skill in the art would not know which of the countless other antibodies or TCRs that meet the highly general structural requirements of the claims would also be able to specifically bind the SEQ ID: 170 and can be used for treating cancer. And none of the dependent claims provide sufficient additional structure or a structure/function correlation to provide an adequate written description of the genera claimed. Therefore, the skilled artisan would not reasonably conclude that the inventors, at the time the application was filed, had full possession of antibodies or TCRs as broadly claimed. Given the lack of shared structural properties that provide the claimed binding activity, the limited number of species described, and the fact that the species that were described cannot be considered representative of the broad genus, Applicant was not in possession of the invention as claimed.
Claim Rejections - 35 USC § 102
10. 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)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
11. Claims 9 and 13-15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lin et al. (WO 2000032039, published on 8 June 2000).
Claims 9 and 13-15 are herein drawn to a binding moiety that binds a polypeptide comprising the amino acid sequence of SEQ ID NO: 170 (SLSNRLYYL), wherein the binding moiety is an antibody.
Lin et al. teach antibodies bind to polypeptides of human PIWI (HIWI) set forth in SEQ ID NOs: 2, 4 and 6, and fragments of the polypeptides; see entire document, e.g., page 6, claims 1, 4 and 6-13.
SEQ ID NOs: 2, 4 and 6 are 100% local identical with the instant claimed SEQ ID NO: 170; see below sequence alignment.
Given the “comprising” language in the instant claim 9, the fragments of the polypeptides of Lin et al. meet the limitation of the instant claimed polypeptide.
For claim 13, Lin et al. teach therapeutic use of the antibodies; see pages 52-53.
For claim 14, Lin et al. teach that administering of antibodies against the polypeptides provides treatment of tumor; see bridging paragraph of pages 51-52.
For claim 15, Lin et al. teach pharmaceutically acceptable carrier; see page 65.
Double Patenting
12. 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. A nonstatutory double patenting rejection is appropriate where the claims at issue are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); 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. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form 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.
13. Claims 9-15, 23 and 27-28 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 12,195,534. Although the conflicting claims are not identical, they are not patentably distinct from each other because for the following reasons:
Claims 9-15, 23 and 27-28 are herein drawn to a binding moiety that binds a polypeptide comprising the amino acid sequence of SEQ ID NO: 170 (SLSNRLYYL), wherein the binding moiety is a T cell receptor (TCR).
Claims 1-22 of U.S. Patent No. 12,195,534 are drawn to a binding molecule comprising a TCR alpha chain variable a domain and a TCR beta chain variable domain, wherein the binding molecule has the property of binding to SLSNRLYYL (SEQ ID NO: 1) in complex with HLA-A*02, wherein each of the alpha chain variable domain and the beta chain variable domain comprises FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4, where FR is a framework region and CDR is a complementarity determining region, comprising the following combination of alpha chain CDRs and beta chain CDRs: TABLE-US-00065 Alpha Beta CDR1 CDR2 CDR3 CDR1 CDR2 CDR3 YIAANDF GYKTN LAWGGT SGHGT FHEEGV ASSVDWV (SEQ ID (SEQ ID DLLP (SEQ ID (SEQ ID GDGERQY NO: 23) NO: 24) (SEQ ID NO: 37) NO: 45) (SEQ ID NO: 29) NO: 41).
SEQ ID NO: 1 of U.S. Patent No. 12,195,534 is the same as the instant claimed SEQ ID NO: 170.
In Pfizer, Inc., v. Teva Pharamaceutical USA, inc. (Fed. Cir, 2008), the Court concluded that the safe harbor of section 121 is limited to divisional applications only. The instant application is not filed as a result of a restriction requirement of U.S. Patent No. 12,195,534. The binding molecule claimed in the claims of the patent is the same as the instantly claimed binding moiety.
14. Claims 9-15, 23 and 27-28 are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-2, 6-10, 19, 29, 31, 35, 37, 40 and 45 of copending Application No. 18/966386. Although the conflicting claims are not identical, they are not patentably distinct from each other for the following reasons:
Claims 9-15, 23 and 27-28 are herein drawn to a binding moiety that binds a polypeptide comprising the amino acid sequence of SEQ ID NO: 170 (SLSNRLYYL), wherein the binding moiety is a T cell receptor (TCR).
Claims 1-2, 6-10, 19, 29, 31, 35, 37, 40 and 45 of copending Application No. 18/966386 are drawn to a binding molecule comprising a TCR alpha chain variable domain and a TCR beta chain variable domain, wherein the binding molecule has the property of binding to SLSNRLYYL (SEQ ID NO: 1) in complex with HLA-A*02, wherein each of the TCR alpha chain variable domain and the TCR beta chain variable domain comprises FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4, where FR is a framework region and CDR is a complementarity determining region, and (a) wherein the binding molecule contacts at least N4, R5, Y7 and Y8 of SLSNRLYYL (SEQ ID NO: 1); and/or (b) wherein the TCR alpha chain variable domain CDR1 comprises the sequence X-X-X-X-N-X-Y/F (SEQ ID NO: 98), the TCR alpha chain variable domain CDR3 comprises the sequence X-X-X-G-G-T-D-X-X-X (SEQ ID NO: 104), and the TCR beta chain variable domain CDR3 comprises the sequence X-X-X-X-D-X-V-G-S/D-X-X-X-X-X (SEQ ID NO: 112), where X is any amino acid.
SEQ ID NO: 1 of copending Application No. 18/966386 is the same as the instant claimed SEQ ID NO: 170.
This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
Conclusion
15. No claim is allowed.
16. Applicant's amendment necessitated the new ground(s) of objection/rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action.
17. Any inquiry concerning this communication or earlier communications from the examiner should be directed to YAN XIAO whose telephone number is (571)270-3578. The examiner can normally be reached M-F 8-5 EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis can be reached on 571-270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/YAN XIAO/Primary Examiner, Art Unit 1642
Sequence alignment
AAY90235
ID AAY90235 standard; protein; 861 AA.
XX
AC AAY90235;
XX
DT 29-AUG-2000 (first entry)
XX
DE Human piwi protein, designated hiwi.
XX
KW Piwi family protein; piwi; miwi; hiwi; gene therapy; tissue dystrophy;
KW anaemia; immunodeficiency; male infertility; human.
XX
OS Homo sapiens.
XX
FH Key Location/Qualifiers
FT Misc-difference 76
FT /label= Leu, Ile
FT /note= "encoded by NTA"
FT Misc-difference 303
FT /label= Leu, Ile
FT /note= "encoded by NTA"
FT Misc-difference 735
FT /label= Leu, Ile
FT /note= "encoded by NTA"
XX
CC PN WO200032039-A1.
XX
CC PD 08-JUN-2000.
XX
CC PF 03-DEC-1999; 99WO-US028764.
XX
PR 04-DEC-1998; 98US-0110901P.
XX
CC PA (UYDU-) UNIV DUKE.
XX
CC PI Lin H;
XX
DR WPI; 2000-412085/35.
DR N-PSDB; AAA07588.
XX
CC PT Piwi family nucleic acids, polypeptides, and antibodies, useful in gene
CC PT therapy of diseases such as cancer and in various research and diagnostic
CC PT applications.
XX
CC PS Claim 4; Page 189-194; 201pp; English.
XX
CC This sequence represents the human piwi family protein, designated hiwi.
CC The piwi family nucleic acids and polypeptides are used in gene therapy
CC of diseases such as cancer and also in various research and diagnostic
CC applications. The sequences can also be used to treat tissue dystrophy,
CC anaemia, immunodeficiency, and male infertility
XX
SQ Sequence 861 AA;
Query Match 100.0%; Score 45; Length 861;
Best Local Similarity 100.0%;
Matches 9; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 SLSNRLYYL 9
|||||||||
Db 853 SLSNRLYYL 861
AAY90234
ID AAY90234 standard; protein; 862 AA.
XX
AC AAY90234;
XX
DT 29-AUG-2000 (first entry)
XX
DE Mouse piwi protein, designated miwi.
XX
KW Piwi family protein; piwi; miwi; hiwi; gene therapy; tissue dystrophy;
KW anaemia; immunodeficiency; male infertility; mouse; ds.
XX
OS Mus sp.
XX
FH Key Location/Qualifiers
FT Misc-difference 90
FT /label= Leu, Ile
FT /note= "encoded by NTT"
FT Misc-difference 216
FT /note= "unspecified amino acid; encoded by NTC"
FT Misc-difference 383
FT /label= Leu, Ile
FT /note= "encoded by NTC"
FT Misc-difference 816
FT /label= Leu, Ile
FT /note= "encoded by NTC"
XX
CC PN WO200032039-A1.
XX
CC PD 08-JUN-2000.
XX
CC PF 03-DEC-1999; 99WO-US028764.
XX
PR 04-DEC-1998; 98US-0110901P.
XX
CC PA (UYDU-) UNIV DUKE.
XX
CC PI Lin H;
XX
DR WPI; 2000-412085/35.
DR N-PSDB; AAA07587.
XX
CC PT Piwi family nucleic acids, polypeptides, and antibodies, useful in gene
CC PT therapy of diseases such as cancer and in various research and diagnostic
CC PT applications.
XX
CC PS Claim 4; Page 180-185; 201pp; English.
XX
CC This sequence represents the mouse piwi family protein, designated miwi.
CC The piwi family nucleic acids and polypeptides are used in gene therapy
CC of diseases such as cancer and also in various research and diagnostic
CC applications. The sequences can also be used to treat tissue dystrophy,
CC anaemia, immunodeficiency, and male infertility
XX
SQ Sequence 862 AA;
Query Match 100.0%; Score 45; Length 862;
Best Local Similarity 100.0%;
Matches 9; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 SLSNRLYYL 9
|||||||||
Db 854 SLSNRLYYL 862
Prosecution Insights