DETAILED ACTION
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
1. The Election filed August 04, 2026 in response to the Office Action of June 03, 2026 is acknowledged and has been entered. Applicant's election without traverse of Group I, claims 21-25 and 27-30 and the antibody CDR sequences of 58-63 and the epitope of SEQ ID NO: 38 is acknowledged.
2. Claims 21-25 and 27-39 are pending.
3. Claims 31-39 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
4. Claims 21-25 and 27-30 are currently under consideration.
Priority
5. Acknowledgment is made of applicant's claim for foreign priority based on an application filed in Republic of Korea on July 16, 2021. It is noted, however, that applicant has not filed a certified copy of the KR10-2021-0093657 application as required by 37 CFR 1.55.
6. Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of the first paragraph of 35 U.S.C. 112. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed applications fails to provide adequate support or enablement in the manner provided by the first paragraph of 35 U.S.C. 112 for one or more claims of this application. Examiner has established a priority date of January 16, 2024 for Claims 21, 23-25 and 27-29 because the claims as currently constituted recite
A binding molecule, which is an antibody or a fragment thereof that binds specifically to Lrig-1 (leucine-rich and immunoglobulin-like domains 1) protein, the binding molecule comprising: (a) a heavy-chain variable region (VH) comprising: a heavy-chain variable region (VH) CDR1 selected from the group consisting of an amino acid sequence represented by SEQ ID NO: 58; a heavy-chain variable region (VH) CDR2 selected from the group consisting of an amino acid sequence represented by SEQ ID NO: 59; and a heavy-chain variable region (VH) CDR3 selected from the group consisting of an amino acid sequence represented by SEQ ID NO: 60; and (b) a light-chain variable region (VL) comprising: a light-chain variable region (VL) CDR1 selected from the group consisting of an amino acid sequence represented by SEQ ID NO: 61; a light-chain variable region (VL) CDR2 selected from the group consisting of an amino acid sequence represented by SEQ ID NO: 62; and a light-chain variable region (VL) CDR3 selected from the group consisting of an amino acid sequence represented by SEQ ID NO: 63, wherein: the first S of the amino acid sequence represented by SEQ ID NO: 58 is changed by G, N, or D, or the third D of SEQ ID NO: 58 is changed by Y or A; the amino acid sequence represented by SEQ ID NO: 59 is changed in the following manner: G1 is L, S, W, A, or V; S3 is Y; G6 is S or D; S7 is G; 19 is K or T; D5 is G or S; N8 is S; and P4 is H; the amino acid sequence represented by SEQ ID NO: 60 is changed in the following manner: V1 is G or D; G2 is L or I; L3 is G or S; R4 is L, P, or N; R6 is K or H; Y7 is T, W, or L; E8 is G; A9 is L, R, V, P, or S; S11 is Y; A13 is Y, D, or S; Y14 is D or N; G15 is A; D1 is G; A2 is L; G3 is Y or D; L4 is S or A; S5 is N or F; W6 is P; A7 is N or R; and G8 is E or P; the amino acid sequence represented by SEQ ID NO: 61 is changed in the following manner: S13 is N, T, or Y; S1 is T; S9 is N; Y11 is N, S, T, or D; and G2 is D; the amino acid sequence represented by SEQ ID NO: 62 is changed in the following manner: S1 is D or A; H4 is N or Q; S3 is N; and D2 is N; the amino acid sequence represented by SEQ ID NO: 63 is changed in the following manner: A1 is G; T2 is S or A; S5 is D or Y; N8 is S; and G9 is A; wherein the binding molecule binds specifically to an epitope consisting of SEQ ID NO: 38 and a review of the parent applications does not reveal the claimed limitation. Applicant is invited to submit evidence pointing to the serial number, page and line where support can be found establishing an earlier priority date.
Claim 22 has a priority date of July 14, 20222 based on the disclosure of PCT/KR2022/010262.
It is noted that the disclosure of KR10-2021-0093657 cannot be reviewed because it has not been submitted. If KR10-2021-0093657 is written in Korean and Applicant wants to use it to establish a priority date thereto, then Applicant is invited to submit a proper translation of the priority document and to point to page and line where support can be found establishing an earlier priority date. If Applicants choose to file a translation, then the translation must be filed together with a statement that the translation of the certified copy is accurate. See 35 U.S.C. 119 (b)(3), 37 C.F.R. 1.55(g)(3)(4), 37 C.F.R. 1.78(d)(7), and MPEP 1895.01.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
7. Claim 22 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 22 depends on claim 21 and comprises a Lrig-1 antibody comprising a heavy chain comprising CDRs 1-3 of SEQ ID NOs: 58-60 and a light chain comprising CDRs 1-3 of SEQ ID NOs: 61-63. Claim 21 is drawn to variants of
Claim 21 variants of the Lrig-1 antibody comprising a heavy chain comprising CDRs 1-3 of SEQ ID NOs: 58-60 and a light chain comprising CDRs 1-3 of SEQ ID NOs: 61-63. None of the variants comprise CDRs 1-3 of SEQ ID NOs: 58-60 and a light chain comprising CDRs 1-3 of SEQ ID NOs: 61-63 because the claim 21 requires changes to SEQ ID NOs: 58-63. Thus, claim 22 fails to include all the limitations of the claim upon which it depends.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
8. Claim 21, 23-25 and 27-30 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.
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 fully characterized antigen no longer is sufficient written description of an antibody to that antigen. Accordingly, the instant claims have been evaluated in view of that guidance.
Scope of the claimed genus
The claims are drawn broadly drawn to a binding molecule, which is an antibody or a fragment thereof that binds specifically to Lrig-1 (leucine-rich and immunoglobulin-like domains 1) protein, the binding molecule comprising: (a) a heavy-chain variable region (VH) comprising: a heavy-chain variable region (VH) CDR1 selected from the group consisting of an amino acid sequence represented by SEQ ID NO: 58; a heavy-chain variable region (VH) CDR2 selected from the group consisting of an amino acid sequence represented by SEQ ID NO: 59; and a heavy-chain variable region (VH) CDR3 selected from the group consisting of an amino acid sequence represented by SEQ ID NO: 60; and (b) a light-chain variable region (VL) comprising: a light-chain variable region (VL) CDR1 selected from the group consisting of an amino acid sequence represented by SEQ ID NO: 61; a light-chain variable region (VL) CDR2 selected from the group consisting of an amino acid sequence represented by SEQ ID NO: 62; and a light-chain variable region (VL) CDR3 selected from the group consisting of an amino acid sequence represented by SEQ ID NO: 63, wherein: the first S of the amino acid sequence represented by SEQ ID NO: 58 is changed by G, N, or D, or the third D of SEQ ID NO: 58 is changed by Y or A; the amino acid sequence represented by SEQ ID NO: 59 is changed in the following manner: G1 is L, S, W, A, or V; S3 is Y; G6 is S or D; S7 is G; 19 is K or T; D5 is G or S; N8 is S; and P4 is H; the amino acid sequence represented by SEQ ID NO: 60 is changed in the following manner: V1 is G or D; G2 is L or I; L3 is G or S; R4 is L, P, or N; R6 is K or H; Y7 is T, W, or L; E8 is G; A9 is L, R, V, P, or S; S11 is Y; A13 is Y, D, or S; Y14 is D or N; G15 is A; D1 is G; A2 is L; G3 is Y or D; L4 is S or A; S5 is N or F; W6 is P; A7 is N or R; and G8 is E or P; the amino acid sequence represented by SEQ ID NO: 61 is changed in the following manner: S13 is N, T, or Y; S1 is T; S9 is N; Y11 is N, S, T, or D; and G2 is D; the amino acid sequence represented by SEQ ID NO: 62 is changed in the following manner: S1 is D or A; H4 is N or Q; S3 is N; and D2 is N; the amino acid sequence represented by SEQ ID NO: 63 is changed in the following manner: A1 is G; T2 is S or A; S5 is D or Y; N8 is S; and G9 is A; wherein the binding molecule binds specifically to an epitope consisting of SEQ ID NO: 38.
The claimed antibody encompass a large number of mutations to SEQ ID NOs: 58-613. The heavy chain alone contains over six million combinations of mutations. (6 for SEQ ID NO: 58 x 40 for SEQ ID NO: 59 x 27,648 for SEQ ID NO:60 = 6.6 X106 combinations). Thus, the claims encompass a large genus of mutated antibodies and fragments thereof, which are required to bind to SEQ ID NO: 38 and the nucleic acids encoding them.
State of the Relevant Art
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. See 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.
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
The specification discloses the reduction to practice of the Lrig-1 monoclonal antibody GTC210-03 which comprises the CDRs of SEQ ID NOs: 58-63. See p. 53-Table 3.
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.
The specification discloses the reduction to practice of the Lrig-1 monoclonal antibody GTC210-03 which comprises the CDRs of SEQ ID NOs: 58-63. See p. 53-Table 3. The specification teaches GTC210-03 binds the Lrig-1 epitope of S95-L101, i.e. SEQ ID NO: 38. See Example 9-¶¶ -0346 and 0403. The specification teaches acceptable changes to the CDR region of the Lrig-1 antibodies. See Example 6 and Table 4. However, the specification does not produce any mutant Lrig-1 antibodies that bind to SEQ ID NO: 38 or teach which combination of antibody mutant CDR regions can bind to SEQ ID NO: 38. Thus, while applicant has described GTC210-03 which binds SEQ ID NO: 38, the genus of antibodies and fragments thereof is very large and GTC210-03 is specifically excluded from the claimed genus of Lrig-1 antibodies. The species described therefore cannot be considered representative of the recited genus of antibodies and the nucleic acids encoding them. See, e.g., AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014).
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 methods of treating.
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. Although the specification describes the GTC210-03 CDR regions and potential mutations therein, the specification does not produce any mutant Lrig-1 antibodies that bind to SEQ ID NO: 38 or fragments thereof, or teach which combination of antibody mutant CDR regions can bind to SEQ ID NO: 38. 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 non-mutated GTC210-03.
For all of the reasons presented above, one of skill in the art would not know which of the countless other antibodies encompassed by the independent claims that meet the highly general structural requirements of the claims would also be able to specifically bind SEQ ID NO: 38. Neither the specification nor the dependent claims provide sufficient additional structure or a structure/function correlation to provide an adequate written description of the genus claimed. Therefore, the skilled artisan would not reasonably conclude that the inventors, at the time the application was filed, had full possession of antibodies as broadly claimed and the nucleic acids encoding them. 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
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.
9. Claim(s) 22 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO 2021/091359 A1 (Kim et al. May 14, 2021), “Kim”. See US 2025/0243272 A1 (Kim et al. July 31, 2025), the US national stage of Kim, for the translation.
Kim teaches GTC210-03, VH SEQ ID NO: 151 and VL SEQ ID NO: 152, which comprises SEQ ID NOs: 58-63 as claimed. See Table 3 and Appendix.
Although Kim does not teach that GTC210-03 binds SEQ ID NO: 38, GTC210-03 has the same structure as claimed and thus would have the same function.
Conclusion
10. Claims 21-25 and 27-30 are rejected. No claims allowed.
11. Any inquiry concerning this communication or earlier communications from the examiner should be directed to PETER J REDDIG whose telephone number is (571)272-9031. The examiner can normally be reached M-F 8:30-5:30 Eastern Time.
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, Greg Emch can be reached at 571-272-8149. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PETER J REDDIG/ Primary Examiner, Art Unit 1646
APPENDIX
Alignment of SEQ ID NO: 58-60 with SEQ ID NO: 151 of Kim
ALIGNMENT:
Query Match 88.7%; Score 192.4; Length 457;
Best Local Similarity 46.5%;
Matches 40; Conservative 0; Mismatches 0; Indels 46; Gaps 2;
Qy 1 SYDM--------------SGISPDGSNIYYADSVKG------------------------ 22
|||| ||||||||||||||||||
Db 31 SYDMSWVRQAPGKGLEWVSGISPDGSNIYYADSVKGRFTISRDNSKNTLYLQMNSLRAED 90
Qy 23 --------VGLRCRYEACSYAYGMDV 40
||||||||||||||||||
Db 91 TAVYYCAKVGLRCRYEACSYAYGMDV 116
Alignment of SEQ ID NO: 61-63 with SEQ ID NO: 152 of Kim
LIGNMENT:
Query Match 84.8%; Score 137.3; Length 217;
Best Local Similarity 39.7%;
Matches 31; Conservative 0; Mismatches 0; Indels 47; Gaps 2;
Qy 1 SGSSSNIGSNYVS---------------SDSHRPS------------------------- 20
||||||||||||| |||||||
Db 23 SGSSSNIGSNYVSWYQQLPGTAPKLLIYSDSHRPSGVPDRFSGSKSGTSASLAISGLRSE 82
Qy 21 -------ATWDSSLNGYV 31
|||||||||||
Db 83 DEADYYCATWDSSLNGYV 100
Prosecution Insights