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 .
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.
DETAILED ACTION
Claims 1-29 are pending in the instant application.
Priority
This application is a Continuation of PCT/JP22/01617, filed on 1/18/2022 which claims priority to the Japanese application JP2021-005763 filed on 1/18/2021.
Election/Restriction
Applicant’s election without traverse of Group II (claims 10-18) in the reply filed on 8/10/2026 is acknowledged.
Claims 1-9 and 19-29 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected group, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 8/10/2026.
Applicant elected the following species of Formula (II), shown below:
PNG
media_image1.png
250
454
media_image1.png
Greyscale
After further consideration, there is no longer a search burden for the species of reagents described in claims 10-18; thus these other species will be examined.
Claims 10-18
Claims 10-18 are examined herein.
Information Disclosure Statement
The information disclosure statements (IDS) dated 7/18/2023, 11/13/2025, 1/15/2026, and 3/25/2026 comply with the provisions of 27 CFR 1.97, 1.98, and MPEP § 609. Accordingly, they have been placed in the application file and the information therein has been considered as to the merits.
Objections to the Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code on pg 16, para 4. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Correction is required. See MPEP § 608.01.
Claim Interpretation
A “bioorthogonal functional group” has been defined as:
“a group that does not react with biological components (e.g., amino acids, proteins, nucleic acids, lipids, sugars, and phosphoric acids) or has a low reaction rate to the biological components but selectively reacts with components other than the biological components” (pg 26, last para). Applicant also cites several exemplary functional groups including: azide, alkyne, aldehyde, alkene, vinyl, allyl, halogen, tetrazine, nitrone, hydroxylamine nitrile, hydrazine, ketone, boronic acid, cyanobenzothiazol, α-halocarbonyl, isonitrile, sydnone, and selenium (pg 28, para 2-pg 30, para 3). The instant specification cites Sharpless (doi: 10.1002/1521-3773(20010601)40:11) and Bertozzi (doi: 10.1126/science.1059820).
A “thiol group-introduced antibody” has been interpreted as broadly encompassing both:
an antibody with engineered cysteine residues (pg 2, para 1). Applicant cites Wagner (WO201500111; instant spec pg 2, para 2) as incorporated by reference, which teaches a method of tagging engineered cysteine residues using 3-arylpropiolonitrile compounds; and
A chemically-modified side chain other than cysteine that includes a thiol functional group ( instant spec pg 2, para 3-4).
Note claim 17 was not listed as a substantial duplicate of claim 18, because claim 17 is drawn to formulas (1)-(12), while claim 18 is drawn to formulas (2)-(12).
The preamble for claim 10 was interpreted as an intended use as it did not materially modify the chemical structures provided in the formulas. MPEP § 2111.02(II) states:
“If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction.”
Notice
Applicant is advised that should claim 10 be found allowable, claim 17 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim 10,17
In the instant case, claim 10 differs from claim 17 solely in the described intended use in the preamble. However, the preamble fails to supply further structure that modifies the chemical structure described. As such, despite a difference in wording, claims 10 and 17 are substantial duplicates. See the claim interpretation section above.
Objections to the Claims
Claims 10 and 17 contain a list of lists, wherein the major list options need to be separated by semi-colons. Please add semi-colons after each instance of the word “protected” (excluding the last).
Claims 10-11 and 16-18 use the non-standard language “which may be protected”. Please replace all instances of “which may be protected” with “which is optionally protected”.
Claim 15 contains superfluous language and lacks a “wherein” clause. Please replace
“The reagent of claim 10, wherein the divalent group is one group selected from the group consisting of alkylene, arylene, -C(=O)-, -NR2-, -C(=O)-NR2-, -NR2-C(=O)-, -O-, and -(O-R3)m, or the divalent group is a divalent group in which two or more groups selected from the group consisting of alkylene, arylene, -C(=O)-, -NR2-, -C(=O)-NR2-, -NR2-C(=O)-, -0-, and-(O-R3)m are linked, R2 is a hydrogen atom”
with
“The reagent of claim 10, wherein the divalent group is selected from the group consisting of alkylene, arylene, -C(=O)-, -NR2-, -C(=O)-NR2-, -NR2-C(=O)-, -O-, and -(O-R3)m, or a combination thereof; wherein R2 is a hydrogen atom”.
Claims 16 and 18, contain a list of options (1)-(12) that need to be delineated by semi-colons.
Claims 16 and 18, lack the conjunction “and” between items (11) and (12). Please add “and”.
Claim 18, line 2, contains a typo. Please replace “consisiting” with “consisting”.
Correction is required. See MPEP § 608.01(m).
Claim Rejections – 35 USC § 112(b)
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 11-12 and 14 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 11
Claim 11 is a composition claim that contains methods steps to make something other than the claimed composition. Claim 11 reads:
“The reagent of claim 10, wherein the reagent is a reagent for derivatizing the thiol group-introduced antibody or salt thereof by reacting with a thiol group introduced via a side chain of an amino acid residue other than a cysteine residue in a thiol group-introduced antibody or a salt thereof.”
In essence, claim 11 is a product claim that appears to be reciting a method step of “reacting [the reagent] with a thiol group [on the antibody]” MPEP § 2173.05(p)(II) recites:
“Product and Process in the Same Claim
“A single claim which claims both an apparatus and the method steps of using the apparatus is indefinite under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph. See In re Katz Interactive Call Processing Patent Litigation, 639 F.3d 1303, 1318, 97 USPQ2d 1737, 1748-49 (Fed. Cir. 2011). In Katz, a claim directed to “[a] system with an interface means for providing automated voice messages…to certain of said individual callers, wherein said certain of said individual callers digitally enter data” was determined to be indefinite because the italicized claim limitation is not directed to the system, but rather to actions of the individual callers, which creates confusion as to when direct infringement occurs. Katz, 639 F.3d at 1318, 97 USPQ2d at 1749 (citing IPXL Holdings v. Amazon.com, Inc., 430 F.3d 1377, 1384, 77 USPQ2d 1140, 1145 (Fed. Cir. 2005)”.
Because a composition claim drawn to the reagent cannot include method steps of using it to make another compound, this claim is rendered indefinite.
Claim 12
Claim 12 is substantially unclear as to what structures are being invoked. Claim 12 appears to be drawn to an antibody comprising a lysine residue, which has been chemically modified to contain a reactive thiol group, wherein said thiol group resides in the heavy chain constant region, wherein a linker is invoked wherein it is unclear what the structures the linker is linking. It is also further unclear what the linker comprises, as the only limitation supplied on its structure is “which does not contain a peptide”. Given this description, one of skill in the art would not be able to (1) identify the linker; (2) determine what defining features it comprises; or (3) determine where it begins and ends. As a result this claim is rendered indefinite. Dependent claim 14 fails to cure these deficiencies, thus is also rendered indefinite.
Claim 14
Claim 14 is drawn to lysine residues that are divided by slashes wherein it is unclear how to meet the limitations of the claim. For example, one artisan may interpret “246/248” as the antibody containing a lysine at either position as sufficient to satisfy the limitations of the claim. Whereas another artisan may interpret this to require a lysine at both positions 246 and 248 in order to satisfy the limitations of the claim. Because it is unclear how this claim should be interpreted, it is rendered indefinite.
Claim Rejections – 35 USC § 112(d)
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.
Claims 11-14 are 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 11-14
Claims 11-14 are drawn to a composition that includes additional components that are not present in parent claim 10. In essence, claims 11-14 are drawn to an antibody drug conjugate, whereas parent claim 10 is drawn to a reagent whose formulae excludes an antibody. Thus claims 11-14 represent an expansion of scope over parent claim 10.
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 § 102/103
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.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 10-18 are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Fu (US10435479).
Claim 10, 17
Regarding claims 10 and 17, Fu teaches the reagent below, which satisfies the satisfies the limitations of formula (IV), reproduced below, wherein Y is a divalent group; and R is a biorthogonal group (col 14, para 1).
PNG
media_image2.png
213
290
media_image2.png
Greyscale
PNG
media_image3.png
316
548
media_image3.png
Greyscale
MPEP § 2111.02(II) states:
“If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction.”
The preamble of claim 10 includes an intended use: “for derivatizing a thiol group-introduced antibody or salt thereof”. However this intended use does not materially modify the structure of the chemical formulas claimed. As a result, this preamble was found non-limiting. Even if this was an intended limitation, Fu teaches their reagent can be conjugated to a reactive thiol group within an IgG antibody (claim 1). Fu also teaches the alkyne moiety (variable R, a.k.a. DBCO) can react with an azide (claim 1).
Claim 11-14
Claims 11-14 are drawn to intended uses of the reagent and refer to antibody structures that are excluded from the formulas presented in parent claim 10 (and also absent from the elected compound of the invention). However, as described in the rejections above, the structure of Fu describes all the structural requirements of the instantly claimed reagent. MPEP § 2112.01(II) states:
“A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.”
Thus the reagent of Fu has the same capacity for reacting with a thiol group on an IgG antibody, wherein the thiol group is generated chemically or present as an available cysteine residue. The reagent of Fu must also inherently possess the property of being compatible with antibodies comprising a lysine residue, located in one or more positions selected from 246/248, 288/290, and 317 (using EU numbering) within the heavy chain of an IgG antibody; wherein said lysine residue has been chemically modified to accommodate a reactive thiol group. Fu verifies these facts: Fu teaches the reagent can be conjugated to a reactive thiol group within an IgG antibody (claim 1). See the 112(b) rejection above regarding these claims.
Claim 15
Regarding claim 15, Fu teaches the divalent group is a combination of -C(=O)-, alkylene, and -NR2C(=O)-; wherein R2 is hydrogen (col 14, para 1), as shown below.
PNG
media_image4.png
312
554
media_image4.png
Greyscale
Claim 16, 18
Regarding claims 16 and 18, Fu teaches the reagent below which satisfies the satisfies the limitations of formula (10) reproduced below, wherein m is 2; and R is a biorthogonal group (col 14, para 1).
PNG
media_image5.png
179
441
media_image5.png
Greyscale
PNG
media_image6.png
312
554
media_image6.png
Greyscale
Relevant Prior Art
Krantz (US9545449) teaches the following reagent, wherein the thiol moiety on a protein performs a nucleophilic substitution with the primary bromide of the reagent shown below (col 15, para 4).
PNG
media_image7.png
358
467
media_image7.png
Greyscale
Krantz teaches a protein of formula P-SH is designed to react with the compound above to produce the product shown below (col 16, para 1).
PNG
media_image8.png
357
465
media_image8.png
Greyscale
Spidel (US20180044711) teaches modifying antibodies to incorporate lysine residues at positions 228 (para 0019) in order to incorporate DBCO-containing linkers which can be later modified by click reaction (claim 46).
PNG
media_image9.png
215
384
media_image9.png
Greyscale
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAURA ANN ESSEX whose telephone number is 571-272-1103. The examiner can normally be reached Mon - Fri 8:30-5:00.
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, Jeffrey Stucker can be reached on 571-272-0911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/L.A.E./
Examiner, Art Unit 1675
/JEFFREY STUCKER/Supervisory Patent Examiner, Art Unit 1675
