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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 23 December 2025 has been entered.
Status of Application, Amendments and/or Claims
The amendment of 23 December 2025 has been entered in full. Claims 15, 29, 31, 46, and 47 are amended. Claims 1-14, 16-18, 24-28, 30, and 33 are cancelled. Claims 51-53 are added.
Claim 48 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12 September 2024.
Claims 15, 19-23, 29, 31, 32, 34-47, and 49-53 are under consideration in the instant application.
Withdrawn Objections and/or Rejections
1. The objections to claim 46 as set forth at pages 3-4 of the previous Office Action of 24 September 2025 are withdrawn in view of the amended claim (23 December 2025).
NEW 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.
2. Claim 53 is 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.
2a. Claim 53 is rejected as being indefinite because one skilled in the art would not be apprised of a “cysteine engineered light chain trastuzumab L205C” (as recited in lines 1-2). The light chain of trastuzumab comprises a Valine (“V”) at position 205 and not a Leucine (“L”). For example, the prior art of Fong et al. (US 2009/0226466) teaches the amino acid sequence of trastuzumab light chain in Figure 1, wherein position 205 is a Valine (see Figure 1 of Fong et al., reproduced below). Therefore, recitation of “L205C” appears to be a typographical error and this issue could be overcome by amending claim 53 to recite “V205C”.
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NEW 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.
3. Claim 53 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 53 recites the conjugate of claim 15, wherein PBRM is cysteine engineered light chain trastuzumab L205C. However, claim 15 recites that the “PBRM is an antibody or antibody fragment comprising a light chain V205C, wherein the PBRM is connected to each LP through the light chain V205C…”.
Therefore, recitation of a cysteine engineered light chain trastuzumab L205C in claim 53 fails to include all the limitations of claim 15, which requires a light chain V205C.
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.
Maintained Claim Rejections – 35 USC § 103
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
4. Claims 15, 19-23, 29, 31, 32, 34-47, and 49-52 are rejected under 35 U.S.C. 103 as being unpatentable over Yurkovetskiy et al. (WO 2018/098269 (cited on the IDS of 02 May 2022) or US 2018/0154018) and Shen et al. (Nature Biotechnol 30(2): 184-191, 2012 (cited on the IDS of 02 May 2022)). The basis for this rejection is set forth at pages 4-14 of the previous Office Action of 24 September 2025 and at pages 23-24 of the Office Action of 18 December 2024. As both specifications of Yurkovetskiy et al. are the same, for brevity, the teachings will refer to WO 2018/098269. It is also noted that new claims 51 and 52 are included in the rejection because the limitations of these claims are taught in Yurkovetskiy et al.
For example, Yurkovetskiy et al. teach that the PBRM-drug conjugates comprise one or more occurrences of “D”, wherein D is a therapeutic agent (page 161, [00466]). Yurkovetskiy et al. indicate that D may be a vinca compound or an auristatin compound (such as dolastatin, monomethylauristatin E, monomethylauristatin F, auristatin F, phenylenediamine, etc., meeting the limitations of instant claims 51 and 52 (page 161, [00468-00470]).
(i) At the bottom of page 22 of the Response of 23 December 2025, Applicant argues that a skilled artisan would have been motivated by Yurkovetskiy to develop the conjugates therein rather than to modify the conjugates at all, and certainly not in a way to arrive at the instantly claimed conjugates. Applicant also asserts that Yurkovetskiy is entirely silent toward any conjugate comprising a site specific engineered cysteine, much less one featuring the specific light chain V205C modification, as recited in amended claim 15.
Applicant’s arguments have been fully considered but are not found to be persuasive. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
As discussed in the previous Office Actions of 24 September 2025 and 18 December 2024, Yurkovetskiy et al. teach a conjugate comprising a targeting moiety and one or more linker-drug moieties covalently bonded to the targeting moiety (page 2, [0005]). Yurkovetskiy et al. disclose the same conjugates of Formula (I) as recited in instant claim 15 (see conjugates (I) of Yurkovetskiy et al.; page 3, [0007]; page 179; pages 181-184, 262-269). Yurkovetskiy et al. teach that PBRM is a protein based recognition molecule, such as an antibody or antibody fragment (page 6, [0011]). Yurkovetskiy et al. disclose that the linker-drug is conjugated with PBRMs by utilizing a cysteine-based bioconjugation strategy, meeting the limitations of instant claim 15 (page 163, [00493-00494]; bottom of page 26 through the top of page 27). Yurkovetskiy et al. state that the PBRM includes the anti-HER2 antibody, trastuzumab, and generate and screen numerous conjugates with such antibody (page 26, [0072]; page 158, [00453, 00457]; pages 179-180, 184, 246, 248-252, 256, 258-269).
Although Yurkovetskiy et al. do not teach that the trastuzumab in the conjugates comprising trastuzumab and one or more linker-drug moieties, comprises a light chain with a V205C substitution, such deficiency is taught by Shen et al. Shen et al. teach a therapeutic HER2/neu antibody, trastuzumab, engineered with a cysteine in the light chain (at V205C) as conjugation site for coupling to thiol-reactive linkers in the generation of antibody conjugates (abstract; page 184, column 2, 2nd and 3rd full paragraphs).
(ii) At the bottom of page 22, Applicant contends that even if a skilled artisan were motivated to modify the conjugates therein (which the Applicant does not concede), one would not have been motivated by Yurkovetskiy to look toward modification with any antibody comprising an engineered cysteine, much less the LC-V205C antibody of Shen. Even if a skilled artisan were motivated to combine Yurkovetskiy and Shen, which the Applicant does not concede, the Office has not articulated any reason why one would be motivated to combine Yurkovetskiy and Shen in such a manner as to arrive at the instantly claimed conjugates.
Applicant’s arguments have been fully considered but are not found to be persuasive. In response to Applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, the skilled artisan would have been motivated to modify the trastuzumab drug conjugates of Yurkovetskiy et al. by engineering the light chain of trastuzumab with a cysteine at position 205 (V205C) as taught by Shen et al. in order to stabilize the trastuzumab drug conjugates and enhance therapeutic efficacy (see Shen et al., page 185, column 1, 1st and 2nd full paragraphs; page 186, top of column 2; page 187, columns 1-2; Figure 1).
Shen et al. clearly disclose that the LC-V205C conjugate has the greatest in vivo therapeutic activity (including anti-tumor activity) as compared to other sites in trastuzumab modified with an engineered cysteine (that result in differences in solvent accessibility and charge) (abstract; page 185, column 1, 1st and 2nd full paragraphs; Figure 1d). For example, Shen et al. state that:
“We next compared in vivo therapeutic efficacy using the MMTV-HER2 Fo5 trastuzumab-resistant mammary tumor model, previously shown to be responsive to trastuzumab [antibody-drug conjugates] (ADCs), but not the unconjugated antibody. We observed significant differences in therapeutic efficacy after a single intravenous dose of 10 mg/kg. The LC-V205C conjugate showed the greatest activity…” (page 185, column 1, 1st full paragraph)
Shen et al. teach that the LC-V205C-type conjugation sites that are surrounded by a positively charged environment might rapidly undergo succinimide ring hydrolysis in the linker, thereby preventing further linker-maleimide exchange and enabling stability in vitro and in vivo (page 186, bottom of column 1 through the top of column 2; page 187, column 1, 2nd full paragraph through column 2). This stabilized conjugate shows improved efficacy (page 186, top of column 2; page 187, columns 1-2; Figure 1).
The person of ordinary skill in the art also reasonably would have expected success because antibody conjugates (including trastuzumab) with a light chain V205C chemically linked to chemotherapeutic drugs or other functional moieties were already being successfully generated at the time the invention was made (see Shen et al., page 184, column 1, 1st paragraph through column 2; entirety of Shen et al.). Applicant is reminded that a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to anticipated success, it is likely not the product of innovation but of ordinary skill and common sense (see KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007)).
(iii) At page 23, Applicant argues that Yurkovetskiy discloses, at least, 28 linker moiety options for LM (see, e.g., paragraphs [0035]-[0039] of Yurkovetskiy for disclosure of LM as a bond, trivalent linker formulae, and tetravalent linker formulae). Applicant asserts that the Office has not articulated why a skilled artisan would be motivated toward the particular LM , WP , and MP moieties recited in amended claim 15, in view of the various options disclosed in Yurkovetskiy (see, e.g., paragraphs [0028] and [0033] of Yurkovetskiy for 43 options for WP and 14 options for MP). Applicant argues that combination with Shen does not remedy this deficiency in Yurkovetskiy, at least, because Shen is entirely silent toward any linker or conjugate of the instant claims or any particular advantage afforded by such a linker or conjugate. Accordingly, a prima facie case of obviousness for amended claim 15 has not been established based on Yurkovetskiy and Shen, alone or in combination.
Applicant’s arguments have been fully considered but are not found to be persuasive. Applicant is reminded that Yurkovetskiy et al. disclose a finite list of particular LM , WP , and MP moieties. The comprehensiveness of the LM , WP , and MP moieties does not negate the fact that the particular LM , WP , and MP moieties recited in claim 15 are each taught as one of those LM , WP , and MP moieties. There are a finite number of identified, predictable solutions and one skilled in the art has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense (KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007)). Furthermore, one skilled the art actually would be guided to select the specific LM , WP , and MP moieties recited in claim 15 because Yurkovetskiy et al. disclose numerous functional conjugates with these LM , WP , and MP moieties. For example, please see conjugates #53A-53E, 55A-55C, 57, 59, 61, 66-68, 76, 78, 79, 83, and 85 (pages 181-187; pages 262-281). Yurkovetskiy et al. teach that many of these conjugates have anti-proliferative properties in tumor cell lines and in in vivo mouse models (pages 281-285; Table II; Figures 2-6).
(iv) At the bottom of page 23 of the Response Applicant submits that a skilled artisan would not have any reasonable expectation of success that the instantly claimed conjugates can be useful for treating cancer. For instance, Yurkovetskiy and Shen are each entirely silent toward any conjugate of the amended claims with the required site specific conjugation or any therapeutic activity thereof. The cited references fail to provide any reasonable expectation of success in view of the unpredictability of the development of conjugates for treating cancer due to, e.g., off-target toxicity or premature clearance in the subject, which can reduce the anti-tumor activity of a conjugate. Applicant states, in contrast, the as-filed specification demonstrates that the instantly claimed conjugates have anti-tumor activity and are unexpectedly superior for the treatment of cancer, particularly as compared to non-engineered congeners. For instance, Examples 5 and 6 of the as-filed specification present the comparative anti-cancer effects of Conjugates 2, 3, and 4, wherein Conjugates 2 and 3 are non-engineered conjugates and Conjugate 4 is an engineered conjugate of claim 15. Example 5 assessed the tumor growth rate response in a mouse model, following administration of one of Conjugates 2, 3, or 4. As shown in Figure 1, administration of Conjugate 4 resulted in smaller tumor volume at the end of the study, compared to either Conjugate 2 or 3 when administered at the same dose. Accordingly, engineered Conjugate 4 exhibits more potent anti-cancer activity as compared to non-engineered Conjugates 2 and 3. Further, Example 6 assessed the payload exposure in a mouse model, following administration of Conjugate 2, 3, or 4. As shown in Figure 2, administration of Conjugate 4 resulted in significantly higher payload exposure (measured in AUC(0-14)(day*ng/mL)), compared to either Conjugate 2 or 3 when administered at the same dose. Accordingly, administration of engineered Conjugate 4 is more effective at delivering the conjugated drug analyte in vivo as compared to non-engineered Conjugates 2 or 3. Thus, Yurkovetskiy and/or Shen would not have provided a skilled artisan with any reasonable expectation of success for the anti-tumor activity of the instantly claimed conjugates (e.g., Conjugate 4), much less the superior activity of the instantly claimed conjugates compared to the non-engineered congeners.
Applicant’s arguments have been fully considered but are not found to be persuasive. Applicant is reminded that the instant claims are directed to a conjugate and a pharmaceutical composition comprising the conjugate. The instant claims are not directed to methods of treating cancer by administering the claimed conjugate. Furthermore, although the results in Examples 5 and 6 of the instant specification are informative and interesting, Applicant is reminded that MPEP 716.02(c)(II) states that “expected beneficial results are evidence of obviousness of a claimed invention, just as unexpected results are evidence of unobviousness thereof.” (In re Gershon, 372 F.2d 535, 538, 152 USPQ 602, 604 (CCPA 1964); Ex parte Blanc, 13 USPQ2d 1383 (Bd. Pat. App. & Inter. 1989)).
Upon reading the combined teachings of the prior art of Yurkovetskiy et al. and Shen et al., one of ordinary skill in the art would expect superior activity of a conjugate comprising an antibody (such as trastuzumab) with a light chain V205C chemically linked to chemotherapeutic drugs or other functional moieties for several reasons. First, Yurkovetskiy et al. teach that many of their conjugates have anti-proliferative properties in tumor cell lines and in in vivo mouse models (see conjugates #53A-53E, 55A-55C, 57, 59, 61, 66-68, 76, 78, 79, 83, and 85 (pages 181-187; pages 262-285; Table II; Figures 2-6). Second, Shen et al. disclose that their LC-V205C conjugate has the greatest in vivo therapeutic activity (including anti-tumor activity) as compared to other sites in trastuzumab modified with an engineered cysteine (that result in differences in solvent accessibility and charge) (abstract; page 185, column 1, 1st and 2nd full paragraphs; Figure 1d). Shen et al. also teach that the LC-V205C-type conjugation site enables stability in vitro and in vivo, as well as improved efficacy (page 186, bottom of column 1 through the top of column 2; page 187, column 1, 2nd full paragraph through column 2; Figure 1).
The person of ordinary skill in the art also reasonably would have expected success because antibody conjugates (including trastuzumab) with a light chain V205C chemically linked to chemotherapeutic drugs or other functional moieties were already being successfully generated at the time the invention was made (see Shen et al., page 184, column 1, 1st paragraph through column 2; entirety of Shen et al.). Applicant is reminded that a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to anticipated success, it is likely not the product of innovation but of ordinary skill and common sense (see KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007)).
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. A nonstatutory double patenting rejection is appropriate where the conflicting claims 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); 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 nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined 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 § 2146 et seq. 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 filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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 www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
5. Claims 15, 19-23, 29, 31, 32, 34, 38-44, 46, 47, 49, and 50 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 11,135,307 (cited on the IDS of 06 December 2023) in view of Shen et al. (Nature Biotechnol 30(2): 184-191, 2012 (cited on the IDS of 02 May 2022)).
The basis for this rejection is set forth at pages 14-15 of the previous Office Action of 24 September 2025 and in-depth at pages 25-31 of the Office Action of 18 December 2024.
(i) At the middle of page 32 of the Response of 16 June 2025, Applicant states that without conceding to the propriety of the rejection, Applicant requests the rejection to be held abeyance until otherwise allowable patentable subject matter has been identified.
Applicant is reminded that only objections or requirements as to form not necessary to further consideration of the claims may be held in abeyance until allowable subject matter is indicated (see 37 CFR 1.11(b)). Additionally, MPEP §804(I)(B)(1) states that a complete response to a nonstatutory double patenting (NSDP) rejection is either a reply by applicant showing that the claims subject to the rejection are patentably distinct from the reference claims, or the filing of a terminal disclaimer in accordance with 37 CFR 1.321 in the pending application(s) with a reply to the Office action. Therefore, the rejection is maintained and Applicant is encouraged to submit a terminal disclaimer at Applicant’s earliest convenience.
6. Claims 51 and 52 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 11,135,307 (cited on the IDS of 06 December 2023) in view of Shen et al. (Nature Biotechnol 30(2): 184-191, 2012 (cited on the IDS of 02 May 2022)) as applied to claims 15, 19-23, 29, 31, 32, 34, 38-44, 46, 47, 49, and 50 above, and further in view of Yurkovetskiy et al. (US 2012/0321583; hereinafter, “Yurkovetskiy2”).
The teachings of the ‘307 patent claims and Shen et al. are set forth at pages 14-15 of the previous Office Action of 24 September 2025 and in-depth at pages 25-31 of the Office Action of 18 December 2024.
The claims of the ‘307 patent and Shen et al. do not teach that the each occurrence of D (which is independently a therapeutic agent having a molecular weight < about 5 kDa) in the claimed conjugate is selected from vinca alkaloids, auristatins, duocarmycins, kinase inhibitors, MEK inhibitors, KSP inhibitors, PI3 kinase inhibitors, calicheamicins, SN38, camptothecin, topoisomerase inhibitors, non-natural camptothecins, protein synthesis inhibitor, RNA polymerase inhibitor, pyrrolobenzodiazepines, maytansinoids, DNA-binding drugs, DNA intercalation drugs, NAMPT inhibitors, tubulysin, immunomodulatory compounds, auristatin E, auristatin EB, auristatin EFP, monomethyl auristatin E, monomethyl auristatin F, auristatin F, auristatin F phenylenediamine, auristatin F hydroxylpropylamide, monomethyl auristatin F hydroxylpropylamide, and dolastatin.
Yurkovetskiy2 teach conjugates comprising a protein based recognition-molecule (PBRM), such as trastuzumab, and a polymeric carrier substituted with one or more -LD-D (abstract; page 1, [0005-0006]; Figures 1-8; Examples 3, 4, 7, 8, 19, 21, 27, 29, 32, 35, 38, 41, 52, 55, 56, 57, 60, 66, 70, 72). Yurkovetskiy2 disclose that each occurrence of D is independently a therapeutic agent having a molecular weight < about 5 kDa (page 1, [0007]; page 36, [0292]). Yurkovetskiy2 indicate that D may be selected from vinca alkaloids, auristatins (including auristatin E, auristatin EB, auristatin EFP, MMAE, MMAF, dolstatin), tubulysins, duocarmycins, kinase inhibitors, MEK inhibitors, KSP inhibitors, (page 3, [0061]; page 22, [0210]; page 27, [0267]; pages 36-37, [0298-0302]; page 38, [0324]).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to modify the V205C light chain-engineered trastuzumab drug conjugates of the ‘307 patent and Shen et al. by utilizing drugs selected from vinca alkaloids, auristatins (including auristatin E, auristatin EB, auristatin EFP, MMAE, MMAF, dolstatin), tubulysins, duocarmycins, kinase inhibitors, MEK inhibitors, and KSP inhibitors, as taught by Yurkovetskiy2. The person of ordinary skill in the art would have been motivated to make that modification because both the ‘307 patent claims and Yurkovetskiy2 require that the drugs utilized in the conjugates have a molecular weight < about 5 kDa. One skilled in the art also would have been motivated to utilize the drugs of Yurkovetskiy2 in the conjugates of the ‘307 patent claims in order to obtain protein-polymer drug conjugates that are biodegradable, biocompatible, exhibit high drug load, and that are able to deliver medications intact to specifically targeted areas of the body (see Yurkovetskiy2 page 1, [0003-0005]). The person of ordinary skill in the art reasonably would have expected success because other protein-polymer drug conjugates with such drugs were already being generated at the time the invention was made.
Conclusion
No claims are allowable.
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BEB
Art Unit 1647
13 March 2026
/BRIDGET E BUNNER/Primary Examiner, Art Unit 1647