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
Applicant’s election of Group I, claims 1, 3, 4, 7, 29-33, 52, 53, 57, 58, 60, 61, 63, 68-70, 72, 73, 97, and 98, as well as the species: the first structure of claim 97, wherein Z is 4, BA is an antibody, filed on August 11, 2026, is acknowledged.
Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
It is noted that the elected species (shown below) comprises an antibody, a linker of Dibenzocyclooctyl-Peg4-Val-Cit-PABC, a spacer of -CH2-NH-CO-CH2-NH-, and a glucocorticoid.
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Claims 1-4, 7, 29-33, 52, 53, 57, 58, 60, 61, 63, 64, 68-70, 72, 73, 76-79, 95, 97-99, and 101 are pending.
Claims 2, 4, 31, 32, 64, 72, 76-79, 95, 99, and 101 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions or species, there being no allowable generic or linking claim.
Claims 1, 3, 7, 29, 30, 33, 52, 53, 57, 58, 60, 61, 63, 68-70, 73, 97, and 98 are examined to the extent of elected species.
Priority
It is acknowledged that this application is a continuation of US Application No. 16/243,020 filed January 8, 2019, which claims the benefit of priority to U.S. Provisional Patent Appl. No. 62/614, 905 filed January 8, 2018. The priority date has been established as: January 8, 2018.
Information Disclosure Statement
The Information Disclosure Statements filed on 09/10/2024, 11/01/2024, 01/05/2026 and 08/11/2026 have been considered and entered by examiner.
Claim Objections
Claim 60 is objected to because of the following informalities: “MSR1” should be “an anti-MSR1 antibody” for clarity. Appropriate correction is required.
Claim 98 is objected to because of the following informalities: “wherein Ab is MSR1” should be “wherein Ab is anti-MSR1 antibody” for clarity. Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 63, 68, 69, 70, 73, and 97 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 63 recites the limitation "where L1" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim 68 recites “L is -L1-L2-(L3)0-1-“. However, it is unclear what the definition for L1, L2 and L3 and which structures are encompassed by the recited “L”.
Claim 68 recites “L3 is where the NH group is attached to L2”. It is not clear what L3 is, or what “the NH group” is referred to.
Claim 69 recites “L is -L1-L2-(L3)0-1-“. Claim 69 further defines L2. However, it is unclear what the definition for L1 and L3 and which structures are encompassed by the recited “L”.
Claim 70 recites “L is -L1-L2-(L3)0-1-“. Claim 70 further defines the structure of L2. However, it is unclear what the definition for L1 and L3 and which structures are encompassed by the recited “L”.
Claim 73 recites “L is -L1-L2-(L3)0-1-“. Claim 73 further defines the structure of -L2-(L3)0-1-. However, it is unclear what the definition for L1 and which structures are encompassed by the recited “L”.
Claim 97 recites “the following structure
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…”. However, z is not defined in this claim.
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.
Claim 97 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 97 depends on claim 1 which recites a compound of Formula (III) wherein “SP is –(C1-C10-alkylene)-NR50C(O)-(C1-C10-alkylene)-NR50a- where NR50a is attached to L, or –C(O)-(C1-C10-alkylene)-NR50C(O)-(C1-C10-alkylene)-NR50a- where NR50a is attached to L and where each C1-C10-alkylene is independently optionally substituted with one or more hydroxy; NR50 and NR50a are independently hydrogen or C1-C6-alkyl. However, claim 97 recites compounds comprising a SP not encompassed by claim 1, for example (on page 32):
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Each of the structures above comprise a SP of “-CH2-NH-“, where NH- is attached to L. The spacer of “-CH2-NH-“ is not encompassed by the amended claim 1. Thus, claim 97 fails to include all the limitations of claim 1.
Applicant may cancel the claim, amend the claim to place the claim in proper dependent form, rewrite the claim in independent form, or present a sufficient showing that the dependent claim complies with the statutory requirements.
Claim Rejections - 35 USC § 103
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 (i.e., changing from AIA to pre-AIA ) 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.
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 1, 3, 29, 30, 33, 52, 53, 57, 61, and 68-70 are rejected under 35 U.S.C. 103 as being unpatentable over Kern (Kern et al., Bioconjugate Chem. 2016, 27, 2081-2088, Publication Date: 07-28-2016, cited in IDS of 09/10/2024) and in view of Hettmann (Hettmann et al., US 2017/0021031 A1, Publication Date: 01/26/2017, cited in IDS of 08/11/2026).
Claim 1 is drawn to an ADC of budesonide or budesonide variants (a species of Formula III).
Kern teaches that antibody drug conjugates (ADCs) have been developed to deliver drug to targeted location (§ Introduction).
Kern teaches that targeted delivery of glucocorticoid steroids to immune cells for the potential treatment of immunological diseases (page 2081, col. 2, para. 2).
Kern teaches that ADC with budesonide would have impressive potency and short circulating half-life, which would aid in limiting systemic concentrations and further decrease the risk of undesired effects (page 2081, col. 2, para. 2).
Kern teaches three distinct approaches to adapt the cathepsin B linker strategy to the aliphatic alcohol of budesonide that differ only in their spacer. See page 2081, col. 2, para. 3.
Kern teaches a design that PAB was linked to budesonide via an ethylene diamine spacer. See page 2082, bridging paragraph of col.1-2.
Kern teaches different spacers have different properties, e.g. stability. See page
2082, bridging paragraph of col.1-2.
Kern teaches different linkers in the format of Val-Cit-PABC-SP-budesonide linked to antibody see Fig. 1, e.g. Structures 2-4.
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Kern’s structure 3 comprises Budesonide-SP-Linker-antibody, as shown below:
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Kern teaches that different spacers have different properties. For example, carbamate linker 6 (structure 3 above) approach resulted in a carbamate connection which proved too stable for intramolecular cyclization and, therefore, did not release free budesonide. In the case of the carbonate linker 5 (structure 2 above), the carbonate showed signs of blood instability and the drug-linker did not possess sufficient aqueous solubility to support conjugation to antibodies. See § Conclusions.
It is noted that both Rx of budesonide are hydrogen. Kern teaches a compound comprising budesonide, a spacer, a linker and antibody (a binding agent), wherein R4 is -CH2-CH2-CH3; both Rx are hydrogen; and z = 1 as set forth above. However, Kern does not teach the structure of SP as instantly recited by claim 1.
Hettmann teaches that antibody drug conjugate (ADC) can deliver the drug selectively to the targeted cells and is thus expected to cause accumulation of the drug in the targeted cells and to kill the targeted cells ([0003]).
Hettmann teaches antibody-drug conjugate (12) whose linker comprises a “-CH2-NH-CO-CH2-NH-” structure, wherein the terminal amino group is connected to the linker, and the other terminal CH2- group is connected to -O-CH2-CO-drug (See Example 12, from pages 90-92). The structure of ADC (12) is shown below:
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Thus, the main difference between the Compound of Formula (III) of instant claim 1 and the ADC (12) of Hettmann is that the conjugated drugs are different.
Hettmann teaches that the ADC (12) had excellent anti-tumor activity, safety, and physical properties and exhibited anti-cancer activities for various cancers ([0459]).
It would have been prima facie obvious to one of ordinarily skilled in the art before the time invention was filed to make ADC3 as taught by Kern, and to try and replace the linker or spacer in ADC3 with a linker or spacer in ADC(12) taught by Hettmann, because the linker and spacer in ADC(12) can generate ADC with excellent antitumor activity, safety, and physical properties. One of ordinary skill in the art would have the motivation to expand the options for spacers and have a reasonable expectation of success because the linker or spacer is well known and widely used in the art, as evidenced by Hettmann. One of ordinary skill in the art would have been motivated to try different spacers for improving performance of the budesonide-antibody conjugate.
Regarding claim 3, as shown above, in budesonide, R4 is -CH2-CH2-CH3 a linear alkyl.
Regarding claims 29, 30, 33, and 52, the spacer of “-CH2-NH-CO-CH2-NH-“ taught by Hettmann reads on these claims, wherein alkylene is linear C1 alkylene, NR50 and NR50a are hydrogen.
Regarding claim 53, as set forth above, the antibody-drug conjugate of Kern has z = 1 (see Fig. 1).
Regarding claim 57, as set forth above, the antibody-drug conjugate of Kern has an antibody as the binding agent (see Fig. 1).
Regarding claim 61, as shown in process 9 on page 92 of Hettmann, ADC (12) has a linker (L), wherein L is -L1-L2-, L1 is a reactive group residue (to form bond with antibody) and L2 is a connecting linker between L1 and spacer.
Regarding claims 68-70, the linker of ADC (12) of Hettmann has a di-peptide group (-Phe-Gly-), as shown above. In addition, the linker of ADC (12) of Hettmann above comprises the structure:
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Thus, the ADC taught by Kern with a linker taught by Hettmann would read on claims 61, and 68-70.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Kern (Kern et al., Bioconjugate Chem. 2016, 27, 2081-2088, Publication Date: 07-28-2016, cited in IDS of 09/10/2024) and in view of Hettmann (Hettmann et al., US 2017/0021031 A1, Publication Date: 01/26/2017, cited in IDS of 08/11/2026), as applied to claims 1, 3, 29, 30, 33, 52, 53, 57, 61, and 68-70 above, and further in view of Lemke (Lemke et al., Foye’s Principles of Medicinal Chemistry, Chapter 44, pp. 1253, Publication Year: 2008, cited in IDS of 09/10/2024).
Kern and Hettmann teach the Compound of Formula (III) as set forth above, however, Kern and Hettmann do not teach that R4 group is in the (R)-configuration.
Lemke teaches that the R-epimer was twofold more active than the S-epimer, in receptor affinity study.
It would have prima facie been obvious to one of ordinarily skilled in the art before the time the invention was filed to relate the teaching of Kern, Hettmann and Lemke to use R-budesonide, which is more active than S-budesonide, in the ADC, because doing so would potentially enhance the therapeutic efficacy of the antibody-budesonide conjugate, as taught by Lemke.
Claims 58, 63, 73 and 97 are rejected under 35 U.S.C. 103 as being unpatentable over Kern (Kern et al., Bioconjugate Chem. 2016, 27, 2081-2088, Publication Date: 07-28-2016, cited in IDS of 09/10/2024) and in view of Hettmann (Hettmann et al., US 2017/0021031 A1, Publication Date: 01/26/2017, cited in IDS of 08/11/2026), as applied to claims 1, 3, 29, 30, 33, 52, 53, 57, 61, and 68-70 above, and further in view of Bregeon (Bregeon et al., Pub. No.: US 2015/0165064 A1, Publication Date: 06-18-2015, cited in IDS of 09/10/2024) and Tsuchikama (Tsuchikama et al., US2020/0115326 A1, effectively filed as of May 24, 2017, US 62/510,505, cited in IDS of 09/10/2024).
Kern and Hettmann teach the Compound of Formula (III) as set forth above, however, Kern and Hettmann do not teach the specific configuration of BA as recited by claim 58, or specific configuration of L1 as recited by claim 63, or specific configuration of -L2-L3- as recited by claim 73, or the elected species of claim 97.
The elected species (shown below) comprises an antibody, a linker of Dibenzocyclooctyl-Peg4-Val-Cit-PABC, a spacer of -CH2-NH-CO-CH2-NH-, and a glucocorticoid.
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It is noted that the elected species would read on claims 63 (the first structure), 73 (the second last structure) and 97.
Bregeon teaches compound IVb-8, which has DBCO-PEG4-Val-Cit-PAB and using the linker-spacer to link payload to an antibody (Q) (page 53).
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Bregeon teaches that each antibody can have 4 payloads (antibody composition have (m) functionalized acceptor glutamine residues (Q) per antibody, wherein m is an integer selected from 1, 2, 3, or 4 [0255]; two acceptor glutamines per antibody heavy chain, provides a strategy to couple moieties of interest onto four acceptor glutamines per full antibody ([0857]). This reads on the structure of claim 58.
Bregeon teaches that the linker has improved processes for click-chemistry functionalization, improved stability (Examples 11-13).
Tsuchikama at [0139] and FIG. 7A and 8 teaches DBCO-PEG4-Val-Cit-PABC and using the linker-spacer to link 4 payloads to an antibody. Note Fig. 7b and 7c.
Tsuchikama teaches that PEG spacers in the linker could help reduce the hydrophobicity of the ADCs to be constructed, which may prevent protein aggregation and fast clearance from the antibody. See [0362].
Therefore, it would have been prima facie obvious to one of ordinary skill before the time the invention was filed given that the level of skill in the art was high to attach four Dibenzocyclooctyl-Peg4-Val-Cit-PABC-SP-budesonides to an antibody to make the claimed antibody with a reasonable expectation of success for the purpose of providing budesonide to immune cells by a way of ADCs. One of ordinary skill in the art would have been motivated to substitute linker taught by Kern and Hettmann by a linker of DBCO-PEG4-Val-Cit-PABC taught by Bregeon and Tsuchikama to make budesonide-antibody ADC as part of an effort to expand the use of ADCs beyond the field of oncology, to develop a better linker-spacer (e.g. better chemistry functionalization, improved stability and solubility) for ADC, and to improve the DAR of the ADC as taught by Kern, Hettmann, Bregeon and Tsuchikama. It is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention, because the linker and spacer has been widely used in the art, as evidenced by the references.
Claims 60 and 98 are rejected under 35 U.S.C. 103 as being unpatentable over Kern (Kern et al., Bioconjugate Chem. 2016, 27, 2081-2088, Publication Date: 07-28-2016, cited in IDS of 09/10/2024), Hettmann (Hettmann et al., US 2017/0021031 A1, Publication Date: 01/26/2017, cited in IDS of 08/11/2026), Bregeon (Bregeon et al., Pub. No.: US 2015/0165064 A1, Publication Date: 06-18-2015, cited in IDS of 09/10/2024) and Tsuchikama (Tsuchikama et al., US2020/0115326 A1, effectively filed as of May 24, 2017, US 62/510,505, cited in IDS of 09/10/2024), as applied to claims 1, 3, 29, 30, 33, 52, 53, 57, 58, 61, 63, 68-70, 73, and 97 above, and further in view of Svendsen (Svendsen et al., Molecular Therapy: Methods & Clinical Development, Vol. 4, 50-61, Publication Date: March, 2017, cited in IDS of 09/10/2024) and Dai (Dai et al., Biochemical and Biophysical Research Communications, 431, 496-500, Publication Date: 01-16-2013, cited in IDS of 09/10/2024).
Kern, Hettmann, Bregeon and Tsuchikama teach the Compound of Formula (III) such as the elected species of claim 97, as set forth above. However, they do not teach claim 60 or 98, which is drawn to MSR1.
Svendsen teaches that macrophage targeting by antibody-directed anti-inflammatory low-dose glucocorticoid therapy is a promising approach for safe treatment of liver inflammation (whole document, Abstract in particular).
Dai teaches that the scavenger receptor MSR1 is one of three receptors on macrophage membrane. MSR1 and CD36 can account for greater than 90% of the lipid accumulation in macrophages (Introduction and Fig. 4).
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to relate the teachings of Kern and Tsuchikama to generate an Ab-(DBCO-PEG4-Val-Cit-PABC-SP-budesonides)4 to treat inflammation, and to use MSR1 antibody in the ADC for targeting macrophage, since MSR1 is highly expressed on surface of macrophages, as taught by Dai. The motivation is to minimize the side-effects of the ADC and enhance the therapeutic efficacy, as taught by Svendsen.
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.
Claims 1, 3, 7, 29, 30, 33, 52, 53, 57, 58, 60, 61, 63, 68-70, 73, 97, and 98 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 11,760,775 B2 (hereinafter referred to as “reference patent”, cited in IDS of 09/10/2024) in view of Kern (Kern et al., Bioconjugate Chem. 2016, 27, 2081-2088, Publication Date: 07-28-2016, cited in IDS of 09/10/2024) and in view of Hettmann (Hettmann et al., US 2017/0021031 A1, Publication Date: 01/26/2017, cited in IDS of 08/11/2026) for the instant claims 1, 3, 29, 30, 33, 52, 53, 57, 61, and 68-70, further in view of Lemke (Lemke et al., Foye’s Principles of Medicinal Chemistry, Chapter 44, pp. 1253, Publication Year: 2008, cited in IDS of 09/10/2024) for the instant claim 7, or further in view of Bregeon (Bregeon et al., Pub. No.: US 2015/0165064 A1, Publication Date: 06-18-2015, cited in IDS of 09/10/2024) and Tsuchikama (Tsuchikama et al., US2020/0115326 A1, effectively filed as of May 24, 2017, US 62/510,505, cited in IDS of 09/10/2024) for the instant claims 58, 63, 73 and 97; and further in view of Svendsen (Svendsen et al., Molecular Therapy: Methods & Clinical Development, Vol. 4, 50-61, Publication Date: March, 2017, cited in IDS of 09/10/2024) and Dai (Dai et al., Biochemical and Biophysical Research Communications, 431, 496-500, Publication Date: 01-16-2013, cited in IDS of 09/10/2024) for the instant claims 60 and 98.
Claims 1, 3, 7, 29, 30, 33, 52, 53, 57, 58, 60, 61, 63, 68-70, 73, 97, and 98 are rendered obvious by the combined teachings of the prior art above as discussed in the 103 rejection, the 103 being incorporated here. The addition of the patented claims of the reference patent over related subject matter only further supports this obviousness.
Reference patent claim 1 is drawn to a conjugate compound comprising an antibody or antigen binding fragment conjugated to a compound of Formula A, shown below.
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It is specifically noted that in Formula A: R1 and R2 are independently hydrogen, alkyl, alkyl-C(O)-O-, -OH, halo or may together form the structure shown below wherein R4 may be alkyl, aryl, arylalkyl, or a nitrogen-containing heterocycloalkyl; R3 is -NRaRb wherein Ra and Rb may each independently be hydrogen, alkyl, an optionally substituted aryl, or may cyclize to form a cycloheteroalkyl comprising the nitrogen atom they are attached to; R5 is independently -OH, halo, alkyl, or arylalkyl positioned on any ring atom where n is an integer from 0-19; and the antibody or antigen binding fragment thereof is covalently bonded to R3.
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Reference patent claims 2-5 further specify structures of conjugate compounds, and shown below are exemplary conjugate compounds of reference patent claim 4. In particular, reference patent claim 5 discloses full conjugate structures wherein the linker and BA structures are provided, e.g. the structure shown below comprising a glucocorticoid, a spacer, a DBCO-PEG4-Val-Cit-PABC linker and a
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:
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Claim 5 of reference patent is considered to be most closely related to the instant invention. Thus, the reference patent is generally drawn to steroid compounds and conjugates thereof. However, it is noted that the reference patent does not specifically disclose the elected compound, and subsequently the conjugate thereof, of the instant invention, particularly with regard to the budesonide, or SP structure recited by the instant claims, or specific antibody e.g. MSR1. These deficiencies are addressed by the cited references, as provided by the teachings specified in the 103 section.
The above-listed reference patents, Kern, Hettmann, Lemke, Bregeon, Tsuchikama, Svendsen and Dai are considered to be analogous to the present invention as they are in the same field of biologically active compounds/agents and their modification for improved delivery/efficacy. Thus, it would have been obvious to one of ordinary skill in the art that the compounds of the reference patent claims could be modified to be budesonide-based antibody conjugates as disclosed by Kern, wherein said compounds could further comprise a spacer of -CH2-NH-CO-CH2-NH- as disclosed by Hettmann, which could subsequently be conjugated to an antibody (e.g. MSR1) using the DBCO-PEG4-Val-Cit-PABC linker and a
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, as disclosed by the reference claims, Bregeon, Tsuchikama, Svendsen and Dai, combining prior art elements according to known methods would be expected to yield predictable results. Based on the above, one of ordinary skill could therefore arrive at a compound of the elected species of claim 97, shown below, wherein the drug is budesonide, the spacer is -CH2-NH-CO-CH2-NH-, the linker is DBCO-PEG4-Val-Cit-PABC, the BA is MSR1-[NH-(CH2-CH2-O)n-R-]z, and n is 3, R is -CH2-CH2-, and Z is 1 (e.g.
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).
One of ordinary skill in the art would be motivated to modify the compounds of the reference patents based on the teachings of Kern, Hettmann, Lemke, Bregeon, Tsuchikama, to arrive at the instantly claimed compound(e.g. the elected compound of instant claim 97), wherein such a compound could be conjugated to an antibody (e.g. MSR1) as suggested by Svendsen and Dai, in order to facilitate targeted delivery of the steroid payload to target cells, targeted by the antibody, which would be useful in the treatment of, for example, immunological diseases as taught by Kern.
Similarly, claims 1, 3, 7, 29, 30, 33, 52, 53, 57, 58, 60, 61, 63, 68-70, 73, 97, and 98 are rejected on the ground of nonstatutory double patenting as being unpatentable over the pertinent claims of the U.S. Patent Nos. listed below in view of Kern (Kern et al., Bioconjugate Chem. 2016, 27, 2081-2088, Publication Date: 07-28-2016, cited in IDS of 09/10/2024) and in view of Hettmann (Hettmann et al., US 2017/0021031 A1, Publication Date: 01/26/2017, cited in IDS of 08/11/2026) for the instant claims 1, 3, 29, 30, 33, 52, 53, 57, 61, and 68-70, further in view of Lemke (Lemke et al., Foye’s Principles of Medicinal Chemistry, Chapter 44, pp. 1253, Publication Year: 2008, cited in IDS of 09/10/2024) for the instant claim 7, or further in view of Bregeon (Bregeon et al., Pub. No.: US 2015/0165064 A1, Publication Date: 06-18-2015, cited in IDS of 09/10/2024) and Tsuchikama (Tsuchikama et al., US2020/0115326 A1, effectively filed as of May 24, 2017, US 62/510,505, cited in IDS of 09/10/2024) for the instant claims 58, 63, 73 and 97; and further in view of Svendsen (Svendsen et al., Molecular Therapy: Methods & Clinical Development, Vol. 4, 50-61, Publication Date: March, 2017, cited in IDS of 09/10/2024) and Dai (Dai et al., Biochemical and Biophysical Research Communications, 431, 496-500, Publication Date: 01-16-2013, cited in IDS of 09/10/2024) for the instant claims 60 and 98.
Patent No.
Brief Description of the Invention
Pertinent Claims
10711032
Steroid Compounds and Conjugates Thereof
1-3, 7-10
12070506
Steroid Compounds and Conjugates Thereof
1-21
12377159
Steroid Compounds and Conjugates Thereof
1-7, 9, 10, 13
It is noted that Pat. No. 10711032 was cited in IDS of 09/10/2024; 12070506 was cited in IDS of 11/01/2024; and 12377159 was cited in IDS of 01/05/2026.
Claims 1, 3, 7, 29, 30, 33, 52, 53, 57, 58, 60, 61, 63, 68-70, 73, 97, and 98 are rendered obvious by the combined teachings of the prior art above as discussed in the 103 rejection, the 103 being incorporated here. The addition of the patented claims of the reference patent over related subject matter only further supports this obviousness.
It is specifically noted that all of the above-listed reference patents are drawn to steroid compounds and conjugates thereof, wherein the steroid compounds all have similar/overlapping structures with those of the reference patent 11,760,775 as presented above. However, it is noted that the above-listed reference patents do not specifically disclose the elected compound, and subsequently the conjugate thereof, of the instant invention, particularly with regard to the budesonide, SP structure recited by the instant claims, the specific linker, and/or specific antibody e.g. MSR1. These deficiencies are addressed by the cited references, as provided by the teachings specified in the 103 section.
The above-listed reference patents, Kern, Hettmann, Lemke, Bregeon, Tsuchikama, Svendsen and Dai are considered to be analogous to the present invention as they are in the same field of biologically active compounds/agents and their modification for improved delivery/efficacy. Thus, it would have been obvious to one of ordinary skill in the art that the compounds of the reference patent claims could be modified to be budesonide-based antibody conjugates as disclosed by Kern, wherein said compounds could further comprise a spacer of -CH2-NH-CO-CH2-NH- as disclosed by Hettmann, which could subsequently be conjugated to an antibody (e.g. MSR1) using the DBCO-PEG4-Val-Cit-PABC linker and a
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74
150
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, as disclosed by the reference claims, Bregeon, Tsuchikama, Svendsen and Dai, combining prior art elements according to known methods would be expected to yield predictable results. Based on the above, one of ordinary skill could therefore arrive at a compound of the elected species of claim 97, shown below, wherein the drug is budesonide, the spacer is -CH2-NH-CO-CH2-NH-, the linker is DBCO-PEG4-Val-Cit-PABC, the BA is MSR1-[NH-(CH2-CH2-O)n-R-]z, and n is 3, R is -CH2-CH2-, and Z is 1 (e.g.
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64
84
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).
One of ordinary skill in the art would be motivated to modify the compounds of the reference patents based on the teachings of Kern, Hettmann, Lemke, Bregeon, Tsuchikama, to arrive at the instantly claimed compound(e.g. the elected compound of instant claim 97), wherein such a compound could be conjugated to an antibody (e.g. MSR1) as suggested by Svendsen and Dai, in order to facilitate targeted delivery of the steroid payload to target cells, targeted by the antibody, which would be useful in the treatment of, for example, immunological diseases as taught by Kern.
Similarly, claims 1, 3, 7, 29, 30, 33, 52, 53, 57, 58, 60, 61, 63, 68-70, 73, 97, and 98 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the pertinent claims of the copending Application Nos. (reference applications) listed below in view of Kern (Kern et al., Bioconjugate Chem. 2016, 27, 2081-2088, Publication Date: 07-28-2016, cited in IDS of 09/10/2024) and in view of Hettmann (Hettmann et al., US 2017/0021031 A1, Publication Date: 01/26/2017, cited in IDS of 08/11/2026) for the instant claims 1, 3, 29, 30, 33, 52, 53, 57, 61, and 68-70, further in view of Lemke (Lemke et al., Foye’s Principles of Medicinal Chemistry, Chapter 44, pp. 1253, Publication Year: 2008, cited in IDS of 09/10/2024) for the instant claim 7, or further in view of Bregeon (Bregeon et al., Pub. No.: US 2015/0165064 A1, Publication Date: 06-18-2015, cited in IDS of 09/10/2024) and Tsuchikama (Tsuchikama et al., US2020/0115326 A1, effectively filed as of May 24, 2017, US 62/510,505, cited in IDS of 09/10/2024) for the instant claims 58, 63, 73 and 97; and further in view of Svendsen (Svendsen et al., Molecular Therapy: Methods & Clinical Development, Vol. 4, 50-61, Publication Date: March, 2017, cited in IDS of 09/10/2024) and Dai (Dai et al., Biochemical and Biophysical Research Communications, 431, 496-500, Publication Date: 01-16-2013, cited in IDS of 09/10/2024) for the instant claims 60 and 98.
Appl. No.
Brief Description of the Invention
Pertinent Claims
17612204
Steroid Compounds and Conjugates Thereof
1, 35, 90, 94-114, 145
18670314
Steroid Compounds and Conjugates Thereof
2-4, 7-9, 12,15, 26, 29, 33, 44, 46, 52, 64, 65, 68-73, 76-83, 88, 91-95
19201075
Steroid Compounds and Conjugates Thereof
39, 43-46, 51,
Claims 1, 3, 7, 29, 30, 33, 52, 53, 57, 58, 60, 61, 63, 68-70, 73, 97, and 98 are rendered obvious by the combined teachings of the prior art above as discussed in the 103 rejection, the 103 being incorporated here. The addition of the patented claims of the reference patent over related subject matter only further supports this obviousness.
It is specifically noted that all of the above-listed reference applications are drawn to steroid compounds and conjugates thereof, wherein the steroid compounds all have similar/overlapping structures with those of the reference patent 11,760,775 as presented above. However, it is noted that the above-listed reference applications do not specifically disclose the elected compound, and subsequently the conjugate thereof, of the instant invention, particularly with regard to the budesonide, SP structure recited by the instant claims, the specific linker, and/or specific antibody e.g. MSR1. These deficiencies are addressed by the cited references, as provided by the teachings specified in the 103 section.
The above-listed reference applications, Kern, Hettmann, Lemke, Bregeon, Tsuchikama, Svendsen and Dai are considered to be analogous to the present invention as they are in the same field of biologically active compounds/agents and their modification for improved delivery/efficacy. Thus, it would have been obvious to one of ordinary skill in the art that the compounds of the reference patent claims could be modified to be budesonide-based antibody conjugates as disclosed by Kern, wherein said compounds could further comprise a spacer of -CH2-NH-CO-CH2-NH- as disclosed by Hettmann, which could subsequently be conjugated to an antibody (e.g. MSR1) using the DBCO-PEG4-Val-Cit-PABC linker and a
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74
150
media_image2.png
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, as disclosed by the reference claims, Bregeon, Tsuchikama, Svendsen and Dai, combining prior art elements according to known methods would be expected to yield predictable results. Based on the above, one of ordinary skill could therefore arrive at a compound of the elected species of claim 97, shown below, wherein the drug is budesonide, the spacer is -CH2-NH-CO-CH2-NH-, the linker is DBCO-PEG4-Val-Cit-PABC, the BA is MSR1-[NH-(CH2-CH2-O)n-R-]z, and n is 3, R is -CH2-CH2-, and Z is 1 (e.g.
PNG
media_image12.png
64
84
media_image12.png
Greyscale
).
One of ordinary skill in the art would be motivated to modify the compounds of the reference applications based on the teachings of Kern, Hettmann, Lemke, Bregeon, Tsuchikama, to arrive at the instantly claimed compound(e.g. the elected compound of instant claim 97), wherein such a compound could be conjugated to an antibody (e.g. MSR1) as suggested by Svendsen and Dai, in order to facilitate targeted delivery of the steroid payload to target cells, targeted by the antibody, which would be useful in the treatment of, for example, immunological diseases as taught by Kern.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 3, 29, 30, 33, 52, 53, 57, 58, 60, 61, 63, 68-70, 73, 97, and 98 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. 12,497,460 B2 (hereinafter referred to as “reference patent”).
Claim 1, 3, 29, 30, 33, 52, 53, 57, 58, 60, 61, 63, 68-70, 73, 97, and 98 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. 12,497,460 B2 (hereinafter referred to as “reference patent”). Although the claims at issue are not identical, they are not patentably distinct from each other because:
The claims of the reference patent are drawn to an antibody-drug conjugate, wherein the antibody binds to MSR1 (claim 1), through a linker and wherein the drug can be a steroid (claim 3).
Claim 4 of the reference patent teaches a compound read on the elected species of instant claim 97, as shown below (see col. 1263 of reference patent publication):
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or a stereoisomeric form thereof, or a regioisomer thereof, or a mixture of regioisolers thereof, wherein each Ab is the anti-MSR1 antibody; each BA is Ab-[NH-(CH2-CH2-O)m-R]n-, wherein Ab is the anti-MSR1 antibody; R is C2-4 alkylene, m is an integer selected from 2, 3, or 4; and each n is an integer selected from 1 to 4 inclusive.
The compound shown above comprises an anti-MSR1 antibody, a linker of Dibenzocyclooctyl-Peg4-Val-Cit-PABC, a spacer of -CH2-NH-CO-CH2-NH-, and a glucocorticoid. As set forth above, the claims of reference patent teach a compound read on instant claims 1, 3, 29, 30, 33, 52, 53, 57, 58, 60, 61, 63, 68-70, 73, 97, and 98.
Claim 7 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. 12,497,460 B2 (hereinafter referred to as “reference patent”), as applied to claims 1, 3, 29, 30, 33, 52, 53, 57, 58, 60, 61, 63, 68-70, 73, 97, and 98 above, and further in view of Lemke (Lemke et al., Foye’s Principles of Medicinal Chemistry, Chapter 44, pp. 1253, Publication Year: 2008, cited in IDS of 09/10/2024).
The claims of the reference patent teach the Compound of Formula (III) as set forth above, however, the claims of the reference patent do not teach that R4 group is in the (R)-configuration.
Lemke teaches that the R-epimer was twofold more active than the S-epimer, in receptor affinity study.
It would have prima facie been obvious to one of ordinarily skilled in the art before the time the invention was filed to relate the teaching of the claims of reference patent and Lemke to use R-budesonide, which is more active than S-budesonide, in the ADC, because doing so would potentially enhance the therapeutic efficacy of the antibody-budesonide conjugate, as taught by Lemke.
Conclusion
No claims are allowed.
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/CHENG LU/ Examiner, Art Unit 1642
/SAMIRA J JEAN-LOUIS/ Supervisory Patent Examiner, Art Unit 1642
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