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 .
This is the first action on the merits.
Election/Restrictions
Applicant’s election of Group (I) in the reply filed on January 22, 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)). Group (I), drawn to compounds of formula (I), and compositions thereof, embraced by claims 1-3 ,6, 14, 40, 47, 56, 57, 144 and 145 was elected by Applicant. Applicant has not pointed to any errors in the Examiner’s analysis of the different inventions. The requirement is still deemed proper and is therefore made FINAL.
Applicant elected the following species:
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, and indicated the species is found on page 37 of the instant specification and claims 1-3, 6, 14, 40, 47, 56-59, 67, 68, 76-78, 86, 102, 103 and 143-145 read on said species. However, the elected species is found on page 75 of the instant specification, see below, and only claims 1-3 ,6, 14, 40, 47, 56, 57, 144 and 145 read on the elected species from the elected Group (I).
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Claims 1-3 ,6, 14, 40, 47, 56, 57, 144, 145, 67, 68, 76-78, 86, 102, 103 and 143-145 are pending and claims 1-3 ,6, 14, 40, 47, 56, 57, 144 and 145 are under examination. Claims 67, 68, 76-78, 86, 102, 103 and 143 are withdrawn based on the restriction requirement.
Priority
Applicant's claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) (PROVISIONAL) or 119(a) (FOREIGN) or under 35 U.S.C. 120 (CONT/CIP), 121(DIV), or 365(c) (WO) is acknowledged. Applicant still has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows: The later-filed application must be an application for a patent application (the parent for an invention which is also disclosed in the prior 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 application, Application No. 62958102 and Application No. 63030020, fail to provide adequate support or enablement in the manner provided by the first paragraph of 35 U.S.C. 112 for claims 1-3 ,6, 14, 40, 47, 56, 57, 144 and 145 of this application. The elected species with a phosphate linker is not found in these two documents. There may be other omissions as well. Thus, the effective filing date of the present claims 1-3 ,6, 14, 40, 47, 56, 57, 144 and 145 is the international filing date of January 7, 2021.
Claim Rejections
Claims 1, 3, 6, 14, 40, 56 and 57 are rejected as each directed to an improper Markush group. These Markush claims are rejected under the judicially approved ‘‘improper Markush grouping’’ doctrine when the claim contains an improper grouping of alternatively useable species. In re Harnisch, 206 USPQ 300 (CCPA 1980). A Markush claim contains an ‘‘improper Markush grouping’’ if: (1) the species of the Markush group do not share a ‘‘single structural similarity,’’ or (2) the species do not share a common use. The species of the present claims do not share a ‘‘single structural similarity. Therefore, a rejection on the basis that the claims contain an ‘‘improper Markush grouping’’ is appropriate. The rejection of the claims will be maintained on the basis that the claims contain an ‘‘improper Markush grouping’’ until the claims are amended to include only species that share a single structural similarity and a common use, or the applicant presents a sufficient showing that the species in fact share a single structural similarity and a common use.
Under principles of compact prosecution, the applicant elected a single disclosed species for search and examination (i.e., an election of species). The prior art search did not find the elected species in the prior art, and the search has been extended to those additional species that fall within the scope of a permissible Markush claim. In other words, the search has been extended to the species that share a single structural similarity and a common use. Proper Markush claims will be examined for patentability over the prior art with respect to the elected species or group of indistinct species, as well as the species that share a single structural similarity and a common use with the elected species or group of indistinct species (i.e., the species that would fall within the scope of a proper Markush claim). Federal Register, Vol. 76, No. 27, 02-09-2011, page 7166.
Claims 1, 3 ,6, 14, 40, 56 and 57, directed to the nonelected species, are withdrawn from further consideration. The prior art search will not be extended unnecessarily to cover all nonelected species.
Claim 1 is drawn to a compound of formula (I), wherein G1 is a folate, antifolate or folate analog, see 112b rejection below for analog, which is incorporated here. The Examiner suggests amending claim 1, to the elected species, wherein G1 is a folate moiety of claim 2, the steroid is dexamethasone connected through the OH at the C22 position of dexamethasone, to overcome the rejection.
BRI for the claims: The term radical is defined on page 20 of the specification.
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 1, 3, 6 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 pre-AIA the applicant regards as the invention.
Regarding claims 1 and 3, the term “analog” is indefinite. The metes and bounds of "analog" is not defined in the specification. An analog is a chemical compound that is structurally similar to another but differs slightly in composition (as in the replacement of one atom by an atom of a different element or in the presence of a particular functional group). Is the folate radical in claim 2 also a folate analog radical? Thus, claims 1 and 3 are indefinite.
In claim 3, the term “derivatizable” is vague. Said is not further defined in the specification, and therefore, the metes and bounds of said term is not known.
With regards to claim 3 and 14, the term “comprising” is vague. Chemical compounds should be defined using closed language.
Further, the “and/or” in claims 3 and 6 are vague. The G1 and G2 variables are defined and there cannot be more than one in formula (I). Therefore, the “and” is vague.
The following rejection is being made based on the cited art in the 103 art rejection below although, presently, a species election is in place.
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.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-3 ,6, 14, 40, 47, 56, 57, 144 and 145 is/are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Low et al. (US 20090214636).
The reference teaches the following species:
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, see page 13, Example 12. The reference further teaches adding said compound to a liposomal formulation, see Examples 19 and 23 on page 18 and claim 18 on page 21.
Therefore, said claims are anticipated.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103(a) 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.
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
Claims 1-3 ,6, 14, 40, 47, 56, 57, 144 and 145 are rejected under AIA 35 U.S.C. 103(a) as being unpatentable over Low et al. (US 20090214636) in view of Kern et al. (JACS, 2016, 138, 1430-1445) and Burger et al. (WO 2020236825).
The presently claimed elected species is shown below.
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. The reference further teaches adding said compound to a liposomal formulation, see Examples 19 and 23 on page 18 and claim 18 on page 21.
[AltContent: ]Low et al. teaches the following species:
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, see page 13, Example 12.
The only difference between the claimed elected species and the cited species in the Low reference is the linker as shown above in the circled region of both molecules. Low does not teach a pyrophosphate-PEG cleavable linker with the phosphate attached to the steroid. This is remedied by Kern et al. and Burger et al.
Kern et al. teach an ADC (antibody-drug conjugate) with dexamethasone phosphate linker, see page 1433, Scheme 2, and an alkyne for click chemistry to add an antibody:
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. The pyrophosphate group may be used because said group is enzymatically cleaved. The reference does not teach the PEG spacer portion of the linker.
Burger et al. teaches a pyrophosphate-PEG as part of an ADC with a different G1 and G2 group, see page 3, paragraphs 12 and 13, and page 48, which shows the ADC precursor with the necessary azide group for the click chemistry to form the ADC with the antibody, see compound L15-C5, see below:
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. The PEG group may be used to help increase the solubility and provide the appropriate length between the two tethered groups.
Thus, it would be obvious to use the teachings of Low and modify using the teachings of Low and Berger to make the elected species.
Claims 1-3 ,6, 14, 40, 47, 56, 57, 144 and 145 are rejected under AIA 35 U.S.C. 103(a) as being unpatentable over Low et al. (US 20090214636) in view of Kern et al. (JACS, 2016, 138, 1430-1445) and Usui et al. (WO 2018045245).
The presently claimed elected species is shown below.
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[AltContent: ]Low et al. teaches the following species:
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, see page 13, Example 12.
The only difference between the claimed elected species and the cited species in the Low reference is the linker as shown above in the circled region of both molecules. Low does not teach a pyrophosphate-PEG cleavable linker with the phosphate attached to the steroid. This is remedied by Kern et al. and Usui et al.
Kern et al. teach an ADC (antibody-drug conjugate) with dexamethasone phosphate linker, see page 1433, Scheme 2, and an alkyne for click chemistry to add an antibody:
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. The pyrophosphate group may be used because said group is enzymatically cleaved. The reference does not teach the PEG spacer portion of the linker.
Usui et al. teaches a pyrophosphate-PEG as part of a conjugated compound, see pages 7-8, and page 106, compound L24, see below:
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. The PEG group may be used to help increase the solubility and provide the appropriate length between the two tethered groups. The spacer between the phosphate groups and the PEG is longer than the presently claimed elected species, 5 carbon alkyl group versus Applicant’s 2 carbon alkyl group. However, these compounds are homologues and considered equivalent. The MPEP 2144.09 states “Compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977).
Thus, it would be obvious to use the teachings of Low and modify using the teachings of Low and Berger to make the elected species.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SUSANNA MOORE whose telephone number is (571)272-9046. The examiner can normally be reached Monday - Friday, 10:00 am to 7:00 pm.
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 Murray can be reached on 571-272-9023. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SUSANNA MOORE/Primary Examiner, Art Unit 1624
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