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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 9/30/2025 has been entered.
Claim Status
Claims 1, 4, and 6-8 are pending. Claims 1, 4, and 7 were amended, and claims 2-3 were canceled in the Reply filed 9/30/2025. Claims 6-7 remain withdrawn. Claims 1-4 and 8 are presently considered.
Election/Restrictions
Applicant’s election of the species of Example 6 (see, e.g., Spec. filed 8/26/2021 at page 37-39) in the reply filed on 7/22/2024 was previously 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)).
Applicant identified that the originally elected species read upon claims “1-5 and 8-10” (see, e.g., Reply filed 7/22/2024 at 4). However, claim 10 does not exist on record and is not pending.
The originally elected species has been understood to require the administration of HSA-Slit3 LRRD2 fusion proteins in mice, wherein the drug was injected by intravenous injection once daily, using a dose of 37.13 mg (see, e.g., Spec. filed 8/26/2021 at page 37, Table 8 on 37). The Fusion construct has been understood to comprise the HSA corresponding to SEQ ID NO: 2, the LRRD2 sequence has been understood to comprise SEQ ID NO: 3 (see, e.g., Spec. filed 8/26/2021 at page 37-39). The disease treated/prevented has been understood to correspond to bone mineral density.
Amended claims 1, 4, and 8, as filed 9/30/2025 are understood to continue reading upon the originally elected species, and specifically to the bone disease of osteoporosis or bone loss. Accordingly, the originally elected species has been searched a third time.
Following extensive search and examination, the originally elected species has again been deemed anticipated and/or obvious in view of the prior art as applied below. Per MPEP § 803.02(III)(A),
Following election, the Markush claim will be examined fully with respect to the elected species and further to the extent necessary to determine patentability. Note that where a claim reads on multiple species, only one species needs to be taught or suggested by the prior art in order for the claim to be anticipated or rendered obvious...
If the Markush claim is not allowable, the provisional election will be given effect and examination will be limited to the Markush claim and claims to the elected species, with claims drawn to species patentably distinct from the elected species held withdrawn from further consideration.
Accordingly, claims 1, 4, and 8 are rejected in view of the originally elected species and claims that do not read upon the originally elected species are withdrawn. Examination has not proceeded beyond the originally elected species at this time.
Claims 6-7 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 7/22/2024.
During the search and examination of the originally elected species, art pertinent to other non-elected species was incidentally discovered. Although examination has not been extended beyond the non-elected species identified above per MPEP § 803.02, as a courtesy to the Applicant, this art has been applied below.
Claims 1, 4 and 8 are presently considered.
Priority
Examiner acknowledges that on 7/22/2024 documents submitted as “claims” (1 page), “specification” (26 pages), “Drawings” (3 pages), and an “abstract” (1 page) was submitted, along with the assertion in the response that “a certified English translation of the Foreign Application KR10-2019-0023376” was “placed on record” (see, e.g., Reply filed 7/22/2024 at 4).
Accordingly, priority to Foreign Application KR10-2019-0023376 as filed 2/27/2019 is acknowledged. However, it is noted that the priority document differs substantially relative to the originally filed disclosure in the instant case.
Claim Interpretation
For purposes of examination, the claim scope has been interpreted as set forth below per the guidance set forth at MPEP § 2111.
Amended claim 1 is representative of the pending claim scope and presently recites:
1. (Currently Amended) A method of treating bone-related diseases, comprising parenterally administering to a subject in need thereof a therapeutically effective amount of an albumin-bound second leucine-rich repeat domain (LRRD2) of the SLIT3 protein, wherein the LRRD2 of the SLIT3 protein consists of an amino acid sequence of SEQ ID NO: 3, and wherein the bone-related disease is any one or more selected from the group consisting of osteoporosis, fractures, and bone loss, wherein the albumin is human serum albumin bound to the N-terminus of the LRRD2 of the SLIT3 protein.
Therefore, the claims are directed to methods. The applicable claim interpretations are set forth below.
“Comprising” is an open-ended transitional term (see, e.g., MPEP § 2111.03(I)), wherein additional steps or components are not excluded. However, “‘[c]omprising’ is a term of art used in claim language which means that the named elements are essential” (see, e.g., id.; see also Genentech, Inc. v. Chiron Corp., 112 F.3d 495, 501, 42 USPQ2d 1608, 1613 (Fed. Cir. 1997)).
“Consisting of” excludes any elements, step, or ingredient not specified (see, e.g., MPEP § 2111.03(II)). When the phrase "consists of" appears in a clause of the body of a claim, rather than immediately following the preamble, the "consisting of" phrase limits only the element set forth in that clause; other elements are not excluded from the claim as a whole (see, e.g., MPEP § 2111.03(II)).
LRRD2 is functionally-defined on record (see, e.g., Spec. filed 8/26/2021 at 7 at final ¶ to 8 at 2nd full ¶), but is understood to be limited to “the LRRD2 of the SLIT3 protein consist[ing] of …. SEQ ID NO: 3” (see, e.g., amended claim 1 as filed 1/30/2025; see also Spec. filed 8/26/2021 at 5 at 4th full ¶, 7 at final ¶ to 8 at 2nd full ¶ ). SEQ ID NO: 3 has the following 209-mer sequence:
ISCPSPCTCSNNIVDCRGKGLMEIPANLPEGIVEIRLEQNSIKAIPAGAFTQYKKLKRIDISKNQISDIAPDAFQGLKSLTSLVLYGNKITEIAKGLFDGLVSLQLLLLNANKINCLRVNTFQDLQNLNLLSLYDNKLQTISKGLFAPLQSIQTLHLAQNPFVCDCHLKWLADYLQDNPIETSGARCSSPRRLANKRISQIKSKKFRCS
SEQ ID NO: 3 is a prior art element and art-recognized domain, as evidenced by NP_003053.11, which comprises instant SEQ ID NO: 3 at positions 278 to 486:
Claimed structure: Amended claim 1 now recites both “comprising” and “consists of”. “Albumin-bound …[LRRD2] of the SLIT3 protein… wherein the albumin is human serum albumin bound to the N-terminus of the LRRD2 of the SLIT3 protein” is understood to refer to a fusion protein comprising an albumin protein fused to the N-terminus of SEQ ID NO: 32, either directly or via a linking sequence3:
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Accordingly, the protein of “albumin-bound LRRD2”, as shown above, may comprise additional, arbitrary and unspecified domains or N- or C- trailer sequences or domains, and may comprise an arbitrary linker sequence between the HSA and LRRD2 domain (see also instant claim 6, noting that a linker may be present). The only domain impacted by the “consisting of” language is understood to be the LRRD2 domain, which must “consist of” SEQ ID NO: 3. However, additional LRRD domains (e.g., LRRD3, LRRD4, LRRD5, etc.) are not excluded from being present in the linker or trailer sequences, as shown above. This interpretation is reasonable because it is consistent with dependent claims 6-7, and because the “consists of” limitation only limits the scope of the LRRD2 domain, which has been defined by the Applicant as SEQ ID NO: 3.
“Bone-related diseases” is not defined on record, but is understood to be limited to the diseases now explicitly recited at amended claim 1, which includes osteoporosis, fractures, and bone loss (see, e.g., Spec. filed 8/26/2021 at 3 at lines 10-16, prior claim 9, instantly amended claim 1). Following amendments filed 9/30/2025, claim 1 excludes osteoarthritis, metastatic bone cancer, and Paget’s disease.
“Administering” was limited to parenteral administration in the amendments filed 9/30/2025. Parenteral administration is any systemic administration route that bypasses the gastrointestinal tract; accordingly, it includes intraperitoneal, subcutaneous, intravenous, intramuscular, intradermal, intrathecal, and intraosseous injections (see, e.g., Spec. filed 8/26/2021 at 10-11 at bridging ¶).
“Subject” is undefined on record, but is reasonably understood to include at least mice and humans.
“Therapeutically effective amount” is not defined, but is exemplified on record to include at least daily dosages of “0.01 to 100 mg” or alternatively 0.01 to 10 mg per 1 kg of body weight daily (see, e.g., Spec. filed 8/26/2021 at 13 at 1st full ¶).
Additional claim interpretations are set forth below.
Withdrawn Claim Rejections
The rejection of claims 1-4 and 8 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement, has been successfully in view of the cancellation of claims 2-3, and amendments to claim 1 limiting the claims to parenteral administration, and amendments to claim 1 excluding osteoarthritis, metastatic bone cancer, and Paget’s disease.
Maintained Claim Rejections
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.
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.
Claims 1 and 8 are rejected under 35 U.S.C. 103 as being unpatentable over US9802994 (Koh et al.; Oct. 31, 2017; cited in previous action) in view of Rogers et al.4. and further in view of NP_003053.15.
Claim interpretation: The applicable claim interpretation has been set forth in a preceding rejections and also in a separate section above, and those discussions and interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below.
Regarding instant claim 1 and 8, US’994 teaches, discloses, and claims methods of treating osteoporosis comprising administering a therapeutically effective amount of a Leucine-rich repeat 2 (LRR2) domain of SLIT3 protein to a subject in need thereof, wherein the LRR2 domain comprises SEQ ID NO: 46 of US’994 (see, e.g., US’944 at claims 1-2). Regarding claim 8 and administration by injection, US’944 explicitly teaches that “administering” includes intravenous injection (see, e.g., US’944 at claims 1-2, col. 8 at lines 12-36). Regarding treating bone diseases, US’944 explicitly teaches that such treatments can be utilized to treat fractures and osteoporosis (see, e.g., US’944 at claims 1-2, col. 8 at lines 12-36, noting that the treatment of osteoporosis or fractures would be obvious variants of the claimed invention).
The prior art of US’994 differs from the claimed invention as follows: US’994 does not explicitly teach the conjugation of a LRRD2 domain of SLIT3 that consists of instant SEQ ID NO: 3 to a human serum albumin.
Regarding the LRRD2 consisting of instant SEQ ID NO: 3: As noted above, US’994 directs artisans to utilize LRR2 generally (see, e.g., US’994 at col. 2 at lines 45-50, col. 3 at lines 25-30, col. 12 at lines 42-47), and even identifies that the entire SLIT3 protein may be utilized to treat fracture and osteoporosis (see, e.g., US’994 at col. 7 at lines 18-29, col. 21 at lines 1-15, col 24 at lines 1-15). Accordingly, US’994 is understood to claim and direct artisans to methods of treating osteoporosis by administering any protein comprising an LRR2 domain comprising SEQ ID NO: 46 (see, e.g., US’994 at claims 1-26). This is pertinent because NP_003053.1 evidences that the full LRRD2 domain comprising SEQ ID NO: 46 of US’994 was known in the prior art (compare instant SEQ ID NO: 3 with NP_003053.1 at residues 278-486, sharing 100% sequence identity). Accordingly, instant SEQ ID NO: 3 is understood to be a fragment of a known protein, corresponding to a known LRR2 domain, which fully comprised SEQ ID NO: 46 of US’994. Accordingly, the threshold question is “would it have been obvious to one of ordinary skill in the art to practice the claimed invention of US’944 using a longer SLIT3 fragment that still fully comprised SEQ ID NO: 46, exactly as taught, claimed, and suggested by US’944?”. In view of US’994, the answer to this question is “yes”, because US’994 directs artisans to utilize LRR2 generally (see, e.g., US’994 at col. 2 at lines 45-50, col. 3 at lines 25-30, col. 12 at lines 42-47), and even identifies that the entire SLIT3 protein may be utilized to treat fracture and osteoporosis (see, e.g., US’994 at col. 7 at lines 18-29, col. 21 at lines 1-15, col 24 at lines 1-15). Accordingly, an artisan would readily appreciate and predict that longer fragments of the LRR2 domain of SLIT3 that still comprised SEQ ID NO: 46 as disclosed by US’994 could predictably and successfully be utilized to treat osteoporosis, exactly as taught and suggested by US’994, which would include all fragments of the LRR2 domain of SLIT comprising at least the 130-mer minimal LRR2 domain of SLIT3 (i.e., SEQ ID NO: 46 of US’994) (see, e.g., NP_003053.1 at position 207-846)7. Accordingly, all such sequences would be reasonably understood to be obvious variants of each other for the purposes of treating osteoporosis and fractures, exactly as taught, claimed, and suggested by US’994.
Regarding the usage of HSA fusion constructs: Rogers is cited herein to establish that human serum albumin fusion constructs were well-known in the prior art, and were predicted and expected to desirably and beneficially extend plasma half-life of therapeutic proteins (see, e.g., Rogers at abs, Table 1 on 1900, 1901 at col II at § “Albumin Fusion proteins to extend plasma half-life”, 1905 at col II at § Conclusion). Regarding claim 1, and the usage of human serum albumin in fusion constructs generally, Rogers identifies that “albumin fusion proteins are simple to construct, easy to purify, and stable to formulate” (see, e.g., Rogers at abs, Table 1 on 1900), wherein “albumin” is understood to refer to human serum albumin (HSA) (see, e.g., Rogers at 1900 at col I-II at § Construction of Albumin Fusion proteins). Regarding instant claim 3 and the placement of albumin at the N-terminus, Rogers teaches that albumin can be fused to either the N- or C-terminus (see, e.g., Rogers at 1901 at col I, 1902 at Table 2). Therefore, an artisan would readily appreciate that albumin could be conjugated to either end, and readily appreciate that only two finite possibilities for placement existed.
Therefore, it would have been obvious to one of ordinary skill in the art, either before the effective filing date of the claimed invention (AIA ) or otherwise at the time the invention was made (pre-AIA ), to arrive at the instantly claimed invention in view of the prior art for at least the following reason(s): The claimed invention is the obvious application and the known half-life extending technique of creating a HSA fusion peptide as taught by Rogers upon the subgenus of obvious variants of therapeutic peptides comprising SEQ ID NO: 46 as taught, claimed, and suggested by US’994 in view of NP_003053.1 (i.e., the LRR domain of SLIT3 comprising at least SEQ ID NO: 46), wherein such modification with HSA would predictably yield an HSA-[LRR2 domain of SLIT3] fusion protein, predictably usable in the methods of treating fractures and osteoporosis as taught, disclosed, claimed, and suggested by US’994, but wherein the fusion protein would be predicted and expected to exhibit improved plasma half-life relative to the unmodified LRR2 domain (see, e.g., MPEP § 2143(I)(B), (C), (D), (F), and (G), MPEP §2144.06(II)). Furthermore, each portion of the fusion construct (i.e., HSA, and the LRRD of SLIT3 comprising SEQ ID NO: 46) would merely perform their art-recognized function in combination as they do separately.
Furthermore, there would be a reasonable expectation of success because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). Furthermore, it is well-within the ordinary skill in the art to identify and simply substitute equivalent obvious variants of a peptide sequence comprising a known, required sequence such as SEQ ID NO: 46 of US’994. Furthermore, it is well-within the ordinary skill in the art to simply modify a known therapeutic peptide, known for use in a prior art treatment, by using known prior art methods of extending plasma half-life of therapeutic peptides, to achieve the exact results taught and suggested in view of the prior art. Such modification are routine in the art, and well-within the ordinary skill in the biochemical and pharmaceutical arts.
Accordingly, claims 1 and 8 are rejected.
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over US9802994 (Koh et al.; Oct. 31, 2017; cited in previous action) in view of Rogers et al.8. and further in view of NP_003053.19 as applied to claims 1 and 8 above, and further in view of US 7939632 B2 (Metzner et al.; May 10, 2011; cited in previous action).
Claim interpretation: The applicable claim interpretation has been set forth in a preceding rejections and also in a separate section above, and those discussions and interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below.
The teachings of US’994 in view of Rogers and NP_003053.1 as applied to claims 1 and 8 have been set forth above, and those teachings are incorporated into the instant rejection.
The prior art of US’994, Rogers, and NP_003053.1 differs from instant claim 4 as follows: Although Rogers directs artisans to utilize albumin and human serum albumin, Rogers does not explicitly disclose a HSA having the sequence as set forth at instant SEQ ID NO: 2.
However, Rogers directs artisans to albumin fusions generally, and directs artisans to utilize HSA (see, e.g., Rogers at abs, Table 1 on 1900, 1900 at col I-II at § Construction of Albumin Fusion proteins, 1901 at col II at § “Albumin Fusion proteins to extend plasma half-life”, 1905 at col II at § Conclusion). Accordingly, an artisan would review the prior art for HSA or HSA equivalents with the reasonable expectation that such albumin (or equivalents thereof) would improve plasma half-life.
US’632 pertains to therapeutic fusion proteins, wherein a therapeutic peptide is fused to a “half-life enhancing polypeptide” (see, e.g., US’632 at abs), including albumin sequences and equivalents thereof (see, e.g., US’632 at col 7 at lines 9-67). Regarding instant claim 4 and the albumin of SEQ ID NO: 4, US’632 identifies and discloses the “Half-life Enhancing Polypeptide” of “mature form of human albumin as shown in SEQ ID NO: 1” (see id.; see id. especially at col. 7 at line 17-31), wherein SEQ ID NO: 1 of US’632 and instant SEQ ID NO: 2 are identical (compare id. at col. 7 at lines 17-31 and SEQ ID NO: 1 with instant SEQ ID NO: 2, showing 100% identity). Accordingly, instant SEQ ID NO: 2 is a prior art element, art-recognized “mature form of human albumin”, and art-recognized for suitability for use as a “Half-Life Enhancing Polypeptide” (see, e.g., US’632 at abs, col 7 at lines 9-67).
Therefore, it would have been obvious to one of ordinary skill in the art, either before the effective filing date of the claimed invention (AIA ) or otherwise at the time the invention was made (pre-AIA ), to arrive at the instantly claimed invention in view of the prior art for at least the following reason(s): The simple substitution of one HSA as disclosed by Rogers for another explicitly disclosed HSA as taught by US’632 (and equivalents thereof) for the same art-recognized use of creating a fusion protein and thereby extending the plasma half-life of a therapeutic peptide is obvious because such invention is the simple combination of prior art elements according to known methods of using HSA as taught by Rogers (see, e.g., MPEP 2143(I)(B)), or otherwise the simple substitution of equivalent HSA sequences that would also be predicted and expected to yield the same benefit in view of US’632 and Rogers (see, e.g., MPEP 2144.06(II)), namely extended plasma half-life of the fused therapeutic peptide; accordingly, the simple substitution of HSA equivalents would predictably yield a HSA fusion peptide as taught by Rogers and US’632, wherein the therapeutic peptide would be the LRR2 domain of SLIT3 as disclosed by US’994, wherein such modification would predictably yield an HSA-[LRR2 domain of SLIT3] fusion protein, predictably usable in the methods of treating fractures and osteoporosis as disclosed and claimed by US’994, but wherein the fusion protein would be predicted and expected to exhibit improved plasma half-life relative to the unmodified LRR2 domain (see, e.g., MPEP §§ 2143(I)(B), (C), (D), (F), and (G); § 2144.06(II)).
Furthermore, there would be a reasonable expectation of success because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). Furthermore, it is well-within the ordinary skill in the art to simply modify a known therapeutic peptide, known for use in a prior art treatment, by using known prior art methods of extending plasma half-life of therapeutic peptides with known HSA sequences (or equivalents thereof), to achieve the exact therapeutic results taught and suggested in view of the prior art. Such modification are routine in the art, and well-within the ordinary skill in the biochemical and pharmaceutical arts.
Accordingly, claims 4 is rejected.
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.
[NSDP 01]
Claims 1, 4, and 8 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 of U.S. Patent No. US9802994 (Koh et al.; Oct. 31, 2017) in view of US 7939632 B2 (Metzner et al.; May 10, 2011) and NP_003053.110.
Claim interpretation: The applicable claim interpretation has been set forth in a preceding rejections and also in a separate section above, and those discussions and interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below.
The applicable analysis for Nonstatutory Double Patenting is set forth at MPEP § 804(II), and specifically at MPEP § 804(II)(B). Here, although the same invention is not being claimed twice (see, e.g., MPEP § 804(II)(A), discussing Statutory Double Patenting), a Nonstatutory Double Patenting rejection is appropriate because although the conflicting claims are not identical, at least one examined application claim is not patentably distinct from the reference claims because the examined application claim is either anticipated by, or would have been obvious over, the reference claims for the reasons set forth in the following paragraph11: Per MPEP § 804(II)(B), “To decide the question above, the examiner should first construe the claim(s) in the application under examination and the claim(s) in the reference application or patent to determine what are the differences”. Accordingly, a comparison of the teachings of the reference claims and the instant pending claims are set forth below:
Regarding instant claims 1, 4, and 8, US’994 claims methods of treating osteoporosis comprising administering a therapeutically effective amount of a Leucine-rich repeat 2 (LRR2) domain of SLIT3 protein to a subject in need thereof, wherein the LRR2 domain comprises SEQ ID NO: 46 of US’994 (see, e.g., US’944 at claims 1-212). Regarding claim 8 and administration by injection, US’944 explicitly teaches that “administering” includes intravenous injection (see, e.g., US’944 at claims 1-2, col. 8 at lines 12-36; see, e.g., MPEP § 804(II)(B)(1), noting that it is permissible to use the disclosure as a dictionary). Regarding treating bone diseases, US’944 explicitly teaches that such treatments can be utilized to treat fractures and osteoporosis (see, e.g., US’944 at claims 1-2, col. 8 at lines 12-36, noting that the treatment of osteoporosis or fractures would be obvious variants of the claimed invention13).
US’944 differs from the instant claim scope as follows: US’944 does not (i) explicitly claim modifying a peptide comprising SEQ ID NO: 46 by conjugating it to a human serum albumin like instant SEQ ID NO: 5, or (ii) explicitly claim the peptide of instant SEQ ID NO: 3.
Regarding instant claim 1 and instant SEQ ID NO: 3, instant SEQ ID NO: 3 comprises the prior art sequence of SEQ ID NO: 46 as recited by US’994 (see, e.g., US’994 at claim 2), and in view of issued claim 2, an artisan would readily appreciate that any sequence comprising at least the 130-mer minimal LRR2 domain of SLIT3 (i.e., SEQ ID NO: 46 of US’994), including the entire SLIT3 protein14, could be utilized to predictably and desirably treat fractures and osteoporosis, exactly as taught and claimed. Accordingly, all such sequences would be reasonably understood to be obvious variants of each other for the purposes of treating osteoporosis and fractures, exactly as taught and disclosed by US’994. NP_003053.1 is cited herein to establish that an artisan would have readily appreciated that SEQ ID NO: 46 of US’944 corresponded to human SLIT3 at positions 309-438, whereas instant SEQ ID NO: 3 is simply a larger portion of human SLIT3 corresponding to positions 278 to 486. Accordingly, both sequences are understood to be functional equivalents within the scope of issued claim 2 of US’994, and because both comprise SEQ ID NO: 46 of US’994, would be readily expected and predicted to treat osteoporosis exactly as claimed. Accordingly, such differences are within the pending claim scope of US’994.
Regarding instant claims 1, 4, 8, and the usage of a human serum albumin having the sequence of instant SEQ ID NO: 2, US’632 pertains to therapeutic fusion proteins, wherein a therapeutic peptide is fused to a “half-life enhancing polypeptide” (see, e.g., US’632 at abs), including albumin sequences and equivalents thereof (see, e.g., US’632 at col 7 at lines 9-67). US’632 is cited herein to establish that the methodology of improving the plasma half-life of a known therapeutic polypeptide by conjugating human serum albumin (or equivalents thereof) to either the N or C termini (the only two possibilities), was well-known and routine in the prior art (see, e.g., US’632 at col 7 at lines 9-67). Regarding instant claim 4 and the albumin of SEQ ID NO: 4, US’632 identifies and discloses the “Half-life Enhancing Polypeptide” of “mature form of human albumin as shown in SEQ ID NO: 1” (see id.; see id. especially at col. 7 at line 17-31), wherein SEQ ID NO: 1 of US’632 and instant SEQ ID NO: 2 are identical (compare id. at col. 7 at lines 17-31 and SEQ ID NO: 1 with instant SEQ ID NO: 2, showing 100% identity). In sum, instant SEQ ID NO: 2 is a prior art element, namely the art-recognized “mature form of human albumin”, and was art-recognized for its suitability for use as a “Half-Life Enhancing Polypeptide” (see, e.g., US’632 at abs, col 7 at lines 9-67). Accordingly, simply conjugating the mature form of human albumin to the N- or C-termini of a known therapeutic polypeptide would merely result in the predicted and expected improvement in the plasma half-life of the therapeutic polypeptide.
Accordingly, the differences between the reference claims and instant claims appear to be obvious in view of the prior art, and primarily the result of obvious variations involving known modifications (i.e., HSA) or substitution of equivalent SLIT3 LRR sequences comprising prior art SEQ ID NO: 46 as recited at US’994 at claim 215; and therefore the answer to the question “Is any invention claimed in the application anticipated by, or an obvious variation of, an invention claimed in the patent”16 is clearly “yes”
MPEP § 804(II)(B)(2)-(3) further identify that a Nonstatutory Double Patenting Rejection may be appropriate based upon either an anticipation analysis or an obviousness analysis (see, e.g., MPEP § 804(II)(B)(2)-(3)). Here, under an obviousness analysis (see, e.g., MPEP § 804(II)(B)(3)), it is noted that the scope and content of the patent claim relative to the application claims at issue have been discussed above (see, e.g., MPEP § 804(II)(B)(3)(A)), and that the differences are that the instant claims attempt to claim a functionally equivalent LRR2 sequence simply conjugated to an HSA as is routine in the prior art (see, e.g., MPEP § 804(II)(B)(3)(B)). Accordingly, the present claims are directed to obvious variants of the reference claims because it is well-within the ordinary skill in the art to practice claims of treating conditions utilizing functionally equivalent peptides comprising a known minimal SLIT3 LRR domain, wherein the therapeutic polypeptide is merely modified using a well-known half-life extending polypeptide such as HSA (see, e.g., MPEP § 804(II)(B)(3)(C)-(D); see also MPEP §§ 2143(A), (B), (C), (D), and (G)). Therefore, the instant claims are directed to obvious variants of the issued claims.
As issued claims in a U.S. patent, the reference claims are presumed to satisfy all statutory requirements in the absence of evidence to the contrary. Accordingly, the instant claims are directed to an obvious variant of the patented claims.
As required at (C) of MPEP § 804(II), the rejection is not prohibited by 35 U.S.C. 121.
Accordingly, instant claims 1, 4 and 8 are rejected.
[NSDP 02]
Claims 1, 4 and 8 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 10,897,923 in view of US 7939632 B2 (Metzner et al.; May 10, 2011) and Reginster et al.17.
Claim interpretation: The applicable claim interpretation has been set forth in a preceding rejections and also in a separate section above, and those discussions and interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below. The applicable legal analysis for non-statutory double patenting has been discussed above, and is not repeated.
Instant claims 1, 4 and 8 substantially and materially overlap in scope as follows: Both conflicting claim sets are directed to methods of administering either SLIT3 protein or a LRRD2 domain of the SLIT3 protein to patients (compare instant claims 1, 4 and 8 with US’923 at claims 1-4). Regarding the amendment to instant claim 1 requiring that “the LRRD2 of the SLIT3 protein consists of an amino acid sequence of SEQ ID NO: 3”, US’923 explicitly identifies that the entire SLIT3 protein of SEQ ID NO: 1 may be utilized (see, e.g., US’923 at claims 1-2). This protein satisfies the newly added limitation as follows: SLIT3 comprises instant SEQ ID NO: 3, wherein SEQ ID NO: 3 is an “LRRD2 of the SLIT3 protein [that] consists of an amino acid sequence of SEQ ID NO: 3”
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The remainder of the SLIT3 protein sequence may be arbitrarily deemed to be a linker between HSA and the remaining portion of SLIT3 may be arbitrarily deemed to be a trailer sequence (i.e., an “unspecified” sequence, shown above). Such additional sequences are not excluded from the scope of instant claim 1 because instant claim 1 merely limits a single portion of the fusion construct corresponding to the “LRRD2”, but does not exclude the presence of whole or partial domains corresponding to other non-limited domains, such as LRRD3, LRRD4, LRRD5, etc., etc. Regarding claim 8 and “injection”, the issued claims of US’923 encompass all forms of administration as claimed, as well as injections (see, e.g., US’923 at col 12 at lines 55-6518).
US’023 ostensibly differs in scope with the pending claims as follows: US’023 does not (i) identify that the SLIT3 proteins are conjugated to HSA, or (ii) explicitly recite “bone-related diseases”.
Regarding instant claims 1, 4, 8, and the usage of a human serum albumin having the sequence of instant SEQ ID NO: 2, US’632 pertains to therapeutic fusion proteins, wherein a therapeutic peptide is fused to a “half-life enhancing polypeptide” (see, e.g., US’632 at abs), including albumin sequences and equivalents thereof (see, e.g., US’632 at col 7 at lines 9-67). US’632 is cited herein to establish that the methodology of improving the plasma half-life of a known therapeutic polypeptide by conjugating human serum albumin (or equivalents thereof) to either the N or C termini (the only two possibilities), was well-known and routine in the prior art (see, e.g., US’632 at col 7 at lines 9-67). Regarding instant claim 4 and the albumin of SEQ ID NO: 4, US’632 identifies and discloses the “Half-life Enhancing Polypeptide” of “mature form of human albumin as shown in SEQ ID NO: 1” (see id.; see id. especially at col. 7 at line 17-31), wherein SEQ ID NO: 1 of US’632 and instant SEQ ID NO: 2 are identical (compare id. at col. 7 at lines 17-31 and SEQ ID NO: 1 with instant SEQ ID NO: 2, showing 100% identity). In sum, instant SEQ ID NO: 2 is a prior art element, namely the art-recognized “mature form of human albumin”, and was art-recognized for its suitability for use as a “Half-Life Enhancing Polypeptide” (see, e.g., US’632 at abs, col 7 at lines 9-67). Accordingly, simply conjugating the mature form of human albumin to the N- or C-termini of a known therapeutic polypeptide would merely result in the predicted and expected improvement in the plasma half-life of the therapeutic polypeptide.
Regarding instant claims 1, 4, 8, and the treatment of “bone-related diseases”, US’023 recites the treatment of a muscle disease (see, e.g., US’023 at claims 1-4), which is understood to include at least sarcopenia (see, e.g., US’023 at title, abs, col 2 at lines 5-2019). This is pertinent because “sarcopenia” is understood to include “the risk of osteoporotic fracture” (see, e.g., US’023 col 2 at lines 5-2020), which reasonably means that sarcopenia is a “bone-related disease” related to fractures and osteoporosis within the scope of the instant claims (compare id. with instant claims 1-4, 8-9). In addition, or alternatively, Reginster discloses that osteoporosis and sarcopenia (compare instant claim 9 with App’388 at 17) may be considered one disease due to the common pathology and “cross-talk” between the “bone-muscle unit” (see, e.g., Reginster at title, abs, 31 at col II, 32 at col I at § Key Points). Furthermore, Reginster identifies that the existence of an overlapping patient population wherein obesity, sarcopenia, and osteoporosis can be concomitantly found that may be referred to as “osteosarcopenic obesity”, as well as patients simply showing both sarcopenia and osteoporosis attributable to aging (see, e.g., Reginster at 31-32 at bridging ¶, 32 at col I at § Key Points). Accordingly, in view of Reginster, an artisan would readily appreciate that osteoporosis and sarcopenia are highly related diseases, and jointly occur in known patient populations.
Under an obviousness analysis (see, e.g., MPEP § 804(II)(B)(3)), it is noted that the scope and content of the co-pending claims relative to the application claims at issue have been discussed above (see, e.g., MPEP § 804(II)(B)(3)(A)), and that the differences are that the instant claims ostensibly are directed to the treatment of different sets of diseases and include a well-known HSA modification to enhance plasma half-life; however, as established in view of Reginster, these sets of diseases substantially and materially overlap in scope. Accordingly, both pending claim scopes therefore encompass the treatment of the same or overlapping patient populations (i.e., patients with both sarcopenia and osteoporosis, or osteosarcopenic obesity, or geriatric pateints) using the same drugs at the same concentration via the same administration route, except that the instant claims are further modified using HSA as taught and suggested in view of the prior art to predictably extend plasma half-life (see, e.g., MPEP § 804(II)(B)(3)(B)). Accordingly, the conflicting claim sets are not patentably distinct, since the patient populations materially overlap in scope, and the only substantive difference is the addition of a well-known and understood HSA moiety (see, e.g., MPEP §§ 2143(A), and (G)). Therefore, the conflicting claims are not patentably distinct.
Claims 1, 4 and 8 are rejected. This is a provisional nonstatutory double patenting rejection.
[Provisional NSDP 01]
Claims 1-4 and 8 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4-13, 15-19 of copending Application No. 17/434,388 in view of Reginster et al.21.
This is a provisional nonstatutory double patenting rejection.
Claim interpretation: The applicable claim interpretation has been set forth in a preceding rejections and also in a separate section above, and those discussions and interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below. The applicable legal analysis for non-statutory double patenting has been discussed above, and is not repeated.
Instant claims 1, 4 and 8 substantially and materially overlap in scope as follows: Both copending applications are directed to methods of administering human serum albumin conjugated to the N-terminus of the LRRD2 of the SLIT3 protein, via injection, at a therapeutically effective amount, for the treatment of diseases (compare instant claims 1-5 and 8-9 with App’388 at claims 1-19; see esp., App’388 at claims 1, 15-19), wherein the “LRRD2 of the Slit3 protein consists of the amino acid sequence of SEQ ID NO: 3” compare instant claim 1 with App’388 at claim 1 as filed 11/06/2024).
App’388 ostensibly differs in scope with the pending claims as follows: Ostensibly, the claim scope of App’388 is directed to the treatment of “muscle diseases” rather than “bone-related diseases” such as osteoporosis. However, these terms are ill-defined and do not appear to be patentably distinct because of well-established interactions between components of the musculoskeletal systems and diseases thereof.
As an example, Reginster discloses that osteoporosis and sarcopenia (compare instant claim 9 with App’388 at 17) may be considered one disease due to the common pathology and “cross-talk” between the “bone-muscle unit” (see, e.g., Reginster at title, abs, 31 at col II, 32 at col I at § Key Points). Furthermore, Reginster identifies that the existence of an overlapping patient population wherein obesity, sarcopenia, and osteoporosis can be concomitantly found that may be referred to as “osteosarcopenic obesity”, as well as patients simply showing both sarcopenia and osteoporosis attributable to aging (see, e.g., Reginster at 31-32 at bridging ¶, 32 at col I at § Key Points). Accordingly, in view of Reginster, an artisan would readily appreciate that osteoporosis and sarcopenia are highly related diseases, and jointly occur in known patient populations. Accordingly, such substantially related and overlapping patient populations are not patentably distinct.
Under an obviousness analysis (see, e.g., MPEP § 804(II)(B)(3)), it is noted that the scope and content of the co-pending claims relative to the application claims at issue have been discussed above (see, e.g., MPEP § 804(II)(B)(3)(A)), and that the differences are that the instant claims ostensibly are directed to the treatment of different sets of diseases (i.e., muscle diseases in App’388 and “bone-related diseases” in the instant application); however, these sets of diseases substantially and materially overlap in scope. Accordingly, both pending claim scopes therefore encompass the treatment of the same or overlapping patient populations (i.e., patients with both sarcopenia and osteoporosis, or osteosarcopenic obesity, or geriatric pateints) using the same drugs at the same concentration via the same administration route (see, e.g., MPEP § 804(II)(B)(3)(B)). Accordingly, the co-pending claim sets are not patentably distinct, since merely practicing the full scope of either would necessarily overlap in scope with the conflicting claim set (see, e.g., MPEP §§ 2143(A), and (G)). Therefore, the conflicting claims are not patentably distinct.
Claims 1, 4 and 8 are rejected. This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant's arguments filed 9/30/2025 have been fully considered but they are not persuasive. Arguments directed to withdrawn rejections are moot. Examiner notes that the Examiner’s prior response remains pertinent in view of maintained rejection above, and therefore the prior response is incorporated into the instant action. Applicable arguments are addressed below.
35 USC 103
It is the Examiner’s understanding that Applicant traverses the rejections under 35 USC 103 at pages 7-9 (see, e.g., Reply filed 9/30/2025 at 7 at § II to p. 9 at 2nd full ¶), and these arguments are addressed below.
The claimed invention appears broader than that implied by Applicant’s statements: It is the Examiner’s understanding that Applicant attempts to compare embodiments of the claimed invention, but it ostensibly appears as if the arguments assume a claim scope narrower than presently examined and considered on record (see, e.g., Reply filed 9/30/2025 at 8 at 1st full ¶ to 9 at 1st partial ¶, referring to Table 2). The applicable claim interpretation has been set forth above, and that description is incorporated into the instant response. In brief, the pending claim scope is not limited to methods involving instant SEQ ID NO: 9, or excluding LLRD2-2, LRRD2-5, or LLRD2-8, but is instead understood to read upon and encompass all species (i.e., >>millions) of sequences having the generic structure of
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Accordingly, Applicant is advised that arguments addressing unclaimed inventions are generally not persuasive because examination pertains to the invention as it is actually claimed.
Arguments against individual references rather than the combination are not persuasive: Examiner notes that Applicant addresses the teachings of US’994 (“Koh”), Rogers, and NP_003053.1 individually (see, e.g., Reply filed 9/30/2025 at 7-8 at bridging ¶). 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).
A showing of prima facie obviousness has been established: The Examiner’s rationale(s) for supporting a determination of obviousness are explicitly set forth in the rejection (see, e.g., rejection above, noting the expressly recited rationales under MPEP § 2143(I)(B), (C), (D), (F), and (G) and MPEP §2144.06(II). Applicant fails to directly address these rationales, or identify how the elements for each rationale were not fully satisfied by the rejection of record. Accordingly, such rationales are presently undisputed on record and therefore maintained.
Allegations of unexpected results are not commensurate in scope with the requirements of MPEP §716, §716.01, and §716.02: It is the Examiner’s understanding that Applicant repeatedly alleges the existence of unexpected results commensurate in scope with the requirements of MPEP §716, §716.01, and §716.02, wherein such results are sufficient to rebut prima facie obviousness (see, e.g., Reply filed 9/30/2025 at 8 at 1st full ¶ to 9 at 2nd full ¶). However, to establish such unexpected results, the allegations must be timely and supported by objective evidence (see, e.g., 37 C.F.R. 1.132; see MPEP §§ 716.01, 716.01(a), 716.01(c)); to be of probative value the proffered evidence must be related to the claimed invention (see MPEP §§ 716.01(b), discussing nexus requirement and noting that "[w]here the offered secondary consideration actually results from something other than what is both claimed and novel in the claim, there is no nexus to the merits of the