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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 Claims 6-7 remain withdrawn.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 claimed invention"); the evidence must establish that the expected results occur to an unexpected extent (see, e.g., MPEP § 716.02(a)(I)), on the basis of statistically and practically significant evidence (see, e.g., MPEP § 716.02(b)(I)), which is fully explained (see, e.g., MPEP § 716.02(b)(II)), commensurate in scope with the claimed invention (see, e.g., MPEP § 716.02(d)), and wherein a comparison of the claimed invention with the closest prior art of record is provided (see, e.g., MPEP § 716.02(e)). Furthermore, even if evidence satisfying MPEP §§ 716.02, 716.02(a), 716.02(b), 716.02(d), and 716.02(e) is set forth on record, such evidence may not be sufficient to rebut prima facie obviousness because the evidence of expected and unexpected results must be weighed (see, e.g., MPEP § 716.02(c)(I)) and the totality of the record considered (see, e.g., MPEP §§ 716.01(d), 716.02(f)), including teachings in the prior art and evidence of expected results which weigh in favor of a determination of obviousness (see, e.g., MPEP § 716.02(c)(II)). Here, the allegations of unexpected results are understood to be premised upon the data shown at Tables 2 and 7-8, Examples 2-3, 5, and 7, Figures 3-5 (see, e.g., Reply filed 9/30/2025 at 8 at 1st full ¶ to 9 at 2nd full ¶), which has been fully reviewed, but deemed insufficient to establish unexpected results for the following reasons:
First, the information has not be set forth in an affidavit or declaration (see, e.g., 37 C.F.R. 1.132, MPEP §§ 716, 716.01(c)(I)-(II), 716.02).
Second, the proffered data shows that compounds comprising known substances (i.e., peptides comprising LRR2 domain of SLIT3) as taught by US9802994 could be successfully utilized to achieve the exact result taught and suggested US’994, namely to treat osteoporosis (see, e.g., US’994 at claims 1-2; see also rejection above). Accordingly, these proffered results confirm the expected results of the prior art, which weighs in favor of a determination of obviousness (see, e.g., MPEP § 716.02(c)(II)).
Third, the proffered data appears to substantially pertain to unclaimed inventions (i.e., Examples 2-3, 5, and 7), which fails to support a determination of unexpected results because proffered evidence in support of unexpected results “must compare the claimed subject matter” (see, e.g., MPEP § 716.02(e); see also MPEP § 716.02(b)(III) referring to “comparison of the claimed invention”; MPEP § 716.02(d), referring to data that must be “Commensurate in Scope With Claimed Invention”). Here, the claimed invention is a method of parenterally administering a protein comprising HSA and SEQ ID NO: 3 at a “therapeutically effective amount” sufficient to treat “osteoporosis, fractures, and bone loss” (see, e.g., instant claim 1). Accordingly, data directed to an unclaimed invention raises concerns regarding lack of nexus to the claimed invention (see, e.g., MPEP § 716.01(b), noting that the “Applicant or patent owner bears the burden of establishing a nexus between the objective evidence of nonobviousness and the claimed invention” and that "Where 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 claimed invention."). Accordingly, such data does not meaningfully appear to pertain to the claimed invention.
Fourth, upon review, the instant disclosure of at best, provides one method of intravenously administering 37.13 mg/kg/day of SEQ ID NO: 9 to SCID mice, which was shown to improve bone mineral density relative to a negative control (see, e.g., Spec. filed 8/26/2021 at 30-32 and 37-39, Table 8 at 37). This data is not statistically or practically significant as follows: The statistical analysis is relative to a negative control rather than the closest prior art and therefore it is unclear if the experimental compound is statistically or practically different relative to the closest existing prior art as required by MPEP §§ 716.02(b)(I) and 716.02(e). In addition, a method comparing a single administration route of a single compound at a single dosage in a single subject cannot reasonably be said to be commensurate in scope with the instant claims, which are understood to read upon >millions of species of methods, as required by MPEP §§ 716.02(d). Furthermore, the Example utilizes only 10 mg of LRRD2 but 37.13 mg of SEQ ID NO: 9 (see, e.g., Spec. filed 8/26/2021 at 30-32 and 37-39, Table 8 at 37), and the statistical and practical significance of this difference is not addressed by the Applicant as required by MPEP §§ 716.02(b)(I)-(II).
Fifth, the differences shown among SEQ ID NOs: 7-18 (see, e.g., instant Figure 3) fails to compare the claimed invention with the closest prior art, because all such sequences are encompassed by the instant claims. Accordingly, such data fails to satisfy MPEP §§ 716.02(b)(I)-(II) and 716.02(e).
Sixth, the proffered data is not commensurate in scope with the instant claims. Even assuming arguendo in the light most favorable to Applicant, at best, the proffered data pertains to SEQ ID NOs: 7-18 (Table 2-3), but the claims read upon >>millions of methods involving multiple types of injection routes (e.g., intraperitoneal, subcutaneous, intravenous, intramuscular, intradermal, intrathecal, and intraosseous injections, etc.), multiple types of subjects (e.g., mice, rabbits, primates, humans, etc.), at a “therapeutically effective” amount that presumably spans multiple orders of magnitude (see, e.g., Spec. filed 8/26/2021 at 13 at 1st full ¶, disclosing dosages of “0.01 to 100 mg” or alternatively 0.01 to 10 mg per 1 kg of body weight daily), and >>millions of sequences having the generic structure of
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Accordingly, the proffered data fails to satisfy MPEP § 716.02(d) because the limited data is not reasonably commensurate in scope with the claimed invention.
Seventh, it is neither unexpected nor unpredicted that conjugating a known structure to HSA would improve its plasma half-life. Rather, such improvement in half-life is the predicted and expected outcome as evidenced by the art of record. Notably, Strohl22 identifies that fusion of a polypeptide to HSA may improve half-life by “140-fold” (see, e.g., Strohl at 222 at col II at § 4.3). Accordingly, improvement in the range of 1-140 fold is within the predicted and expected results, wherein HSA merely performs its art-recognized function. Accordingly, evidence of improved half-life of a known compound when conjugated to a known half-life extending moiety (i.e., HSA) merely confirms the expected and predicted results of the prior art, which weighs in favor of a determination of obviousness (see, e.g., MPEP § 716.02(c)(II)).
Accordingly, the proffered data of record has been fully considered but not found sufficient to rebut prima facie obviousness by establishing unexpected results commensurate in scope with the requirements of MPEP §§ 716, 716.01, and 716.02. Accordingly, all arguments premised upon the existence of unexpected results are not persuasive.
No evidence of unexpected results or criticality of range has been placed on record: To date, zero evidence of unexpected results sufficient to rebut prima facie obviousness and commensurate in scope with the requirements of MPEP §§ 716, 716.01, and 716.02 has been placed on record. No evidence showing criticality of range has been placed on record. Rather the instant claims achieve the predicted and expected result taught and suggested by the prior art and therefore evidence confirming the expectations of the prior art actually weigh in favor of a determination of obviousness (see, e.g., MPEP § 716.02(c)(II)).
Allegations suggesting “lack of predictability” or “lack of reasonable expectation of success”: It is the Examiner’s understanding that Applicant is alleging a lack of predictability or otherwise a lack of reasonable expectation of success (see, e.g., Reply filed 9/30/2025 at 9 at 2nd full ¶). This is not persuasive because the Applicant’s assertions do not reflect the proper legal standards for evaluating predictability. MPEP § 2143.02(II) explains that “[o]bviousness does not require absolute predictability”, but instead clarifies that only “at least some degree of predictability is required” (see, e.g., MPEP § 2143.02(II)). Here, the rejection explicitly addresses predictability and reasonable expectation of success, but Applicant fails to address the explicitly identified predicted and expected results set forth in the rejection. Here, the Examiner’s basis for “predictability” is merely based upon the presumption that the prior art is fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). As explained at MPEP § 2143.02, predictability and reasonable expectation of success are satisfied when “all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art”. Here zero evidence of unexpected results commensurate in scope with the requirements of MPEP 716.02 have been set forth on record, all elements of the claimed invention were known in the prior art, one of ordinary skill was fully enabled to combined each component using routine methods in the biochemical arts per the guidance of the primary reference, and the elements would have merely performed their art-recognized, respective functions (see Rejection, above). Accordingly, such arguments are not persuasive.
Allegations suggesting “skepticism of experts”: It is the Examiner’s understanding that Applicant’s statements amount to a suggestion that the Examiner’s position would be met with skepticism of experts (see, e.g., Reply filed 9/30/2025 at 9 at 2nd full ¶). If Applicant means to suggest the existence of skepticism of experts, such evidence should be filed per MPEP § 716.05 as evidence is required to establish skepticism of experts. In the absence of such evidence, such statements are understood to be unsupported conjecture of counsel. 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)), including “all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments” (see, e.g., MPEP § 2123(I)), and no objective evidence rebutting this presumption has been placed on record to date.
Allegations suggesting “inoperability” or lack of enabling disclosure regarding a prior art reference: It is the Examiner’s understanding that Applicant’s statements amount to a suggestion that the prior art is not fully enabled or operable (see, e.g., Reply filed 9/30/2025 at 9 at 2nd full ¶, suggesting that it would not be predictably for the prior art elements to perform their prior art functions in combination). If Applicant is attempting to allege that the prior art is not enabling or inoperable Applicant is directed to MPEP § 2121(I), which notes that the prior art is presumed fully enabled for all that it discloses, and the burden is on the Applicant to rebut the presumption of operability (see, e.g., MPEP § 2121(I); MPEP § 716.07). No evidence of inoperability commensurate in scope with the requirements of MPEP § 716.07 have been placed on record at this time; critically, arguments of counsel cannot take the place of evidence in the record (see, e.g., In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965), and evidence is required to rebut the presumption of operability. The Examiner’s position is that 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)), including “all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments” (see, e.g., MPEP § 2123(I)). Accordingly, the Applicant has not satisfied their burden to rebut the presumption of operability of the prior art at this time (see, e.g., MPEP § 2121(I); MPEP § 716.07).
The Examiner’s position is reflected in the maintained rejections of record. It is the Examiner’s position that modifying the known method of treating osteoporosis as taught by the primary reference by conjugating the active component (or obvious variants thereof) to the known half-life extending moiety of HSA would lead to predictably results, namely the expected treatment outcome wherein the HSA-fusion would exhibit improved half-life. Critically, the courts have explained that
“The combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.”
KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007).
and stated that
“If a person of ordinary skill can implement a predictable variation, § 103 likely bars its patentability.”
Id. at 417.
Here, taking a compound comprising SEQ ID NO: 46 of US’994 and using it to achieve the exact result disclosed by US’994 is neither surprising nor unexpected. Accordingly, such results support a determination of obviousness (see, e.g., MPEP § 716.02(c)(II), noting that “Expected beneficial results are evidence of obviousness”).
Accordingly, all applicable arguments pertaining to revised rejections under 35 USC 103 have been considered but not found persuasive. Accordingly, the rejections of record are maintained.
Double Patenting
It is the Examiner’s understanding that Applicant traverses the Double Patenting rejections at pages 9-10 (see, e.g., Reply filed 9/30/2025 at 9 at § III to p. 10 at final ¶). Examiner’s prior response to arguments regarding the maintained rejections remains pertinent and is incorporated herein. These arguments are addressed below.
Allegation of unexpected results is not persuasive. It is the Examiner’s understanding that Applicant alleges unexpected results (see, e.g., Reply filed 9/30/2025 at 9 at 5th full ¶, 10 at 3rd full ¶). The response provided above is incorporated herein explaining that zero evidence of unexpected results commensurate in scope with the requirements of MPEP §§ 716, 716.01, and 716.02 has been placed on record.
Arguments alleging that a reference or teachings of a reference would be ignored or dismissed by artisans is not persuasive: It is the Examiner’s understanding that Applicant alleges that an artisan would ignore or dismiss the disclosure of Reginster (see, e.g., Reply filed 9/30/2025 at 9-10 at bridging ¶). Presumably, the Applicant is alleging that one of ordinary skill in the relevant art (a) could not use modern search engines to find relevant prior art, (b) would otherwise be unaware of the prior art, or (c) would just dismiss the existence of the Reginster. This is not persuasive because, per MPEP § 2141.03, “The person of ordinary skill in the art is a hypothetical person who is presumed to have known the relevant art at the relevant time” (see, e.g., MPEP § 2141.03(I)). Here, the Applicant does not dispute that all references constitute “prior art”. Furthermore, the Applicant does not dispute that prior art pertaining to osteoporosis and sarcopenia is “relevant art” for the rejections at issue, Therefore, the entire reference constitutes “relevant art” available “at the relevant time”. Accordingly, any arguments suggesting that a reasonable artisan would be unaware of the Reginster or otherwise just dismiss the reference is not persuasive because it amounts to an attempt to simply dismiss or ignore facts that are inconvenient to Applicant’s position.
Allegations suggesting “inoperability” or lack of enabling disclosure regarding a prior art reference: It is the Examiner’s understanding that Applicant is alleging that the full disclosure of Reginster is not operable or otherwise enabled (see, e.g., Reply filed 9/30/2025 at 9-10 at bridging ¶, suggesting that it would not be predictably for the copending methods to treat an identical patient population taught by Reginster having both the “bone-related disease” of osteoporosis and simultaneously having the “muscle disease” of sarcopenia, such as “aging” patients or patients suffering from “osteosarcopenic obesity”). If Applicant is attempting to allege that the prior art is not enabling or inoperable Applicant is directed to MPEP § 2121(I), which notes that the prior art is presumed fully enabled for all that it discloses, and the burden is on the Applicant to rebut the presumption of operability (see, e.g., MPEP § 2121(I); MPEP § 716.07). No evidence of inoperability commensurate in scope with the requirements of MPEP § 716.07 have been placed on record at this time; critically, arguments of counsel cannot take the place of evidence in the record (see, e.g., In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965), and evidence is required to rebut the presumption of operability. The Examiner’s position is that 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)), including “all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments” (see, e.g., MPEP § 2123(I)). Accordingly, the Applicant has not satisfied their burden to rebut the presumption of operability of the prior art at this time (see, e.g., MPEP § 2121(I); MPEP § 716.07).
Arguments premised upon misconstruing relevant facts are not persuasive. It is the Examiner’s understanding that Applicant attempts to limit the scope of the copending claim sets by “intent” and alleges that patients with the “muscle-disease” of sarcopenia do not overlap in scope with patients with the “bone-related” disease of osteoporosis (see, e.g., Reply filed 9/30/2025 at 9-10 at bridging ¶). This is not persuasive because
A person with “intent” to treat the “bone-related” disease of osteoporosis would treat all patients having osteoporosis with the instantly claimed method, without exception, including “aging” patients or patients suffering from “osteosarcopenic obesity” as taught by Reginster;
Likewise, in view of the copending claims of App’388, a person with “intent” to treat the “muscle-disease” of sarcopenia would treat all patients having sarcopenia with the claimed methods of App’388, without exception, including “aging” patients or patients suffering from “osteosarcopenic obesity” as taught by Reginster;
However, as established by Reginster, the patient populations of the instant claims and the copending claims of App’388 overlap in scope because there exists patient populations having both the “bone-related disease” of osteoporosis and simultaneously having the “muscle disease” of sarcopenia, namely “aging” patients or patients suffering from “osteosarcopenic obesity” (see citations set forth in maintained rejection above). This means
In view of both copending claim sets, an artisan would treat the same, overlapping patient population by administering the same compound at the same dosage and dosage frequency, both with the intent to treat a different disease present within the same patient population.
Accordingly, the “intent” of the copending claims directs artisans to treat the same patient population in the same exact manner, which would therefore lead to the exact same results regardless of original intent. The fact that the intent in both cases ostensibly differ does not render the instant claims patentably distinct because the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the relevant art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985). Here, Reginster discloses that osteoporosis (i.e., a “bone-related disease” presently claimed at claim 1) and sarcopenia (i.e., a “muscle disease” recited by App’388 at claims 13 and 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). Accordingly, App’388 and the instant claims are directed to overlapping patient populations. In addition, 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 jointly occur in known patient populations (e.g., “aging patients” and patients with “osteosarcopenic obesity”). Accordingly, following the instantly claimed methods and the methods of App’388 would necessarily mean that both copending claim sets were directed to overlapping subject matter directed to the treatment of aging patients or patients with “osteosarcopenic obesity”, with the same compound administered via the same route and administered at the same dosage and dosage frequency. Accordingly, the copending claim sets are not patentably distinct.
Reliance on caselaw is not explained and appears misplaced: It is the Examiner’s understanding that Applicant alleges
The claim language is for a "subject in need thereof' so that the method has to be carried out with the intent to treat that disease (see Jansen v. Rexall Sundown, Inc., 342 F.3d 1329, 1333-34, 68 USPQ2d 1154, 1158 (Fed. Cir. 2003)).
(see, e.g., Reply filed 9/30/2025 at 9-10 at bridging ¶);
and it is the Examiner’s understanding that Applicant relies upon Jansen for support of their position that the Rejection is improper (see id). First, the reliance upon Jansen is misplaced because Applicant fails to meaningfully analyze or apply the facts of Jansen to the instant facts. Second, the lack of analysis by Applicant is pertinent because the relevance of Jansen is unclear since Jansen pertained to a question summary judgement of post-grant infringement wherein one party attempted to expand, post-filing, the meaning of “a human in need thereof” in the claims of U.S. Patent 4,945,083 a manner not supported by the prosecution history of U.S. Patent 4,945,083, and wherein the case turned upon a determination of patent infringement requiring a two-step analysis, and turned upon prosecution history wherein the preamble was explicitly added to claims to gain allowance (see, e.g., Jansen v. Rexall Sundown, Inc., 342 F.3d 1329, 1333-34, 68 USPQ2d 1154, 1158 (Fed. Cir. 2003), passim). Notably, the instant case does not involve summary judgment, post-grant infringement proceedings, does not turn upon a two-step analysis for determining patent-infringement, and the scope of “in need thereof” is actively being determined by prosecution prior to grant. Third, even assuming arguendo and viewed in the light most favorable to the Applicant, Jansen at best identifies that a claim should be “interpreted to require that the method be practiced with the intent to achieve the objective stated in the preamble” (see Jansen, passim), which does not alter or change the analysis of the instant rejection. Rather, in the rejection at issue, a common patient population identified by Reginster suffers, simultaneously, from both a “muscle” disease enumerated by the claims of App’388 and also a “bone-related” disease enumerated by the instant claims. Accordingly, as explained in the preceding paragraph, the “intent” of the preamble in both respective claim sets is fully satisfied because an artisan would treat the same patients with the same compounds at the same dosage and dosage frequencies, and would do so explicitly for the intent identified in each respective claim set. Accordingly, the copending claim scopes require identical treatment of identical patients but with the intent to treat one of two conditions present within the same patient population, which would necessarily and inherently lead to the same outcome. This is a materially different situation from Jansen because here the patient population in both claim sets does, in fact, overlap23. Notably, the courts have explained that the fact that an artisan recognizes a different “advantage” does not render an invention patentably indistinct relative to the prior art because the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the relevant art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985). In sum, Applicant’s reliance upon Jansen appears wholly misplaced, and at best Jansen still does not weigh in favor of a determination of patentably distinctiveness in the instant case because both claim sets treat an overlapping patient population using identical steps.
Accordingly, all applicable arguments pertaining to the Double Patenting rejections have been considered but not found persuasive. Accordingly, the rejections are maintained as set forth above.
Summary
Accordingly, all applicable arguments have been fully considered but not found persuasive. Accordingly, the rejections are maintained as set forth above.
Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Abstract FR0167 (2016 Annual Meeting of the American Society for Bone and Mineral Research Atlanta, GA September 16-19, 2016. J Bone Miner Res. 2017 Feb;31(S1):1. doi: 10.1002/jbmr.3107. PMID: 28196292; cited in previous action) discloses that injection of a “recombinant Slit3 remarkedly rescued bone loss” (see, e.g., id. at 1).
Abstract MON-0650 (2018 Annual Meeting of the American Society for Bone and Mineral Research Palais des congrès de Montréal in Montréal, Quebéc, Canada September 28 - October 1, 2018. J Bone Miner Res. 2018 Nov;33(S1):S1-S464. doi: 10.1002/jbmr.3621. PMID: 30444937; cited in previous action) identifies that SLIT3 was art-recognized as a “novel clastokine that influences bone formation and resorption by promoting osteoblast migration and suppressing osteoclast differentiation” (see id. at 1).
US20130195863A1 (Clezardin et al.; Aug. 1, 2013; cited in previous action) teaches that bone mineral density can be treated using a “ROBO1 modulator” (see, e.g., US’863 at claim 16, 24, 26). It is noted that the SLIT3 is understood to be a “ROBO1 modulator” (see, e.g., US’863 at [0022]).
US20160120940A1 (Robinson et al; May 5, 2016; cited in previous action) discloses methods of treating fibrosis by administering a “Slit variant” to a patient (see, e.g., id. at title, abs, claims).
US20150175673A1 (cited in previous action) is the PG Pub corresponding to US’994 discussed above.
US20170281726A1 (Robinson et al; Oct. 5, 2017; cited in previous action) discloses methods of treating fibrosis by administering a “Slit variant” to a patient (see, e.g., id. at title, abs, claims).
US20180163214A1 (Li et al; Jun. 14, 2018; cited in previous action) discloses SLIT2D2-(human serum albumin) conjugates for use in the treatment of tumors (see, e.g., id. at title, abs). Accordingly, the use of HAS conjugation with portions of SLIT proteins was already known and practiced in the prior art prior to filing.
US 9,493,529 B2 (Blanche et al.; Nov. 15, 2016; cited in previous action) discloses the SLIT3 protein and explicitly teaches a sequence understood to comprise the LRR2 domain as SEQ ID NO: 22 (see, e.g., US’529 at col. 8 at lines 19-30, SEQ ID NO: 22).
Strohl (Fusion Proteins for Half-Life Extension of Biologics as a Strategy to Make Biobetters. BioDrugs. 2015 Aug;29(4):215-39. doi: 10.1007/s40259-015-0133-6. PMID: 26177629; PMCID: PMC4562006; cited in previous action) discusses half-life extension techniques and approaches known in the pharmaceutical arts (see, e.g., Strohl at title, abs, passim).
EP2036921A1 (March 18, 2009; cited in previous action) discloses the use of Slit3 fragments to treat cartilage diseases, including osteoarthritis (see, e.g., EP’921 at abs, [0003]).
US2004/0265808 A1 (Garcia et al.; Dec. 30, 2004; cited in previous action) claims methods of treating bone diseases by administering to the subject proteins (see, e.g., US’808 at claims 13-14, 18, 27-28, 56), wherein SEQ ID NO: 166 is human SLIT3 (see, e.g., US’808 at SEQ ID NO: 166).
WO2019161136A1 (Aug. 22, 2019; cited in previous action) is intervening art that discloses methods of using SLIT3 compositions to modify bone growth (see, e.g., WO’136 at title, abs, claims).
Panaroni et al24 discloses that bone disease is a defining characteristic of multiple myeloma (see, e.g., id. at title, abs). Accordingly, “bone-related disease” presumably encompasses diseases such as multiple myeloma.
Kim et al.25 expressly teaches and discloses the usage of LRRD2 of SLIT3 for the treatment of stimulating bone formation in mice following administration of a therapeutically effective amount of a truncated SLIT3 protein via injection (see, e.g., Kim at title, abs, 1439 at col I at 1st full ¶, Fig. 6 at 1437, 1439 at col I at 1st ¶, Supp. Table 5 on 25), wherein such treatment is understood to be pertinent to metabolic bone disorders such as osteoporosis (see, e.g., Kim at 1429 at col I, 1436 at col II at final ¶). Although Kim does not reduce to practice methods wherein a truncated SLIT3 protein comprising a LRRD2 domain is conjugated to human serum albumin, Kim provides express guidance directing artisans to modify the polypeptide sequence by acknowledging an art-recognized problem, namely that the “half-life of LRRD2 in vivo is likely to be short”, and then proffering a clear solution, namely directing artisans to “maximize the therapeutic effects of an LRRD2-based agent” by “development of long-acting LRRD2 using drug modification technologies, such as albumin-binding” (see, e.g., Kim at 1439 at col I at 1st full ¶).
Qi et al.26 discloses a disease that is both a “muscle disease” and a “bone-related disease”, namely Fibrodysplasia ossificans progressive, which is a disease involving the abnormal ossification of muscles, tendons, and ligaments (see, e.g., Qi at title, abs, 242 at col I-II at bridging ¶).
ACS27 teaches that bone cancers are not preventable (see, e.g., ACS at 1).
Cleveland28 discloses that “there’s nothing you can do to prevent Paget’s disease of the bone” (see, e.g., Cleveland at 6).
Conclusion
No claims are allowed.
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RANDALL L BEANE whose telephone number is (571)270-3457. The examiner can normally be reached Mon.-Fri., 7 AM to 2 PM ET.
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, Lianko G. Garyu can be reached at (571) 270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/RANDALL L BEANE/Primary Examiner, Art Unit 1654
1 NCBI, slit homolog 3 protein isoform 2 precursor [Homo sapiens], NP_003053.1, 7 pages (PRI 03-OCT-2017), also available at https://www.ncbi.nlm.nih.gov/protein/11321571?sat=46&satkey=132997919 (last visited 9/27/2024); hereafter “NP_003053.1”; cited in previous action.
2 The usage of “consists of” is limited to the exact structure of only the LRRD2 portion, which “consists of . . . SEQ ID NO: 3” (see, e.g., MPEP § 2111.03(II))
3 The presence of a linking sequence is reasonable because amended claim 1 does not preclude embodiments wherein HSA is “bound to the N-terminus of” SEQ ID NO: 3 via an intervening linker sequence. Furthermore, instant claim 6 confirms that a linker may be present between the HSA and the LRRD2 of SLIT3.
4 Rogers et al., Recombinant human serum albumin fusion proteins and novel applications in drug delivery and therapy. Curr Pharm Des. 2015;21(14):1899-907. doi: 10.2174/1381612821666150302120047. PMID: 25732550; hereafter “Rogers”; cited in previous action.
5 NCBI, slit homolog 3 protein isoform 2 precursor [Homo sapiens], NP_003053.1, 7 pages (PRI 03-OCT-2017), also available at https://www.ncbi.nlm.nih.gov/protein/11321571?sat=46&satkey=132997919 (last visited 9/27/2024); hereafter “NP_003053.1”; cited in previous action.
6 Note that US’994 at claims 1-2 utilize the word “has” rather than “comprising”. However, the word “has” is given the broadest reasonable interpretation consistent with MPEP § 2111.03(IV), and is therefore understood to mean “comprising”, which is reasonably in view of the teachings of US’994 directing artisans to utilize the SLIT3 domain of LRR2 generally, and teachings that the entire SLIT3 protein could be utilized to treat osteoporosis (see US’994 at col. 2 at lines 45-50, col. 3 at lines 25-30, col. 12 at lines 42-47, and col. 7 at lines 18-29, col. 21 at lines 1-15, col 24 at lines 1-15, as discussed above). Accordingly, in view of the Specification, the phrase is not reasonably interpreted as “consisting of”.
7 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).
8 Rogers et al., Recombinant human serum albumin fusion proteins and novel applications in drug delivery and therapy. Curr Pharm Des. 2015;21(14):1899-907. doi: 10.2174/1381612821666150302120047. PMID: 25732550; hereafter “Rogers”; cited in previous action.
9 NCBI, slit homolog 3 protein isoform 2 precursor [Homo sapiens], NP_003053.1, 7 pages (PRI 03-OCT-2017), also available at https://www.ncbi.nlm.nih.gov/protein/11321571?sat=46&satkey=132997919 (last visited 9/27/2024); hereafter “NP_003053.1”; cited in previous action.
10 NCBI, slit homolog 3 protein isoform 2 precursor [Homo sapiens], NP_003053.1, 7 pages (PRI 03-OCT-2017), also available at https://www.ncbi.nlm.nih.gov/protein/11321571?sat=46&satkey=132997919 (last visited 9/27/2024); hereafter “NP_003053.1”.
11 See, e.g., MPEP § 804(II)(B), noting that “In determining whether a nonstatutory basis exists for a double patenting rejection, the first question to be asked is: Is any invention claimed in the application anticipated by, or an obvious variation of, an invention claimed in the patent? If the answer is yes, then a nonstatutory double patenting rejection may be appropriate.”
12 Note that US’994 at claims 1-2 utilize the word “has” rather than “comprising”. However, the word “has” is given the broadest reasonable interpretation consistent with MPEP § 2111.03(IV), and is therefore understood to mean “comprising”, which is reasonably in view of the teachings of US’994 directing artisans to utilize the SLIT3 domain of LRR2 generally, and teachings that the entire SLIT3 protein could be utilized to treat osteoporosis (see US’994 at col. 2 at lines 45-50, col. 3 at lines 25-30, col. 12 at lines 42-47, and col. 7 at lines 18-29, col. 21 at lines 1-15, col 24 at lines 1-15, as discussed above). Accordingly, in view of the Specification, the phrase is not reasonably interpreted as “consisting of”.
13 see, e.g., MPEP § 804(II)(B)(1), “those portions of the specification which provide support for the reference claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application”.
14 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).
15 See, e.g., 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.
16 See, e.g., MPEP § 804(II)(B), noting that “In determining whether a nonstatutory basis exists for a double patenting rejection, the first question to be asked is: Is any invention claimed in the application anticipated by, or an obvious variation of, an invention claimed in the patent? If the answer is yes, then a nonstatutory double patenting rejection may be appropriate.”
17 Reginster et al., Osteoporosis and sarcopenia: two diseases or one? Curr Opin Clin Nutr Metab Care. 2016 Jan;19(1):31-6. doi: 10.1097/MCO.0000000000000230. PMID: 26418824; PMCID: PMC4888925; hereafter “Reginster”.
18 see, e.g., MPEP § 804(II)(B)(1), “those portions of the specification which provide support for the reference claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application”.
19 see, e.g., MPEP § 804(II)(B)(1), “those portions of the specification which provide support for the reference claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application”.
20 see, e.g., MPEP § 804(II)(B)(1), “those portions of the specification which provide support for the reference claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application”.
21 Reginster et al., Osteoporosis and sarcopenia: two diseases or one? Curr Opin Clin Nutr Metab Care. 2016 Jan;19(1):31-6. doi: 10.1097/MCO.0000000000000230. PMID: 26418824; PMCID: PMC4888925; hereafter “Reginster”; cited in previous action.
22 Strohl, Fusion Proteins for Half-Life Extension of Biologics as a Strategy to Make Biobetters. BioDrugs. 2015 Aug;29(4):215-39. doi: 10.1007/s40259-015-0133-6. PMID: 26177629; PMCID: PMC4562006; cited in previous action.
23 This makes the Applicant’s statement regarding situations wherein “the patient populations do not necessarily overlap” moot (see, e.g., Reply filed 9/30/2025 at 9-10 at bridging ¶), since in the instant case a patient population does in fact exist wherein the claimed patient populations “in need thereof” do in fact overlap.
24 Panaroni et al., Myeloma and Bone Disease. Curr Osteoporos Rep. 2017 Oct;15(5):483-498. doi: 10.1007/s11914-017-0397-5. PMID: 28861842; hereafter “Panaroni”; cited in previous action.
25 Kim et al., Osteoclast-secreted SLIT3 coordinates bone resorption and formation. J Clin Invest. 2018 Apr 2;128(4):1429-1441, 46 pages of Supplemental Information. doi: 10.1172/JCI91086. Epub 2018 Mar 5. PMID: 29504949; PMCID: PMC5873876; hereafter “Kim”; cited in Requirement mailed 5/23/2024; cited in previous action.
26 Qi et al., Fibrodysplasia ossificans progressiva: Basic understanding and experimental models. Intractable Rare Dis Res. 2017 Nov;6(4):242-248. doi: 10.5582/irdr.2017.01055. PMID: 29259851; PMCID: PMC5735276; hereafter “Qi”; cited in previous action.
27 Can Bone Cancer Be Prevented?, American Cancer Society, 7 pages (2021); also available at https://www.cancer.org/cancer/types/bone-cancer/causes-risks-prevention/prevented.html (last visited 9/25/2024); hereafter “ACS”); cited in previous action.
28 Paget's Disease of the Bone (Osteitis Deformans), Cleveland Clinic, 8 pages (2021); attached as pdf, also available at https://my.clevelandclinic.org/health/diseases/21929-pagets-disease-of-the-bone (last visited 9/25/2024); hereafter “Cleveland”; cited in previous action.
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