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 .
Finality Withdrawn
Applicant's request for reconsideration of the finality of the rejection of the last Office action is persuasive and, therefore, the finality of that action is withdrawn.
Claim Status
Claims 1, 3, 5, and 7 are pending as filed 11/20/2025. Claim 1 and 7 are withdrawn as directed to the non-elected invention of Group I. Claim 3 is presently withdrawn as directed to a non-elected species of regenerating hyaline cartilage. Claim 5 is presently considered.
Election/Restrictions
Applicant’s election without traverse of Group II (claims 3-6 as filed 5/13/2021) and species of Example 1 with SEQ ID NO: 1 in the reply filed on 4/02/2024 was previously acknowledged.
The originally elected species was Example 1 (see, e.g., Spec. filed 4/22/2021 at ¶¶[0032]-[0042]), wherein SEQ ID NO: 11 was administered to mice with a surgically induced “cartilage defect” (see, e.g., Spec. filed 4/22/2021 at ¶¶[0032]-[0042]), which was reasonably inferred to be a “traumatic cartilage defect of joint” (see, e.g., Action mailed 5/22/2025 at pages 3-4, identifying the originally elected species).
In the Reply filed 5/22/2025, Applicant amended the pending claims to exclude “traumatic cartilage defects”, and therefore the amended claim scope excludes the originally elected species.
Per MPEP § 803.02(III)(A), examination has now been extended to a non-elected species, namely methods of treating a “cartilage disorder” in a subject having “osteoarthritis of an extremity joint”, namely the “hip joint”, wherein the “treating” is selected from the group consisting of “ameliorating and alleviating” inflammation associated with osteoarthritis, by administering a peptide consisting of instant SEQ ID NO: 1 to a patient having osteoarthritis of an extremity joint2.
Following extensive search and examination, the non-elected species has been deemed obvious in view of the prior art as applied below. Per MPEP § 803.02(III)(A), claims that do not read upon the originally elected species are withdrawn.
Claims 1 and 7 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention (Group I), there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 4/02/2024.
Claims 3 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species requiring regeneration of hyaline cartilage, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 4/02/2024.
Examination has not been extended to additional, non-elected species at this time.
Claim 5 is presently considered.
Priority
The priority claim to PCT/JP2019/042015 (filed 10/25/2019) is acknowledged.
Examiner notes that no certified translation of the Foreign Application JP2018-200866 (filed 10/25/2018) has been placed on record. If applicant wants the application to be accorded benefit of the non-English language application, a certified translation is required (see 35 U.S.C. 119(b)(3), 37 CFR 1.55(g)(1)-(4)). Applicant is advised that any showing of priority that relies on a non-English language application is prima facie insufficient if no certified translation of the application is on file. See 37 CFR 41.154(b).
Information Disclosure Statement
No IDS statements have been filed to date on record following the Reply filed 11/20/2025.
Claim Interpretation
For purposes of examination, the claim scope has been interpreted as set forth below per the guidance set forth at MPEP § 2111. If Applicant disputes any interpretation, Applicant is invited to unambiguously identify any alleged misinterpretations or specialized definitions in the subsequent response to the instant action. Applicant is advised that a specialized definition should be properly supported and specifically identified (see, e.g., MPEP § 2111.01(IV), describing how Applicant may act as their own lexicographer).
Independent claim 5 is representative of the pending claim scope, and the applicable claim interpretation is set forth below.
Claim 5 recites “consisting of the amino acid sequence set forth in SEQ ID NO: 1”. “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)). Accordingly, a “peptide consisting of …. SEQ ID NO: 1” is understood to limit the structure of the peptide to SEQ ID NO: 1, which is discussed below.
Regarding the preamble phrase “for treating a cartilage disorder” (claim 5), per MPEP § 2111.02 and MPEP § 2111.04(I), the preamble is reasonably inferred to require that a patient actually have a “cartilage disorder”, namely one selected from osteoarthritis of an extremity joint or osteochondritis dissecans of an extremity joint. .
The term “subject” is understood to include any mammal, bird, or fish (see, e.g., Spec. filed 4/23/2021 at ¶[0023]). The term subject is identified as “interchangeable with the term “patient”, “individual”, or “animal” (see id).
The term “treating” is understood to include the following types of treatment: “alleviation, delay, arrest, amelioration, remission, cure, and complete remission” (see, e.g., Spec. filed 4/23/2021 at ¶[0022], not that “prevention” is identified as “alleviation, delay, and arrest” at ¶[0022]). However, as filed 11/20/2025, amended claim 5 is understood to limit “treating” to specifically the acts of ameliorating and alleviating (see amended claim 5 as filed 11/20/2025 at final line).
“Ameliorating and alleviating” are not defined on record, and are therefore given the broadest reasonable interpretation in view of the prior art. Namely, amelioration and alleviation of any symptom of osteoarthritis of an extremity joint is understood to satisfy the intended use of “for treating” as recited at the claim preamble.
SEQ ID NO: 1 is understood to be known in the art as Redasemtide; S-005151; OVE619G496 (UNII); and 1606186-88-2 (CAS). SEQ ID NO: 1 is understood to have the exact structure of MGKGDPKKPRGKMSSYAFFVQTCREEHKKKHPDASVNFSEFSKK. Instant SEQ ID NO: 1 is understood to be an art-recognized “HMGB1 fragment” (see, e.g., US 9623078 B2 at claim 1, noting both sequences at issue are 100% identical).
The phrase “administering” is interpreted in view of the specification, and is understood to not be limited (see, e.g., Spec. filed 4/23/2021 at ¶¶[0024]-[0026]). Accordingly, the term is understood to read upon systemic and local administration routes (i.e., oral, intravenous, anal, subdermal, vaginal, intramuscular, topical, eyelid, nasal, etc.).
The phrase “effective amount” was removed from claims 3 and 5 by amendment in the Reply filed 9/23/2024. Regarding the application of prior art, the method of claim 5 is presumed to necessarily occur if SEQ ID NO: 1 is administered at “about 0.0000001 µg to about 1000 mg per kg of body weight” (see, e.g., Spec. filed 4/22/2021 at ¶[0028]; see also id. at ¶[0035]) to the same or overlapping patient population.
The term “cartilage disorder” is described in the originally filed disclosure as
Examples of the cartilage disorder in the present application include, but are not limited to, traumatic cartilage defect, osteoarthritis, osteochondritis dissecans, meniscal damage, traumatic arthritis, inflammatory arthritis (e.g., rheumatoid arthritis), and infectious arthritis (e.g., suppurative arthritis). Osteoarthritis includes primary osteoarthritis for which the cause is unclear and secondary osteoarthritis for which the cause is clear. Examples of the secondary osteoarthritis include, but are not limited to, osteoarthritis caused by ligament damage, cartilage damage, meniscal damage, or the like.
(see, e.g., Spec. filed 4/22/2021 at ¶[0010]; emphasis added).
Accordingly, “cartilage disorder” encompasses traumatic cartilage injuries as well as arthritis. However, in the Reply filed 11/20/2025, claim 5 was amended to limit the claim scope of “cartilage disorder” to “osteoarthritis of an extremity joint” and “osteochondritis dissecans of an extremity joint”, thereby excluding other patient populations, including patients having “traumatic cartilage defect of the joint” (i.e., the originally elected species).
The term “osteoarthritis” is not defined on record but is reasonably understood to be a degenerative joint disease resulting from the breakdown of joint cartilage and bone. Other names for the condition used in the art include arthrosis, osteoarthrosis, degenerative arthritis, and degenerative joint disease. The specification discusses “examples” of osteoarthritis (see, e.g., Spec. filed 4/23/2021 at ¶[0010]), and explicitly identify that the term includes primary osteoarthritis (where the cause is clear) and secondary osteoarthritis (where the cause is unclear), which includes “ligament damage, cartilage damage, meniscal damage, or the like” (see, e.g., Spec. filed 4/23/2021 at ¶[0010]). Secondary osteoarthritis is understood to include causes related to rheumatoid arthritis, infectious arthritis, psoriatic arthritis, etc. (see, e.g., Hsu et. al.3 at page 2, listing “possible causes of secondary” osteoarthritis). Osteoarthritis is known in the art to be a systemic disease.
The phrase “extremity joint” is understood to refer to the “shoulder joint, elbow joint, hand joint, hip joint, knee joint”, and “ankle joint” (see, e.g., Spec. filed 4/23/2021 at ¶[0012]). Each of these joints and all technical equivalents and synonyms are reasonably understood to read upon the instant claims in the absence of further clarification in the originally filed disclosure. Accordingly, the “shoulder joint” is understood to include both the glenohumeral joint and the acromioclavicular (AC) joint. Similarly, the “hand joint” is understood to include carpometacarpal joints (wrist to palm), metacarpophalangeal joints (knuckles, palm to finger), and interphalangeal joints (within fingers, thumbs). Similarly, the “ankle joint” is understood to include at least the Talocrural joint, subtalar joint, and the inferior tibiofibular joint. The term “hip joint” is understood to include the acetabulofemoral joint. The “foot” is understood to be an “extremity”, and therefore all “foot joints” are understood to be included by the instant claim scope, which include at least subtalar joints, Midtarsal (Chopart’s) joint, Tarsometatarsal (Lisfranc) joint, metatarsophalangeal joints, and interphalangeal joints.
The term “osteochondritis dissecans” is not defined on record but is reasonably understood in the art to be a joint disorder primarily of the subchondral bone in which cracks form in the articular cartilage and the underlying subchondral bone.
The term “hyaline cartilage” is not defined on record but is understood in the art to be a type of cartilage (glass-like, translucent cartilage) found on joint surfaces, and found in ribs, nose, larynx, and trachea.
Additional claim interpretations are discussed in the rejections below.
Withdrawn Claim Rejections
All prior rejections are withdrawn. This action is non-final.
New 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.
[Prior Art Rejection 01]
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over U.S. Patent No. 9,688,733 B24 in view of Bickelhaupt et al.5, Flis et al6, and WO2006/0245477.
Claim interpretation: The applicable claim interpretation has been set forth above in a separate section and in preceding rejections, and those interpretations are incorporated herein.
The administered peptide is a prior art element: Regarding instant claims 3 and 5, and the structure of administered peptide of instant SEQ ID NO: 1, US’733 teaches and claims methods of treating all possible spinal cord injuries (at any time point following spinal injury) by administering a peptide consisting of SEQ ID NO: 5 (compare US’733 at claims 1-2 and SEQ ID NO: 5 with instant SEQ ID NO: 1, showing 100% sequence identity). The prior art teaches methods of administering the same peptide to patients via the same administration route and at the same or overlapping concentration: US’733 identifies that “administering” includes any route (compare US’733 at claims 1-2, col 8 at lines 35-61 with Spec. filed 4/23/2021 at ¶¶[0024]-[0026]). US’733 directs artisans to administer the same effective amount, namely 0.0000001 mg to 1000 mg per kg of body weight (see, e.g., US’733 at col 8 at lines 61-67; compare id. with Spec. filed 4/23/2021 at ¶[0028], instant claims 3-6). In sum, the prior art of US’733 teaches the administration of the same peptide to subjects at the same therapeutically effective amount, wherein administration is via the same route, and wherein administration may be made at any time after a spinal cord injury occurs (i.e., claim 1 of US’733 is presumed fully enabled for treatment of an SCI seconds, years, or decades after SCI occurs, as the issued claims do not limit the treatment with respect to timing, and US’733 does not disclose that such methods are limited to treatment of SCI patients only within some, but not all timeframes).
US’733 differs from instant claims 3 and 5 as follows: US’733 discloses and claims methods of treating subjects having spinal cord injuries, but does not specifically recite or specify that such subjects include spinal cord injury patients also having osteoarthritis of an extremity joint, such as the “hip joint”.
Bickelhaupt is cited herein to establish that one of ordinary skill in the SCI arts would readily appreciate that osteoarthritis is “common” among SCI patients: Bickelhaupt explains that “OA is common among . . . SCI patients”, but notes that “the insidious progression of OA may not be noticed if it is below the level of [SCI] injury” (see, e.g., Bickelhaupt at title, abs, 1050 at col I at 1st full ¶, 1050 at cols I-II at bridging ¶, 1050 at col II at 1st full ¶), wherein the unchecked progression of OA is reasonably inferred to contribute to the progression of autonomic dysreflexia (AD), which is a life-threatening complication of spinal cord injury, which may lead to tachycardia, bradycardia, hypertension, diaphoresis, mydriasis, headaches, sinus congestion, intracerebral hemorrhage, seizures, myocardial ischemia or infarction, microvascular injury, atrial fibrillation, cerebrovascular infarction, and death (see, e.g., Bickelhaupt at 1047 at col I-II at bridging ¶, 1049-1050 at bridging ¶, 1050 at col II at 1st full ¶). Bickelhaupt concludes by emphasizing that
The prevalence, severity, and monitoring of hip OA in the SCI population warrants further investigation and study. This case presentation highlights the importance of recognizing unusual causes of AD and the need for the medical community to develop treatment plans for . . . OA, in this complicated population.
(see, e.g., Bickelhaupt at 1050 at col II at 1st full¶, noting that “this complicated population” refers to “the SCI population” having “hip OA” as shown by the first sentence).
Accordingly, as established by Bickelhaupt, one of ordinary skill in the SCI arts would have readily appreciated and understood that “OA is common among . . . SCI patients” and that the patients having both OA and SCI includes “nearly 27 million Americans” (see, e.g., Bickelhaupt at title, abs, 1050 at col I at 1st full ¶, 1050 at cols I-II at bridging ¶, 1050 at col II at 1st full ¶). Accordingly, Bickelhaupt identifies that the patient population having both OA and SCI encompasses millions of patients in America, and therefore these patient populations substantially and materially overlap in scope.
Bickelhaupt and Flis establish that patients having spinal cord injuries include patients that specifically have osteoarthritis of an extremity joint, namely the “hip joint”, as required by the amended claims: Bickelhaupt discloses a patient having a spinal cord injury, namely a C4 AIS B incomplete tetraplegia (see, e.g., Bickelhaupt at title, abs, 1047 at col II at § Case Presentation), and further discloses that the same patient also had severe osteoarthritis in the right and left hip joints (see, e.g., Bickelhaupt at title, abs, 1048 at Fig. 1(A), 1050 at col I at 1st and 2nd full ¶¶, 1050 at col II at 1st partial and 1st full ¶¶, noting that “this complicated population” refers to “the SCI population”). Accordingly, Bickelhaupt discloses a patient in need of treatment for a SCI that also exhibited osteoarthritis of the hip joints (see, e.g., Bickelhaupt at title, abs, 1047 at col II at § Case Presentation, 1048 at Fig. 1). Flis discloses a patient with a spinal cord injury that also exhibits “right hip osteoarthritis” (see, e.g., Flis at title, abs, 283 at col I at 1st and 2nd full ¶¶). In sum, Bickelhaupt and Flis establish the existence of patients simultaneously possessing both a spinal cord injury and osteoarthritis of an extremity joint, namely the “hip joint”.
Predicted and expected results of regarding osteoarthritis and other diseases: Critically, one of ordinary skill in the HMGB1 arts would readily appreciate that SEQ ID NO: 5 (i.e., instant SEQ ID NO: 1) of US’733 is variant and fragment of HMGB1 Box A consisting of amino acids 1 to 44 of HMGB1 (compare US’733 at col. 1 at lines 15-21, col. 3 at lines 5-20 with WO’547 at Figure 3a, showing HMGB1 Box A sans Met), because HMGB1 Box A fragments were understood to comprise a portion of the 84 amino acid residue Box A of HMGB1 (see, e.g., WO’547 at 2 at line 20 to page 3 at line 2, Fig. 3a), wherein “biologically active fragments of native HMGB1 Box-A are fragments of at least 20… amino acids” (see, e.g., WO’547 at 12 at lines 20-30). Accordingly, SEQ ID NO: 5 of US’733 would be readily understood by an artisan to be a fragment of HMGB1 Box A. Such fragments had known and art-recognized activity, and were expected and predicted to act “as an antagonist to the pathological conditions induced and/or sustained by the B-Box and HMGB1” (see, e.g., WO’547 page 2 at line 20 to page 3 at line 2; see also id. at 8 at lines 5-15). Of direct relevance is the unambiguous identification that such fragments could be utilized to treat HMGB1-associated pathologies, including inflammatory diseases (see, e.g., WO’547 at claim 1 and 23-25, 22 at line 5 to p. 25 at line 6). WO’547 explicitly identifies that “inflammatory diseases” included “osteoarthritis, inflammatory bowel disease” (see, e.g., WO’547 at 23 at lines 1-6), “myocardial infarction” (see, e.g., WO’547 at 23 at lines 18-20), and “spinal cord injury” (see, e.g., WO’547 at 25 at lines 1-2). Accordingly, circa 2006, artisans had already identified, predicted, and disclosed that HMGB-1 Box A fragments comprising at least 20 amino acids of HMGB-1 Box A could be utilized to predictably treat osteoarthritis, spinal cord injuries, and myocardial infarctions.
Additional predicted and expected results regarding mechanism of action: In addition to acting as an antagonist to the pathological conditions induced and/or sustained by the B-Box and HMGB1” (see, e.g., WO’547 page 2 at line 20 to page 3 at line 2; see also id. at 8 at lines 5-15), US’733 identifies additional mechanistic details regarding how SEQ ID NO: 5 mediates activity. Namely, in view of US’733, performing the prior art method would be expected and predicted to “treat” all patients having any type of “injury of the spinal cord” within any timeframe after the spinal cord injury occurs, wherein administering the prior art peptide would be expected and predicted to stimulate “migration of mesenchymal stem cells” to the injury (see, e.g., US’733 at claim 1). This is pertinent because, wherein US’733 expressly identifies that mesenchymal stem cells can differentiate into “cartilage and such”, and thereby “promote healing of the tissue damage” (see, e.g., US’733 at col 1 at lines 15-40; see also id. at col 6 at lines 1-10), wherein US’733 explicitly teaches that such mesenchymal stem cells can differentiate into chondrocytes (i.e., cartilage) (see, e.g., US’733 at col 6 at lines 33-38, cols. 6-7 at bridging ¶). Accordingly, an artisan would readily appreciate that mesenchymal stem cells stimulated by administration of SEQ ID NO: 5 (i.e., instant SEQ ID NO: 1) to the patients having a spinal cord injury would be predicted and expected migrate to the damaged tissue, and promote healing by differentiating into cells at the site of injury following systemic administration of the peptide, including sites of cartilage and chondrocytes tissue (see, e.g., US’733 at claims 1-2, col 1 at lines 15-40, col 6 at lines 1-10, col 6 at lines 33-38, cols. 6-7 at bridging ¶).
Predicted and expected outcome: Upon performance of the issued methods of US’733 (see, e.g., US’733 at claim 1) upon the patients of Bickelhaupt and Flis (or similar patients having a SCI in addition to OA), an artisan would predict and expect in view of US’733 and WO’547 that such patients would desirably and beneficially be treated for both the SCI, as well as osteoarthritis.
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 reasons: The claimed invention is application of a known peptide at a known concentration via a known route of administration to patients having both a spinal cord injury as well as osteoarthritis of an extremity joint, wherein performance of the prior art method as taught and suggested by US’733 would predictably and expectedly yield the exact results and benefits taught and claimed by US’733 and WO’547, namely the successful treatment of both the spinal cord injury8 and also the osteoarthritis (see, e.g., MPEP § 2143(I)(A), (C), (D), (F), and (G)).
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 perform a known method of administering a known compound to a known patient population at a known concentration via a known route of administration to predictably achieve the exact results taught and disclosed by the prior art (e.g., treatment of both the spinal cord injuries and osteoarthritis).
Accordingly, claim 5 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 Rejection 01]
Claim 5 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 of U.S. Patent No. 9,688,733 B29 in view Bickelhaupt et al.10 and WO2006/02454711.
Claim interpretation: The applicable claim interpretation has been set forth above in a separate section and in preceding rejections, and those interpretations are incorporated herein. Additional 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 paragraph[1]: 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 claim 5: issued claims 1-2 of US’733 encompass the treatment of any possible spinal cord injury by administering a peptide consisting of SEQ ID NO: 5 (compare US’733 at claims 1-2 and SEQ ID NO: 5 with instant SEQ ID NO: 1, showing 100% sequence identity), wherein administration may be made at any time after a spinal cord injury occurs. Critically, issued claim 1 of US’733 is presumed fully enabled for treatment of any SCI within any timeframe, including seconds, years, or even decades after SCI occurs, as the issued claims do not limit the treatment with respect to timing, and US’733 does not disclose that such methods are limited to treatment of SCI patients only within some, but not all timeframes). This is reasonable, because as an issued patent, the full-scope of the issued claim is presumed fully enabled, and no evidence or arguments alleging or admitting that the full-scope of the issued claims is not enabled has been placed on record at this time.
US’733 at claims 1-2 differ from instant claim 5 as follows: Although US’733 claims methods of treating subjects having any type of spinal cord injury, the claims and disclosure of US’733 does not specifically recite or specify that subjects having spinal cord injuries include patients with SCI that also have osteoarthritis of an extremity joint, such as the “hip joint”. Accordingly, the relevant issue is whether or not the pending claim scope and issued claim scope materially or substantially overlap, such as when the two patient populations recited in the claims would be reasonably understood to include the same patients.
Bickelhaupt is cited herein to establish that one of ordinary skill in the SCI arts would readily appreciate that osteoarthritis is “common” among SCI patients: Bickelhaupt explains that “OA is common among . . . SCI patients”, but notes that “the insidious progression of OA may not be noticed if it is below the level of [SCI] injury” (see, e.g., Bickelhaupt at title, abs, 1050 at col I at 1st full ¶, 1050 at cols I-II at bridging ¶, 1050 at col II at 1st full ¶), wherein the unchecked progression of OA is reasonably inferred to contribute to the progression of autonomic dysreflexia (AD), which is a life-threatening complication of spinal cord injury, which may lead to tachycardia, bradycardia, hypertension, diaphoresis, mydriasis, headaches, sinus congestion, intracerebral hemorrhage, seizures, myocardial ischemia or infarction, microvascular injury, atrial fibrillation, cerebrovascular infarction, and death (see, e.g., Bickelhaupt at 1047 at col I-II at bridging ¶, 1049-1050 at bridging ¶, 1050 at col II at 1st full ¶). Bickelhaupt concludes by emphasizing that
The prevalence, severity, and monitoring of hip OA in the SCI population warrants further investigation and study. This case presentation highlights the importance of recognizing unusual causes of AD and the need for the medical community to develop treatment plans for . . . OA, in this complicated population.
(see, e.g., Bickelhaupt at 1050 at col II at 1st full¶, noting that “this complicated population” refers to “the SCI population” having “hip OA” as shown by the first sentence).
Accordingly, as established by Bickelhaupt, one of ordinary skill in the SCI arts would have readily appreciated and understood that “OA is common among . . . SCI patients” and that the patients having both OA and SCI is “nearly 27 million Americans” (see, e.g., Bickelhaupt at title, abs, 1050 at col I at 1st full ¶, 1050 at cols I-II at bridging ¶, 1050 at col II at 1st full ¶). Accordingly, Bickelhaupt identifies that the patient population having both OA and SCI encompasses millions of patients in America, and therefore these patient populations substantially and materially overlap in scope.
Bickelhaupt is cited herein to establish that one of ordinary skill in the SCI arts would readily appreciate that patients having both spinal cord injuries and osteoarthritis, including osteoarthritis of the “hip joint”, did in fact exist: Bickelhaupt discloses a patient having a spinal cord injury, namely a C4 AIS B incomplete tetraplegia (see, e.g., Bickelhaupt at title, abs, 1047 at col II at § Case Presentation), and further discloses that the same patient also had severe osteoarthritis in the right and left hip joints (see, e.g., Bickelhaupt at title, abs, 1048 at Fig. 1(A), 1050 at col I at 1st and 2nd full ¶¶, 1050 at col II at 1st partial and 1st full ¶¶, noting that “this complicated population” refers to “the SCI population”). Accordingly, Bickelhaupt discloses a patient in need of treatment for a SCI that also exhibited osteoarthritis of the hip joints (see, e.g., Bickelhaupt at title, abs, 1047 at col II at § Case Presentation, 1048 at Fig. 1).
In sum, Bickelhaupt establishes (i) OA is common in patients with SCI, and (ii) the existence of patients simultaneously possessing both a spinal cord injury and osteoarthritis of an extremity joint, namely the “hip joint”.
Predicted and expected results of regarding osteoarthritis and other diseases: Critically, one of ordinary skill in the HMGB1 arts would readily appreciate that SEQ ID NO: 5 (i.e., instant SEQ ID NO: 1) of US’733 is variant and fragment of HMGB1 Box A consisting of amino acids 1 to 44 of HMGB1 (compare US’733 at claims 1-2 and SEQ ID NO: 5 with WO’547 at Figure 3a, showing HMGB1 Box A sans Met), because HMGB1 Box A fragments were understood to comprise a portion of the 84 amino acid residue Box A of HMGB1 (see, e.g., WO’547 at 2 at line 20 to page 3 at line 2, Fig. 3a), wherein “biologically active fragments of native HMGB1 Box-A are fragments of at least 20… amino acids” (see, e.g., WO’547 at 12 at lines 20-30). Accordingly, at the time US’733 was issued, one of ordinary skill in the HMGB1 arts would readily appreciate that SEQ ID NO: 5 of US’733 was a fragment of HMGB1 Box A, and that such fragments were expected and predicted to act “as an antagonist to the pathological conditions induced and/or sustained by the B-Box and HMGB1” (see, e.g., WO’547 page 2 at line 20 to page 3 at line 2; see also id. at 8 at lines 5-15). Of direct relevance is the unambiguous identification that such fragments could be utilized to treat HMGB1-associated pathologies, including inflammatory diseases (see, e.g., WO’547 at claim 1 and 23-25, 22 at line 5 to p. 25 at line 6). WO’547 explicitly identifies that “inflammatory diseases” included “osteoarthritis, inflammatory bowel disease” (see, e.g., WO’547 at 23 at lines 1-6), “myocardial infarction” (see, e.g., WO’547 at 23 at lines 18-20), and “spinal cord injury” (see, e.g., WO’547 at 25 at lines 1-2). Accordingly, circa 2006 and at the time of issuance of US’733, an artisan would readily appreciate that HMGB-1 Box A fragments comprising at least 20 amino acids of HMGB-1 Box A could be utilized to predictably treat osteoarthritis, inflammatory bowel disease, spinal cord injuries, and myocardial infarctions.
Accordingly, the treatment of a single patient having both OA of the hip joint (or OA of any other joint impacted by SCI) as well as a spinal cord injury by performing the method of the issued claims would have been obvious to perform prior to the filing of the instant application, wherein such treatment would have predictably and expectedly treated the SCI as claimed by the issued patent, wherein such treatment would be reasonably inferred to treat or alleviate issues resulting from the SCI, and would additionally be understood and expected to also treat osteoarthritis present in the patient as explained by WO’547. 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”12 is clearly “yes”.
Obviousness analysis: 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 materially overlapping group of methods, but wherein both claim sets read upon the same methods of treating the same patient populations, namely patients having both a spinal cord injury as well as osteoarthritis of an extremity joint, such as a hip joint, as disclosed by Bickelhaupt. Accordingly, because such patients have spinal cord injuries and are in need of treatment for spinal cord injuries, in view of the issued claims of US’733 and guidance of WO’547, an artisan would have given such patients the same, exact peptide, at the same dosages, and via the same route of administration as directed by the claims of US’733, which would be expected to yield the same outcomes, namely treatment of HMGB-1 inflammatory disorders, including both spinal cord injury and also osteoarthritis (see, e.g., MPEP § 804(II)(B)(3)(B)). Accordingly, the present claims are directed to obvious variants of the representative claims because it is well-within the ordinary skill in the art to combine explicitly claimed known peptides, for use in treating the same or overlapping patient population, via known administration routes, and known dosages, to predictably achieve either the explicitly claimed outcome identified in the primary reference, namely the successful treatment of the SCI, and/or outcomes well-known and expected in the HMGB-1 Box A fragment arts (see, e.g., MPEP § 804(II)(B)(3)(C)-(D); see also MPEP §§ 2143(A), (B), (E), and (G)).
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. Specifically, US’733 is presumed fully enabled for the full scope of the issued claims, including the treatment of any SCI with any timeframe (e.g., seconds, years, or even decades after SCI occurs), as the issued claims of US’733 do not limit the treatment to a specific timeframe, and US’733 does not disclose that such methods are limited to treatment of SCI patients only within some, but not all timeframes. Accordingly, the rejection is premised upon the assumption that the issued claims are fully enabled. Accordingly, the instant claims are directed to an obvious variant of the issued claims, namely an art-recognized subpopulation of SCI patients. Therefore, the instant claims substantially overlap in scope with the issued claims and unambiguously encompass obvious variants of the issued claims.
As required at (C) of MPEP § 804(II), the rejection is not prohibited by 35 U.S.C. 121.
As noted at MPEP § 804(II)(B)(4), the reference at issue and the instant Application are understood to require only a one-way test for distinctiveness.
Accordingly, instant claim 5 is rejected.
[NSDP Rejection 02]
Claim 5 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. 11,298,40313 in view of Arvikar14 and WO2006/02454715.
Claim interpretation: The applicable claim interpretation has been set forth above in a separate section and in preceding rejections, and those interpretations are incorporated herein. Additional 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 paragraph16: 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:
Pending claim scope: The pending claims are understood to encompass methods of administering “an effective amount” of at least instant SEQ ID NO: 1 to patients having a “cartilage disorder”, such as osteoarthritis of an extremity joint (see, e.g., Spec. filed 4/23/2021 at ¶[0012], instant claims 3 and 5) by administering via any route (see, e.g., Spec. filed 4/23/2021 at ¶¶[0024]-[0026], instant claims 3, 5), at least “about 0.0000001 mg to about 1000 mg per kg of body weight” (see, e.g., Spec. filed 4/23/2021 at ¶[0028], instant claims 3, 5).
Issued claim scope: US’403 claims methods of treating any and all inflammatory bowel diseases in any subjects in need thereof, by administering the same, exact polypeptide (compare instant claims 3, 5, SEQ ID NO: 1 with US’403 at claims 1-6 and SEQ ID NO: 1, wherein sequences show 100% sequence identity). The issued claims of US’403 are not explicitly limited by administration route or dosage (see, e.g., US’403 at claims 1-6). However, per MPEP § 804(II)(B)(1), it is permissible to use the specification as a dictionary to learn the meaning of a term in a claim (see, e.g., MPEP § 804(II)(B)(1)). This is pertinent because “administering” is used in the same manner as the instant claims, wherein it may include any route (see, e.g., US’403 at col 6 at lines 43-65), and wherein “administering” implies at least a dosage within the range of “0.0000001 mg to 1000 mg per kg of body weight” (see, e.g., US’403 at col 7 at lines 4-19).
The instant claims ostensibly differ from the issued claims of US’403 as follows: Ostensibly, the claims at issue all pertain to treating some condition in a patient population by administering the same, exact peptide the same way at the same dosage; however, the explicitly recited patient populations differ because the pending claims are directed to the treatment of “cartilage disorders” such as osteoarthritis of extremity joints, and the issued claims of US’403 are directed to the treatment of inflammatory bowel disease.
Accordingly, the relevant issue is whether or not the pending claim scope and issued claim scope materially or substantially overlap, such as when the two patient populations recited in the claims would be reasonably inferred to include the same patients (i.e., patients having both osteoarthritis of an extremity joint as well as some type of inflammatory bowel disease).
Arvikar is cited herein to establish that one of ordinary skill in the Inflammatory Bowel Disease arts would readily appreciate that patients having both Inflammatory Bowel Disease as well as osteoarthritis of the extremity joints did in fact exist and were well-known in the prior art: Arvikar explains that
Arthritis is the most common extrainstestinal manifestation of inflammatory bowel disease (IBD)….
(see, e.g., Arvikar at title, abs).
Arvikar identifies that well-known complications of IBD include enthesitis, arthralgia, septic arthritis, oligoarticular arthritis, joint pain, etc. (see, e.g., Arvikar at 124 at col II at 1st full ¶). Although Arvikar does not explicitly recite the phrase “osteoarthritis of an extremity joint”, Arvikar identifies that IBD-associated arthropathies include “axial, peripheral, or a combination of both joint manifestations” (see, e.g., Arvikar at abs, 123-124 at bridging ¶, 124 at col I at 1st full ¶). This is pertinent because “peripheral joints” would be readily understood by one of ordinary skill in the art to include joints of the arms and legs (e.g., knees, ankles, wrists, elbows, hips, and shoulders). Furthermore, specifically regarding osteoarthritis, Arvikar identifies that the term “arthritis” is utilized to include any arthropathy (see, e.g., Arvikar at title, abs, 123 at col II at § Methods), wherein osteoarthritis would be readily understood to be an arthropathy by one of skill in the art. At Table 1, Arvikar identifies that peripheral arthritis is an arthropathy that occurs in patients having an inflammatory bowel disease (see, e.g., Arvikar at Table 1 on 125). Accordingly, one of ordinary skill in the art would readily appreciate that the patient population claimed and disclosed by the issued patent (i.e., patients having any type of inflammatory bowel disease) include patients having IBD-associated arthropathies, including arthritis of extremity joints (i.e., peripheral joints). This is pertinent because a patient having both IBD as well as a type of peripheral joint arthropathy would be treated using the method of US’403, which would predictably treat the IBD.
Predicted and expected results of regarding osteoarthritis and other diseases: Critically, one of ordinary skill in the HMGB1 arts would readily appreciate that SEQ ID NO: 1 is variant and fragment of HMGB1 Box A consisting of amino acids 1 to 44 of HMGB1 (compare sequence with WO’547 at Figure 3a, showing HMGB1 Box A sans Met), because HMGB1 Box A fragments were understood to comprise a portion of the 84 amino acid residue Box A of HMGB1 (see, e.g., WO’547 at 2 at line 20 to page 3 at line 2, Fig. 3a), wherein “biologically active fragments of native HMGB1 Box-A are fragments of at least 20… amino acids” (see, e.g., WO’547 at 12 at lines 20-30). Accordingly, one of ordinary skill in the HMGB1 arts would readily appreciate that SEQ ID NO: 1 is a fragment of HMGB1 Box A, and that such fragments were expected and predicted to act “as an antagonist to the pathological conditions induced and/or sustained by the B-Box and HMGB1” (see, e.g., WO’547 page 2 at line 20 to page 3 at line 2; see also id. at 8 at lines 5-15). Of direct relevance is the unambiguous identification that such fragments could be utilized to treat HMGB1-associated pathologies, including inflammatory diseases (see, e.g., WO’547 at claim 1 and 23-25, 22 at line 5 to p. 25 at line 6). WO’547 explicitly identifies that “inflammatory diseases” included “osteoarthritis, inflammatory bowel disease” (see, e.g., WO’547 at 23 at lines 1-6), “myocardial infarction” (see, e.g., WO’547 at 23 at lines 18-20), and “spinal cord injury” (see, e.g., WO’547 at 25 at lines 1-2). Accordingly, circa 2006, an artisan would readily appreciate that HMGB-1 Box A fragments comprising at least 20 amino acids of HMGB-1 Box A could be utilized to predictably treat osteoarthritis, inflammatory bowel disease, spinal cord injuries, and myocardial infarctions.
Obviousness analysis: 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 different, but materially overlapping patient population as evidenced by the secondary reference; however, in view of both claim sets, an artisan attempting to treat a patient exhibiting common IBD-associated arthritis or other IBD-associated arthropathy (e.g., peripheral arthritis in the joints of limbs) would treat the exact same patient population by administering the exact same peptide, at the exact same dosage, and via the same exact route of administration, wherein in view of WO’547 an artisan would readily predicted and expected that treatment for IBD in a patient having both IBD and osteoarthritis, would have also desirably and beneficially treated osteoarthritis. Accordingly, the present claims are directed to obvious variants of the representative claims because it is well-within the ordinary skill in the art to treat an art-recognized patient population (i.e., patients having a type of IBD that also exhibit common IBD-associated arthritis or other IBD-associated arthropathy in peripheral joints) using the methods of the issued claims, wherein such treatment would merely perform the expected and predicted result, namely the treatment of IBD and osteoarthritis (see, e.g., MPEP § 804(II)(B)(3)(C)-(D); see also MPEP §§ 2143(A), (B), (E), and (G)).
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 rejection is premised upon the assumption that the issued claims are fully enabled for the treatment of any type of IBD in any patient having an IBD. Accordingly, the instant claims are directed to an obvious variant of the issued claims, namely an art-recognized subpopulation of IBD patients. Therefore, the instant claims substantially overlap in scope with the issued claims and unambiguously encompass obvious variants of the issued claims.
As required at (C) of MPEP § 804(II), the rejection is not prohibited by 35 U.S.C. 121.
Accordingly, instant claim 5 is rejected.
[NSDP Rejection 03]
Claim 5 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 9,623,078 in view of Hall et al.17, Nielen et al.18, and WO2006/02454719.
Claim interpretation: The applicable claim interpretation has been set forth above in a separate section and in preceding rejections, and those interpretations are incorporated herein. Additional interpretations are set forth below.
The applicable analysis for Nonstatutory Double Patenting has been set forth above in a preceding rejection and is not repeated.
Regarding instant claim 5, US’078 teaches and discloses instant SEQ ID NO: 1 as SEQ ID NO: 3 (compare US’078 at claim 1 and SEQ ID NO: 3 with instant SEQ ID NO: 1, showing 100% sequence identity). Accordingly, US’078 claims a method of administering the same exact peptide as presently claimed, at the same or overlapping dosage, and via the same or overlapping administration route (compare instant claim 5 with US’078 at claim 1).
The instant claims ostensibly differ from the issued claims of US’078 as follows: Ostensibly, the claims at issue all pertain to treating some condition in a patient population by administering the same, exact peptide the same way at the same dosage; however, the explicitly recited patient populations differ because the pending claims are directed to the treatment of “cartilage disorders” such as osteoarthritis of extremity joints, and the issued claims of US’078 are directed to the treatment of myocardial infarction. The issued claim is directed to a method “for treating” myocardial infarction in a patient, and therefore presumably the issued claim scope includes all types of treatment, including prophylactic treatments for myocardial infarction.
Accordingly, the relevant issue is whether or not the pending claim scope and issued claim scope materially or substantially overlap, such as when the two patient populations recited in the claims would be reasonably inferred to include the same patients (i.e., patients having both osteoarthritis of an extremity joint as well as myocardial infarction).
Hall is cited herein to establish that one of ordinary skill in the Myocardial Infarction and Osteoarthritis arts would readily appreciate that patients having both Myocardial Infarctions (MI) as well as osteoarthritis of the extremity joints did in fact exist and were well-known in the prior art: Hall discloses the existence of patients having osteoarthritis and patients having cardiovascular disease was already known in the prior art (see, e.g., Hall at title, abs). Hall identifies the existence of people having both osteoarthritis as well as myocardial infarctions (see, e.g., Hall at Table I on 941, Fig. 2 on 942 at Study 1.1.3)). Accordingly, patients having both osteoarthritis and also myocardial infarctions exist (see id.).
Hall more explicitly establishes that patients having osteoarthritis of extremity joints and also MI were known in the prior art: Hall discloses patients having both “MI” (myocardial infarction) and osteoarthritis (see, e.g., Hall at Table I on 941, Fig. 2 on 942 at Study 1.1.3). Critically, this data does not explicitly identify the specific joint/region suffering from osteoarthritis (see id), but Hall identifies that “joints affected by osteoarthritis” was “extracted” from the base studies (see, e.g., Hall at 939-940 at bridging ¶), and this data is provided in the supplementary data and identified as derived, in part, from “Nielen” (see Hall at Supp. Table 3 referring to “Nielen[29]” and “Ong[30]”). Nielen is cited herein to establish that the study included patients with osteoarthritis using the ICPC codes L89 and L90, which correspond to osteoarthritis of the knee and osteoarthritis of the hip (see, e.g., Nielen at 2 at col II at § Population Selection). Nielen further identifies that “CVD” includes ICPC code K75, which stands for myocardial infarction (see, e.g., Nielen at 2 at col II at § Population Selection). Accordingly, all references to “osteoarthritis” in the Nielen study refer to OA of extremity joints (e.g., knee and hip). Nielen discloses that patients having both OA (of either knee or hip) and acute myocardial infarction (AMI) existed and were known in the prior art (see, e.g., Nielen at Table 1 on 3).
Accordingly, one of ordinary skill in the art would readily appreciate that the patient population claimed and disclosed by the issued patent (i.e., patients in need of treatment for myocardial infarction), would be readily understood by artisans to include all such patients, including patients having OA of the knee or hip, exactly as taught in view of Hall and Nielen. This is pertinent because a patient having both myocardial infarction as well as OA of the knee and/or hip would be treated using the methods of the issued patent to predictably treat such patients for myocardial infarction.
Predicted and expected results of regarding osteoarthritis and other diseases: Critically, one of ordinary skill in the HMGB1 arts would readily appreciate that SEQ ID NO: 3 of US’078 is a variant and fragment of HMGB1 Box A consisting of amino acids 1 to 44 of HMGB1 (compare sequence with WO’547 at Figure 3a, showing HMGB1 Box A sans Met), because HMGB1 Box A fragments were understood to comprise a portion of the 84 amino acid residue Box A of HMGB1 (see, e.g., WO’547 at 2 at line 20 to page 3 at line 2, Fig. 3a), wherein “biologically active fragments of native HMGB1 Box-A are fragments of at least 20… amino acids” (see, e.g., WO’547 at 12 at lines 20-30). Accordingly, one of ordinary skill in the HMGB1 arts would readily appreciate that SEQ ID NO: 3 of US’078 is a fragment of HMGB1 Box A, and that such fragments were expected and predicted to act “as an antagonist to the pathological conditions induced and/or sustained by the B-Box and HMGB1” (see, e.g., WO’547 page 2 at line 20 to page 3 at line 2; see also id. at 8 at lines 5-15). Of direct relevance is the unambiguous identification that such fragments could be utilized to treat HMGB1-associated pathologies, including inflammatory diseases (see, e.g., WO’547 at claim 1 and 23-25, 22 at line 5 to p. 25 at line 6). WO’547 explicitly identifies that “inflammatory diseases” included “osteoarthritis, inflammatory bowel disease” (see, e.g., WO’547 at 23 at lines 1-6), “myocardial infarction” (see, e.g., WO’547 at 23 at lines 18-20), and “spinal cord injury” (see, e.g., WO’547 at 25 at lines 1-2). Accordingly, circa 2006, an artisan would readily appreciate that HMGB-1 Box A fragments comprising at least 20 amino acids of HMGB-1 Box A, including SEQ ID NO: 3 of US’078, could be utilized to predictably treat osteoarthritis, inflammatory bowel disease, spinal cord injuries, and myocardial infarctions.
Obviousness analysis: 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 different, but materially overlapping patient population as evidenced by the secondary reference; however, in view of both claim sets, an artisan attempting to treat a patient for myocardial infarction that also had osteoarthritis of an extremity joint, would treat the exact same patient population for myocardial infarction by administering the exact same peptide, at the exact same dosage, and via the same exact route of administration as set forth in the issued claim of the primary reference, wherein in view of WO’547 an artisan would have readily appreciated that such treatment would predictably treat osteoarthritis as well as myocardial infarction in such patients. Accordingly, the present claims are directed to obvious variants of the representative claims because it is well-within the ordinary skill in the art to treat an art-recognized patient population (i.e., the extant patients exhibiting both myocardial infarction or at risk thereof, wherein such patients also have osteoarthritis of an extremity joint as known in the art as established by Hall and Nielen) using the exact same methods of the issued claim, with the reasonable expectation that treating such patients would predictably and expectedly yield the benefits of the primary reference and WO’547, namely treatment of the myocardial infarction and osteoarthritis (see, e.g., MPEP § 804(II)(B)(3)(C)-(D); see also MPEP §§ 2143(A), (B), (E), and (G)).
As required at (C) of MPEP § 804(II), the rejection is not prohibited by 35 U.S.C. 121.
Accordingly, instant claim 5 is rejected.
Response to Arguments
Applicant’s arguments with respect to the examined claims have been considered but are substantially rendered moot in view of the new grounds of rejection, made in view of the combination of references of record and in further view of WO’547, wherein the teachings of WO’547 were not addressed in the arguments filed 4/09/2026 or in the arguments filed 11/20/2025. Remaining applicable arguments are addressed below.
Allegations of Unexpected Results
To date, zero evidence of unexpected results commensurate in scope with the requirements of MPEP § 716, § 716.01, and § 716.02 have been placed on record to date for reasons previously discussed on record (see, e.g., Action mailed 12/02/2024 at pages 26-32 and 36-39), which are incorporated herein. Notably, all objective, experimental evidence of record was limited to surgically-induced traumatic injury to knee cartilage, which is now excluded from the pending claim scope.
The predicted and expected results have been disclosed on record, and are addressed the rejections with respect to the primary reference, and are further discussed in the Pertinent Prior Art section, below (see, e.g., discussions regarding US20040053841A1 and US2008/0038309 A1, which were both cited in previous actions).
In addition, the revised rejections now incorporate WO’547, which explicitly teaches and discloses the expected and predicted effects, applications, and utility of fragments of HMGB1 Box A comprising at least 20 amino acids of native HMGB1 Box A (see, e.g., WO’547 at 2 at line 20 to page 3 at line 2, Fig. 3a, 12 at lines 20-30). Namely, such fragments of HMGB1 Box A, including instant SEQ ID NO: 1, would have been expected and predicted to act “as an antagonist to the pathological conditions induced and/or sustained by the B-Box and HMGB1” (see, e.g., WO’547 page 2 at line 20 to page 3 at line 2; see also id. at 8 at lines 5-15), wherein such fragments could be utilized to treat HMGB1-associated pathologies exactly as taught and suggested by the prior art, wherein such HMGB1-associated pathologies included inflammatory diseases (see, e.g., WO’547 at claim 1 and 23-25, 22 at line 5 to p. 25 at line 6), which included “osteoarthritis, inflammatory bowel disease” (see, e.g., WO’547 at 23 at lines 1-6), “myocardial infarction” (see, e.g., WO’547 at 23 at lines 18-20), and “spinal cord injury” (see, e.g., WO’547 at 25 at lines 1-2). Accordingly, circa 2006, an artisan would readily appreciate that HMGB-1 Box A fragments comprising at least 20 amino acids of HMGB-1 Box A could predictably and desirably be utilized to treat osteoarthritis, inflammatory bowel disease, spinal cord injuries, and myocardial infarctions with 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)).
Accordingly, arguments and data simply confirming the expected results in view of WO’547, namely that an HMGB-1 Box fragment could successfully treat osteoarthritis, inflammatory bowel disease, spinal cord injuries, and/or myocardial infarctions confirms the expected result, and therefor weighs in favor of a determination of obviousness rather than non-obviousness (see, e.g., MPEP § 716.02.02(c)(II), noting that "Expected beneficial results are evidence of obviousness of a claimed invention, just as unexpected results are evidence of unobviousness thereof.").
US’733 is Presumed Fully Enabled
It is the Examiner’s understanding that Applicant again suggests that the issued claims in US’733 are limited to exemplified embodiments (see, e.g., Reply filed 11/20/2025 at 8 at 3rd full ¶, referring to the examples of US’733). As previously noted on record, this does not reflect US Patent law because prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). Regarding disclosed examples, MPEP §§ 2123(I)-(II) explicitly identifies that “disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure”. Accordingly, it is the Examiner’s position that the issued patent of US’733 is fully enabled for the entire scope of the claimed invention as set forth in the issued claims; zero objective evidence to the contrary has been placed on record to date.
In addition, Examiner notes that Applicant’s suggested interpretation, attempting to limit patent scope to exemplified embodiments, would not be favorable to the Applicant in the instant Application, since zero examples pertaining to the claimed subject matter presently claimed were actually exemplified on record (i.e., all exemplified embodiments pertain to surgically-induced, and therefore traumatic, cartilage injury). If Applicant’s position is that in this particular art, explicit experimental examples are required, Applicant should so clearly state in any subsequent reply; however, such admission may necessitate a rejection under 35 USC §112.
Accordingly, the pending claims of US’733 are presumed fully enabled for all that they encompass, including the treatment of any type of spinal cord injury, using any route of administration and dosage, regardless of the timeframe (i.e., US’733 does not limit the scope of the claim to treatment within a specified timeframe following a SCI, and therefore treatment may occur at any time a SCI persists).
Unclaimed Limitations
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., timing limitations of SCI and osteoarthritis limitations at 3 in the Arguments filed 4/09/2026) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Unknown Mechanisms
It is the Examiner’s understanding that Applicant argues lack of obviousness based upon unknown molecular mechanisms (see, e.g., Arguments filed 4/09/2026 at 4-5 at § III). This is not credible as numerous commercially available drugs lack defined molecular mechanisms (e.g., Acetaminophen, lithium, colchicine, etc. all lack defined molecular mechanisms of action). Furthermore, the prior art of record of WO’547 explicitly identified that HMGB-1 Box A fragments comprising at least 20 amino acids of HMGB-1 Box A could predictably and desirably be utilized to treat osteoarthritis, inflammatory bowel disease, spinal cord injuries, and myocardial infarctions with a reasonable expectation of success (see, e.g., WO’547 at claim 1 and 23-25, 2 at line 20 to page 3 at line 2, Fig. 3a, 12 at lines 20-30, 23 at lines 1-6, 23 at lines 18-20, 25 at lines 1-2), and that such compounds were expected and predicted to act “as an antagonist to the pathological conditions induced and/or sustained by the B-Box and HMGB1” (see, e.g., WO’547 page 2 at line 20 to page 3 at line 2; see also id. at 8 at lines 5-15). Notably, Applicant fails to address such evidence of record, which contradicts their position regarding mechanisms of action or otherwise a lack of linkage between HMGB-1 Box A fragments and treatment of osteoarthritis, inflammatory bowel disease, spinal cord injuries, and myocardial infarctions.
Allegations of Overlapping Patient Populations
It is the Examiner’s understanding that Applicant alleges that the “Examiner’s rejection[s] improperly rel[y] on overlapping patient population” (see, e.g., Pre-Appeal Brief at 4/09/2025 at 2 at final ¶, 4 at § II, 4 at § III, 5-6 at § IV). Applicant provides zero supporting case law supporting the assertion that an overlapping patient population is an improper basis for a rejection. Notably, an examiner need not rely upon the Applicant’s rationale for arriving at a claimed invention (see, e.g., 2143(IV), noting that “it is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant”). Here, the existence of an “overlapping patient population”, that existed in the prior art, which would have been treated exactly the same, using the same compound, same dosage, and same route of administration would necessarily yield the same exact outcome because all active “hand-of-man” steps are identical, and "Products of identical chemical composition cannot have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Accordingly, the additional benefit recognized by Applicant (i.e., the treatment of an additional disease present in extant patients that were obvious to treat the same exact way, but for another purpose) would have therefore occurred by simply following the guidance of the prior art, and treating the extant, overlapping patient population exactly as taught by the prior art. As explained at MPEP § 2145(II), the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior 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). Accordingly, in the absence of any cited case law or legal basis, arguments alleging that the “Examiner’s rejection[s] improperly rel[y] on overlapping patient population” (see, e.g., Pre-Appeal Brief at 4/09/2025 at 2 at final ¶, 4 at § II, 4 at § III, 5-6 at § IV) appear to be without credible legal basis.
However, to explicitly clarify the ordinary skill in the HMGB-1 arts and address the known and expected advantages of HMGB-1 Box A fragments (which had previously been set forth in the Pertinent Prior Art section), the Examiner has set forth new rejections explicitly reciting WO’547. WO’547 identifies that HMGB-1 Box A fragments were well-known in the prior art, and were already expected and predicted to be able to predictably and expectedly treat inflammation cased by HMGB-1 in spinal cord injuries, osteoarthritis, inflammatory bowel disease, and/or myocardial infarctions in patients in need thereof. Accordingly:
The compound administered was known in the prior art.
The dosage and administration routes utilized with the compound were known in the art.
The effect of HMGB-1 Box A fragments were already known in the prior art.
The claimed compound would be readily understood to be an HMBG-1 Box A fragment.
The Examiner’s position is that the claimed invention is obvious because the claims merely recite an outcome that had already been taught, disclosed, and recognized in the art for the entire class of HMGB-1 fragments, and 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)), which would include the treatment of spinal cord injuries, osteoarthritis, inflammatory bowel disease, and/or myocardial infarctions in patients in need thereof, by administering HMGB-1 Box A fragments. The Court has stated that
"[W]hen a patent 'simply arranges old elements with each performing the same function it had been known to perform' and yields no more than one would expect from such an arrangement, the combination is obvious."
KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398 , 417 , 127 S. Ct. 1727 , 167 L. Ed. 2d 705 (2007) (quoting Sakraida v. Ag Pro, Inc., 425 U.S. 273 , 282 , 96 S. Ct. 1532 , 47 L. Ed. 2d 784 (1976)).
Likewise, the Supreme Court has rejected rigid tests for obviousness and has emphasized that
[t]he 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 v. Teleflex Inc., 550 U.S. 398, 415 (2007), at 416.
The Court has also emphasized that
“If a person of ordinary skill can implement a predictable variation, § 103 likely bars its patentability.”
KSR Int'l v. Teleflex Inc., 550 U.S. 398, 415 (2007), at 417.
Here, utilizing a known HMGB-1 Box A fragment to achieve the exact results taught by the prior art, is readily predictable, and such “old elements” are only shown “performing the same function it had been known to perform”, and therefore the Examiner’s position is that the claimed invention is obvious.
Summary
Accordingly, all applicable arguments have been fully considered but not found persuasive for the reasons discussed above. The claims remain rejected in view of the new rejections set forth above.
Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Gong et al.20 discloses that the anti-inflammatory activity of HMGB1 A-box can be advantageously fused with the C-terminal acidic tail of HMGB1 (see, e.g., Gong at title, abs), wherein such HMGB1 A-box derivatives have predicted and expected utility in the clinical management of sepsis, and inflammatory disorders (see, e.g., Gong at 1 at col I at final ¶, 2 at col I at 1st full ¶, Fig. 1 on 3).
Kokkola et al21 was discussed and applied under 35 USC 102 in a previous action, and those discussions regarding HMGB-1 truncated proteins are incorporated herein.
Brand et al. (Collagen-induced arthritis. Nat Protoc. 2007;2(5):1269-75. doi: 10.1038/nprot.2007.173. PMID: 17546023; hereafter “Brand”; cited in previous action) was discussed and applied as an evidentiary reference in rejections of record, and those discussions are incorporated herein.
WO2006/024547 (cited in previous action) discloses that “biologically active fragments of HMGB1 Box-A” include at least fragments consisting of 20 to 80 amino acids in length relative to the native HMGB1 Box A domain (see, e.g., WO’547 at 12 at lines 20-32, claims 1-5, 22-25, and 37), and that such fragments presumably act by “competitively displacing the saturable binding of HMGB1 to macrophages” (see, e.g., WO’547 at 7 at lines 1-12). Furthermore, WO’547 informed artisans, circa 2006, that such fragments could be utilized to treat HMGB-1 mediated pathological conditions, which included “osteoarthritis, inflammatory bowel disease” (see, e.g., WO’547 at 22 at line 5 to p. 25 at line 6), “myocardial infarction” (see, e.g., WO’547 at 23 at lines 18-20), and “spinal cord injury” (see, e.g., WO’547 at 25 at lines 1-2). WO’547 teaches that HMGB1 Box A-derived sequence could be administered to patients via any route of administration, including repeated dosages, wherein daily dosages include 0.001 to 10 mg/kg, and particularly 0.1 to 5 mg/kg (see, e.g., WO’547 at 28 at lines 4-18). Accordingly, circa 2006, one of ordinary skill in the HMGB-1 arts had already predicted, expected, and disclosed that HMGB-1 Box A fragments could be utilized to treat osteoarthritis, spinal cord injuries, and myocardial infarctions.
Ulloa22 discloses that HMGB-1 has the following structure:
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(see, e.g., Ulloa et al. at Fig. 1 on 190). This is important because although HMGB-1 is understood to “comprise” instant SEQ ID NO: 1, it was well-known in the prior art that injecting full-length HMGB-1 into “murine joints induce[d] arthritis symptoms in 80% of the animals” (see, e.g., Ulloa at 194 at col II at 2nd full ¶), and HMGB-1 was generally associated with chronic rheumatoid arthritis and inflammatory conditions (see id). However, it was also well-known in the art circa at least 2006 that the A-box portion of HMGB-1 (i.e., amino acids 1-85) presumably acted “as a competitive antagonist to the full-length HMGB1 protein” (see, e.g., Ulloa at 195 at 1st partial ¶).
Jaumard23 discloses spinal facet joint biomechanics and discusses injuries (see, e.g., Jaumard at title, abs). Jaumard identifies that “facet trauma is also associated with the occurrence of damage to other soft tissues of the spin, such as disc tearing, spinal cord trauma, and/or nerve root compression….” (see, e.g., Jaumard at 071010-14 at col I at § 5), wherein fact trauma is understood to include facet joint injuries as well as cartilage damage (see, e.g., Jaumard at 071010-14 at col I-II at §§ 5.1, 071010-15 at col I-II at §§ 5.3). Jaumard identifies that facet joint degradation, including damages to articular cartilage, “can indue pain and modify local inflammation at the nerve root as well as modify inflammation in the dorsal root ganglion and spinal cord” ( see, e.g., Jaumard at 071010-19 at col I at §§ 6.7).
Ruckstuhl et al.24 discusses humeral cartilage in individuals with spinal cord injuries (see, e.g., id. at title, abs, passim).
Lim et al.25 discusses a patient with a spinal cord injury originating from an OCD-like lesion (see, e.g., id. at title, abs, passim).
US20040053841A1 (cited in previous action) identifies what constitutes a truncated HMGB1 A-box polypeptide, namely fragments of box A having “one or more” of a particular set of biological activities that also meet certain structural limitations (see, e.g., US’841 at ¶¶[0065]-[0070] and [0124]-[0125], claims 1, 5, 7, 14-15). Note that per ¶[0125], treatment of spinal cord injury, Crohn’s disease, ulcerative colitis, arthritis, arthritides, arthralgias, etc. are expected and predicted disorders treatable using HMGB1 A-box polypeptides.
US2008/0038309 A126 disclosed that “biologically active fragments of HMGB1 Box-A” could be utilized to predictably treat HMGB-1 mediated diseases (see, e.g., US’309 at ¶¶[0020], [0026], [0029], [0039], [0085]-[0086], claims 1, 23, 25, and 37), wherein a “biologically active fragment of HMGB1 Box-A” is identified as comprising at least 20-80 amino acids of human HMGB1 Box-A (see, e.g., US’309 at ¶¶[0040], [0044]). Accordingly, an artisan would readily appreciate that SEQ ID NO: 5 of US’733 was a fragment of HMGB1 Box A (compare id. with US’733 at title, abs, claims 1-2, SEQ ID NO: 5). Truncated HMGB-1-derived A-box polypeptides were generally recognized in the art as suitable for the treatment of “HMGB-1 mediated diseases”: US’309 reasonably informs artisans that “biologically active fragments of HMGB1 Box-A” could be utilized to predictably treat HMGB-1 mediated diseases (see, e.g., US’309 at ¶¶[0020], [0026], [0029], [0039], [0085]-[0086], claims 1, 23, 25, and 37). HMGB1-mediated diseases were well-known in the prior art and included osteoarthritis: US’309 reasonably informs artisans that “biologically active fragments of HMGB1 Box-A” could be utilized to predictably treat HMGB-1 mediated diseases (see id.), wherein such “HMGB-1 mediated diseases” would have been readily understood to include at least osteoarthritis, “spinal cord injury”, and inflammatory bowel disease (see, e.g., US’309 at ¶¶[0085]-[0086], claims 1, 23, 25, and 37). The general dosing and dosage frequency required to treat HMGB-1 mediated diseases with Truncated HMGB-1-derived A-box polypeptides was known in the prior art: US’309 identifies that single or repeated doses could be utilized, and that daily dosages between 0.001 to 10 mg/kg could be utilized to treatHMGB-1 mediated diseases (see, e.g., US’309 at ¶¶[0095]). The administration of a truncated HMGB-1-derived A-box polypeptide to a patient with an HMGB-1 mediated disease would yield predicted and expected results: In view of US’309, an artisan would reasonably predict and expect that a truncated HMGB-1-derived A-box polypeptide could be utilized to alleviate and/or treat an HMGB1-mediated disease, exactly as taught and suggested by the prior art (see, e.g., US’309 at ¶¶[0020], [0026], [0029], [0039], [0085]-[0086], claims 1, 23, 25, and 37).
US20040136979A1 (cited in previous action) pertains to HMGB-1 inhibitors and/or antagonists for the treatment of vascular diseases (see, e.g., id. at title, abs, claims).
US20150273017A1 (cited in previous action) discloses instant SEQ ID NO: 1 as SEQ ID NO: 3, and teaches that it is an HMGB1 fragment usable in the treatment of cardiac infarction (see, e.g., id. at title, abs, claims).
Färkkilä et al.27 discloses the existence of patients with both cervical spine injuries as well as mandibular fractures (see, e.g., id. at title, abs).
D’Aunoy28 discusses the typical injuries a lawyer might expect to see in clients that suffered a motor vehicle accident (see, e.g., id. at passim).
Koubaa et al29 pertains to a patient with a spinal cord injury, that also has “advanced osteoarthritis” in a knee, requiring “total knee arthroplasty” (see, e.g., id. at title, abs).
Berney et al.30 discloses traumatic spinal injuries on farms, and discusses additional injuries, including torn meniscus (see, e.g., id. at title, abs, passim).
Lalani et al.31 teaches and discloses patients having both cervical spine injuries and maxillofacial trauma (see, e.g., id. at title, abs, passim).
Morris et al.32 details typical approaches and complications when dealing with facial trauma and coexisting injuries (see, e.g., id. at title, abs, passim). Critically, Morris states that “To prevent irreversible neurologic injury, spinal cord injury should be suspected in all trauma patients until it is ruled out” (see, e.g., Morris at 606 at col II).
Jose et al.33 details typical approaches and complications when dealing with facial trauma and coexisting injuries, given the proximity to the cervical spine (see, e.g., id. at title, abs, 73, passim). Jose identifies that C-spine injuries may be suspected in such patients (see, e.g., id. at 74 at col II, passim; see also id. at Figs. 1-2, reproduced in part below). Such injuries would be readily understood to involve traumatic cartilage damage of the jaw joints.
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Bickelhaupt et al.34 identifies a patient having a spinal cord injury and advanced hip osteoarthritis (see, e.g., Bickelhaupt at title, abs).
Ohry et al.35 teaches and discloses a patient population of patients having spinal cord injuries in patients following limb amputation (see, e.g., Ohry at title, abs). Specifically, Ohry identifies the patient of “Case I”, which is identified as having multitrauma resulting from falling into a combined harvester machine, which resulted in a spinal cord injury and the loss of a “lower limb through the knee”, which is reasonably inferred to include traumatic cartilage injury (see, e.g., Ohry at 260 at § Case Reports).
Wong et al.36 pertains to a patient having osteochondritis dissecans (see, e.g., Wong at 56 at col I, 57 at col I at 1st partial and 1st full ¶¶, 57 at col I-II at § Comments). Notably, the patient is understood to have a spinal cord injury because Wong reports that the OCD lesion is on the left articular process of C6-7 (see, e.g., Wong at 57 at col II at 1st full ¶), and identifies the existence of axonal degeneration in the “adjacent segments of spinal cord” (see, e.g., Wong at 57 at col I at 1st full ¶). Wong concludes that “the OCD lesion and associated spinal cord degeneration contributed to the neurologic signs” observed (see id). Accordingly, because “spinal cord degeneration” is a type of “spinal cord injury”, such patient would reasonably be treated for spinal cord injury.
Karsy37 discloses a type of reconstructive maxillofacial surgery requiring substantial surgically-induced trauma to hard and soft tissues of the jaw (see, e.g., Karsy at title, abs, Fig. 1 on 465, reproduced in part below).
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Karsy explains that this type of surgery is utilized to treat micrognathia and to improve surgical access to the ventral cervical spine in patients with severe kyphosis (see, e.g., Karsy at title, abs). The surgery is invasive and requires incisions of the mandibular ramus (which supports the condylar process), wherein the surgery directly impacts the mobility of the jaw (see, e.g., Karsy at Fig. 1 on 465, 465-466 at bridging ¶, 466 at 2nd full ¶, 466 at col II at 1st partial ¶). Accordingly, such patients have undergone traumatic cartilage defect of the jaw, including the jaw joint (see id). Notably, such patients include patients having spinal cord injuries and conditions placing the patient at risk for spinal cord injuries, including ventral cord compression38, basilar invagination39, myeloradiculopathy 40, syringohydromyelia 41, and progressive syringomyelia42 (see, e.g., Karsy at Table at 466). Accordingly, because such patients either have or are at high risk of having spinal cord injuries, and artisan would reasonably treat such patients using the methodology of the primary reference to desirably and beneficially treat such patients for existing or potential spinal cord injuries.
ABC of Spinal Cord Injury43 (Grundy) establishes that the common evaluation of “Spinal cord injuries” by medical professionals routinely involves consideration of damage and trauma to both cartilage and soft tissue damage (see, e.g., Grundy at 12, noting that the “C” in “ABCs of Spinal Cord Injury” is for “‘C’ for cartilages”, and that the “S” is for “soft tissues”). For example, Grundy identifies that spinal cord injuries may be caused by disc (cartilage) materials being pushed into the spinal cord (see, e.g., id.; see also id. at 13 at 1st and 2nd ¶¶).
Taylor44 discusses traumatic “common spinal lesions consistently observed . . . from crash studies” (see Taylor at abs), and Taylor identifies that “large herniations impinge on the dura or spinal cord . .They may include . . . part of a cartilage plate torn off the vertebral end plate” (see Taylor at 3rd page of attached file, 1st ¶ beginning with “Rim lesions”).
Koubaa et al45 presents a case study of a patient having a spinal-cord injury (see, e.g., Koubaa at title, abs), and wherein the patient was subsequently diagnosed with “advanced osteoarthritis” (see Koubaa at abs, 589 at col II at 1st full ¶).
Eriks-Hoogland et al.46 pertains to patients with acromioclavicular joint arthritis (i.e., a “shoulder joint”) as well as a SCI (see id. at title, abs).
Vanwanseele et al.47 identifies patients having both OA of the knees and SCI (see id. at title, abs, 3380 at col I-II).
Nakajima et al.48 discloses a patient having “rapidly progressive osteoarthritis of her right knee” and “a huge extruded left-sided cervical intervertebral disc at the C4-5 level”, which was understood to be “compressing the spinal cord” (see, e.g., Nakajima at title, abs, 812-813 at bridging ¶).
Yung et al.49 appears relevant to the instant claims, US11298403, and US9688733B2. Yung pertains to a patient having both Crohn's disease as well as an acute spinal cord injury (see, e.g., Yung at title, abs).
Slot et al.50 appears relevant to the instant claims, US11298403, and US9688733B2. Slot discloses a patient with active Crohn's disease resulting in ischemic spinal cord injury (see, e.g., Slot at title, abs).
Freitag et al.51, pertains to “the treatment of a large osteochondral defect of the knee following unsuccessful surgical intervention of osteochondritis dissecans” by using mesenchymal stem cell therapy (see, e.g., Freitag at title, abs).
Conclusion
No claims are allowed.
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 MGKGDPKKPRGKMSSYAFFVQTCREEHKKKHPDASVNFSEFSKK
2 Following the Pre-Appeal conference decision, the recitations of intended use in the preambles have been reconsidered. Critically, the scope of claims 3 and 5 are presently deemed non-identical and therefore claim 3 is directed to different species of methods requiring regeneration of hyaline cartilage in extremity joints of patients having osteoarthritis or osteochondritis dissecans at this time. Examination has not been extended to these non-elected species at this time, and therefore this action correctly identifies that claim 3 is withdrawn at this time.
3 Hsu et. al., Knee Osteoarthritis. [Updated 2023 Jun 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan. Available from: https://www.ncbi.nlm.nih.gov/books/NBK507884/; cited in previous action; hereafter “Hsu”; cited in previous action.
4 Cited in previous action.
5 Bickelhaupt et al., Advanced Hip Osteoarthritis Causing Autonomic Dysreflexia and Severe Spasticity in a Patient With Spinal Cord Injury: A Case Report. PM R. 2017 Oct;9(10):1047-1050. doi: 10.1016/j.pmrj.2017.02.015. Epub 2017 Mar 31. PMID: 28366524; hereafter “Bickelhaupt”.
6 Flis et al., Left Hip Pain Caused by Right Hip Osteoarthritis in a Patient With an Incomplete Cervical Spinal Cord Injury: A Case Report. PM R. 2016 Mar;8(3):282-5. doi: 10.1016/j.pmrj.2015.09.007. Epub 2015 Sep 25. PMID: 26409197; hereafter “Flis”.
7 Cited in IDS filed 4/23/2024 as cite “N”, and cited in previous actions.
8 Any additional benefits obtained from performing the prior art methodology for the purpose of obtaining the art-recognized benefits disclosed by the primary reference would flow naturally from following the suggestion of the prior art, and 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).
9 Cited in previous action.
10 Bickelhaupt et al., Advanced Hip Osteoarthritis Causing Autonomic Dysreflexia and Severe Spasticity in a Patient With Spinal Cord Injury: A Case Report. PM R. 2017 Oct;9(10):1047-1050. doi: 10.1016/j.pmrj.2017.02.015. Epub 2017 Mar 31. PMID: 28366524; hereafter “Bickelhaupt”.
11 Cited in previous action.
[1] 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 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.”
13 Cited in previous action.
14 Arvikar et al., Inflammatory bowel disease associated arthropathy. Curr Rev Musculoskelet Med. 2011 Sep;4(3):123-31. doi: 10.1007/s12178-011-9085-8. PMID: 21710141; PMCID: PMC3261248.; hereafter “Arvikar”; cited in previous action.
15 Cited in previous action.
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 Hall et al., Association between osteoarthritis and cardiovascular disease: Systematic review and meta-analysis. Eur J Prev Cardiol. 2016 Jun;23(9):938-46 and 10 pages of Supplemental. doi: 10.1177/2047487315610663. Epub 2015 Oct 13. PMID: 26464295; hereafter “Hall”.
18 Nielen et al., Cardiovascular disease prevalence in patients with inflammatory arthritis, diabetes mellitus and osteoarthritis: a cross-sectional study in primary care. BMC Musculoskelet Disord. 2012 Aug 21;13:150. doi: 10.1186/1471-2474-13-150. PMID: 22906083; PMCID: PMC3493278; hereafter “Nielen”.
19 Cited in previous action.
20 Gong et al., The anti-inflammatory activity of HMGB1 A box is enhanced when fused with C-terminal acidic tail. J Biomed Biotechnol. 2010;2010:915234. doi: 10.1155/2010/915234. Epub 2010 Apr 1. PMID: 20379370; PMCID: PMC2850157; hereafter “Gong”; cited in previous action.
21 Kokkola et al. , Successful treatment of collagen-induced arthritis in mice and rats by targeting extracellular high mobility group box chromosomal protein 1 activity. Arthritis Rheum. 2003 Jul;48(7):2052-8. doi: 10.1002/art.11161. PMID: 12847700; hereafter “Kokkola”; cited in previous action.
22 Ulloa et al., High-mobility group box 1 (HMGB1) protein: friend and foe. Cytokine Growth Factor Rev. 2006 Jun;17(3):189-201. doi: 10.1016/j.cytogfr.2006.01.003. Epub 2006 Mar 2. PMID: 16513409; hereafter “Ulloa”; cited in previous action.
23 Jaumard et al., Spinal facet joint biomechanics and mechanotransduction in normal, injury and degenerative conditions. J Biomech Eng. 2011 Jul;133(7):071010. doi: 10.1115/1.4004493. PMID: 21823749; PMCID: PMC3705911; hereafter “Jaumard”; cited in previous action.
24 Ruckstuhl et al., A quantitative study of humeral cartilage in individuals with spinal cord injury. Spinal Cord 46, 129–134 (2008); hereafter “Ruchstuhl”; cited in previous action.
25 Lim et al., Osteochondritis dissecans-like lesions of the occipital condyle and cervical articular process joints in a Saddlebred colt horse. Acta Vet Scand 59, 76 (2017). https://doi.org/10.1186/s13028-017-0345-5; hereafter “Lim”; cited in previous action.
26 Cited in previous action.
27 Färkkilä et al., Risk Factors for Cervical Spine Injury in Patients With Mandibular Fractures. J Oral Maxillofac Surg. 2019 Jan;77(1):109-117. doi: 10.1016/j.joms.2018.07.032. Epub 2018 Aug 7. PMID: 30172763; cited in previous action.
28 D’Aunoy, Head On Auto Accidents and Collisions, 13 pages, attached as pdf (Sept. 12, 2018), also available at https://lawyerdon.com/head-on-wrecks-and-collision/ (last visited 5/14/2025); hereafter “D’Aunoy” ; cited in previous action.
29 Koubaa, et al, (Total knee arthroplasty in a spinal cord-injured patient: A case report, Annals of Physical and Rehabilitation Medicine, Volume 52, Issues 7–8, 2009, Pages 588-593, ISSN 1877-0657, https://doi.org/10.1016/j.rehab.2009.06.008; cited in previous action.
30 Berney et al, Traumatic spinal injuries on farms: Patients treated in the national spinal unit of Ireland 2005-2015. J Orthop. 2017 Jan 9;14(1):211-215. doi: 10.1016/j.jor.2016.12.013. PMID: 28115799; PMCID: PMC5226670; cited in previous action.
31 Lalani et al., Cervical spine injury in maxillofacial trauma, British Journal of Oral and Maxillofacial Surgery, Volume 35, Issue 4, 1997, Pages 243-245, ISSN 0266-4356, https://doi.org/10.1016/S0266-4356(97)90041-3; cited in previous action.
32 Morris et al., Complications in Facial Trauma, Facial Plast Surg Clin N Am 21 (2013) 605–617; hereafter “Morris” ; cited in previous action.
33 Jose et al., Management of maxillofacial trauma in emergency: An update of challenges and controversies. J Emerg Trauma Shock. 2016 Apr-Jun;9(2):73-80. doi: 10.4103/0974-2700.179456. PMID: 27162439; PMCID: PMC4843570; cited in previous action.
34 Bickelhaupt et al., Advanced Hip Osteoarthritis Causing Autonomic Dysreflexia and Severe Spasticity in a Patient With Spinal Cord Injury: A Case Report. PM R. 2017 Oct;9(10):1047-1050, attached as abstract only, doi: 10.1016/j.pmrj.2017.02.015. Epub 2017 Mar 31. PMID: 28366524.l hereafter “Bickelhaupt”; cited in previous action.
35 Ohry et al., The needs and unique problems facing spinal cord injured persons after limb amputation. Paraplegia. 1983 Aug;21(4):260-3. doi: 10.1038/sc.1983.41. PMID: 6622052; hereafter “Ohry”; cited in previous action.
36 Wong et al., What Is Your Diagnosis? Osteochondrotic lesions. J Am Vet Med Assoc. 2016 Jan 1;248(1):55-7. doi: 10.2460/javma.248.1.55. PMID: 26684090; hereafter “Wong”; cited in previous action.
37 Karsy et al., Bilateral sagittal split mandibular osteotomies for enhanced exposure of the anterior cervical spine in children: technical note. J Neurosurg Pediatr. 2017 Apr;19(4):464-471. doi: 10.3171/2016.11.PEDS16530. Epub 2017 Feb 10. PMID: 28186477; hereafter “Karsy”; cited in previous action.
38An artisan would appreciate that ventral cord compression, also known as anterior cord syndrome, occurs when the anterior (front) portion of the spinal cord is damaged, typically due to blood flow interruption.
39 An artisan would appreciate that Basilar invagination is a condition where the top of the second cervical vertebra (C2) moves upwards and into the base of the skull, potentially compressing the brainstem and spinal cord.
40 An artisan would appreciate that myeloradiculopathy is a condition that affects both the spinal cord (myelopathy) and the spinal nerve roots (radiculopathy). It's often caused by compression or irritation of these structures, commonly due to degenerative changes in the spine
41 An artisan would appreciate that syringohydromyelia is a rare neurological disorder characterized by the formation of fluid-filled cavities (syrinxes) within the spinal cord.
42 An artisan would appreciate that progressive syringomyelia is a neurological disorder characterized by the formation of a fluid-filled cyst (syrinx) within the spinal cord, which can expand over time. This expansion can damage the spinal cord.
43 ABC of Spinal Cord Injury, 4th ed, Edited by David Grundy et al., BMJ Books, (2002), attached as 24 pages including title, TOC, and pages 1-16, also available at https://unitedparalysis.org/files/27.pdf (last visited 5/14/2025); hereafter “Grundy”; cited in previous action.
44 Taylor, The pathology of whiplash: Neck sprain, BC Medical Journal, vol. 44(5), p. 252-256 (June 2002); hereafter “Taylor”; cited in previous action.
45 Koubaa, et al, Total knee arthroplasty in a spinal cord-injured patient: A case report, Annals of Physical and Rehabilitation Medicine, Volume 52, Issues 7–8, 2009, Pages 588-593, ISSN 1877-0657, https://doi.org/10.1016/j.rehab.2009.06.008; cited in previous action.
46 Eriks-Hoogland I et al., Acromioclavicular joint arthritis in persons with spinal cord injury compared to able-bodied persons. Top Spinal Cord Inj Rehabil. 2012 Spring;18(2):128-31. doi: 10.1310/sci1802-128. PMID: 23459223; PMCID: PMC3584756; hereafter “Eriks”; cited in previous action.
47 Vanwanseele et al., Longitudinal analysis of cartilage atrophy in the knees of patients with spinal cord injury. Arthritis Rheum. 2003 Dec;48(12):3377-81. doi: 10.1002/art.11367. PMID: 14673989; hereafter “Vanwanseele”; cited in previous action.
48 Nakajima et al., Rapidly progressive neuropathic arthropathy of the knee in possible association with a huge extruded cervical intervertebral disc herniation. Rheumatol Int. 2010 Apr;30(6):811-5. doi: 10.1007/s00296-009-0999-z. Epub 2009 Jun 18. PMID: 19536541; hereafter “Nakajima”; cited in previous action.
49 Yung et al., Crohn's disease in a patient with acute spinal cord injury: a case report of diagnostic challenges in the rehabilitation setting. Arch Phys Med Rehabil. 2001 Sep;82(9):1274-8. doi: 10.1053/apmr.2001.24921. PMID: 11552203; hereafter “Yung”; cited in previous action.
50 Slot et al., Severe thrombotic complications in a postpartum patient with active Crohn's disease resulting in ischemic spinal cord injury. Dig Dis Sci. 1995 Jun;40(6):1395-9. doi: 10.1007/BF02065558. PMID: 7781467; hereafter “Slot”; cited in previous action.
51 Freitag et al., The effect of autologous adipose derived mesenchymal stem cell therapy in the treatment of a large osteochondral defect of the knee following unsuccessful surgical intervention of osteochondritis dissecans - a case study. BMC Musculoskelet Disord. 2017 Jul 14;18(1):298. doi: 10.1186/s12891-017-1658-2. PMID: 28705162; PMCID: PMC5513163; hereafter “Freitag”; cited in previous action.
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