DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This is a Track One application.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 11/21/25 has been entered.
Priority
The instant application, filed 01/10/2025 is a Continuation of 17294079 , filed 05/14/2021 and having 1 RCE-type filing therein
17294079 is a National Stage entry of PCT/IB2019/059889, International Filing Date: 11/18/2019
claims foreign priority to PCT/IB2018/059100, filed 11/19/2018.
Information Disclosure Statement
The Examiner has considered the reference(s) provided in the 11/21/25 Information Disclosure Statement, and provides a signed and dated copy of such herewith.
Claim Status
Claims 1, 2 and 4-9 are pending and under examination.
Claims 1, 2 and 4-9 are rejected.
Specification Objections
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed.
The disclosure is objected to because of the following informalities: The first full sentence on page 3 lacks word(s) to give the sentence a clear meaning – at least one word appears lacking between “disclose” and “of”, or the “nor” should be deleted, and it appears “his” is a typographical error of “this” or “its”. Any amendment must be properly supported.
Appropriate correction is required.
Claim Rejections - 35 USC § 102/103
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
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.
Claim(s) 1, 2, 5 and 9 are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over U.S. Patent No. 9592272 (‘272), as evidenced by Scanzell and Goldring, Bone 51 (2012) 249–257 (SG, previously provided).
Claim 1 is directed to a method for improving synovial membrane health in an osteoarthritis patient, comprising administering to said patient Glucagon Like Peptide-1 (GLP-1) or GLP-1 analogue, or a composition comprising said GLP-1 or GLP-1 analogue, wherein the GLP-1 or GLP-1 analogue or the composition is administered intra-articularly.
Claim 2 is directed to the method according to claim 1, wherein the method is for reducing synovitis.
Claim 4 is directed to the method according to claim 1, wherein the GLP-1 analogue is selected from the group consisting of exenatide, liraglutide, lixisenatide, albiglutide, dulaglutide, and semaglutide.
Claim 5 is directed to the method according to claim 1, wherein GLP-1 analogue is liraglutide.
Claim 9 is directed to a method for improving synovial membrane health in an osteoarthritis patient having synovial membrane inflammation, comprising administering to said patient Glucagon Like Peptide-1 (GLP-1) or GLP-1 analogue, or a composition comprising said GLP-1 or GLP-1 analogue, wherein the GLP-1 or GLP-1 analogue or the composition is administered intra-articularly.
Because “synovitis” is reasonably understood to mean inflammation of the synovial membrane, essentially claim 9 is ‘met’ when the limitations of claims 1 and 2 are met, because claim 2’s reducing synovitis would be one way to achieve claim 9’s preamble’s intended result of improving synovial membrane health in an osteoarthritis patient having synovial membrane inflammation.
When interpreting whether to give weight to the stated-in-preamble “for improving synovial membrane health in an osteoarthritis patient” (of both claims 1 and 9), this for thoroughness of prosecution, per MPEP 2111.04, this is claim language that does not limit a claim to a particular structure, and is not given weight when it simply expresses the intended result of a process step positively recited.
Related to this, MPEP 2112.02 states that “[w]hen the claim recites using an old composition or structure and the "use" is directed to a result or property of that composition or structure, then the claim is anticipated. In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978).” This is the case here: the same compound or composition that the ‘271 administered, including liraglutide, by the same intra-articular administering method that is found in instant claim 1, would necessarily and inherently provide the instantly claimed result of improving synovial membrane health in an osteoarthritis patient, these patients also the target population of the ‘272. This use or result that applicant considers newly discovered is inherent. The prior art ‘272 reference that teaches administering the same compound the same way to the same tissue area of the same target population, osteoarthritis patients, anticipates the instantly claimed same administering of the same compound to the same tissue area of the same target population – this because the newly discovered and claimed result is a result or property of the same compound that is being administered, in the ‘272 also intra-articularly. This is not a case where a new method addresses a different tissue or different underlying mechanisms, such as promoting hair growth by administering the same compound that had been previously used to treat a heart disease.
The ‘272 teaches, and claims in claim 1, a method of treating osteoarthritis comprising administering intra-articularly a therapeutically effective dose of a peptide selected from the group consisting of a glucagon-like peptide 1 (GLP-1), a gastric inhibitory peptide (GIP) and analogues thereof resistant to dipeptidyl peptidase IV (DPP-IV) to a subject having osteoarthritis, wherein the therapeutically effective dose of the peptide or the analogue thereof inhibits or slows down the arthritic cartilage destruction. Claims 6-8 progressively narrow the selection of peptide, with claim 8 stating that the peptide is selected from the group consisting of exenatide and liraglutide.
Additionally, the ‘272 specification para 7 teaches that “The imbalance between the anabolic and catabolic mechanisms essentially results in an increase in the synthesis of metalloproteases (MMPs) (Blanc et al., 1999), a decrease in the synthesis of TIMPs (tissue inhibitors of metalloproteinases, the physiological inhibitors of MMPs) and an inhibition of matrix constituent synthesis by chondrocytes. This imbalance is accentuated by an accelerated chondrocyte apoptosis phenomenon (Hashimoto et al., 1998) and by chondrocyte activation via various mediators released by the synovial tissue (Sellam and Berenbaum, 2010). The pro-inflammatory cytokine IL-1β synthesized by chondrocytes and synoviocytes has a major role in this arthrotic destruction process. It induces not only an increase in MMP production by chondrocytes, but also a reduction of the anabolic capacities and the apoptosis of these cells (Goldring et al., 2008). Furthermore, the subchondral bone also participates in matrix-degrading phenomena, in particular by means of the secretion of proteolytic enzymes by osteoblasts (Sanchez et al., 2012).” The ‘272 teaches that MPP-3, MMP-9 and MMP-13 are particularly involved in degradation, and can be inhibited by incretin hormones GLP-1 (glucagon-like peptide 1) and GIP (gastric inhibitory peptide or glucose-dependent insulinotropic polypeptide), see paras 14, Figs. 1 and 2 and their descriptions. The ’272 experiments in Examples also teaches that the addition of GLP-1 (7-36) amide, GIP or GLP-1 (7-37) inhibits the overexpression of the prodegradative enzymes MMP-3, MMP-9 and/or MMP-13 observed in the chondrocytes in response to an IL-1β treatment (FIG. 1), and the addition of GLP-1 (7-36) amide, GLP-1 (7-37) or GIP inhibits the overexpression of the prodegradative enzymes MMP-3 and MMP-13 observed in the osteoblasts in response to an IL-1β treatment (FIGS. 2A, B and C). The addition of GLP-1 (7-36) amide also inhibits the overexpression of MMP-9 (FIG. 2D).
As evidenced by SG, synovitis plays a role in OA pathogenesis, Title, Abstract, the latter stating in part, “The histological changes observed in the SM [synovium] in OA generally include features indicative of an inflammatory “synovitis”; specifically they encompass a range of abnormalities, such as synovial lining hyperplasia, infiltration of macrophages and lymphocytes, neoangiogenesis and fibrosis.”
SG also evidences “In addition to the development of synovitis, TLR activation has implications for cartilage degeneration in OA. Enzymes involved in articular matrix turnover and degradation include matrix metalloproteinases (MMPs) and aggrecanases, which may be produced by both chondrocytes and synovial cell populations. In cartilage, TLR-2 and -4 are upregulated specifically in lesional areas in patients with OA [52]. A more recent study demonstrated that TLR2 and TLR4 signals are important in mediating catabolic responses and in increasing MMP-3 and MMP-13 production in murine cartilage explants [63], page 253.
Because the ‘272 teaches and claims administering the same peptides to the same body part directly, intra-articularly, such that the administered peptide, including liraglutide, would contact synovial membrane and cells therein, and by such contact via the same administering method as instantly claimed, so would have the same effect on synovial health as instantly claimed, the ‘272 anticipates claims 1-5 and 9. Please see MPEP 2112, particularly parts I, II, and III. As to part IV, the technical reasoning to “reasonably support the determination that the allegedly inherent characteristic necessarily flows from the teachings of the applied prior art” is as follows. The ‘272 administers the same compound class and particular compounds directly, intra-articularly, to the same body part, a joint that comprises a synovium, to a subject having OA to treat OA, and demonstrates that members of the peptide class claimed by the ‘272 (this including instantly claimed peptides) inhibit specific MMPs that are taught, and as evidenced by SG, to be the same MMPs reasonably involved in the development of synovitis in the affected joints of OA subjects. The examiner restates by itself a sentence from the ‘272 citation above: “The pro-inflammatory cytokine IL-1β synthesized by chondrocytes and synoviocytes has a major role in this arthrotic destruction process.” Based on the entire quoted passage above, there is a reasonable technical basis, and also a very reasonable expectation, that the same agents administered in the ‘272 would have the same ameliorative effect on both chondrocytes and synoviocytes when countering the pro-inflammatory cytokine IL-1β and related degradative pathways common to chondrocytes and synoviocytes, and have an anti-inflammatory effect on both cell types and associated tissues. All of this establishes a reasonable basis to support that the same chemical administered to the same body part provides the claimed result, and to support the rejection based on inherency.
Regarding MPEP 2112.02 II, there it is taught, “…when the claim recites using an old composition or structure and the "use" is directed to a result or property of that composition or structure, then the claim is anticipated.” This further supports the instant anticipation rejection because what applicant presents in the instant application is, in the examiner’s view, merely using an old composition (comprising an agent, here a peptide) for a newly identified property or result of the previously administered peptide.
Accordingly, claims 1-5 and 9 are anticipated.
The level of skill in the art is high.
As an alternative to anticipation under this section, it would have been obvious to administer a Glucagon Like Peptide-1 (GLP-1) or GLP-1 analogue, or a composition comprising said GLP-1 or GLP-1 analogue, including a peptide such as liraglutide, these taught by the ‘272 to treat OA, to also improve synovial health, because as evidenced by SG, “The histological changes observed in the SM [synovium] in OA generally include features indicative of an inflammatory “synovitis”; specifically they encompass a range of abnormalities, such as synovial lining hyperplasia, infiltration of macrophages and lymphocytes, neoangiogenesis and fibrosis,” and the underlying mechanism for such changes reasonably involves MMP generation, which as taught and claimed by the ‘272 is inhibited by GLP-1 and its analogs. This presents a reasonable underlying mechanism to improve synovial membrane health in an OA patient. There would have been a reasonable expectation of success given the results in the ‘272 with regard to inhibiting specific MMP generation.
Therefore in the alternative claims 1-5 and 9 would have been obvious.
Response to Arguments and Affidavit
Applicant's arguments filed 11/21/25, and the Affidavit also of record 11/21/25 have been fully considered but they are not persuasive.
Applicant, page 5, states:
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As stated this is confusing by stating “synovial membrane health would not necessarily occur in all OA patients. Perhaps applicant meant that the need to improve synovial membrane health, or synovial inflammation, would not necessarily occur or be present when practicing the prior art method on some OA patients. That however is not the point of the inherency-based anticipation rejection. The point is that when administering the same compound to the same location of an OA patient, the same compound has a property that provides the instantly claimed result, here for claims 1 and 9 for improving synovial membrane health in an OA patient, and in claim 2 for reducing synovitis. If in some OA patients there is a completely healthy synovial membrane absolutely not in need of improvement (which per below is doubtful), this does not diminish the fact that when the ‘272 claimed administering would be done to OA patients who do have an impaired synovial membrane that could be improved, the administering of the compounds by the ‘272 administering very reasonably would favorably affect those synovial membranes to afford improvement based on the applied teachings of the references including the evidentiary reference, including the underlying common technical bases regarding, at least, inflammation.
Further to applicant’s explanation that “synovial membrane inflammation is not present in all patients”, Hugle and Geurts, Rheumatology 2017;56:1461-1471 (HG), page 1461 teaches, ” Instead of being a pure cartilage disorder, OA is now considered as a whole-joint disease that affects various anatomical structures in and around the joint capsule. These include muscle, ligaments, entheses, synovial tissue and the subchondral bone [3]. Inflammatory symptoms such as joint effusion or articular stiffness are common in OA and synovial inflammation detected by sonography occurs in more than half of the patients with early OA [4]. The advent of MRI has underlined the pathogenic role of both synovitis and the subchondral bone tissue in OA. A substantial volume of synovitis in suprapatellar, infrapatellar and intercondylar regions considerably increases the risk for incident radiographic knee OA [5]. A nested case-control longitudinal MRI study identified the presence of effusion and Hoffa synovitis at baseline as major risk factors for development of radiographic OA [6].” Please note that “at baseline” suggests involvement of synovitis very early in development of radiographic OA. Given these statements and the difference between sonography (ultrasound) and MRI, applicants explanation in part may have been based on earlier studies that used sonography.
Also from HG, page 1463, and further regarding the suggested influence of synovitis on OA development:
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As concluded by HG, “Rather than being separate and independent joint tissues, the articular cartilage, subchondral bone and bone marrow compartments as well as the synovium closely interact at mechanical and biological levels in health and OA (Fig. 6). Increased remodelling of each of these compartments has been demonstrated during the onset and progression of OA. … Synovitis can induce cartilage damage by fibrin deposition, pannus formation or via inflammatory cytokine expression and triggers osteopenia, notably in early OA stages.”
From the above excerpts and the entire HG article, given the clear and substantial relationship between synovium and OA development and progression, and the common inflammatory mechanisms that reasonably would be ameliorated by the same GLP-1 receptor analogs, and responding to applicant Remarks as best as reasonably understood given the statement “synovial membrane health would not necessarily occur or be present in the prior art” and the reference to synovial membrane inflammation preceding this, the examiner maintains that the inherent characteristic of improving synovial membrane health, such as by reducing synovitis, necessarily flows from the teachings of the ‘272.
Regarding statements on page 5 about data regarding fibrosis and a healthy synovial membrane, the reduction or elimination of fibrosis in a synovial membrane does not impact the analysis above for the claims as set forth. This appears to be an another inherent result of the ‘272 administered compound liraglutide that is not specifically claimed. Also, Blom et al., OsteoArthritis and Cartilage (2004) 12, 627e635, provides data that indicates that fibrosis of the synovium is related to synovial macrophages, which also contributes to synovial inflammation in OA patients.
Based on HG’s teachings and also those of Felson, previously presented, and Orlowsky and Kraus, Rheumatol 2015;42:363–71 (OK), copy provided, the examiner has reconsidered a previous statement that emphasized the presence of synovial inflammation in later stages of OA, this because based on these teachings there is a basis that synovitis and/or other synovial disorders are present throughout the progression of OA (and even before radiographic OA) for a substantial percentage of OA patients. And where no evidence of synovial inflammation or other disturbance thereof has been reported, this per the teachings may be due to the diagnostic method chosen.
These points are stated in part to counter applicant’s continued assertions directed toward synovial membrane inflammation not being present in all OA patients, this apparently an attempt to counter the requirements for the 35 USC 102 inherency anticipation rejection.
The examiner has previously raised the distinction between the instant facts and those of Ex Parte Levy, cited in MPEP 2112 IV for the “necessarily” statement. Given the reappraisal based on the entirety of the references’ teachings, that the synovium and cells therein are involved throughout the progression of OA, the following is stated when distinguishing from the facts in Ex Parte Levy.
The ‘272 treats osteoarthritis with the same group of compounds that applicant claims to treat the synovial membrane/tissue/cells. It necessarily follows that when any stage of osteoarthritis is treated with the same compounds as claimed per the ‘272 claim methods, then the ‘272 administering the same compounds as claimed to such subject would have the same effect as claimed. This is NOT the case where, as in Ex Parte Levy, the underlined ‘necessarily’ related to a particular issue as to whether, in a prior art reference directed to a catheter, the process of making that catheter resulted in the claimed biaxially oriented, flexible polymeric balloon having particular properties. See previously provided Ex Parte Levy, 17 USPQ2d 1461. In that case it was held after weighing the evidence that the prior art did not produce what was claimed; this was based on evidence that pertained to whether the prior art process would result in the claimed product. It appears inappropriate to the examiner to transpose that reasoning and evidence that resulted in the “necessarily” statement to a progressive disorder like osteoarthritis where during most or all stages of OA, a major percentage of patients, based on a number of assessments using advanced MRI diagnosis, reasonably possess the disturbed synovium and cells thereof whose conditions, including macrophages releasing cytokines resulting in inflammation as well as other phenomenon contributing to or resulting from inflammation (such as fibrosis, see Blom, above), and that these OA patients most reasonably from a technical standpoint would be improved via some of the same mechanisms that the ‘272 administered compounds improve for nearby joint tissues and cells.
As such, the technical reasoning supports that the inherent characteristic necessarily flows from the prior art teachings even if the diagnostic results of a percentage of OA patients in various studies do not indicate identifiable perturbance to the synovium.
As previously stated, at the time of filing the instant application it was well-known in the art that synovial inflammation is associated with osteoarthritis. See for example Felson et al., Osteoarthritis and Cartilage, 24 (2016) 458-464, previously provided, which was able to utilize non-contrast MRI on a large number of control and OA knees, and after carrying out multivariable regression analyses adjusting for age, sex, BMI, alignment and cartilage and meniscal damage, stated that synovitis was associated with incident OA, Abstract, and on page 463 concluded, “In summary, synovitis is an independent cause of incident knee OA, especially synovitis of sufficient severity to increase synovial thickness or increase signal intensity in affected areas of the knee.”
Applicants arguments against a reasonable expectation of success also are not persuasive given the relationships taught in HG, above, also quoted below. The examiner also notes that reasonable expectation of success relates to the 35 USC 103 rejection, not to the 35 USC 102 rejection.
As to “The claims are directed to the treatment of a subpopulation of patients that was not disclosed in the patent ‘272,” the examiner is confounded by this statement because the instant claims as presented to not identify a particular subpopulation, and nowhere in the application as filed has the examiner been able to identify disclosure of a particular subpopulation. Clarification may be in order.
At the top of page 6 applicant states,
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This has largely been addressed above. The inherency is based on the same compound providing the claimed result based on its previously unappreciated property, from MPEP 2112 I, “"[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977).”
As to the arguments about a separate population, this has not been specifically identified, and even if one were, the basis for the inherency anticipation rejection is the underlying similar mechanisms and interrelatedness of OA development and progression and synovial disturbances, not that every OA patient at every stage is clearly identified by a particular diagnostic technique as having a detectable synovial histological or immunological or enzymatic perturbance at the time evaluated.
The following responds to the Affidavit provided 11/21/25, the statements, arguments, and evidence found, after weighing all relevant evidence, unpersuasive by the examiner.
Regarding para 6, the examiner does not dispute that sprifermin, a fibroblast growth factor-18 analog, would favorably affect cartilage but not synovium, nor that any particular therapeutic agent “can be “disease-modifying” for cartilage without affecting synovial membrane.”
Nor does the examiner dispute differing effects of corticosteroids, para 7, nor para 8, that “Given the data with sprifermin, the skilled artisan in the art would have understood that protecting cartilage did not automatically imply protecting synovial inflammation.”
However, as to the requirement for ‘further data’ to have a reasonable expectation of success, in the sentence following the last excerpted sentence, the examiner respectfully disagrees. This is because there was a reasonable underlying technical basis for the same compounds as administered in the ‘272 patent to have a beneficial effect on synovium, this explained above and supported by a number of references. Further data is not required to establish a reasonable expectation of success.
Regarding (iii) of para 9, the failures of sprifermin and corticosteroids would not necessarily impact the understanding of one of ordinary skill in the art when different mechanisms were at issue for different therapeutic compounds.
Based on the teachings of the references, including the known factors and mechanisms related to inflammation and resultant damage and the known effects of GLP-1 RAs, the examiner maintains that there was a reasonable expectation of success that the known GLP-1 RAs would positively impact inflamed synovium to provide improved synovial membrane health.
Finally, the examiner notes that various studies may have underestimated the relationship between the presence of synovitis and OA development, progression and stage based on difference imaging, such as MRI vs ultrasound, and also scoring or grading criteria. Among statements from SG,
Page 251:
There are multiple MRI-based “whole-organ” grading systems that score specific
anatomic features in the joint, including semi-quantitative characterization
of the magnitude of synovial change [45,78]. The most
commonly used methods define synovitis according to the extent of
synovial cavity distension or total synovial volume. These systems
have been mostly applied to non-contrast imaging, but more recent
studies have incorporated the use of contrast-enhanced MR imaging
techniques to distinguish synovial thickening from effusion [31,39].
For example, in a recent study by Roemer et al. [85], the authors used
both contrast-enhanced and non-enhanced images to examine a
group of subjects with knee OA, and noted that synovitis was present
in over 95% of the knee joints with an effusion, but also in 70% of
knee joints in patients without an effusion. These findings suggest
that in many cases synovial thickening may be independent of effusion,
and may perhaps be a more reliable indicator of intraarticular
pathology than the presence of joint effusion.
Page 253
Despite differences in methods for detecting and defining synovitis,
there is general agreement that the prevalence and severity of synovitis
increases with advancing stage of OA defined by extent of
cartilage lesions and radiographic changes. We showed that suprapatellar
synovial inflammatory infiltrates were more prevalent (75% vs.
43%) and of higher histologic grade in patients with advanced knee
OA than in a cohort of patients undergoing arthroscopic meniscectomy
with no radiographic OA [87]. Further support for a relationship between
stage of knee OA and synovial changes is provided by the recent
publication of Krasnokutsky et al. [55]. The authors assessed synovitis
using 3 T contrast-enhanced MRI in a group of 58 patients with knee
OA. Fixed-flexion radiographs were used to determine joint-space
width, narrowing and disease stage by the Kellgren–Lawrence (KL)
score. They showed that infrapatellar synovitis was present in 38% of
patients with KL stage 2–3 disease, compared with 83% of patients
with KL stage 4 disease. Measurements of joint space narrowing and
width were consistent with their findings with KL score. Therefore,
although synovitis is present early in disease and even at preradiographic
stages, the proportion of patients with synovitis appears
to increase with advancing structural deterioration. Whether
any impact of synovitis on structural disease or symptoms will be
the same at all stages remains to be determined.
Claim Rejections - 35 USC § 103
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.
Claim(s) 6 is rejected under 35 U.S.C. 103 as being unpatentable over the ‘272 as evidenced by SG, as applied to claim 1 above.
Claim 6 depends from claim 4 and requires the concentration of the GLP-1 analogues listed in claim 4 “is about 0.1 nM to 625 µM”.
The level of skill in the art is high.
MPEP 2144.05 II A states in part, “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical.” Here, applicant claims a range extending over 6 orders of magnitude as to concentration and does not set forth a unit dosage, frequency or other dosing parameters. There is no evidence of criticality across this range, particularly when this is only the concentration of agent, with no mention of dosage. Given the level of skill in the art, one of ordinary skill in the art would reasonably understand the need to develop appropriate dosing to treat OA, following the claims of the ‘272, and such development would reasonably include more than just a concentration, also unit doses for particular patients based on their conditions, and through repeated efforts would have a reasonable expectation of success given the known properties of GLP-1 analogues including liraglutide. Additionally, the concentration of liraglutide would have been limited by its solubility, and fallen within this very broad claimed concentration range.
Accordingly, claim 6’s range would have been obvious, and claim 6 is rejected under this section.
Claim(s) 7 and 8 are rejected under 35 U.S.C. 103 as being unpatentable over the ‘272 as evidenced by SG, as applied to claim 1 above, and further in view of US 8716204, inventors Stark et al., issued 5/6/14 (Stark).
Claim 1 is rejected based on the ‘272 as evidenced by SG as set forth above.
Claim 7 is directed to the method according to claim 1, wherein the composition “comprises at least 5% of more weight of a pharmaceutically acceptable formulation vehicle to be used in combination.” This is interpreted to require at least five percent of the formulation vehicle on a weight of formulation vehicle to total weight of composition basis.
Claim 8 depends from claim 7 and states that the pharmaceutically acceptable formulation vehicle is albumin. Considering the interpretation of claim 7 above, claim 8 requires at least five percent of albumin on a weight of albumin to total weight of composition basis.
The level of skill in the art is high.
The ‘272 teaches that some forms of GLP-1 analogues are covalently bonded to albumin, para 18, however does not teach adding a pharmaceutically acceptable formulation vehicle at 5% or more, nor adding albumin as a pharmaceutically acceptable formulation vehicle at 5% or more, as claimed in claims 7 and 8.
Stark teaches :
(4) Synovial fluid is a biological fluid that is found in the synovial cavity of the joints (e.g., knee, hip, shoulder) of the human body between the cartilage and synovium of facing articulating surfaces. Synovial fluid provides nourishment to the cartilage and also serves as a lubricant for the joints. The cells of the cartilage and synovium secrete fluid and the fluid lubricates and reduces friction between the articulating surfaces.
(5) Human synovial fluid is comprised of approximately 85% water. It is derived from the dialysate of blood plasma, which itself is made up of water, dissolved proteins, glucose, clotting factors, mineral ions, hormones, etc. The proteins, albumin and globulins, are present in synovial fluid and are believed to play an important role in the lubrication of the joint area. Other proteins are also found in human synovial fluid, including the glycoproteins such as AGP, A1AT and lubricin.
Stark’s synthetic fluid compositions comprise “about 6-18 mg/ml of albumin, about 4-12 mg/ml of gamma-globulin, about 0.04-0.1 mg/ml of phospholipid, and about 2-4 mg/ml of hyaluronic acid in a phosphate buffered saline solution. The composition has a pH of about 7.0-7.4 mg/ml and an osmolality of about 280-320 mOsm/kg,” para 17.
One of ordinary skill in the art, recognizing that per Stark albumin present in the synovial fluid and believed to play an important role in the lubrication of the joint area, would have been motivated to add albumin to a therapeutic composition that comprises a GLP-1 analogue such a liraglutide, taught by the ‘272 to treat OA (and as noted above OA affects synovial membrane as evidenced by SG). This is based on the motivation of one or ordinary skill in the art to improve the lubrication of the joint area of a joint already in a pathological state given the presence of OA. The motivation is to improve a therapeutic composition’s effect by adding an additional agent believed to function to lubricate the joint area, where such lubrication would be expected to provide a modicum of relief from OA, with regard both to pain and to structural improvement by adding more of a lubricating protein. There would have been a reasonable expectation of success given the teachings in Stark that albumin is present in the synovial fluid and is believed to function to lubricate the joint area.
Regarding the concentration limitation in claim 7, MPEP 2144.05 II A states in part, “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical.” Here, in claim 7 applicant claims an open-ended “at least” five percent pharmaceutically acceptable formulation vehicle (specifically albumin in claim 8) concentration. There is no evidence of criticality across this range, particularly when this is only the concentration in the composition, and no mention of dosage regimens. Given the level of skill in the art, one of ordinary skill in the art would reasonably understand the need to develop appropriate dosing to treat OA, following the claims of the ‘272, and Stark, and would also understand that when administering a small volume dosage into a joint, such as by intra-articular injection, a higher concentration of albumin in the small volume dosage would diffuse and become diluted/less concentrated in the joint volume of synovial fluid. Such insight would reasonably lead to more than just an open-ended range, including for particular patients based on their conditions, and through repeated efforts would have a reasonable expectation of success given the known properties of GLP-1 analogues including liraglutide, and of albumin. That is, routine optimization would ensue.
Accordingly, at least based on the statement from the MPEP, given the open-ended range and lack of any evidence of criticality and dosing to a particular joint having OA, claim 7’s open-ended range would have been obvious, and additionally based on the teachings of Stark claims 7 and 8 are rejected under this section.
Response to Arguments
Applicant's arguments filed 11/21/25 have been fully considered but they are not persuasive.
The responses to similar arguments set forth above are incorporated herein.
In particular, see above regarding arguments related to fibrosis.
Also see above regarding responses to the Affidavit.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 2, and 4-6 and 9 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6, 7 and 8 of U.S. Patent No. 9592272 (“reference patent”).
Claim 1 is directed to a method for improving synovial membrane health in an osteoarthritis patient, comprising administering to said patient Glucagon Like Peptide-1 (GLP-1) or GLP-1 analogue, or a composition comprising said GLP-1 or GLP-1 analogue wherein the GLP-1 or GLP-1 analogue or the composition is administered intra-articularly.
Claim 2 is directed to the method according to claim 1, wherein the method is for reducing synovitis.
Claim 4 is directed to the method according to claim 1, wherein the GLP-1 analogue is selected from the group consisting of exenatide, liraglutide, lixisenatide, albiglutide, dulaglutide, and semaglutide.
Claim 5 is directed to the method according to claim 1, wherein GLP-1 analogue is liraglutide.
Claim 9 is directed to a method for improving synovial membrane health in an osteoarthritis patient having synovial membrane inflammation, comprising administering to said patient Glucagon Like Peptide-1 (GLP-1) or GLP-1 analogue, or a composition comprising said GLP-1 or GLP-1 analogue wherein the GLP-1 or GLP-1 analogue or the composition is administered intra-articularly.
Because “synovitis” is reasonably understood to mean inflammation of the synovial membrane, essentially claim 9 is ‘met’ when the limitations of claims 1 and 2 are met, because the latter would be one way to achieve the preamble’s intended result of improving synovial membrane health in an osteoarthritis patient having synovial membrane inflammation.
When interpreting whether to give weight to the stated-in-preamble “for improving synovial membrane health in an osteoarthritis patient,” this for thoroughness of prosecution, per MPEP 2111.04, this is claim language that does not limit a claim to a particular structure, and is not given weight when it simply expresses the intended result of a process step positively recited, so the rejection focuses directly on the teachings and claims of the Reference patent that administers liraglutide (see paragraph immediately below referencing MPEP 2112.02). Further, per MPEP 2111.04, because the wherein clause language of instant claims 2’s for reducing synovitis, and they simply express the intended result of a process step positively recited, the rejection is focused directly on the administering of the compound(s) as claimed.
MPEP 2112.02 states that “[w]hen the claim recites using an old composition or structure and the "use" is directed to a result or property of that composition or structure, then the claim is anticipated. In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978).” This is the case here: the Reference patent’s administering of the same compound or composition is now directed to a result of the activities of the administered GLP-1 analogue, including liraglutide, that may result in improving synovial membrane health in an osteoarthritis patient, instantly claimed, however, this use or result that applicant considers newly discovered is inherent. This is not a case where a new method addresses a different tissue or different underlying mechanisms, such as promoting hair growth by administering the same compound that had been previously used to treat a heart disease.
Although the claims at issue are not identical, they are not patentably distinct from each other because the therapeutically effective dose of GLP-1 administered in claim 1 of the Reference patent administers the same liraglutide encompassed by instant claim 5’s method.
The Reference patent claim 1 claims a method of treating osteoarthritis comprising administering intra-articularly a therapeutically effective dose of a peptide selected from the group consisting of a glucagon-like peptide 1 (GLP-1), a gastric inhibitory peptide (GIP) and analogues thereof resistant to dipeptidyl peptidase IV (DPP-IV) to a subject having osteoarthritis, wherein the therapeutically effective dose of the peptide or the analogue thereof inhibits or slows down the arthritic cartilage destruction. Reference patent claims 6-8 progressively narrow the selection of peptide, with Reference patent claim 8 stating that the peptide is selected from the group consisting of exenatide and liraglutide.
Because the Reference patent claims administering the same peptides to the same body part directly, intra-articularly, such that the administered peptide, including liraglutide, would contact synovial membrane and cells therein, claims 1, 2, 4 and 5 are rejected under this section. Please see MPEP 2112, particularly parts I, II, and III. As to part IV, the technical reasoning to reasonably support the determination that the allegedly inherent characteristic necessarily flows from the teachings of the applied prior art is as follows. The Reference patent claims administer the same compound class and particular compounds directly, intra-articularly, to the same body part, a joint that comprises a synovium, to treat OA, and would have the same effect as the same compound instantly claimed to be administered to treat the same body part.
Regarding MPEP 2112.02 II, there it is taught, “…when the claim recites using an old composition or structure and the "use" is directed to a result or property of that composition or structure, then the claim is anticipated.” This further supports the instant rejection because what applicant presents in the instant application is, in the examiner’s view, merely using an old composition (comprising an agent, here a peptide) for a newly identified property of the same class and same specific peptides administered in Reference patent claims 1 and 6-8 to treat OA.
Instant claim 6 requires the concentration of the GLP-1 analogues listed in claim 4 “is about 0.1 nM to 625 µM”. This is interpreted for this rejection to mean “is about 0.1 nM to 625 µM.”
The level of skill in the art is high.
MPEP 2144.05 II A states in part, “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical.” Here, applicant claims a range extending over 6 orders of magnitude as to concentration and does not set forth a unit dosage, frequency or other dosing parameters. There is no evidence of criticality across this range, particularly when this is only the concentration of agent, with no mention of dosage. Given the level of skill in the art, one of ordinary skill in the art would reasonably understand the need to develop appropriate dosing to treat OA, following the claims of the ‘272, and such development would reasonably include more than just a concentration, also unit doses for particular patients based on their conditions, and through repeated efforts would have a reasonable expectation of success given the known properties of GLP-1 analogues including liraglutide. Additionally, the concentration of liraglutide would have been limited by its solubility, and fallen within this very broad claimed concentration range.
Accordingly, claim 6’s range would have been obvious, and claim 6 is rejected under this section.
Claim(s) 7 and 8 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6, 7 and 8 of U.S. Patent No. 9592272 (“reference patent”), as applied to claim 1 above, and further in view of US 8716204, inventors Stark et al., issued 5/6/14 (Stark).
Instant claim 1 is rejected based on the Reference patent claims 1 and 6-8 as set forth above.
Instant claim 7 is directed to the method according to claim 1, wherein the composition “comprises at least 5% of more weight of a pharmaceutically acceptable formulation vehicle to be used in combination.” This is interpreted to require at least five percent of the formulation vehicle on a weight of formulation vehicle to total weight of composition basis.
Instant claim 8 depends from instant claim 7 and states that the pharmaceutically acceptable formulation vehicle is albumin. Considering the interpretation of instant claim 7 above, instant claim 8 requires at least five percent of albumin on a weight of albumin to total weight of composition basis.
The level of skill in the art is high.
The Reference patent does not claim adding a pharmaceutically acceptable formulation vehicle at 5% or more, nor adding albumin as a pharmaceutically acceptable formulation vehicle at 5% or more, as claimed in instant claims 7 and 8.
However Stark teaches :
(4) Synovial fluid is a biological fluid that is found in the synovial cavity of the joints (e.g., knee, hip, shoulder) of the human body between the cartilage and synovium of facing articulating surfaces. Synovial fluid provides nourishment to the cartilage and also serves as a lubricant for the joints. The cells of the cartilage and synovium secrete fluid and the fluid lubricates and reduces friction between the articulating surfaces.
(5) Human synovial fluid is comprised of approximately 85% water. It is derived from the dialysate of blood plasma, which itself is made up of water, dissolved proteins, glucose, clotting factors, mineral ions, hormones, etc. The proteins, albumin and globulins, are present in synovial fluid and are believed to play an important role in the lubrication of the joint area. Other proteins are also found in human synovial fluid, including the glycoproteins such as AGP, A1AT and lubricin.
Stark’s synthetic fluid compositions comprise “about 6-18 mg/ml of albumin, about 4-12 mg/ml of gamma-globulin, about 0.04-0.1 mg/ml of phospholipid, and about 2-4 mg/ml of hyaluronic acid in a phosphate buffered saline solution. The composition has a pH of about 7.0-7.4 mg/ml and an osmolality of about 280-320 mOsm/kg,” para 17.
One of ordinary skill in the art, recognizing that per Stark albumin present in the synovial fluid and is believed to play an important role in the lubrication of the joint area, would have been motivated to add albumin to a therapeutic composition that comprises a GLP-1 analogue such a liraglutide, claimed per Reference patent claims 1 and 6-8 to treat OA. This is based on the motivation of one or ordinary skill in the art to improve the lubrication of the joint area of a joint already in a pathological state given the presence of OA. The motivation is to improve a therapeutic composition’s effect by adding an additional agent believed to function to lubricate the joint area, where such lubrication would be expected to provide a modicum of relief from OA, with regard both to pain and to structural improvement by adding more of a lubricating protein. There would have been a reasonable expectation of success given the teachings in Stark that albumin is present in the synovial fluid and is believed to function to lubricate the joint area.
Regarding the concentration limitation in claim 7, MPEP 2144.05 II A states in part, “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical.” Here, in claim 7 applicant claims an open-ended “at least” five percent pharmaceutically acceptable formulation vehicle (specifically albumin in claim 8) concentration. There is no evidence of criticality across this range, particularly when this is only the concentration in the composition, and no mention of dosage regimens. Given the level of skill in the art, one of ordinary skill in the art would reasonably understand the need to develop appropriate dosing to treat OA, following the claims of the Reference patent, and Stark, and would also understand that when administering a small volume dosage into a joint, such as by intra-articular injection, a higher concentration of albumin in the small volume dosage would diffuse and become diluted/less concentrated in the joint volume of synovial fluid. Such insight would reasonably lead to more than just an open-ended range, including for particular patients based on their conditions, and through repeated efforts would have a reasonable expectation of success given the known properties of GLP-1 analogues including liraglutide, and of albumin.
Accordingly, claim 7’s open-ended range would have been obvious, and based on that and on the teachings of Stark combined with the Reference patent claims, claims 7 and 8 are rejected under this section.
Claims 1, 2 and 4-6 and 9 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 4, 5 and 19 of copending Application No. 18573737 (6 page claim set filed 12/22/23, “reference application” or claims thereof).
Reference application claims 1, 2, 4 and 5 administer liraglutide to treat at least one joint disease in a composition that also includes a buffer and an isotonic agent.
By so administering liraglutide into a joint via intraarticular injection into the joint cavity, the reference application claims 1, 2, 4 and 5 administer the same class of peptides and specific peptides that the instant claims administer, so would have the same result as claimed in the instant claim 1 preamble and claims 2’s and 3’s wherein clauses. See MPEP 2112.02. Further, per MPEP 2111.04, because the wherein clause language of claims 2 and 3 do not limit a claim to a particular structure, and they simply express the intended result of a process step positively recited, the rejection is focused directly on the administering of the compound(s) as claimed.
Based on the above, claims 1-5 and 9 are rejected under this section.
Instant claim 6 is rejected when also considering reference application claim 19, the range of which overlaps with instant claim 18. See MPEP 2144.05 regarding overlapping ranges.
This is a provisional nonstatutory double patenting rejection.
Claim(s) 7 and 8 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 4, 5 and 19 of copending Application No. 18573737 (6 page claim set filed 12/22/23, “reference application” or claims thereof), as applied to claim 1 above, and further in view of US 8716204, inventors Stark et al., issued 5/6/14 (Stark).
Instant claim 1 is rejected based on the Reference application claims 1, 2, 4 and 5 as set forth above.
Instant claim 7 is directed to the method according to claim 1, wherein the composition “comprises at least 5% of more weight of a pharmaceutically acceptable formulation vehicle to be used in combination.” This is interpreted to require at least five percent of the formulation vehicle on a weight of formulation vehicle to total weight of composition basis.
Instant claim 8 depends from instant claim 7 and states that the pharmaceutically acceptable formulation vehicle is albumin. Considering the interpretation of instant claim 7 above, instant claim 8 requires at least five percent of albumin on a weight of albumin to total weight of composition basis.
The level of skill in the art is high.
The Reference application does not claim adding a pharmaceutically acceptable formulation vehicle at 5% or more, nor adding albumin as a pharmaceutically acceptable formulation vehicle at 5% or more, as claimed in instant claims 7 and 8.
However Stark teaches :
(4) Synovial fluid is a biological fluid that is found in the synovial cavity of the joints (e.g., knee, hip, shoulder) of the human body between the cartilage and synovium of facing articulating surfaces. Synovial fluid provides nourishment to the cartilage and also serves as a lubricant for the joints. The cells of the cartilage and synovium secrete fluid and the fluid lubricates and reduces friction between the articulating surfaces.
(5) Human synovial fluid is comprised of approximately 85% water. It is derived from the dialysate of blood plasma, which itself is made up of water, dissolved proteins, glucose, clotting factors, mineral ions, hormones, etc. The proteins, albumin and globulins, are present in synovial fluid and are believed to play an important role in the lubrication of the joint area. Other proteins are also found in human synovial fluid, including the glycoproteins such as AGP, A1AT and lubricin.
Stark’s synthetic fluid compositions comprise “about 6-18 mg/ml of albumin, about 4-12 mg/ml of gamma-globulin, about 0.04-0.1 mg/ml of phospholipid, and about 2-4 mg/ml of hyaluronic acid in a phosphate buffered saline solution. The composition has a pH of about 7.0-7.4 mg/ml and an osmolality of about 280-320 mOsm/kg,” para 17.
One of ordinary skill in the art, recognizing that per Stark albumin present in the synovial fluid and is believed to play an important role in the lubrication of the joint area, would have been motivated to add albumin to a therapeutic composition that comprises a GLP-1 analogue such a liraglutide, claimed per Reference patent claims 1 and 6-8 to treat OA (and as noted above OA affects synovial membrane as evidenced by SG). This is based on the motivation of one or ordinary skill in the art to improve the lubrication of the joint area of a joint already in a pathological state given the presence of OA. The motivation is to improve a therapeutic composition’s effect by adding an additional agent believed to function to lubricate the joint area, where such lubrication would be expected to provide a modicum of relief from OA, with regard both to pain and to structural improvement by adding more of a lubricating protein. There would have been a reasonable expectation of success given the teachings in Stark that albumin is present in the synovial fluid and is believed to function to lubricate the joint area.
Regarding the concentration limitation in claim 7, MPEP 2144.05 II A states in part, “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical.” Here, in claim 7 applicant claims an open-ended “at least” five percent pharmaceutically acceptable formulation vehicle (specifically albumin in claim 8) concentration. There is no evidence of criticality across this range, particularly when this is only the concentration in the composition, and no mention of dosage regimens. Given the level of skill in the art, one of ordinary skill in the art would reasonably understand the need to develop appropriate dosing to treat OA, following the claims of the Reference patent, and Stark, and would also understand that when administering a small volume dosage into a joint, such as by intra-articular injection, a higher concentration of albumin in the small volume dosage would diffuse and become diluted/less concentrated in the joint volume of synovial fluid. Such insight would reasonably lead to more than just an open-ended range, including for particular patients based on their conditions, and through repeated efforts would have a reasonable expectation of success given the known properties of GLP-1 analogues including liraglutide, and of albumin.
Accordingly, claim 7’s open-ended range would have been obvious, and based on that and on the teachings of Stark combined with the Reference patent claims, claims 7 and 8 are rejected under this section.
This is a provisional nonstatutory double patenting rejection.
Claims 1,2 and 4-9 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 15-23 of copending Application No. 17294079 (“reference application” or claims thereof).
Reference application claims 15-17 administer liraglutide to an OA patient “having a cartilage degeneration score of 3.7 or higher”, with a preamble-stated intended purpose “for cartilage regeneration.”
By so administering liraglutide the reference claims would have the same effects as instantly claimed on synovial condition, whether in the preamble of claim 1 or a wherein clause of claims 2 and 3, see MPEP 2112.02. As noted, per MPEP 2111.04, because the wherein clause language of claims 2 and 3 do not limit a claim to a particular structure, and they simply express the intended result of a process step positively recited, the rejection is focused directly on the administering of the compound(s) as claimed.
As set forth above including based on administering the same peptide, instant claims 1-5 and 9 are rejected over reference application claims 15-17 under this section.
Instant claim 6 is rejected when also considering reference application claim 18, the range of which is identical. See also MPEP 2144.05 regarding overlapping ranges.
Instant claims 7 and 8 are rejected over reference application claims 19-23, which considered together make obvious instant claims 7 and 8 as to including albumin in a composition as a pharmaceutically acceptable formulation vehicle at a concentration of 5% (wt/wt) of the formulation.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant's arguments filed 11/21/25 have been fully considered but they are not persuasive.
Applicant argues against the rejections based on arguments against the obviousness based on the ‘272 patent; these are responded to above and incorporated herein. Also, Applicant has requested that the nonstatutory obviousness-type double patenting rejections be held in abeyance. However, this is not persuasive as the MPEP does not provide for holding the rejection in abeyance. The rejections are still deemed proper and stand for the reasons of record.
Conclusion
No claim is allowed.
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/JOSEPH FISCHER/Examiner, Art Unit 1658