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 SECOND NON-FINAL OFFICE ACTION.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 7/21/25 has been entered.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-7, 15-24, and 26, in the reply filed on 8/29/23 is acknowledged.
Applicant’s further species election of liraglutide as the species of GLP-1 analogue, and “no formulation vehicle” for the formulation vehicle, in the reply filed on 8/29/23 is acknowledged.
Claims 8-14, 25, are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 8/29/23.
Claims 5, 6, 19-24, are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 8/29/23.
Priority
The instant application, filed 05/14/2021, having one RCE filed therein, is a National Stage entry of PCT/IB2019/059889, International Filing Date: 11/18/2019, and claims foreign priority to PCT/IB2018/059100, filed 11/19/2018.
In response to applicant’s request on page 4 of 1/19/24 Remarks, both PCT applications in the chain of priority are noted above; these WIPO/PCT applications are not considered “foreign” applications for which a notation need be made of receipt of a certified priority document, please see MPEP 213.
Claim Status
Claims 15-29 are pending.
Claims 1-14 are cancelled.
Claim 25 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 8/29/23.
Claims 19-24 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 8/29/23.
Claims 15-18, and 26-29 are under current examination.
Claims 15-18, and 26-29 are rejected.
Specification
The disclosure is objected to because of the following informalities: On page 42, fifth line of the table on that page the “Days -1, 14, 28 a” appears incomplete.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 15-18, and 26-29 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
There are multiple bases for this rejection, pertaining to 1) what is the meaning of the added “having a cartilage degeneration score of 3.7 or higher” (and 4.0 or higher in new claim 29) as to lesions an osteoarthritis patient and how to classify and treat such patient per the claims, and 2) who is the patient population given 1).
The basis for addition of the “having a cartilage degeneration score of 3.7 or higher” is histology assessments of joints of rats in an experiment, see Table 10 and associated text in the specification.
This assessment was made by killing the rats and preparing the joints for histology, Id.
Gerwin et al., Osteoarthritis and Cartilage, 10 (2010) S24-S34, the specification-cited reference for this procedure and scoring, “recommend its use for evaluation of different rat OA models as well as assessment of disease-modifying effects of treatments in these models” page S24.
Applicant on 7/21/25 directs the Office to Roemer et al., Arthritis and Rheumatism, 64(2), 2012, 429-437, apparently to substantiate an argument that it would be “highly unlikely that cartilage regeneration in a osteoarthritis patient with lesions having a cartilage degeneration score of 3.7 or higher or 4.0 or higher comprising (sic) would be achieved,” page 9.
All of this is confusing.
First, Gerwin and Roemer use different grading:
Gerwin measures at 3 regions, see Fig. 6, in histological specimens taken from a subject based on a scale of zero to 5:
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Roemer (following Whole-Organism Magnetic Resonance Imaging Score (WORMS), see page 431 in its entirety), measures using MRI with a scale of zero to 6, with different criteria based on what is observed using MRI:
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The metes and bounds of what is being claimed in claim 1 are unclear because:
The 3.7 or higher, and 4.0 values, are from histology samples of sacrificed rodents, and do not clearly align with a standard used for living human or other living subjects, including that used by Roemer which has a different scale and scores based on different observations using MRI1;
The measured/graded per Gerwin histological changes were assessed in several rat knees following Medial Ligament Transection (MLT). The examiner believes that these were those of 1M for which the scores of 4.00, 4.70 and 3.70, for Z1, Z2 and Z3 regions, were reported. If correct, this is not representative of damages suffered by human subjects, who do not have the same damage as caused by MLT, so the rat-MLT-based scoring would not be expected to translate in a meaningful way to measurements of damage to living human OA subjects; and
As a result of 1) and/or 2) above, it is unclear who is included in the claimed patient population, this lack of clarity including a lack of clear understanding of what stage of OA by what measurement(s) and what cartilage degeneration is/are encompassed in this claimed patient population.
On these bases one of ordinary skill in the art cannot reasonably ascertain the metes and bounds of what is claimed, and consequently claims 15-18, and 26-29 are rejected as unclear and indefinite.
Response to Arguments and Consideration of Affidavit/Declaration
Applicant's arguments and the Affidavit/Declaration of Revital Rattenbach filed 1/29/26 have been fully considered but they are not persuasive.
First, the presence of Z1-Z3 zone cartilage degeneration scores at Day 36 in controls appears not relevant given that the 7M and 8M treatment regimens were administered the formulated liraglutide weekly for five weeks prior to Day 36, see Table 9, pages 41-42. The data does not provide support for cartilage regeneration in an human osteoarthritis patient who has a cartilage degeneration score of 3.7 or higher at least because this was never demonstrated in this rodent experiment, where the decrease from the 2M treatment of group degeneration scores to the 8M treatment group degeneration scores occurred during no administration of liraglutide, the latter values taken more than 3 weeks after cessation of the administering of the formulated liraglutide (the examiner also noting that the sum of the 2M values, curiously, are greater than the sum of the control 1M values at 56 days, suggesting slight but not statistically greater degeneration in this treatment group during the administering period). Additionally based on known and generally accepted progression of degeneration due to OA, most of the time during the five week administering period the formulated liraglutide reasonably was administered to rodents having cartilage degeneration scores far less than 3.7 on any relevant scale. Further as to applicants arguments on page 4, regardless of whether Day 36 does or does not correspond to an early disease state, a substantial amount of the administering in this experiment was conducted during early disease progression. There is no administering starting at Day 36.
The following addresses both Remarks statements and arguments on pages 4-5 regarding Doan et al, Osteoarthritis Early-, Mid- and Late-Stage Progression in the Rat Medial Meniscus Transection Model, 2021, 35 pages, preprint copy provided (the examiner did not find an attached copy and based on Figure 9 believes that this is the Doan reference referred to), and the Affidavit/Declaration of Revital Rattenbach.
What is claimed “a cartilage degeneration score of 3.7” has no basis for human knee scoring, see rejection above. The comparison of Doan did not set forth any numerical correspondence. Doan never “explains” anything regarding Day 36.
Doan does argue for evaluating at later stages of osteoarthritis and also comments, “The benefit of the rat osteoarthritis model is its relatively fast onset of osteoarthritis (within first 3 weeks of surgery) and the quantitative method for analysis, making it ideal for testing therapeutics and determining their efficacy in a whole animal.
Many therapies have looked promising and showed therapeutic benefits in the rat MMT model; however, no therapeutics, to date, have effectively translated into clinical practice. Our study herein shows 3-weeks of MMT-induction in the rat results in early signs of osteoarthritis, which is unlikely a stage when symptomatic osteoarthritis patient seeks and receives treatment. Instead, MMT-induction out to 12-weeks post-surgery shows osteoarthritis deterioration closer to OARSI score of 4-6, which may be the point when osteoarthritis patient may exhibit pain and eventual immobility. As therapeutics are further developed, treatment efficacy should be initiated at mid- and/or late- stage of the rat MMT animal model and this would be a closer match to clinical relevance.” (pages 15-16)
In contrast to such recommendation, applicant’s administering of formulated liraglutide begins at a very early stage and does not extend to 12 weeks post-surgery which Doan corresponds to OARSI score range of 4-6.
Further regarding the Affidavit/Declaration, the examiner does not disagree that the Z1-Z3 zone cartilage degeneration scores that exceed 3.7 do not correspond to an early disease stage (but see above regarding when treatment/administering started). However, the examiner finds nothing in Doan that explicitly states that the OARSI-modified scores greater than 3.7 “align with” OARSI grades greater than or equal to 3, although Doan does state regarding earlier stages, “Articular cartilage damage is evident within the early stage of rat osteoarthritis and is resembles grades 1-3 of human OARSI scores,” page 15. Overall, there remains a lack of correspondence for what applicant is attempting to claim for the claimed osteoarthritis patient.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 15-18, and 26-29 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Instant claim 1 is:
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As applicant has argued and attempted to distinguish what is claimed, this claim and claims depending from it (and also claim 29) “are directed to a specific patient population, which is in no way disclosed or suggested in US ‘272. … the claims are limited specifically to a method for cartilage regeneration in an osteoarthritis patient with lesions having a cartilage degeneration score of 3.7 or higher as defined in claim 15 or a score of 4.0 or higher as defined in claim 29,” page 6 of 1/29/26 Remarks.
Example 4 is the only example of the instant specification that provides OA joint staging numerical results in an animal model. This uses an albumin-based formulation of liraglutide in a surgically induced model of OA in rats, and begins on page 38. Table 9 starting on page 41 describes the timeline, this includes that there were repeated IA (intra-articular) administrations once a week for five weeks, starting at Day -1 (a day before surgical OA induction). Groups 1M-6M were terminated on Day 36, and Groups 7M and 8M were terminated 21 days later on Day 57. The cartilage degeneration scores from such Groups were made by observing histological samples harvested respectively on days 36 and 57, see Table 10 page 46. The Table 10 data includes columns for percent of recovery for vehicle (control) and Liraglutide IA, this for the high dose 2M based on Day 36 termination and the 8M Day 57 termination (same end dates for 1M and 7M vehicle/controls, respectively).
The 1M control (vehicle) Z3 region score of 3.7 was based on that region’s condition at Day 36.
No administering of the albumin-based formulation of liraglutide was administered to any rats in Groups 2M or 8M on or after Day 36 (2M Group animals having been sacrificed on that day). To the contrary the administering of the albumin-based formulation of liraglutide was conducted beginning at very early stages of the progression of OA in these rat models, beginning at Day -1 and ending five weeks later.
Although the 2M cartilage degeneration scores in Table 10, presumably taken at Day 36 given Table 9, exceed 3.7 for each of Z1 to Z3 (and the total of these curiously is higher than the total of Z1 to Z3 for the 1M vehicle control also based on Day 36 samples), the administering started on Day -1, so encompassed treating all levels of degradation from an initial degree of degradation. There is no support in the application as filed for stating that the treating is only for OA patients having a score of 3.7 or higher when this 3.7 score was for a single control score at a single time point at a single location, Z3, given that the actual administering was for a time period from Day -1 to just before Day 36 (presumably Day 34 or 35, based on five weeks from Day -1). Nor is there support for only administering when the score (on whatever basis) is 4.0 or higher per claim 28; the 4.0 value is found in 1M and 7M controls, at Z1 and Z2 respectively. Nowhere in the application as filed are these values disclosed to be a value relating to when to administer a composition comprising a GLP-1 analog, such as liraglutide, to osteoarthritis patients in a method for cartilage regeneration wherein such composition administered to such patients induces chondrocyte proliferation and/or stem cell differentiation into chondrocytes (nor when/how converted to a score used for human OA patients). Further as to the claimed effects, the observed chondrocyte nests were observed in 3 of 9 animals in the high dose group, which applicant admits when considering the lesser numbers in lower doses “suggests an attempt at cartilage regeneration,” page 45, and on page 46 applicant admits as to 7M control vs 8M treatment, “No differences were observed in degeneration scores and total degeneration width” (although actually there were numerical differences but not statistically significant, and at Z2 the control degeneration was slightly less than the treatment degeneration). There is neither a strong nor a statistically significant basis for claiming what is claimed as to inducing chondrocyte proliferation and/or stem cell differentiation into chondrocytes; at 37 Days the sum of Z1-Z3 scores for 2M is numerically greater than the sum of Z1-Z3 for the 1M vehicle/control, and also as to percent recovery, which does not appear meaningful to what is being claimed, indicates greater percent numerical recovery by vehicle/control (1M 7M) versus high dose liraglutide (2M 8M).
Any effects and/or conditions and/or limitations in the dependent claims also are not supported by the application as filed based on the above.
Based on the above analysis, applicant was not in possession of what is claimed in claims 15-18, and 26-29.
Additionally, applicant is not in possession of the scope of what is claimed in claim 15 and claims depending therefrom, nor from claim 29. This is at least because Figure 4 evidences that non-formulated liraglutide increases cartilage matrix loss and also cartilage degeneration relative to the control vehicle. Formulation 6 yielded results in Figure 4 that were most reduced as to these metrics relative to the control vehicle (achieving statistical significance for cartilage degeneration metric), yet that formulation is not what is claimed. This one species of formulations is not representative of the genus of possible formulations, including for the claimed effects on cells in the claim 15 wherein clause.
Claim Rejections - 35 USC § 102
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.
Claim(s) 15-17, 26, 28 and 29 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by U.S. Patent No. 9592272 (‘272).
Claim 15 is directed to a method for cartilage regeneration in an osteoarthritis patient with lesions having a cartilage degeneration score of 3.7 or higher comprising administering to said osteoarthritis patient a composition which comprises a Glucagon Like Peptide-1 analogue, wherein the composition induces chondrocyte proliferation and/or stem cell differentiation into chondrocytes.
Liraglutide is the elected species of GLP-1 analogue.
The ‘272 teaches and claims administering liraglutide to treat osteoarthritis patients, claims 1, 7 and 8. Para 40 teaches administering by intra-articular injection, in particular at a rate of one to three injections every three months, so teaches repeating over time the administration of a GLP-1 analogue such as liraglutide (equivalent to the claim 28 “wherein the composition is administered by repeated administrations”). This administering liraglutide over time at a rate of one to three injections every three months, without an end time limit to the claimed treatment, encompasses treating a living human subject who progresses to more severe osteoarthritis, and also reasonably encompasses beginning treatment with liraglutide to living human subjects who have more advanced stages of osteoarthritis at the start of such claimed treatment.
However, the ‘272 does not explicitly teach:
administering the composition which comprises a Glucagon-Like Peptide-1 analogue to an osteoarthritis patient with lesions having a cartilage degeneration score of 3.7 or higher, nor
the claimed resultant “wherein” clause that states, “wherein the composition induces chondrocyte proliferation and/or stem cell differentiation into chondrocytes.”
Because “lesions having a cartilage degeneration score of 3.7 or higher” as applied to living OA patient(s) for whom a therapeutic treatment would be administered does not have an ordinary and customary meaning to those of ordinary skill in the art, see also 35 USC 112b rejection above, the broadest reasonable interpretation (BRI) of this open-end range ‘term’ as applied to a living OA patient for the instant rejection is that such OA patient has two or more OA lesions that result in a determination by a physician that the patient has sufficient osteoarthritis in the patient’s joints to warrant treatment with a therapeutic agent such as liraglutide (e.g., the patient’s symptoms, pain, limited range of motion, etc., warrant a physician’s diagnosis of OA for which treatment a prescription therapeutic drug such as liraglutide is reasonably prescribed, this versus the common and less costly OA treatments of over the counter NSAIDs, exercise, etc., the latter generally also having fewer side effects). Please see the flowchart in MPEP 2111.01 V.
Because the ‘272 teaches and claims administering the same as elected liraglutide to treat osteoarthritis patients, and also per its para 40 teaches administering at a rate of one to three injections every three months, which per above is open-ended as to duration of treatment, given the above BRI and the teachings and claims of the ‘272, the ‘272 teaches administering to OA patients included in the above BRI of the term “lesions having a cartilage degeneration score of 3.7 or higher”.
With regard to the claimed result(s) of “wherein the composition induces chondrocyte proliferation and/or stem cell differentiation into chondrocytes,” per MPEP 2111.04 “claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed.” Here, after consideration the examiner concludes that the effect of the liraglutide does not impart a limiting effect on the administering, at least because this is a result of the properties of the liraglutide peptide (please see MPEP 2112, stating in part, “"[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),” “"Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id.”, “Under the principles of inherency, if a prior art device, in its normal and usual operation, would necessarily perform the method claimed, then the method claimed will be considered to be anticipated by the prior art device. When the prior art device is the same as a device described in the specification for carrying out the claimed method, it can be assumed the device will inherently perform the claimed process,” “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. In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978),” and “"While the references do not show a specific recognition of that result, its discovery by appellants is tantamount only to finding a property in the old composition." “
The technical reasoning for making this rejection is that the ‘272 drug and compositions comprising it, being the same as or encompassed by what is instantly claimed, when administered to the same subject class, this even including those having more advanced OA, would reasonably operate via the same pathways and achieve the same results, at cellular and tissue levels, as that instantly claimed because the active ingredient is the same and the pathology is the same. The ‘272 clearly teaches and claims administering the same compounds to treat the same problem locus, where OA is, so anticipates the instant claims.
Based on the above, including all alternatives, the ‘272 anticipates claims 15-17, 26, 28 and 29.
Response to Arguments
Applicant's arguments filed 1/29/26 have been fully considered but they are not persuasive.
Applicant’s arguments regarding “standard human OARSI scoring” are addressed in part in the Response to Arguments set forth above.
Applicant does not explain why “… it cannot be said that the combination of reference would inherently result in a method for cartilage regeneration in osteoarthritis patients with marked to severe lesions,” the examiner also noting only one reference is applied to the instant rejection, so the examiner cannot respond to this other than to state there is a lack of reasoning, data, and/or technical basis to respond to.
Regarding the last paragraph of Applicant on page 6 regarding this rejection, if 14.5% of all human OA patients had cartilage degeneration scores of 3.7 or higher, then about one in seven human OA patients administered liraglutide per the ‘272 patent would fall in this category. This is statistically likely based on the examiner’s calculations, not “statistically improbable” as applicant asserts.2
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 18 is rejected under 35 U.S.C. 103 as being unpatentable over U.S. Patent No. 9592272 (‘272).
The rejection of claims 15-17 is set forth above.
Claim 18 depends from claim 17 and requires the concentration of the GLP-1, which is liraglutide per claim 17, “is of 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 18’s range would have been obvious, and claim 18 is rejected under this section.
Claim 27 is rejected under 35 U.S.C. 103 as being unpatentable over U.S. Patent No. 9592272 (‘272), as applied above to claim 15, and further in view of WO 2006/051110, published 5/18/06 (‘110, previously provided).
The rejection of claim 15 is set forth above.
Claim 27 depends from claim 15 and states that the composition of claim 15 comprises a therapeutically effective amount of the GLP-1 analogue and an excipient selected from the list of “non-ionic surfactant, cellulose, polyether, glucan, glycerophospholipids, polysaccharides, proteins, and combinations thereof.”
The ‘272 does not teach excipients from the list of claim 27.
The level of skill in the art is high.
The ’110 teaches stable formulations of insulinotropic peptides, Title, those peptides including liraglutide, featured in experiments the results of which are in Figures 1-5, 7-17, and also teaches excipients in its formulations of the insulinotropic peptides, including liraglutide, the excipients including non-ionic surfactants, see page 5 line 23 to page 6, line 22, this list including poloxamer 188 which was added to the formulation with liraglutide in Examples 1, 2, 4 and 5, and also see claims 1, 4, 5, and 17-20.
Accordingly, one of ordinary skill in the art would have been motivated to improve the 272’s administering of liraglutide, whether to more effectively affect chondrocytes or merely to improve therapeutic effectiveness to treat osteoarthritis, by adding an excipient such as a non-ionic surfactant to form a stable formulation, and there would have been a reasonable expectation of success given that the ‘110 taught this surfactant to be used in stable formulations of insulinotropic peptides, that include liraglutide.
Therefore claim 27 would have been obvious.
Response to Arguments
Applicant's arguments filed 1/29/26 have been fully considered but they are not persuasive.
Applicant raises questions regarding the ‘very small population” and “… in fact, highly unlikely … However, administering the same compound would provide the same result. Even regarding claim 29 and assuming “approximately 10%” is correct, one in ten OA subjects administered per the teachings of the ‘272 patent is not a rarity, and as noted, again, administering the same compound would provide the same result.
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 15-18, 26 and 29 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7 and 8 of U.S. Patent No. 9592272 (“reference patent”).
Claim 15 is set forth above.
The wherein clause is modified from the deleted phrase of amended claim 26. When interpreting to give weight to the stated inducement of chondrocyte proliferation and/or stem cell differentiation into chondrocytes, for cartilage regeneration, 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, the rejection focuses directly on the teachings and claims of the ‘272 that administers liraglutide (see paragraph immediately below referencing MPEP 2112.02).
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 ‘272’s administering of the same compound or composition is now directed to a result of the activities of the GLP-1 analogue, including liraglutide, that induces chondrocyte proliferation, 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 ‘272 reference patent administers the same liraglutide encompassed by instant claim 15’s method for cartilage regeneration that comprises administering a GLP-1 analog (see also reference patent claim 7 which lists the elected liraglutide, and reference patent claim 8, further narrowing the list of claim 7 to two agents, liraglutide being one of them, clearly indicating the scope of reference patent claim 1’s GLP-1 includes analogs such as liraglutide, and also anticipating the elected species liraglutide), and would inherently achieve the claimed cartilage regeneration of claim 15, in the OA patient population as interpreted under the BRI, wherein the composition induces chondrocyte proliferation and/or stem cell differentiation into chondrocytes.
Regarding the requirement that of administering to an osteoarthritis patient with lesions having a cartilage degeneration score of 3.7 or higher, or 4.0 or higher for claim 29, see the 35 USC 112 rejection and the claim interpretation in the 35 USC 102 rejection above. The administering to OA patients as claimed in the ‘272 treats this population as so interpreted.
Accordingly, instant method claims 15-17, 26 and 29 are rejected under this section.
Claim 18 depends from claim 17, which specifies liraglutide, which through claim 16 depends from claim 15. Claim 18 imposing the concentration of liraglutide GLP-1 analogue to be about 0.1 nM to 625 uM. This range extends beyond six orders of magnitude of concentration.
MPEP 2144.05 II A states, “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.” There is no evidence across the breadth of the claimed range that this very expansive concentration range is critical. As such claim 18 is rejected under this section.
Claim 27 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7 and 8 of U.S. Patent No. 9592272 (“reference patent”), and further in view of WO 2006/051110, published 5/18/06 (‘110, previously provided).
Claim 15 is rejected as set forth above.
Claim 27 depends from claim 15 and states that the composition of claim 15 comprises a therapeutically effective amount of the GLP-1 analogue and an excipient selected from the list of “non-ionic surfactant, cellulose, polyether, glucan, glycerophospholipids, polysaccharides, proteins, and combinations thereof.”
Reference patent claims 1, 7 and 8 do not teach these excipients.
The ’110 teaches stable formulations of insulinotropic peptides, Title, those peptides including liraglutide, featured in experiments the results of which are in Figures 1-5, 7-17, and also teaches excipients in its formulations of the insulinotropic peptides, including liraglutide, the excipients including non-ionic surfactants, see page 5 line 23 to page 6, line 22, this list including poloxamer 188 which was added to the formulation with liraglutide in Examples 1, 2, 4 and 5, and also see claims 1, 4, 5, and 17-20.
Accordingly, the method of instant claim 27 in which the administered composition includes liraglutide and a non-ionic surfactant would have been obvious and is rejected under this section.
Claim 28 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7 and 8 of U.S. Patent No. 9592272 (“reference patent”), as applied to claim 15 above, and further in view of US 20150150983, PUBLISHED 2015-06-04 (Byers).
The rejection of claim 15 by the ‘272 as set forth above.
Claim 28 depends from claim 15 and states, “wherein the composition is administered by repeat administrations.”
The level of skill in the art is high.
Byers teaches intra-articular formulations and methods are provided for treating joint conditions, such as osteoarthritis, Abstract, per claim 11 directed to a method of treating a joint condition in a subject in need thereof, comprising administering to the subject via an intra-articular injection an acidic composition comprising an effective amount of recombinant human growth differentiation factor-5 (rhGDF-5).
Byers teaches “The administration of the dose unit can be carried out both by single administration of the composition or administration can be performed in several smaller dose units and also by multiple administrations of subdivided doses at specific intervals,” para 89, and also teaches:
[0091] In one embodiment, the medical condition is osteoarthritis (OA) and the composition is administered in a joint space, such as, for example, a knee, shoulder, temporo-mandibular and carpo-metacarpal joints, elbow, hip, wrist, ankle, and lumbar zygapophysial (facet) joints in the spine. The viscosupplementation may be accomplished via a single injection or multiple intra-articular injections administered over a period of weeks into the knee or other afflicted joints. For example, a human subject with knee OA may receive one, two, three, or more injections or number of injections according to any suitable administration schedule of about 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10 ml or more per knee during the treatment period. For other joints, the administered volume can be adjusted based on the size on the joint, and the subject may receive one, two, three, or more injections or number of injections according to any suitable administration schedule during the treatment period.
[0092] A person skilled in the art will appreciate that the compositions and methods described herein can include various other joint treatment components (combination therapy), including, for example, amino acids, proteins, saccharides, di-saccharides, poly-saccharides, lipids, nucleic acids, buffers, surfactants, and mixtures thereof. Other useful components can include steroids, anti-inflammatory agents, non-steroidal anti-inflammatory agents, analgesics, cells, antibiotics, antimicrobial agents, anti-inflammatory agents, growth factors, growth factor fragments, small-molecule wound healing stimulants, hormones, cytokines, peptides, antibodies, enzymes, isolated cells, platelets, immunosuppressants, nucleic acids, cell types, viruses, virus particles, essential nutrients or vitamins, and combinations thereof. "Combination therapy" is intended to embrace administration of these therapeutic agents in a sequential manner, wherein each therapeutic agent is administered at a different time, as well as administration of these therapeutic agents, or at least two of the therapeutic agents concurrently, or in a substantially simultaneous manner. The therapeutic agents can be administered by the same route or by different routes. For example, a first therapeutic agent of the combination selected may be administered by intra-articular injection while the other therapeutic agents of the combination may be administered orally. Alternatively, for example, all therapeutic agents may be administered by intra-articular injection. The sequence in which the therapeutic agents are administered is not narrowly critical. Therapeutic agents may also be administered in alternation.
Given the high level of skill in the art, one of ordinary skill in the art would clearly have appreciated that administering the liraglutide as taught by the ‘272 as evidenced by Chen and Roku could readily be administered “by repeat administrations” because this clearly was taught in Byers, Byers also teaching that other joint treatment components, including peptides, could be co-administered. Combining the Byers’ teaching of repeated/multiple administrations with the teachings of the ‘272 as evidenced by Chen and Roku is based on using a known technique to improve similar methods, the ‘272 being the “base” method, Byers being a “comparable” method, and the examiner finding that one of ordinary skill in the art could have applied the known "improvement" technique in the same way to the "base" method and the results would have been predictable to one of ordinary skill in the art, this at least based on the Byers paras 89 and 90 and additionally on the concept of the need for repeated administration of therapeutic agents, including for persistent joint conditions. There would have been a reasonable expectation of success given that multiple administrations of a known effective therapeutic agent would reasonably be expected to exhibit its beneficial effects across a longer period of time based on the intervals between such administrations.
Accordingly, claim 28 would have been obvious and is rejected under this section.
Claims 15-18, 26-29 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 4, 5, 7, 8 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 cartilage is inherently regenerated, see MPEP 2112.02, and BRI above in the 35 USC 102 rejection. Further, per MPEP 2111.04, because the wherein clause language of claims 15 and 26 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.
Instant claims 15-17 and 26 are rejected over reference application claims 1, 2, 4 and 5, these being narrower as to the composition limitations, but comprising liraglutide, so anticipatory, so claims 15-17 and 26 are rejected under this section.
Instant claim 18 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.
Instant claim 27 is rejected over reference application claims 1, 2, 4 and 5 given reference application claim 1 including polyethylene glycol, which is a species of instant claim 27’s polyether.
Instant claim 28 is rejected over reference application claims 1, 2, 4 and 5, pertaining to instant claim 15, and reference application claims 7, 8 and 19, which clearly encompass repeated administrations of compounds comprising liraglutide.
New instant claim 29 is rejected on the same basis as instant claim 15.
This is a provisional nonstatutory double patenting rejection.
Claims 15-18, 26-27 and 29 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of copending Application No. 19016974 (“reference application” or claims thereof).
Reference application claims 1-5 administer liraglutide to treat at least one joint condition related to synovial membrane, its claim 6 recites the same concentration range as in instant claim 18, and its claim 7 requires the composition to include a “pharmaceutically acceptable formulation vehicle, which per its claim 8 is albumin (a protein which is a species of instant claim 27’s proteins type excipient).
By so administering liraglutide cartilage is inherently regenerated, as is its synovial condition improved, see MPEP 2112.02, and BRI above in the 35 USC 102 rejection. Further, per MPEP 2111.04, because the wherein clause language of claims 15 and 26 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.
Instant claims 15-17 and 26 are rejected over reference application claims 1-5, so claims 15-17 and 26 are rejected under this section.
Instant claim 18 is rejected when also considering reference application claim 6, the range of which is identical. See also MPEP 2144.05 regarding overlapping ranges.
Instant claim 27 is rejected over reference application claims 1-8.
New instant claim 29 is rejected on the same basis as instant claim 15.
This is a provisional nonstatutory double patenting rejection.
Claim 28 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7 and 8 of copending Application No. 19016974 (“reference application” or claims thereof), as applied to claim 15 above, and further in view of US 20150150983, PUBLISHED 2015-06-04 (Byers).
The rejection of claim 15 by the ‘272 as set forth above.
Claim 28 depends from claim 15 and states, “wherein the composition is administered by repeat administrations.”
The level of skill in the art is high.
Byers teaches intra-articular formulations and methods are provided for treating joint conditions, such as osteoarthritis, Abstract, per claim 11 directed to a method of treating a joint condition in a subject in need thereof, comprising administering to the subject via an intra-articular injection an acidic composition comprising an effective amount of recombinant human growth differentiation factor-5 (rhGDF-5).
Byers teaches “The administration of the dose unit can be carried out both by single administration of the composition or administration can be performed in several smaller dose units and also by multiple administrations of subdivided doses at specific intervals,” para 89, and also teaches:
[0091] In one embodiment, the medical condition is osteoarthritis (OA) and the composition is administered in a joint space, such as, for example, a knee, shoulder, temporo-mandibular and carpo-metacarpal joints, elbow, hip, wrist, ankle, and lumbar zygapophysial (facet) joints in the spine. The viscosupplementation may be accomplished via a single injection or multiple intra-articular injections administered over a period of weeks into the knee or other afflicted joints. For example, a human subject with knee OA may receive one, two, three, or more injections or number of injections according to any suitable administration schedule of about 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10 ml or more per knee during the treatment period. For other joints, the administered volume can be adjusted based on the size on the joint, and the subject may receive one, two, three, or more injections or number of injections according to any suitable administration schedule during the treatment period.
[0092] A person skilled in the art will appreciate that the compositions and methods described herein can include various other joint treatment components (combination therapy), including, for example, amino acids, proteins, saccharides, di-saccharides, poly-saccharides, lipids, nucleic acids, buffers, surfactants, and mixtures thereof. Other useful components can include steroids, anti-inflammatory agents, non-steroidal anti-inflammatory agents, analgesics, cells, antibiotics, antimicrobial agents, anti-inflammatory agents, growth factors, growth factor fragments, small-molecule wound healing stimulants, hormones, cytokines, peptides, antibodies, enzymes, isolated cells, platelets, immunosuppressants, nucleic acids, cell types, viruses, virus particles, essential nutrients or vitamins, and combinations thereof. "Combination therapy" is intended to embrace administration of these therapeutic agents in a sequential manner, wherein each therapeutic agent is administered at a different time, as well as administration of these therapeutic agents, or at least two of the therapeutic agents concurrently, or in a substantially simultaneous manner. The therapeutic agents can be administered by the same route or by different routes. For example, a first therapeutic agent of the combination selected may be administered by intra-articular injection while the other therapeutic agents of the combination may be administered orally. Alternatively, for example, all therapeutic agents may be administered by intra-articular injection. The sequence in which the therapeutic agents are administered is not narrowly critical. Therapeutic agents may also be administered in alternation.
Given the high level of skill in the art, one of ordinary skill in the art would clearly have appreciated that administering the liraglutide as taught by the ‘272 could readily be administered “by repeat administrations” because this clearly was taught in Byers, Byers also teaching that other joint treatment components, including peptides, could be co-administered. Combining the Byers’ teaching of repeated/multiple administrations, the ‘272 teaching the base administering, Byers being a “comparable” method, and the examiner finding that one of ordinary skill in the art could have applied the known "improvement" technique in the same way to the "base" method and the results would have been predictable to one of ordinary skill in the art, this at least based on the Byers paras 89 and 90 and additionally on the concept of the need for repeated administration of therapeutic agents, including for persistent joint conditions. There would have been a reasonable expectation of success given that multiple administrations of a known effective therapeutic agent would reasonably be expected to exhibit its beneficial effects across a longer period of time based on the intervals between such administrations.
Accordingly, claim 28 would have been obvious and is rejected under this section.
This is a provisional nonstatutory double patenting rejection.
Claims 15-18, 26-27 and 29 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of copending Application No. 19391871 (“reference application” or claims thereof).
Reference application claims 1-7 administer GLP-1 or a GLP-1 analogue, specifically liraglutide per claim 4, in a method for reducing the formation of osteophytes in an OA patient, its claim 5 recites the same concentration range as in instant claim 18, and its claim 7 is albumin (a protein which is a species of instant claim 27’s proteins type excipient).
By so administering liraglutide cartilage is inherently regenerated, and the reference claims methods also per instant claim 1’s wherein clause would result in inducing chondrocyte proliferation and/or stem cell differentiation into chondrocytes, see MPEP 2112.02, and BRI above in the 35 USC 102 rejection. Further, per MPEP 2111.04, because the wherein clause language of claims 15, 26 and 27 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.
Instant claims 15-17 and 26 are rejected over reference application claims 1-7, so claims 15-17 and 26 are rejected under this section.
Instant claim 18 is rejected when also considering reference application claim 5, the range of which is identical. See also MPEP 2144.05 regarding overlapping ranges.
Instant claim 27 is rejected over reference application claims 1-7.
New instant claim 29 is rejected on the same basis as instant claim 15.
This is a provisional nonstatutory double patenting rejection.
Claim 28 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 6 and 7 of copending Application No. 19391871 (“reference application” or claims thereof), as applied to claim 15 above, and further in view of US 20150150983, PUBLISHED 2015-06-04 (Byers).
The rejection of claim 15 by the ‘272 as set forth above.
Claim 28 depends from claim 15 and states, “wherein the composition is administered by repeat administrations.”
The level of skill in the art is high.
Byers teaches intra-articular formulations and methods are provided for treating joint conditions, such as osteoarthritis, Abstract, per claim 11 directed to a method of treating a joint condition in a subject in need thereof, comprising administering to the subject via an intra-articular injection an acidic composition comprising an effective amount of recombinant human growth differentiation factor-5 (rhGDF-5).
Byers teaches “The administration of the dose unit can be carried out both by single administration of the composition or administration can be performed in several smaller dose units and also by multiple administrations of subdivided doses at specific intervals,” para 89, and also teaches:
[0091] In one embodiment, the medical condition is osteoarthritis (OA) and the composition is administered in a joint space, such as, for example, a knee, shoulder, temporo-mandibular and carpo-metacarpal joints, elbow, hip, wrist, ankle, and lumbar zygapophysial (facet) joints in the spine. The viscosupplementation may be accomplished via a single injection or multiple intra-articular injections administered over a period of weeks into the knee or other afflicted joints. For example, a human subject with knee OA may receive one, two, three, or more injections or number of injections according to any suitable administration schedule of about 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10 ml or more per knee during the treatment period. For other joints, the administered volume can be adjusted based on the size on the joint, and the subject may receive one, two, three, or more injections or number of injections according to any suitable administration schedule during the treatment period.
[0092] A person skilled in the art will appreciate that the compositions and methods described herein can include various other joint treatment components (combination therapy), including, for example, amino acids, proteins, saccharides, di-saccharides, poly-saccharides, lipids, nucleic acids, buffers, surfactants, and mixtures thereof. Other useful components can include steroids, anti-inflammatory agents, non-steroidal anti-inflammatory agents, analgesics, cells, antibiotics, antimicrobial agents, anti-inflammatory agents, growth factors, growth factor fragments, small-molecule wound healing stimulants, hormones, cytokines, peptides, antibodies, enzymes, isolated cells, platelets, immunosuppressants, nucleic acids, cell types, viruses, virus particles, essential nutrients or vitamins, and combinations thereof. "Combination therapy" is intended to embrace administration of these therapeutic agents in a sequential manner, wherein each therapeutic agent is administered at a different time, as well as administration of these therapeutic agents, or at least two of the therapeutic agents concurrently, or in a substantially simultaneous manner. The therapeutic agents can be administered by the same route or by different routes. For example, a first therapeutic agent of the combination selected may be administered by intra-articular injection while the other therapeutic agents of the combination may be administered orally. Alternatively, for example, all therapeutic agents may be administered by intra-articular injection. The sequence in which the therapeutic agents are administered is not narrowly critical. Therapeutic agents may also be administered in alternation.
Given the high level of skill in the art, one of ordinary skill in the art would clearly have appreciated that administering the liraglutide as taught by the ‘272 could readily be administered “by repeat administrations” because this clearly was taught in Byers, Byers also teaching that other joint treatment components, including peptides, could be co-administered. Combining the Byers’ teaching of repeated/multiple administrations, the ‘272 teaching the base administering, Byers being a “comparable” method, and the examiner finding that one of ordinary skill in the art could have applied the known "improvement" technique in the same way to the "base" method and the results would have been predictable to one of ordinary skill in the art, this at least based on the Byers paras 89 and 90 and additionally on the concept of the need for repeated administration of therapeutic agents, including for persistent joint conditions. There would have been a reasonable expectation of success given that multiple administrations of a known effective therapeutic agent would reasonably be expected to exhibit its beneficial effects across a longer period of time based on the intervals between such administrations.
Accordingly, claim 28 would have been obvious and is rejected under this section.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant's arguments filed 7/21/25 have been fully considered but they are not persuasive.
Applicant has argued that the provisional nonstatutory obviousness-type double patenting rejection be held in abeyance. However, this is not persuasive as the MPEP does not provide for holding the rejection in abeyance. The rejection is still deemed proper and stands for the reasons of record.
Conclusion
No claim is allowed.
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/JOSEPH FISCHER/Primary Examiner, Art Unit 1658
1 While the examiner clearly appreciates that AI search results are not dispositive, the following points to different methods of evaluating cartilage degeneration including those requiring biopsies (e.g., OARSI):
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2 Further regarding “the invention as claimed would be achieved” statement, as set forth in the Remarks section above, the experiment conducted by applicant administered the formulated liraglutide for five weeks at early stages of the experiment, so included administering to early stages. The ‘272, as set forth in the instant rejection, in para 40 teaches administering by intra-articular injection, in particular at a rate of one to three injections every three months, so teaches repeating over time the administration of a GLP-1 analogue such as liraglutide. This administering liraglutide over time at a rate of one to three injections every three months without an end time limit to the claimed treatment encompasses treating a living human subject who progresses to more severe osteoarthritis, and also reasonably encompasses beginning treatment with liraglutide to living human subjects who have more advanced stages of osteoarthritis at the start of such claimed treatment. In comparing what applicant has done and the ‘272 para 40, it appears to the examiner that the ‘272 teaches more extensive administering throughout the progression of OA than applicant has demonstrated.
Prosecution Insights