UNITED STATES PATENT AND TRADEMARK OFFICE
`
`
`
`UNITED STATES DEPARTMENT OF COMMERCE
`United States Patent and Trademark Office
`Address: COMMISSIONER FOR PATENTS
`P.O. Box 1450
`Alexandria, Virginia 2231371450
`www.uspto.gov
`
`15/808,632
`
`11/09/2017
`
`Gregory D. Jay
`
`LUB-030
`
`8457
`
`GOODWIN PROCTER LLP
`
`PATENT ADMINISTRATOR
`100 NORTHERN AVENUE
`
`BOSTON, MA 02210
`
`KOMATSU U N
`
`ART UNIT
`1658
`
`PAPER NUMBER
`
`NOTIFICATION DATE
`
`DELIVERY MODE
`
`11/13/2020
`
`ELECTRONIC
`
`Please find below and/or attached an Office communication concerning this application or proceeding.
`
`The time period for reply, if any, is set in the attached communication.
`
`Notice of the Office communication was sent electronically on above—indicated "Notification Date" to the
`
`following e—mail address(es):
`
`JGoodwin@ goodwinlaw.com
`PSousa-Atwood@ goodwinlaw.com
`US -PatentBos @ goodwinlaw.com
`
`PTOL-90A (Rev. 04/07)
`
`

`

`017/09 A0170” Summary
`
`Application No.
`15/808,632
`Examiner
`U N KOMATSU
`
`Applicant(s)
`Jay et al.
`Art Unit
`1658
`
`AIA (FITF) Status
`Yes
`
`- The MAILING DA TE of this communication appears on the cover sheet wit/7 the correspondence address -
`Period for Reply
`
`A SHORTENED STATUTORY PERIOD FOR REPLY IS SET TO EXPIRE 3 MONTHS FROM THE MAILING
`DATE OF THIS COMMUNICATION.
`Extensions of time may be available under the provisions of 37 CFR 1.136(a). In no event, however, may a reply be timely filed after SIX (6) MONTHS from the mailing
`date of this communication.
`|f NO period for reply is specified above, the maximum statutory period will apply and will expire SIX (6) MONTHS from the mailing date of this communication.
`-
`- Failure to reply within the set or extended period for reply will, by statute, cause the application to become ABANDONED (35 U.S.C. § 133).
`Any reply received by the Office later than three months after the mailing date of this communication, even if timely filed, may reduce any earned patent term
`adjustment. See 37 CFR 1.704(b).
`
`Status
`
`1). Responsive to communication(s) filed on RCE filed on 7/20/2020.
`CI A declaration(s)/affidavit(s) under 37 CFR 1.130(b) was/were filed on
`
`2a)[:] This action is FINAL.
`
`2b)
`
`This action is non-final.
`
`3)[:] An election was made by the applicant in response to a restriction requirement set forth during the interview
`on
`; the restriction requirement and election have been incorporated into this action.
`
`4):] Since this application is in condition for allowance except for formal matters, prosecution as to the merits is
`closed in accordance with the practice under Expade Quay/e, 1935 CD. 11, 453 O.G. 213.
`
`Disposition of Claims*
`
`5)
`
`Claim(s)
`
`1—2,4—20 and 28—44 is/are pending in the application.
`
`5a) Of the above claim(s) 8,10,32 and 34 is/are withdrawn from consideration.
`
`
`
`E] Claim(ss) _ is/are allowed.
`
`Claim(ss) 1 —2 ,4—7, 9, 11—20 ,2—831,33 and 35—44 is/are rejected.
`
`[:1 Claim(ss_) is/are objected to.
`
`) ) ) )
`
`S)
`are subject to restriction and/or election requirement
`C] Claim(s
`* If any claims have been determined allowable, you may be eligible to benefit from the Patent Prosecution Highway program at a
`
`participating intellectual property office for the corresponding application. For more information, please see
`
`httpfiwww.”smogovmatentszinit_events[pph[index.'sp or send an inquiry to PPeredhack@g§ptg.ggv.
`
`Application Papers
`
`10):] The specification is objected to by the Examiner.
`
`11). The drawing(s) filed on 2/28/2018 is/are: a). accepted or b)D objected to by the Examiner.
`Applicant may not request that any objection to the drawing(s) be held in abeyance. See 37 CFR 1.85(a).
`Replacement drawing sheet(s) including the correction is required if the drawing(s) is objected to. See 37 CFR 1.121 (d).
`
`Priority under 35 U.S.C. § 119
`
`12)D Acknowledgment is made of a claim for foreign priority under 35 U.S.C. § 119(a)-(d) or (f).
`Certified copies:
`
`a)I:i All
`
`b)C] Some**
`
`c)[j None of the:
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`1C] Certified copies of the priority documents have been received.
`
`2E] Certified copies of the priority documents have been received in Application No.
`
`3C] Copies of the certified copies of the priority documents have been received in this National Stage
`application from the International Bureau (PCT Rule 17.2(a)).
`
`** See the attached detailed Office action for a list of the certified copies not received.
`
`Attachment(s)
`
`1)
`
`Notice of References Cited (PTO-892)
`
`Information Disclosure Statement(s) (PTO/SB/08a and/or PTO/SB/08b)
`2)
`Paper No(s)/Mail Date 7/20/2020.
`U.S. Patent and Trademark Office
`
`3) E] Interview Summary (PTO-413)
`Paper No(s)/Mail Date
`4) CI Other-
`
`PTOL-326 (Rev. 11-13)
`
`Office Action Summary
`
`Part of Paper No./Mai| Date 20201001
`
`

`

`Application/Control Number: 15/808,632
`Art Unit: 1658
`
`Page 2
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`DETAILED ACTION
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`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
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`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 7/20/2020 has been entered.
`
`1.
`
`The present application, filed on or after March 16, 2013, is being examined
`
`under the first inventor to file provisions of the AIA.
`
`2.
`
`3.
`
`4.
`
`5.
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`6.
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`Claim filed on 7/20/2020 is acknowledged.
`
`Claims 3 and 21 -27 have been cancelled.
`
`New claims 29-44 have been added.
`
`Claims 1, 2, 4-20 and 28-44 are pending in this application.
`
`Claims 8, 10, 32 and 34 are withdrawn from consideration as being drawn to
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`non-elected species.
`
`7.
`
`Applicant elected without traverse of Group 1 (claims 1, 2 and 4-20) and elected
`
`without traverse of the PRG4 sequence of residues 25-1404 of SEQ ID NO: 1 as
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`species of PRG4 or a biologically active fragment thereof; administration by injection as
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`species of route of administering the PRG4 or a biologically active fragment thereof
`
`from claims 6-10; toe joint as species of joint for injection; heel as species of area of
`
`patient’s foot for injection from claim 10; administration of an amount of PRG4 sufficient
`
`to achieve a concentration of PRG4 in a synovial fluid of a joint of the subject of at least
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`

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`Application/Control Number: 15/808,632
`Art Unit: 1658
`
`Page 3
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`200 ug/ml as species of amount of PRG4 or a biologically active fragment thereof;
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`human as species of subject; and weekly administration as species of administering
`
`scheme in the reply filed on 1/17/2019. Because injection as the elected route of
`
`administering the PRG4 or a biologically active fragment thereof from claims 6-10 is not
`
`a species, the Examiner telephoned Applicant’s representative, Crystal A. Komm, on
`
`2/6/2019 for clarification and further species election. Applicant’s representative elected
`
`on the phone intra-articular injection into a toe joint as species of route of administering
`
`the PRG4 or a biologically active fragment thereof on 2/7/2019. Since Applicant elected
`
`toe joint as the area for injection, heel as the elected species of area of injection from
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`claims 10 and 34 would not be searched and examined in current office action.
`
`Restriction requirement was deemed proper and made FINAL in the previous
`
`office actions. Group 1
`
`is drawn to a method of reducing joint pain in a subject with gout
`
`or pseudogout, and/or a method of treating gout or pseudogout in a subject in need
`
`thereof, the method comprising administering to the subject a composition comprising
`
`proteoglycan 4 (PRG4) consisting of the amino acid residues 25-1404 of SEQ ID NO: 1.
`
`A search was conducted on the elected species; and prior art was found. Claim 8, 10,
`
`32 and 34 are withdrawn from consideration as being drawn to non-elected species.
`
`Claims 1, 2, 4-7, 9, 11-20, 28-31, 33 and 35-44 are examined on the merits in this office
`
`action.
`
`Please note: In the notice of Allowance dated 4/21/2020, claims 1, 2, 4-20 and
`
`28 have been indicated to be allowable. However, after further search and careful
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`

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`Application/Control Number: 15/808,632
`Art Unit: 1658
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`Page 4
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`reconsideration, in particular in view of MPEP § 2123, a non-final office action is issued
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`hereby.
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`Rejections
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`Claim Rejections - 35 USC § 103
`
`8.
`
`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
`
`of this title, 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.
`
`9.
`
`The factual inquiries set forth in Graham v. John Deere 00., 383 U.S. 1, 148
`
`USPQ 459 (1966), that are applied 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.
`
`10.
`
`Claims 1, 2, 4-7, 9, 11-20, 28-31, 33 and 35-44 are rejected under 35 U.S.C. 103
`
`as being unpatentable over Jay (US 2013/0116186 A1, filed with IDS), and as
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`

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`Application/Control Number: 15/808,632
`Art Unit: 1658
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`Page 5
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`evidenced by Fryar et al (National Health Statistics Reports, 2018, 122, pages 1-16,
`
`cited and enclosed in the previous office action), and further in view of Schmidt et al (US
`
`2016/0304572 A1, filed with IDS).
`
`The instant claims 1, 2, 4-7, 9, 11-20, 28-31, 33 and 35-44 are drawn to a
`
`method of reducing joint pain in a subject with gout or pseudogout, and/or a method of
`
`treating gout or pseudogout in a subject in need thereof, the method comprising
`
`administering to the subject a composition comprising proteoglycan 4 (PRG4) consisting
`
`of the amino acid residues 25-1404 of SEQ ID NO: 1.
`
`Jay teaches a method of treating subject with an episodic case of gout or
`
`pseudo-gout (one type of joint trauma), the method comprises intra-articularly injecting
`
`lubricin (synonym of PRG4) into the joints such as keen, toe and others, for example,
`
`page 4, paragraph [0029].
`
`It meets the limitations of the patient population and the
`
`active method step recited in instant claims 1 and 2.
`
`lntra-articularly injecting lubricin
`
`(synonym of PRG4) into toe joint in Jay reads on intra-articular injection into a toe joint
`
`as the elected species of route of administering the PRG4 or a biologically active
`
`fragment thereof.
`
`With regards to the limitations recited in instant claims 6, 7, 9, 30, 31 and 33,
`
`although Jay does not explicitly state the toe joint for intra-articular injection of lubricin is
`
`the area affected by gout, since Jay teaches intra-articular injection of lubricin into toe
`
`joint for treating joint trauma such as gout or pseudo-gout and re-establishing joint
`
`homeostasis (see page 4, paragraph [0029]), one of skill in the art would understand
`
`intra-articularly injecting lubricin into toe joint in Jay is injecting lubricin into a joint having
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`

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`Application/Control Number: 15/808,632
`Art Unit: 1658
`
`Page 6
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`gout or an area of the patient’s body affected by gout.
`
`It meets the limitations of instant
`
`claims 6, 7, 9, 30, 31 and 33.
`
`Jay further teaches the lubricin includes lubricating fragments, i.e., polypeptides
`
`which are not full length lubricin, but which possess lubricating activity of lubricin and
`
`sequence identity with lubricin, or naturally occurring, as well as synthetic or
`
`recombinant isoforms and variants; and it can be a recombinant form of a human
`
`lubricin polypeptide, for example, page 2, paragraph [0013]; and page 3, paragraphs
`
`[0022] and [0023].
`
`It meets the limitations of instant claims 5 and 29. Although Jay
`
`does not explicitly state a pharmaceutical composition comprising lubricin and a
`
`pharmaceutically acceptable carrier, Jay teach lubricin is injected as a fluid, for
`
`example, page 4, paragraph [0035]. Therefore, one of skill in the art would understand
`
`a pharmaceutical composition comprising lubricin and a pharmaceutically acceptable
`
`carrier is used for injecting lubricin.
`
`It meets the limitations of instant claims 11 and 35.
`
`Jay also teaches injecting an amount of lubricin sufficient to establish a
`
`bioavailable lubricin concentration in the synovial fluid (as opposed to lubricin bound to
`
`cartilage) within the capsule preferably of between 100 ug/mL and 500 ug/mL,
`
`preferably at least greater than 250 ug/mL, and most preferably between 250 ug/mL
`
`and 450 ug/mL, for example, page 4, paragraph [0033]. A bioavailable lubricin
`
`concentration in the synovial fluid of at least greater than 250 ug/mL and/or between
`
`250 ug/mL and 450 ug/mL in Jay reads on administration of an amount of PRG4
`
`sufficient to achieve a concentration of PRG4 in a synovial fluid of a joint of the subject
`
`of at least 200 ug/ml as the elected species of amount of PRG4 or a biologically active
`
`fragment thereof.
`
`It meets the limitations of instant claims 15 and 39. With regards to
`
`

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`Application/Control Number: 15/808,632
`Art Unit: 1658
`
`Page 7
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`the limitations recited in instant claims 12 and 36, first, based on “(as opposed to
`
`lubricin bound to cartilage)” taught in Jay, one of skill in the art would understand the
`
`lubricin concentration disclosed on page 4, paragraph [0033] in Jay is an amount
`
`insufficient to provide boundary lubrication. Second, since the lubricin concentration in
`
`the synovial fluid of at least greater than 250 ug/mL and/or between 250 ug/mL and 450
`
`ug/mL in Jay meets the limitations of instant claims 15 and 39, the lubricin concentration
`
`in the synovial fluid of at least greater than 250 ug/mL and/or between 250 ug/mL and
`
`450 ug/mL in Jay is an amount sufficient to treat joint pain. Therefore, the lubricin
`
`concentration in the synovial fluid of at least greater than 250 ug/mL and/or between
`
`250 ug/mL and 450 ug/mL in Jay meets the limitations of instant claims 12 and 36.
`
`Furthermore, in the instant case, as stated above, Jay teaches various amounts of
`
`lubricin for treating gout or pseudo-gout. Since the USPTO is not equipped to conduct
`
`experimentation in order to determine whether the amount recited in instant claims 12
`
`and 36 differs and, if so, to what extent, from the amount discussed in Jay; with the
`
`showing of Jay, the burden of establishing non-anticipation by objective evidence is
`
`shifted to the Applicants. With regards to the limitation recited in instant claim 28, the
`
`instant specification discloses that PRG4 at a concentration of 200 ug/ml is sufficient to
`
`decrease phagocytosis of monosodium urate monohydrate crystals by a macrophage in
`
`a joint (see Figures 1 and 4 of instant specification). Therefore, the lubricin
`
`concentration in the synovial fluid of at least greater than 250 ug/mL and/or between
`
`250 ug/mL and 450 ug/mL in Jay meets the limitation of instant claim 28. And as stated
`
`above, since the USPTO is not equipped to conduct experimentation in order to
`
`determine whether the amount recited in instant claim 28 differs and, if so, to what
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`

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`Application/Control Number: 15/808,632
`Art Unit: 1658
`
`Page 8
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`extent, from the amount discussed in Jay; with the showing of Jay, the burden of
`
`establishing non-anticipation by objective evidence is shifted to the Applicants.
`
`Furthermore, Jay teaches lubricin is delivered to the synovial cavity at a
`
`concentration in the range of 20-500 ug/mL in a volume of approximately 0.1 -2 mL per
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`injection, more preferably 1-2 mL; or at a concentration from as low as 20 ug/mL to as
`
`high as 8 mg/mL or even as high as 10 mg/mL in, for example, 2 mL of fluid; or in the
`
`amount of 4 mg/mL-5 mg/mL in, for example, 2 mL of fluid, for example, page 4,
`
`paragraphs [0034] and [0035].
`
`It meets the limitations of instant claims 14 and 38.
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`Furthermore, lubricin at a concentration of 20 ug/mL in 2 mL fluid is 40 pg, at a
`
`concentration of 4 mg/mL-5 mg/mL in 2 mL fluid is 8-10 mg, at a concentration of 8
`
`mg/mL in 2 mL fluid is 16 mg, and at a concentration of 10mg/mL in 2 mL fluid is 20 mg.
`
`These various amounts of lubricin taught in Jay meet the limitations of instant claims 16,
`
`17, 40 and 41. With regards to the limitations recited in instant claims 13 and 37, as
`
`evidenced by Fryar et al, mean age-adjusted body weight for men is 89.8 kg (197.9 lb)
`
`in 2015—2016, and mean age-adjusted body weight for women is 77.4 kg (170.6 lb) in
`
`2015—201 6 (see page 2, left column, the 2nOI paragraph in Section “Weight”).
`
`In the
`
`instant case, for example, if taking 80 kg as a mean age-adjusted body weight for
`
`human, the amount of PRG4 administered in the range of 0.1 ug/kg to 4000 ug/kg
`
`recited in instant claim 13 equals to 8 ug to 320 mg. Therefore, the various amounts of
`
`lubricin taught in Jay meet the limitations of instant claims 13 and 37.
`
`In addition, Jay teaches the subject is a human, for example, page 1, paragraph
`
`[0010].
`
`It reads on human as the elected species of subject; and meets the limitations
`
`of instant claims 18, 19, 42 and 43.
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`

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`Application/Control Number: 15/808,632
`Art Unit: 1658
`
`Page 9
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`The difference between the reference and instant claims 1, 2, 4-7, 9, 11-20, 28-
`
`31, 33 and 35-44 is that the reference does not explicitly teach the PRG4 sequence of
`
`residues 25-1404 of instant SEQ ID NO: 1 as the elected species of PRG4 or a
`
`biologically active fragment thereof; the PRG4 recited in instant claims 1 and 2;
`
`reducing joint pain in a subject with gout or pseudogout recited in instant claim 1; and
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`the limitations of instant claims 4, 20 and 44.
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`However, Jay teaches that depend on the conditions to be treated, lubricin is
`
`administrated at various schemes ranging from hours to months, even to annually, for
`
`example, page 4, paragraphs [0036] and [0037]. Therefore, one of ordinary skilled in
`
`the art would have been motivated to optimize the administrating scheme for effectively
`
`reducing joint pain in a subject with gout or pseudogout and/or effectively treating gout
`
`or pseudogout in a subject in need thereof, including weekly administration.
`
`It reads on
`
`weekly administration as the elected species of administering scheme; and meets the
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`limitations of instant claims 20 and 44. The MPEP states the following: 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 the general conditions of a claim are
`
`disclosed in the prior art, it is not inventive to discover the optimum or workable ranges
`
`by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA
`
`1955) (Claimed process which was performed at a temperature between 40°C and 80°C
`
`and an acid concentration between 25% and 70% was held to be prima facie obvious
`
`over a reference process which differed from the claims only in that the reference
`
`process was performed at a temperature of 100°C and an acid concentration of 10%.);
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`

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`Application/Control Number: 15/808,632
`Art Unit: 1658
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`Page 10
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`see also Peterson, 315 F.3d at 1330, 65 USPQZd at 1382 (“The normal desire of
`
`scientists or artisans to improve upon what is already generally known provides the
`
`motivation to determine where in a disclosed set of percentage ranges is the optimum
`
`combination of percentages”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA
`
`1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the
`
`references were held to be unpatentable thereover because, among other reasons,
`
`there was no evidence of the criticality of the claimed ranges of molecular weight or
`
`molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc.
`
`v. Biocraft Laboratories Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied,
`
`493 US. 975 (1989);
`
`In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990);
`
`and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997) (see MPEP §
`
`2144.05 II A).
`
`Furthermore, Schmidt et al teach full-length human lubricin consists of the amino
`
`acid sequence of SEQ ID NO: 1 (identical to the PRG4 of instant SEQ ID NO: 1),
`
`wherein the signal sequence of human lubricin is residues 1-24 of SEQ ID NO: 1, and
`
`the mature form of human lubricin is residues 25-1404 of SEQ ID NO: 1, for example,
`
`Figure 15; and page 2, paragraph [0014].
`
`It reads on the PRG4 sequence of residues
`
`25-1404 of instant SEQ ID NO: 1 as the elected species of PRG4 or a biologically active
`
`fragment thereof.
`
`Therefore, it would have been obvious to one of ordinary skilled in the art to
`
`combine the teachings of Jay and Schmidt et al to develop a method of treating gout or
`
`pseudogout in human, the method comprising administering to the human with gout or
`
`pseudogout a composition comprising recombinant mature human PRG4 (synonym of
`
`

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`Application/Control Number: 15/808,632
`Art Unit: 1658
`
`Page 11
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`lubricin) consisting of the residues 25-1404 of instant SEQ ID NO: 1 and a
`
`pharmaceutically acceptable carrier, wherein the PRG4 is intra-articularly injected into a
`
`toe join weekly, and wherein the amount of PRG4 administered is sufficient to achieve a
`
`concentration of PRG4 in a synovial fluid of a joint of the subject of at least 200 ug/ml.
`
`With regards to the preamble “a method of reducing joint pain” recited in instant
`
`claim 1, this is a result-oriented limitation.
`
`In the instant case, the method developed
`
`from the combined teachings of Jay and Schmidt et al comprises the same active
`
`method step, i.e., the same patient population and the same compound, therefore,
`
`administering the same compound to the same patient population would lead to the
`
`same effect, i.e., reducing joint pain in a subject with gout or pseudogout. Therefore,
`
`the method developed from the combined teachings of Jay and Schmidt et al is a
`
`method of reducing joint pain recited in instant claim 1.
`
`With regards to the limitation “wherein treating the gout or pseudogout is
`
`achieved by reducing inflammation associated with gout” recited in instant claim 4, this
`
`is a result-oriented limitation.
`
`In the instant case, the method developed from the
`
`combined teachings of Jay and Schmidt et al is a method comprising the same active
`
`method step and the same active component as the method recited in instant claim 2.
`
`Furthermore, the recombinant mature human PRG4 (synonym of lubricin) consisting of
`
`the residues 25-1404 of instant SEQ ID NO: 1 administered in the method developed
`
`from the combined teachings of Jay and Schmidt et al is identical to PRG4 disclosed on
`
`Figure 7 (the mature form of PRG4) of instant application. The instant specification
`
`discloses PRG4 inherently reduces inflammation (see page 3, paragraph [0011]; and
`
`Figures 2A-2D and 3A-3D of instant specification). Therefore, the recombinant mature
`
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`Application/Control Number: 15/808,632
`Art Unit: 1658
`
`Page 12
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`human PRG4 (synonym of lubricin) consisting of the residues 25-1404 of instant SEQ
`
`ID NO: 1 administered in the method developed from the combined teachings of Jay
`
`and Schmidt et al inherently reduces inflammation; and the method developed from the
`
`combined teachings of Jay and Schmidt et al is a method wherein treating the gout or
`
`pseudogout is achieved by reducing inflammation associated with gout.
`
`It meets the
`
`limitation of instant claim 4. Furthermore, since USPTO lacks an experimental facility to
`
`make a further determination, the burden is on Applicant to prove otherwise.
`
`One of ordinary skilled in the art would have been motivated to combine the
`
`teachings of Jay and Schmidt et al to develop a method of reducing joint pain in human
`
`with gout or pseudogout, and/or a method of treating gout or pseudogout in human, the
`
`method comprising administering to the human with gout or pseudogout a composition
`
`comprising recombinant mature human PRG4 (synonym of lubricin) consisting of the
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`residues 25-1404 of instant SEQ ID NO: 1 and a pharmaceutically acceptable carrier,
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`wherein the PRG4 is intra-articularly injected into a toe join weekly, and wherein the
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`amount of PRG4 administered is sufficient to achieve a concentration of PRG4 in a
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`synovial fluid of a joint of the subject of at least 200 ug/ml, because as stated above,
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`Jay teaches that depend on the conditions to be treated, lubricin is administrated at
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`various schemes ranging from hours to months, even to annually. Therefore, one of
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`ordinary skilled in the art would have been motivated to optimize the administrating
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`scheme for effectively reducing joint pain in a subject with gout or pseudogout and/or
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`effectively treating gout or pseudogout in a subject in need thereof, including weekly
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`administration. Schmidt et al teach full-length human lubricin consists of the amino acid
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`sequence of SEQ ID NO: 1 (identical to the PRG4 of instant SEQ ID NO: 1), wherein
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`

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`Application/Control Number: 15/808,632
`Art Unit: 1658
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`Page 13
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`the signal sequence of human lubricin is residues 1-24 of SEQ ID NO: 1, and the
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`mature form of human lubricin is residues 25-1404 of SEQ ID NO: 1.
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`A person of ordinary skilled in the art would have reasonable expectation of
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`success in combining the teachings of Jay and Schmidt et al to develop a method of
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`reducing joint pain in human with gout or pseudogout, and/or a method of treating gout
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`or pseudogout in human, the method comprising administering to the human with gout
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`or pseudogout a composition comprising recombinant mature human PRG4 (synonym
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`of lubricin) consisting of the residues 25-1404 of instant SEQ ID NO: 1 and a
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`pharmaceutically acceptable carrier, wherein the PRG4 is intra-articularly injected into a
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`toe join weekly, and wherein the amount of PRG4 administered is sufficient to achieve a
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`concentration of PRG4 in a synovial fluid of a joint of the subject of at least 200 ug/ml.
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`11.
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`Claims 1, 2, 4-7, 9, 11-20, 28-31, 33 and 35-44 are rejected under 35 U.S.C. 103
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`as being unpatentable over Jay (US 2013/0116186 A1, filed with IDS), and as
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`evidenced by Fryar et al (National Health Statistics Reports, 2018, 122, pages 1-16,
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`cited and enclosed in the previous office action), and further in view of Sullivan et al (US
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`2011/0059902 A1), Jones (July 2004, pages 1-261) and Jin et al (The Journal of
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`Biological Chemistry, 2012, 287, pages 35922-35933, filed with IDS).
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`The instant claims 1, 2, 4-7, 9, 11-20, 28-31, 33 and 35-44 are drawn to a
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`method of reducing joint pain in a subject with gout or pseudogout, and/or a method of
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`treating gout or pseudogout in a subject in need thereof, the method comprising
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`administering to the subject a composition comprising proteoglycan 4 (PRG4) consisting
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`of the amino acid residues 25-1404 of SEQ ID NO: 1.
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`

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`Application/Control Number: 15/808,632
`Art Unit: 1658
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`Page 14
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`Jay teaches a method of treating subject with an episodic case of gout or
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`pseudo-gout (one type of joint trauma), the method comprises intra-articularly injecting
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`lubricin (synonym of PRG4) into the joints such as keen, toe and others, for example,
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`page 4, paragraph [0029].
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`It meets the limitations of the patient population and the
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`active method step recited in instant claims 1 and 2.
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`lntra-articularly injecting lubricin
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`(synonym of PRG4) into toe joint in Jay reads on intra-articular injection into a toe joint
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`as the elected species of route of administering the PRG4 or a biologically active
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`fragment thereof.
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`With regards to the limitations recited in instant claims 6, 7, 9, 30, 31 and 33,
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`although Jay does not explicitly state the toe joint for intra-articular injection of lubricin is
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`the area affected by gout, since Jay teaches intra-articular injection of lubricin into toe
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`joint for treating joint trauma such as gout or pseudo-gout and re-establishing joint
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`homeostasis (see page 4, paragraph [0029]), one of skill in the art would understand
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`intra-articularly injecting lubricin into toe joint in Jay is injecting lubricin into a joint having
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`gout or an area of the patient’s body affected by gout.
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`It meets the limitations of instant
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`claims 6, 7, 9, 30, 31 and 33.
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`Jay further teaches the lubricin includes lubricating fragments, i.e., polypeptides
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`which are not full length lubricin, but which possess lubricating activity of lubricin and
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`sequence identity with lubricin, or naturally occurring, as well as synthetic or
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`recombinant isoforms and variants; and it can be a recombinant form of a human
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`lubricin polypeptide, for example, page 2, paragraph [0013]; and page 3, paragraphs
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`[0022] and [0023].
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`It meets the limitations of instant claims 5 and 29. Although Jay
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`does not explicitly state a pharmaceutical composition comprising lubricin and a
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`

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`Application/Control Number: 15/808,632
`Art Unit: 1658
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`Page 15
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`pharmaceutically acceptable carrier, Jay teach lubricin is injected as a fluid, for
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`example, page 4, paragraph [0035]. Therefore, one of skill in the art would understand
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`a pharmaceutical composition comprising lubricin and a pharmaceutically acceptable
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`carrier is used for injecting lubricin.
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`It meets the limitations of instant claims 11 and 35.
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`Jay also teaches injecting an amount of lubricin sufficient to establish a
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`bioavailable lubricin concentration in the synovial fluid (as opposed to lubricin bound to
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`cartilage) within the capsule preferably of between 100 ug/mL and 500 ug/mL,
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`preferably at least greater than 250 ug/mL, and most preferably between 250 ug/mL
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`and 450 ug/mL, for example, page 4, paragraph [0033]. A bioavailable lubricin
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`concentration in the synovial fluid of at least greater than 250 ug/mL and/or between
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`250 ug/mL and 450 ug/mL in Jay reads on administration of an amount of PRG4
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`sufficient to achieve a concentration of PRG4 in a synovial fluid of a joint of the subject
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`of at least 200 ug/ml as the elected species of amount of PRG4 or a biologically active
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`fragment thereof.
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`It meets the limitations of instant claims 15 and 39. With regards to
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`the limitations recited in instant claims 12 and 36, first, based on “(as opposed to
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`lubricin bound to cartilage)” taught in Jay, one of skill in the art would understand the
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`lubricin concentration disclosed on page 4, paragraph [0033] in Jay is an amount
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`insufficient to provide boundary lubrication. Second, since the lubricin concentration in
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`the synovial fluid of at least greater than 250 ug/mL and/or between 250 ug/mL and 450
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`ug/mL in Jay meets the limitations of instant claims 15 and 39, the lubricin concentration
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`in the synovial fluid of at least greater than 250 ug/mL and/or between 250 ug/mL and
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`450 ug/mL in Jay is an amount sufficient to treat joint pain. Therefore, the lubricin
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`concentration in the synovial fluid of at least greater than 250 ug/mL and/or between
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`

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`Application/Control Number: 15/808,632
`Art Unit: 1658
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`Page 16
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`250 ug/mL and 450 ug/mL in Jay meets the limitations of instant claims 12 and 36.
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`Furthermore, in the instant case, as stated above, Jay teaches various amounts of
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`lubricin for treating gout or pseudo-gout. Since the USPTO is not equipped to conduct
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`experimentation in order to determine whether the amount recited in instant claims 12
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`and 36 differs and, if so, to what extent, from the amount discussed in Jay; with the
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`showing of Jay, the burden of establishing non-anticipation by objective evidence is
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`shifted to the Applicants. With regards to the limitation recited in instant claim 28, the
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`instant specification discloses that PRG4 at a concentration of 200 ug/ml is sufficient to
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`decrease phagocytosis of monosodium urate monohydrate crystals by a macrophage in
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`a joint (see Figures 1 and 4 of instant specification). Therefore, the lubricin
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`concentration in the synovial fluid of at least greater than 250 ug/mL and/or between
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`250 ug/mL and 450 ug/mL in Jay meets the limitation of instant claim 28. And as stated
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`above, since the USPTO is not equipped to conduct experimentation in order to
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`determine whether the amount recited in instant claim 28 differs and, if so, to what
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`extent, from the amount discussed in Jay; with the showing of Jay, the burden of
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`establishing non-anticipation by objective evidence is shifted to the Applicants.
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`Furthermore, Jay teaches lubricin is delivered to the synovial cavity at a
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`concentration in the range of